Close relationship with the glandular capsule：a highly sensitive diagnostic indicator of major salivary gland metastatic malignancies in ultrasound.

OBJECTIVES: To investigate the ultrasound (US) characteristics of metastatic malignancies (MM) in the major salivary glands and to assess the diagnostic value of the close relationship with the glandular capsule in identifying MM. METHODS: From January 2016 and April 2022, 122 patients with major salivary gland malignancies, including 20 patients with MM and 102 patients with primary malignancies (PM) confirmed by histopathological examination, were enrolled in this study. Their clinicopathologic and US data were recorded and analyzed. The diagnostic performance of the close relationship with the glandular capsule for differentiating MM from PM was analyzed. RESULTS: The mean age of MM were older than that of PM (59.50 ± 14.57 vs. 49.96 ± 15.73, p = 0.013). Compared with PM patients, MM were associated with a higher prevalence of local pain symptoms (p = 0.007) and abnormal facial nerve function (p < 0.001). MM were also more frequently characterized by unclear borders, rough margins, irregular shapes, heterogeneous internal echos, absence of cystic areas, presence of calcifications, close relationship with the glandular capsule, and US-reported positive cervical lymph nodes (all p < 0.05). The close relationship with the glandular capsule showed to be a good indicator in distinguishing between MM and PM, with an area under the receiver operating characteristic curve of 0.863, a sensitivity of 100%, a specificity of 72.5%, and an accuracy of 92.2%. Positive and negative predictive were calculated at 41.7% and 100%, respectively. CONCLUSIONS: The US finding of a close relationship with the glandular capsule is a highly sensitive diagnostic indicator for MM. Following this finding, US-guided needle biopsy should be recommended to further confirm the diagnosis.

Diet and the risk of inflammatory bowel disease: A retrospective cohort study in Taiwan.

BACKGROUND/PURPOSE: The incidence of inflammatory bowel disease (IBD) rapidly increases in Asia, and western dietary pattern is suspected to be the major risk factor. Despite this, there has been a lack of studies analyzing the relationship between dietary patterns and IBD in Taiwan. This study examines the dietary habits of Taiwanese individuals with and without IBD to inform clinical dietary recommendations for IBD patients. METHODS: We collected baseline characteristics and dietary habits from both IBD patients and healthy controls from February and August 2022 in Chang Gung memorial hospital using a structured and validated food frequency questionnaire. The dietary habits of IBD patients in this study were focused on the six months leading up to their IBD diagnosis. RESULTS: Our study recruited 98 IBD patients and 184 healthy controls. In demographic characteristics, cigarette smoking is more common in IBD group. Besides, distinct dietary patterns were observed between groups. The healthy controls demonstrated a higher consumption of whole foods and antioxidants. By contrast, the IBD group consumed more western-style foods but the difference didn't reach statistical significance. CONCLUSION: Our study found that healthy controls in Taiwan embraced a dietary pattern rich in whole foods that may prevent IBD or reduce IBD disease activity. Nonetheless, a larger sample size is needed to further provide valuable dietary guidance for general population in Taiwan for IBD prevention or for patients with IBD for disease activity control.

Prenatal diagnosis and appearance of nasal chondromesenchymal hamartoma in a fetus: A case report.

We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid-cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow-up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high-level echo, well-defined margins and moderate vascularity.

The Gene Expression Profiles Associated with Maternal Nicotine Exposure in the Liver of Offspring Mice.

This study aims to investigate the effect of maternal nicotine exposure on the gene expression profiles in the liver of offspring mice. Pregnant mice were subcutaneously injected with either saline vehicle or nicotine twice a day on gestational days 11-21. Total RNA from the liver samples which collected from the offspring mice of postnatal day 7 and 21 was subjected to RNA sequencing. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were conducted to identify the functions of differentially expressed genes (DEGs). Four genes were selected for further validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 448 DEGs and 186 DEGs were identified on postnatal day 7 and 21, respectively. GO analysis revealed that the DEGs on postnatal day 7 mainly participated in the biological functions of cell growth and proliferation, and the DEGs on postnatal day 21 mainly participated in ion transport/activity. KEGG enrichment analysis showed that the DEGs on postnatal day 7 were mainly enriched in the cell cycle, cytokine-cytokine receptor interactions, hypertrophic cardiomyopathy, and the p53 signaling pathway, while the DEGs on postnatal day 21 were mainly enriched in neuroactive ligand-receptor interactions, the calcium signaling pathway, retinol metabolism, and axon guidance. The qRT-PCR results were consistent with the RNA sequencing data. The DEGs may affect the growth of liver in early postnatal period while may affect ion transport/activity in late postnatal period.

Adding nutritional status to the original BCLC stage improves mortality prediction for hepatocellular carcinoma patients in HBV-endemic regions.

Hepatocellular carcinoma (HCC) is associated with high mortality, especially in Asian populations where chronic HBV infection is a major cause. Accurate prediction of mortality can assist clinical decision-making. We aim to (i) compare the predicting ability of Barcelona Clinic Liver Cancer classification (BCLC) stage, neutrophil-to-lymphocyte ratio (NLR), and Albumin-Bilirubin (ALBI) score in predicting short-term mortality (one- and two-year) and (ii) develop a novel model with improved accuracy compared to the conventional models. This study enrolled 298 consecutive HCC patients from our hepatology department. The prognostic values for mortality were assessed by area under the receiver operating characteristic curve (AUROC) analysis. A novel model was established and internally validated using 5-fold cross-validation, followed by external validation in a cohort of 100 patients. The primary etiology of cirrhosis was hepatitis B virus (HBV), with 81.2% of HCC patients having preserved liver function. Significant differences were observed in hemoglobin (Hb) and serum albumin levels, which reflect patients' nutrition status, between patients who survived for one year and those who died. BCLC exhibited superior predictive accuracy compared to NLR but had borderline superiority to the ALBI score. Therefore, a novel model incorporating BCLC, Hb, and serum albumin was developed, internally and externally validated, as well as subgroup sensitivity analysis. The model exhibited significantly higher predictive accuracy for one- and two-year mortality than conventional prognostic predictors, with AUROC values of 0.841 and 0.805, respectively. The novel "BCLC-Nutrition Model", which incorporates BCLC, Hb, and serum albumin, may provide improved predictive accuracy for short-term mortality in HCC patients compared to commonly used prognostic scores. This emphasizes the importance of nutrition in the management of HCC patients.

Synthesis of Quercetin-Acid Esters and Its Reduction of H2 O2 -Triggered PC12 Cells Damage by Down-Regulating ROS.

Quercetin is a kind of polyphenolic flavonoid compounds which has perfect antioxidant properties. However, quercetin is not available in many situations due to its poor bioavailability. In this work, the QAEs with better solubility and even stronger antioxidant properties were synthesized, through the esterification between quercetin and the chlorinated cinnamic acid or its derivatives, whose chlorination were achieved by using SOCl2 . The protective effects of the QAEs were evaluated by the H2 O2 -induced apoptosis experiment in rat adrenal pheochromocytoma cells (PC12 cells) and its ability to remove ROS generated by oxidative stress. Compared with the original quercetin group, the QAEs groups showed much improved cell viability and capability of removing ROS, which means their higher bioavailability than the parent.

Mucinous Adenocarcinoma of the Lung Diagnosed by Radial Endobronchial Ultrasound-guided Bronchoscopic Cryobiopsy and Presenting as Interstitial Lung Disease in a Patient with Systemic Sclerosis.

We report a patient with systemic sclerosis who was diagnosed with advanced-stage mucinous adenocarcinoma of the lungs. The clinical presentation, imaging findings, pathological results, and molecular diagnoses are presented. A 64-year-old woman with systemic sclerosis was administered prednisolone and hydroxychloroquine sulfate to control her disease. High-resolution computed tomography (HRCT) revealed an interstitial pattern in both lungs during annual imaging. Connective tissue disease-associated interstitial lung disease (CTD-ILD) was diagnosed using blood tests, pulmonary function tests, and imaging findings. One year later, the patient underwent follow-up chest HRCT, which showed progressive lung disease. The patient underwent endobronchial ultrasound (EBUS)-guided transbronchial lung cryobiopsy and computed tomography-guided biopsy for a pathological diagnosis. The pathology reports of bilateral lungs disclosed mucinous adenocarcinoma. After tumor staging and mutation testing, the patient received chemotherapy with pemetrexed and cisplatin. The bilateral lung lesions subsided after four cycles of first-line chemotherapy. Patients with CTD and lung involvement may be diagnosed with CTD-ILD. Although histopathological results are not mandatory for ILD diagnosis, EBUS-guided transbronchial lung biopsy or lung cryobiopsy should be considered when ILD has atypical or unexplained features.

Automated 3D segmentation of the aorta and pulmonary artery for predicting outcomes after thoracoscopic lobectomy in lung cancer patients.

Background: Preoperative two-dimensional manual measurement of pulmonary artery diameter in a single-cut axial view computed tomography (CT) image is a commonly used non-invasive prediction method for pulmonary hypertension. However, the accuracy may be unreliable. Thus, this study aimed to evaluate the correlation of short-term surgical outcomes and pulmonary artery/aorta (PA/Ao) diameter ratio measured by automated three-dimensional (3D) segmentation in lung cancer patients who underwent thoracoscopic lobectomy. Materials and methods: We included 383 consecutive lung cancer patients with thin-slice CT images who underwent lobectomy at a single institute between January 1, 2011 and December 31, 2019. Automated 3D segmentation models were used for 3D vascular reconstruction and measurement of the average diameters of Ao and PA. Propensity-score matching incorporating age, Charlson comorbidity index, and lobectomy performed by uniportal VATS was used to compare clinical outcomes in patients with PA/Ao ratio ≥1 and those <1. Results: Our segmentation method measured 29 (7.57%) patients with a PA/Ao ratio ≥1. After propensity-score matching, a higher overall postoperative complication classified by the Clavien-Dindo classification (p = 0.016) were noted in patients with 3D PA/Ao diameter ratio ≥1 than those of <1. By multivariate logistic regression, patients with a 3D PA/Ao ratio ≥ 1 (p = 0.013) and tumor diameter > 3 cm (p = 0.002) both significantly predict the incidence of postoperative complications. Conclusions: Pulmonary artery/aorta diameter ratio ≥ 1 measured by automated 3D segmentation may predict postoperative complications in lung cancer patients who underwent lobectomy.

Research Progress for RNA Modifications in Physiological and Pathological Angiogenesis.

As a critical layer of epigenetics, RNA modifications demonstrate various molecular functions and participate in numerous biological processes. RNA modifications have been shown to be essential for embryogenesis and stem cell fate. As high-throughput sequencing and antibody technologies advanced by leaps and bounds, the association of RNA modifications with multiple human diseases sparked research enthusiasm; in addition, aberrant RNA modification leads to tumor angiogenesis by regulating angiogenesis-related factors. This review collected recent cutting-edge studies focused on RNA modifications (N6-methyladenosine (m6A), N5-methylcytosine (m5C), N7-methylguanosine (m7G), N1-methyladenosine (m1A), and pseudopuridine (Ψ)), and their related regulators in tumor angiogenesis to emphasize the role and impact of RNA modifications.

Correction: Wang et al. Automated 3D Segmentation of the Aorta and Pulmonary Artery on Non-Contrast-Enhanced Chest Computed Tomography Images in Lung Cancer Patients. Diagnostics 2022, 12, 967.

Errors occurred in the standard deviation of the Dice similarity coefficient (DSC) described in the original publication [...].

Automated 3D Segmentation of the Aorta and Pulmonary Artery on Non-Contrast-Enhanced Chest Computed Tomography Images in Lung Cancer Patients.

Pulmonary hypertension should be preoperatively evaluated for optimal surgical planning to reduce surgical risk in lung cancer patients. Preoperative measurement of vascular diameter in computed tomography (CT) images is a noninvasive prediction method for pulmonary hypertension. However, the current estimation method, 2D manual arterial diameter measurement, may yield inaccurate results owing to low tissue contrast in non-contrast-enhanced CT (NECT). Furthermore, it provides an incomplete evaluation by measuring only the diameter of the arteries rather than the volume. To provide a more complete and accurate estimation, this study proposed a novel two-stage deep learning (DL) model for 3D aortic and pulmonary artery segmentation in NECT. In the first stage, a DL model was constructed to enhance the contrast of NECT; in the second stage, two DL models then applied the enhanced images for aorta and pulmonary artery segmentation. Overall, 179 patients were divided into contrast enhancement model (n = 59), segmentation model (n = 120), and testing (n = 20) groups. The performance of the proposed model was evaluated using Dice similarity coefficient (DSC). The proposed model could achieve 0.97 ± 0.66 and 0.93 ± 0.16 DSC for aortic and pulmonary artery segmentation, respectively. The proposed model may provide 3D diameter information of the arteries before surgery, facilitating the estimation of pulmonary hypertension and supporting preoperative surgical method selection based on the predicted surgical risks.

First report of an adult female patient with endobronchial inflammatory myofibroblastic tumor in Taiwan: A case report.

An inflammatory myofibroblastic tumor (IMT) of the respiratory system is an uncommon disease. In Taiwan, there is a lack of previous studies on tracheobronchial IMT. The tumor is characterized by overexpression of anaplastic lymphoma receptor tyrosine kinase (ALK)-1. Surgical resection is the standard treatment of choice nowadays.

Hepatitis B Virus X Protein Increases 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine (8-Oxodg) Level via Repressing MTH1/ MTH2 Expression in Hepatocytes.

BACKGROUND/AIMS: Chronic hepatitis B virus (HBV) infection markedly increases the risk of development of hepatocellular carcinoma (HCC). Among the seven viral proteins that HBV encodes, HBV X protein (HBx) appears to have the most oncogenic potential. The mitochondria-associated HBx can induce oxidative stress in hepatocytes, leading to the production of abundant reactive oxygen species (ROS). High levels of ROS usually induce oxidative DNA damage and 8-hydroxy-2-deoxyguanosine (8-OHdG), also known as 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG), which is one of the major products of DNA oxidation and an important biomarker for oxidative stress and carcinogenesis. Cells have evolved a mechanism to prevent oxidized nucleotides from their incorporation into DNA through nucleotide pool sanitization enzymes of MTH1 (NUDT1), MTH2 (NUDT15), MTH3 (NUDT18) and NUDT5. However, little is known as to whether HBx can regulate the expression of those enzymes and modulate the formation and accumulation of 8-oxodG in hepatocytes. METHODS: The level of 8-oxodG was assessed by ELISA in stable HBV-producing hepatoma cell lines, an HBV infectious mouse model, HBV and HBx transgenic mice and HBV-infected patients versus their respective controls. Expression of MTH1, MTH2, MTH3 and NUDT5 was determined by a real-time quantitative PCR and western blot analysis. Transcriptional regulation of MTH1 and MTH2 expression by HBx and the effect of HBx on MTH1 and MTH2 promoter hypermethylation were examined using a luciferase reporter assay and bisulfite sequencing analysis. RESULTS: In comparison with controls, significantly higher levels of 8-oxodG were detected in the genome and culture supernatant of stable HBV-producing HepG2.2.15 cells, in the sera and liver tissues of HBV infectious mice and HBV or HBx transgenic mice, and in the sera of HBV-infected patients. Expression of HBx in hepatocytes significantly increased 8-oxodG level and reduced the expression of MTH1 and MTH2 at both mRNA and protein levels. It was also demonstrated that HBx markedly attenuated the MTH1 or MTH2 promoter activities through hypermethylation. Furthermore, enhancement of 8-oxodG production by HBx was reversible by overexpression of MTH1 and MTH2. CONCLUSION: Our data show that HBx expression results in the accumulation of 8-oxodG in hepatocytes through inhibiting the expression of MTH1 and MTH2. This may implicate that HBx may act as a tumor promoter through facilitating the mutational potential of 8-oxodG thus connecting a possible link between HBV infection and liver carcinogenesis.

Hepatitis B Virus Surface Antigen Enhances the Sensitivity of Hepatocytes to Fas-Mediated Apoptosis via Suppression of AKT Phosphorylation.

The Fas receptor/ligand system plays a prominent role in hepatic apoptosis and hepatocyte death. Although hepatitis B virus (HBV) surface Ag (HBsAg) is the most abundant HBV protein in the liver and peripheral blood of patients with chronic HBV infection, its role in Fas-mediated hepatocyte apoptosis has not been disclosed. In this study, we report that HBsAg sensitizes HepG2 cells to agonistic anti-Fas Ab CH11-induced apoptosis through increasing the formation of SDS-stable Fas aggregation and procaspase-8 cleavage but decreasing both the expression of cellular FLIPL/S and the recruitment of FLIPL/S at the death-inducing signaling complex (DISC). Notably, HBsAg increased endoplasmic reticulum stress and consequently reduced AKT phosphorylation by deactivation of phosphoinositide-dependent kinase-1 (PDPK1) and mechanistic target of rapamycin complex 2 (mTORC2), leading to enhancement of Fas-mediated apoptosis. In a mouse model, expression of HBsAg in mice injected with recombinant adenovirus-associated virus 8 aggravated Jo2-induced acute liver failure, which could be effectively attenuated by the AKT activator SC79. Based on these results, it is concluded that HBsAg predisposes hepatocytes to Fas-mediated apoptosis and mice to acute liver failure via suppression of AKT prosurviving activity, suggesting that interventions directed at enhancing the activation or functional activity of AKT may be of therapeutic value in Fas-mediated progressive liver cell injury and liver diseases.

A Novel AKT Activator, SC79, Prevents Acute Hepatic Failure Induced by Fas-Mediated Apoptosis of Hepatocytes.

Acute liver failure is a serious clinical problem of which the underlying pathogenesis remains unclear and for which effective therapies are lacking. The Fas receptor/ligand system, which is negatively regulated by AKT, is known to play a prominent role in hepatocytic cell death. We hypothesized that AKT activation may represent a strategy to alleviate Fas-induced fulminant liver failure. We report here that a novel AKT activator, SC79, protects hepatocytes from apoptosis induced by agonistic anti-Fas antibody CH11 (for humans) or Jo2 (for mice) and significantly prolongs the survival of mice given a lethal dose of Jo2. Under Fas-signaling stimulation, SC79 inhibited Fas aggregation, prevented the recruitment of the adaptor molecule Fas-associated death domain (FADD) and procaspase-8 [or FADD-like IL-1ß-converting enzyme (FLICE)] into the death-inducing signaling complex (DISC), but SC79 enhanced the recruitment of the long and short isoforms of cellular FLICE-inhibitory protein at the DISC. All of the SC79-induced hepatoprotective and DISC-interruptive effects were confirmed to have been reversed by the Akt inhibitor LY294002. These results strongly indicate that SC79 protects hepatocytes from Fas-induced fatal hepatic apoptosis. The potent alleviation of Fas-mediated hepatotoxicity by the relatively safe drug SC79 highlights the potential of our findings for immediate hepatoprotective translation.

Hepatitis B virus core protein inhibits Fas-mediated apoptosis of hepatoma cells via regulation of mFas/FasL and sFas expression.

Hepatitis B virus core protein (HBc) has been implicated in hepatocarcinogenesis through several mechanisms. Resistance of hepatitis B virus (HBV)-infected hepatocytes to apoptosis is considered one of the major contributors to the progression of chronic hepatitis to cirrhosis and ultimately to hepatocellular carcinoma. The Fas receptor/ligand (Fas/FasL) system plays a prominent role in hepatocyte death during HBV infection. Here we report that HBc mediates resistance of hepatoma cells to agonistic anti-Fas antibody (CH11)-induced apoptosis. When HBc was introduced into human hepatoma cells, the cells became resistant to CH11 cytotoxicity in a p53-dependent manner. HBc significantly down-regulated the expression of p53, total Fas, and membrane-bound Fas at the mRNA and protein levels and reduced FasL mRNA expression. In contrast, HBc up-regulated the expression of soluble forms of Fas by increasing Fas alternative mRNA splicing. Mechanistically, HBc-mediated Fas alternative mRNA splicing was associated with up-regulation of polypyrimidine tract-binding protein 1 and down-regulation of Fas-activated serine/threonine kinase. These results indicated that HBc may prevent hepatocytes from Fas-induced apoptosis by the dual effects of reducing the expression of the proapoptotic form of Fas and enhancing the expression of the antiapoptotic form of the receptor, which may contribute to the survival and persistence of infected hepatocytes during chronic infection.

Sequelae of iatrogenic periodontal destruction associated with elastics and permanent incisors: literature review and report of 3 cases.

The purpose of this paper was to report 3 cases of localized aggressive periodontal bone destruction related to improper use of orthodontic elastic bands to close diastemas in permanent anterior teeth and to compare the results to previous studies. Some common signs and symptoms of this particular destruction were observed with these patients that had been previously reported when the comparisons of these cases were made. The patients usually experienced a painful sensation, and an isolated pyogenic-like granuloma appeared at the interdental area. Radiographs revealed localized periodontal destruction, with tooth extrusion and clinical crown divergence and radiographic root convergence; the two involved teeth moved simultaneously during mobility testing. Surgical intervention and treatment of the cases was described. The prognosis is usually decided by the severity of the condition, and many factors may influence the healing of treated cases.