Chromatin remodeling-driven autophagy activation induces cisplatin resistance in oral squamous cell carcinoma.

It is still challenging to predict the efficacy of cisplatin-based therapy, particularly in relation to the activation of macroautophagy/autophagy in oral squamous cell carcinoma (OSCC). We studied the effect of selected chromatin remodeling genes on the cisplatin resistance and their interplay with autophagy in 3-dimensional tumor model and xenografts. We analyzed gene expression patterns in the cisplatin-sensitive UMSCC1, and a paired cisplatin-resistant UM-Cis cells. Many histone protein gene clusters involved in nucleosome assembly showed significant difference of expression. Gain- and loss-of-function analyses revealed an inverse correlation between cisplatin resistance and HIST1H3D expression, while a positive correlation was observed with HIST3H2A or HIST3H2B expression. In UM-Cis, HIST3H2A- and HIST3H2B-mediated chromatin remodeling upregulates autophagy status, which results in cisplatin resistance. Additionally, knockdown of HIST3H2A or HIST3H2B downregulated autophagy-activating genes via chromatin compaction of their promoter regions. MiTF, one of the key autophagy regulators upregulated in UM-Cis, negatively regulated transcription of HIST1H3D, suggesting an interplay between chromatin remodeling-dependent cisplatin resistance and autophagy. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, protein expression pattern of the selected histone protein genes were matched with the in vitro data. By examining the relationship between autophagy and chromatin remodeling genes, we identified a set of candidate genes with potential use as markers predicting chemoresistance in OSCC biopsy samples.

Flavonoid gossypetin protects alveolar bone and limits inflammation in ligature-induced periodontitis in mice.

BACKGROUND: Bacterial-induced inflammation instigates the destruction of hard and soft tissues surrounding teeth in periodontitis. In severe cases, the increased number and activity of osteoclasts induces the resorption of alveolar bones, ultimately leading to tooth loss. Because of their diverse chemical structures and bioactivities, natural compounds are often suggested to treat a wide variety of diseases, including inflammatory disorders. METHODS: In the present study, we demonstrated an inhibitory effect of gossypetin, a hexahydroxy flavone, on osteoclast differentiation and bone resorption using in vitro culture of osteoclasts from mouse bone marrow macrophage (BMM) precursors and in vivo model of ligature-induced periodontitis in mice. RESULTS: Gossypetin significantly reduced the differentiation of osteoclasts from mouse BMM precursors in the presence of the receptor activator of nuclear factor κB ligand (RANKL). In vitro, gossypetin inhibited critical signaling events downstream of RANKL including the auto-amplification of nuclear factor of activated T-cells, cytoplasmic 1, Ca2+ oscillations, and the generation of reactive oxygen species. In a mouse ligature-induced periodontitis model, the administration of gossypetin significantly reduced osteoclastogenesis and alveolar bone resorption. Furthermore, gossypetin prevented the ligature-induced increase in macrophages and T cells and reduced the production of tumor necrosis factor-α and interleukin-6. CONCLUSION: Taken together, these results show anti-osteoclastogenic and anti-inflammatory effects of gossypetin, suggesting the potential use of this natural compound in periodontitis.

Endothelial and macrophage interactions in the angiogenic niche.

The interactions between vascular cells, especially endothelial cells, and macrophages play a pivotal role in maintaining the subtle balance of vascular biology, which is crucial for angiogenesis in both healthy and diseased states. These cells are central to ensuring a harmonious balance between tissue repair and preventing excessive angiogenic activity, which could lead to pathological conditions. Recent advances in sophisticated genetic engineering vivo models and novel sequencing approaches, such as single-cell RNA-sequencing, in immunobiology have significantly enhanced our understanding of the gene expression and behavior of macrophages. These insights offer new perspectives on the role macrophages play not only in development but also across various health conditions. In this review, we explore the complex interactions between multiple types of macrophages and endothelium, focusing on their impact on new blood vessel formation. By understanding these intricate interactions, we aim to provide insights into new methods for managing angiogenesis in various diseases, thereby offering hope for the development of novel therapeutic approaches.

Genetically Engineered CLDN18.2 CAR-T Cells Expressing Synthetic PD1/CD28 Fusion Receptors Produced Using a Lentiviral Vector.

This study aimed to develop synthetic Claudin18.2 (CLDN18.2) chimeric antigen receptor (CAR)-T (CAR-T) cells as a treatment for advanced gastric cancer using lentiviral vector genetic engineering technology that targets the CLDN18.2 antigen and simultaneously overcomes the immunosuppressive environment caused by programmed cell death protein 1 (PD-1). Synthetic CAR T cells are a promising approach in cancer immunotherapy but face many challenges in solid tumors. One of the major problems is immunosuppression caused by PD-1. CLDN18.2, a gastric-specific membrane protein, is considered a potential therapeutic target for gastric and other cancers. In our study, CLDN18.2 CAR was a second-generation CAR with inducible T-cell costimulatory (CD278), and CLDN18.2-PD1/CD28 CAR was a third-generation CAR, wherein the synthetic PD1/CD28 chimeric-switch receptor (CSR) was added to the second-generation CAR. In vitro, we detected the secretion levels of different cytokines and the killing ability of CAR-T cells. We found that the secretion of cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) secreted by three types of CAR-T cells was increased, and the killing ability against CLDN18.2-positive GC cells was enhanced. In vivo, we established a xenograft GC model and observed the antitumor effects and off-target toxicity of CAR-T cells. These results support that synthetic anti-CLDN18.2 CAR-T cells have antitumor effect and anti-CLDN18.2-PD1/CD28 CAR could provide a promising design strategy to improve the efficacy of CAR-T cells in advanced gastric cancer.

Differential effect of cancer-associated fibroblast-derived extracellular vesicles on cisplatin resistance in oral squamous cell carcinoma via miR-876-3p.

Rationale: Platinum-based chemotherapy is commonly used for treating solid tumors, but drug resistance often limits its effectiveness. Cancer-associated fibroblast (CAF)-derived extracellular vesicle (EV), which carry various miRNAs, have been implicated in chemotherapy resistance. However, the molecular mechanism through which CAFs modulate cisplatin resistance in oral squamous cell carcinoma (OSCC) is not well understood. We employed two distinct primary CAF types with differential impacts on cancer progression: CAF-P, representing a more aggressive cancer-promoting category, and CAF-D, characterized by properties that moderately delay cancer progression. Consequently, we sought to investigate whether the two CAF types differentially affect cisplatin sensitivity and the underlying molecular mechanism. Methods: The secretion profile was examined by utilizing an antibody microarray with conditioned medium obtained from the co-culture of OSCC cells and two types of primary CAFs. The effect of CAF-dependent factors on cisplatin resistance was investigated by utilizing conditioned media (CM) and extracellular vesicle (EVs) derived from CAFs. The impacts of candidate genes were confirmed using gain- and loss-of-function analyses in spheroids and organoids, and a mouse xenograft. Lastly, we compared the expression pattern of the candidate genes in tissues from OSCC patients exhibiting different responses to cisplatin. Results: When OSCC cells were cultured with conditioned media (CM) from the two different CAF groups, cisplatin resistance increased only under CAF-P CM. OSCC cells specifically expressed insulin-like growth factor binding protein 3 (IGFBP3) after co-culture with CAF-D. Meanwhile, IGFBP3-knockdown OSCC cells acquired cisplatin resistance in CAF-D CM. IGFBP3 expression was promoted by GATA-binding protein 1 (GATA1), a transcription factor targeted by miR-876-3p, which was enriched only in CAF-P-derived EV. Treatment with CAF-P EV carrying miR-876-3p antagomir decreased cisplatin resistance compared to control miRNA-carrying CAF-P EV. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, there was a positive correlation between IGFBP3 and GATA1 expression and cisplatin sensitivity in OSCC tissues from patients. Conclusion: These results provide insights for overcoming cisplatin resistance, especially concerning EVs within the tumor microenvironment. Furthermore, it is anticipated that the expression levels of GATA1 and miR-876-3p, along with IGFBP3, could aid in the prediction of cisplatin resistance.

Evaluation of sample preparation methods for suspect and non-target screening in water, sediment, and biota samples using gas chromatography coupled to high-resolution mass spectrometry.

In this study, the sample preparation methods were proposed for the suspect and non-target screening (SNTS) using gas chromatography coupled to high-resolution mass spectrometry in the aquatic environment. The pretreatment methods were evaluated based on detection rates, recoveries, and screening detection limits (SDLs) for 316 substances spiked into surface water, sediment, and biota samples. The detection rates of the spiked compounds were 92.1 % and 98.7 % by the sample preparation methods for water (solid-phase extraction using HLB cartridge) and sediment (ultrasonic extraction (USE) with HLB cartridge clean-up), respectively. Similarly, USE with HLB cartridge clean-up gave the highest detection rate (87.9 %) for biota samples; however, additional pretreatment method using deactivated silica gel clean-up was necessary for the detection of persistent organic pollutants (POPs). The SDL ranges of spiked compounds by the suggested pretreatment methods were 0.01-23.5 ng/L for surface water, 0.02-37.5 ng/g dry weight for sediment, and 0.01-12.2 ng/g wet weight for biota. Although some pollutants, such as POPs had SDLs that were higher than the levels normally detected in the aquatic environment as reported in previous studies, the analytical methods suggested in the present study were satisfactory for the SNTS of most pollutants originated from anthropogenic sources.

Soft Microdenticles on Artificial Octopus Sucker Enable Extraordinary Adaptability and Wet Adhesion on Diverse Nonflat Surfaces.

Bioinspired soft devices, which possess high adaptability to targeted objects, provide promising solutions for a variety of industrial and medical applications. However, achieving stable and switchable attachment to objects with curved, rough, and irregular surfaces remains difficult, particularly in dry and underwater environments. Here, a highly adaptive soft microstructured switchable adhesion device is presented, which is inspired by the geometric and material characteristics of the tiny denticles on the surface of an octopus sucker. The contact interface of the artificial octopus sucker (AOS) is imprinted with soft, microscale denticles that interact adaptably with highly rough or curved surfaces. Robust and controllable attachment of the AOS with soft microdenticles (AOS-sm) to dry and wet surfaces with diverse morphologies is achieved, allowing conformal attachment on curved and soft objects with high roughness. In addition, AOS-sms assembled with an octopus-arm-inspired soft actuator demonstrate reliable grasping and the transport of complex polyhedrons, rough objects, and soft, delicate, slippery biological samples.

Removal of oxytetracycline from water by liquid-phase plasma process with an iron precipitated TiO2 photocatalyst.

This study developed a new water treatment method using liquid-phase plasma (LPP) process that can decompose oxytetracycline (OTC) remaining in the aquatic environment. Relatedly, the OTC causes damage to the human body and cannot be removed by traditional water treatment methods. The study also prepared Fe/TiO2 photocatalyst responding to visible light using the LPP process. In particular, the OTC decomposition efficiency of the LPP process improved by more than 10% with the use of the Fe/TiO2 photocatalyst as compared to that of the one with the use of bare TiO2 photocatalyst. Further, the optimal LPP process parameters and Fe/TiO2 photocatalyst amount in the LPP process for OTC decomposition were established in the study. Finally, the degradation pathway of the OTC in the LPP process was found based on the five intermediates of the LPP reaction that were detected by the liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis. In particular, the decomposition pathway was estimated to be involving the mineralization of the OTC through demethylation, deamination, dehydration, and ring cleavage.

Pennogenin-3-O-α-L-Rhamnopyranosyl-(1→2)-[α-L-Rhamnopyranosyl-(1→3)]-ß-D-Glucopyranoside (Spiroconazol A) Isolated from Dioscorea bulbifera L. var. sativa Induces Autophagic Cell Death by p38 MAPK Activation in NSCLC Cells.

In our previous study, we reported the isolation of pennogenin-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-ß-D-glucopyranoside (spiroconazol A), a steroidal saponin, from the flowers of Dioscorea bulbifera L. var. sativa. In the present study, we aimed to investigate the effects of spiroconazol A on autophagy and its underlying mechanisms in A549 and NCI-H358 human non-small cell lung cancer (NSCLC) cells. Spiroconazol A inhibited the proliferation of NSCLC cells in a concentration- and time-dependent manner. To determine the type of programmed cell death induced by spiroconazol A, we performed a characterization of apoptosis in spiroconazol A-treated A549 cells. Our results showed that spiroconazol A significantly suppressed A549 cell viability but did not influence cell apoptosis because phosphatidylserine and caspase activation were not detected. Furthermore, spiroconazol A treatment upregulated the expression of LC3-II and autophagy-related Beclin-1 protein, suggesting that spiroconazol A induces autophagy in A549 cells. Moreover, spiroconazol A activated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) but did not affect the phosphorylation of Janus kinase or ERK1/2. Notably, SB203580, a p38 MAPK inhibitor, had a significant inhibitory effect on spiroconazol A-induced autophagic cell death in A549 cells. Our results indicated that spiroconazol A-induced autophagy is dependent on p38 MAPK signaling and has potential as a therapeutic target in NSCLC.

Enhanced osteogenic differentiation of mesenchymal stem cells by surface lithium modification in a sandblasted/acid-etched titanium implant.

This study investigated the osteogenesis-related cell functions of osteoprogenitor cells modulated by surface chemistry modification using lithium (Li) ions in a current clinical oral implant surface in order to gain insights into the future development of titanium (Ti) implants with enhanced osteogenic capacity. Wet chemical treatment was performed to modify a sandblasted/acid-etched (SLA) Ti implant surface using Li ions. The osteogenesis-related cell response to the surface Li ion-modified SLA sample was evaluated using two kinds of murine bone marrow stem cells, bipotent ST2 cells and primary multipotent mesenchymal stem cells (MSCs). The modified surface exhibited the formation of an Li-containing Ti oxide layer with plate-like nanostructures. The Li-incorporated surface enhanced early cellular events, including spreading, focal adhesion formation and integrin mRNA expression (α2, α5, αv and ß3), and accelerated osteogenic differentiation of bipotent ST2 cells compared with unmodified SLA surface. Surface Li modification significantly increased GSK-3ß phosphorylation and suppressed ß-catenin phosphorylation, and promoted the subsequent osteogenic differentiation of primary MSCs. These results indicate that surface chemistry modification of SLA implants by wet chemical treatment with Li ions induces a more favorable osseointegration outcome through the promotion of the osteogenic differentiation of bone marrow MSCs via the positive regulation of GSK-3ß and ß-catenin activity.

Electrostatic-Mechanical Synergistic In Situ Multiscale Tissue Adhesion for Sustainable Residue-Free Bioelectronics Interfaces.

Recent studies on soft adhesives have sought to deeply understand how their chemical or mechanical structures interact strongly with living tissues. The aim is to optimally address the unmet needs of patients with acute or chronic diseases. Synergistic adhesion involving both electrostatic (hydrogen bonds) and mechanical interactions (capillarity-assisted suction stress) seems to be effective in overcoming the challenges associated with long-term unstable coupling to tissues. Here, an electrostatically and mechanically synergistic mechanism of residue-free, sustainable, in situ tissue adhesion by implementing hybrid multiscale architectonics. To deduce the mechanism, a thermodynamic model based on a tailored multiscale combinatory adhesive is proposed. The model supports the experimental results that the thermodynamically controlled swelling of the nanoporous hydrogel embedded in the hierarchical elastomeric structure enhances biofluid-insensitive, sustainable, in situ adhesion to diverse soft, slippery, and wet organ surfaces, as well as clean detachment in the peeling direction. Based on the robust tissue adhesion capability, universal reliable measurements of electrophysiological signals generated by various tissues, ranging from rodent sciatic nerve, the muscle, brain, and human skin, are successfully demonstrated.

Preparation and Characterization of Silver-Iron Bimetallic Nanoparticles on Activated Carbon Using Plasma in Liquid Process.

The mono and bi-metallic nanoparticles have conspicuous properties and are widely used in the environment, energy, and medical fields. In this study, bimetallic nanoparticles composed of silver and iron were precipitated on the surface of activated carbon in a single process using plasma in liquid process (PLP). Silver-iron ions and various radicals were actively generated in the aqueous reactant solution by the PLP. Although metals were precipitated on AC depending on the number of precursors added to the aqueous reactant solution, the standard reduction potential of silver ions was higher than that of iron ions, so silver precipitated on AC. The silver precipitate on AC was a mixture of metallic silver and silver oxide, and iron was present as Fe3O4. Spherical nanoparticles, 100-120 nm in size, were observed on the surface of the Ag-Fe/AC composite. The composition of the bimetallic nanoparticles could be controlled by considering the ionization tendency and standard reduction potential of metal ions and controlling the concentration of the precursors. The PLP presented in this study can be applied to the preparing method of bimetallic nanoparticle/carbon materials and can be expected to be used in the prepare of energy and environmental materials such as MFC and absorption materials for removing pollutants.

Colon cancer cells acquire immune regulatory molecules from tumor-infiltrating lymphocytes by trogocytosis.

Cancer cells can develop an immunosuppressive tumor microenvironment to control tumor-infiltrating lymphocytes. The underlying mechanisms still remain unclear. Here, we report that mouse and human colon cancer cells acquire lymphocyte membrane proteins including cellular markers such as CD4 and CD45. We observed cell populations harboring both a tumor-specific marker and CD4 in the tumor microenvironment. Sorted cells from these populations were capable of forming organoids, identifying them as cancer cells. Live imaging analysis revealed that lymphocyte membrane proteins were transferred to cancer cells via trogocytosis. As a result of the transfer in vivo, cancer cells also acquired immune regulatory surface proteins such as CTLA4 and Tim3, which suppress activation of immune cells [T. L. Walunas et al, Immunity 1, 405-413 (1994) and L. Monney et al., Nature 415, 536-541 (2002)]. RNA sequencing analysis of ex vivo-cocultured splenocytes with trogocytic cancer cells showed reductions in Th1 activation and natural killer cell signaling pathways compared with the nontrogocytic control. Cancer cell trogocytosis was confirmed in the patient-derived xenograft models of colorectal cancer and head and neck cancer. These findings suggest that cancer cells utilize membrane proteins expressed in lymphocytes, which in turn contribute to the development of the immunosuppressive tumor microenvironment.

Differential Angiogenic Potential of 3-Dimension Spheroid of HNSCC Cells in Mouse Xenograft.

The experimental animal model is still essential in the development of new anticancer drugs. We characterized mouse tumors derived from two-dimensional (2D) monolayer cells or three-dimensional (3D) spheroids to establish an in vivo model with highly standardized conditions. Primary cancer-associated fibroblasts (CAFs) were cultured from head and neck squamous cell carcinoma (HNSCC) tumor tissues and co-injected with monolayer cancer cells or spheroids into the oral mucosa of mice. Mice tumor blood vessels were stained, followed by tissue clearing and 3D Lightsheet fluorescent imaging. We compared the effect of exosomes secreted from 2D or 3D culture conditions on the angiogenesis-related genes in HNSCC cells. Our results showed that both the cells and spheroids co-injected with primary CAFs formed tumors. Interestingly, vasculature was abundantly distributed inside the spheroid-derived but not the monolayer-derived mice tumors. In addition, cisplatin injection more significantly decreased spheroid-derived but not monolayer-derived tumor size in mice. Additionally, exosomes isolated from co-culture media of FaDu spheroid and CAF upregulated angiogenesis-related genes in HNSCC cells as compared to exosomes from FaDu cell and CAF co-culture media under in vitro conditions. The mouse tumor xenograft model derived from 3D spheroids of HNSCC cells with primary CAFs is expected to produce reliable chemotherapy drug screening results given the robust angiogenesis and lack of necrosis inside tumor tissues.

Holographic metasurface gas sensors for instantaneous visual alarms.

The rapid detection of biological and chemical substances in real time is particularly important for public health and environmental monitoring and in the military sector. If the process of substance detection to visual reporting can be implemented into a single miniaturized sensor, there could be a profound impact on practical applications. Here, we propose a compact sensor platform that integrates liquid crystals (LCs) and holographic metasurfaces to autonomously sense the existence of a volatile gas and provide an immediate visual holographic alarm. By combining the advantage of the rapid responses to gases realized by LCs with the compactness of holographic metasurfaces, we develop ultracompact gas sensors without additional complex instruments or machinery to report the visual information of gas detection. To prove the applicability of the compact sensors, we demonstrate a metasurface-integrated gas sensor on safety goggles via a one-step nanocasting process that is attachable to flat, curved, and flexible surfaces.

Cancer-Associated Fibroblast Subgroups Showing Differential Promoting Effect on HNSCC Progression.

Background: The critical effect of the tumor microenvironment on cancer progression is well recognized. Recent research suggests that the cancer-promoting properties of the tumor stroma may be attributed to fibroblasts. However, the effect of cancer-associated fibroblast (CAF) on the progression of head and neck squamous cell carcinoma (HNSCC) is not well known. Methods: From the immunohistochemical analysis of head and neck squamous cell carcinoma (HNSCC) tissues, we divided CAF into two groups depending on the presence or absence of a well-demarcated boundary between epithelial cancer cells and the surrounding extracellular matrix (ECM). Primary culture of CAF was performed, followed by co-transplantation with HNSCC cells into mice oral mucosa, and the tumorigenesis was compared. The mRNA expression patterns between these two CAF groups were compared using DNA microarray analysis. Results: CAFs from cancer tissues that showed no demarcation between ECM and epithelial cancer cells (CAF-Promote) tended to stimulate Matrigel invasion of HNSCC cells. Conversely, CAFs from cancer tissues that showed a boundary with epithelial cancer cells (CAF-Delay) caused no remarkable increase in Matrigel invasion. Compared with CAF-P, CAF-D is less effective in promoting FaDu tumorigenicity in the mouse model. In DNA microarray analysis, COL3A1 and COL6A6 showed particularly high expression in the CAF-D group. Conclusions: These cancer stroma-derived collagen proteins might delay the HNSCC progression. These findings are expected to provide vital information for predicting HNSCC prognosis and developing drug targets in the future.

Extravalidation and reproducibility results of a commercial deep learning-based automatic detection algorithm for pulmonary nodules on chest radiographs at tertiary hospital.

INTRODUCTION: To extra validate and evaluate the reproducibility of a commercial deep convolutional neural network (DCNN) algorithm for pulmonary nodules on chest radiographs (CRs) and to compare its performance with radiologists. METHODS: This retrospective study enrolled 434 CRs (normal to abnormal ratio, 246:188) from 378 patients that visited a tertiary hospital. DCNN performance was compared with two radiology residents and two thoracic radiologists. Abnormality assessment (using the area under the receiver operating characteristics (AUROC)) and nodule detection (using jackknife alternative free-response ROC (JAFROC)) were compared among three groups (DCNN only, radiologist without DCNN and radiologist with DCNN). A subset of 56 paired cases, having two CRs taken within a 7-day period, were assessed for intraobserver reproducibility using the intraclass correlation coefficient. Independent characteristics of pulmonary nodules detected by DCNN were assessed by multiple logistic regression analysis. RESULTS: The AUROC for abnormality detection for the three groups were 0.87, 0.93 and 0.96, respectively (P < 0.05), whereas the JAFROC analysis of nodule detection was 0.926, 0.929 and 0.964. Reproducibility for the three groups was 0.80, 0.67 and 0.80, which shows an increase in radiologists using DCNN (P < 0.05). Nodules detected by DCNN were more solid, round-shaped and well marginated, not masked and laterally located (P < 0.05). CONCLUSIONS: Extra validation results of DCNN showed high ROC results and there was a significant improvement in the performance when radiologists used DCNN. Reproducibility by DCNN alone showed good agreement, and there was an improvement from moderate to good agreement for radiologists using DCNN.

Changes in Characteristics of Patients with Liver Cirrhosis Visiting a Tertiary Hospital over 15 Years: a Retrospective Multi-Center Study in Korea.

BACKGROUND: Liver cirrhosis has become a heavy burden not only for patients, but also for our society. However, little is known about the recent changes in clinical outcomes and characteristics of patients with cirrhosis-related complications in Korea. Therefore, we aimed to evaluate changes in characteristics of patients with liver cirrhosis in Daegu-Gyeongbuk province in Korea over the past 15 years. METHODS: We retrospectively reviewed the medical records of 15,716 liver cirrhotic patients from 5 university hospitals in Daegu-Gyeongbuk province from 2000 to 2014. The Korean Standard Classification of Diseases-6 code associated with cirrhosis was investigated through medical records and classified according to the year of first visit. RESULTS: A total of 15,716 patients was diagnosed with cirrhosis. A number of patients newly diagnosed with cirrhosis has decreased each year. In 2000, patients were most likely to be diagnosed with hepatitis B virus (HBV) cirrhosis, followed by alcoholic cirrhosis. There was a significant decrease in HBV (P < 0.001), but alcohol, hepatitis C virus (HCV), and non-alcoholic fatty liver disease (NAFLD) showed a significant increase during the study period (alcohol, P = 0.036; HCV, P = 0.001; NAFLD, P = 0.001). At the time of initial diagnosis, the ratio of Child-Turcotte-Pugh (CTP) class A gradually increased from 23.1% to 32.9% (P < 0.001). The most common cause of liver-related hospitalization in 2000 was hepatocellular carcinoma (HCC) (25.5%); in 2014, gastrointestinal bleeding with esophageal and gastric varices (21.4%) was the most common cause. Cases of hospitalization with liver-related complication represented 76.4% of all cases in 2000 but 70.9% in 2014. Incidence rate of HCC has recently increased. In addition, HCC-free survival was significantly lower in CTP class A than in classes B and C. Finally, there was significant difference in HCC occurrence according to causes (P < 0.001). HBV and HCV cirrhosis had lower HCC-free survival than alcoholic and NAFLD cirrhosis. CONCLUSION: In recent years, the overall number of cirrhosis patients has decreased. This study confirmed the recent trend in decrease of cirrhosis, especially of cirrhosis due to HBV, and the increase of HCV, alcoholic and NAFLD cirrhosis. Targeted screening for at-risk patients will facilitate early detection of liver diseases allowing effective intervention and may have decreased the development of cirrhosis and its complications.

Intralobar pulmonary sequestration with cystic degeneration mimicking a bronchogenic cyst in an elderly patient: A case report and literature review.

INTRODUCTION: Pulmonary sequestration (PS) is a rare congenital malformation defined as nonfunctioning lung tissue supplied by systemic circulation. It is uncommonly diagnosed in adults. Herein, we describe a clinical case of PS with cystic degeneration mimicking a bronchogenic cyst in an elderly patient. PATIENT CONCERNS: A huge cystic mass was incidentally found in a 65-year-old man on chest computed tomography (CT) scans during preoperative workup for a hand laceration. A 15-cm-sized round cystic mass was detected in the right lower lobe. DIAGNOSIS: After reviewing the chest CT scan, we decided to perform contrast-enhanced chest magnetic resonance imaging (MRI) and CT-guided lung aspiration biopsy. On MRI, the lesion had the appearance of a cystic mass with hemorrhagic clots, such as an intrapulmonary bronchogenic cyst. The aspirated specimen was nondiagnostic; thus, we decided to surgically remove the mass. INTERVENTIONS: Upon right lower lobectomy, the mass was diagnosed as a PS. A thin systemic artery supplying the cystic mass was visualized during surgery. OUTCOMES: The patient is undergoing regular follow-up at the outpatient clinic. CONCLUSIONS: PS should be considered as a differential diagnosis in patients with a cystic lung mass. Identification of a systemic artery on radiologic imaging is important in the diagnosis of PS before preoperative workup to prevent unpredicted massive bleeding during surgery.

Potential Salivary mRNA Biomarkers for Early Detection of Oral Cancer.

We evaluated potential biomarkers in human whole saliva for the early diagnosis of oral squamous cell carcinoma (OSCC). We selected 30 candidate genes with relevance to cancer from recent reports in PubMed. Saliva samples were obtained from 34 non-tumor control and 33 OSCC patients. Real-time PCR was performed, and mRNA levels were compared. Normalized mRNA levels of six genes (NGFI-A binding protein 2 (NAB2), cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1), nuclear pore complex interacting protein family, member B4 (NPIPB4), monoamine oxidase B (MAOB), sialic acid acetyltransferase (SIAE), and collagen, type III, alpha 1 (COL3A1)) were significantly lower in saliva of OSCC patients. Receiver operating characteristics (ROC) analysis was used to individually evaluate the predictive power of the potential biomarkers for OSCC diagnosis. The area under the curve (AUC) values were evaluated for the OSCC vs. non-tumor groups via univariate ROC analyses, as well as multivariate ROC analyses of combinations of multiple potential biomarkers. The combination of CYP27A1 + SIAE showed a favorable AUC value of 0.84. When we divided saliva samples into two groups according to age using a 60-year cut-off, with OSCC patients and controls evaluated together, the AUC of MAOB-NAB2 was more predictive of OSCC in the under-60 group (AUC, 0.91; sensitivity, 0.92; and specificity, 0.86) than any other gene combination. These results are expected to aid the early diagnosis of OSCC, especially in patients under 60 years of age. While more studies with larger numbers of patients are necessary, our result suggest that salivary mRNA would be a potent biomarker for early OSCC diagnosis.