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Recently, Helicobacter pylori (HP)-uninfected gastric mucosal cancer has been reported; however, the clinicopathological and molecular features of HP-uninfected gastric cancer have not been elucidated.We evaluated the clinicopathological, immunohistochemical, and genetic alterations in HP-uninfected early gastric adenocarcinoma using next-generation sequencing (NGS).Among 968 primary early gastric carcinomas, 64 (6.6%) were HP-uninfected gastric adenocarcinoma and were pathologically classified as gastric adenocarcinoma of fundic-gland type (GA-FG, n = 39), differentiated gastric adenocarcinoma (DGA, n = 16), and signet-ring cell carcinoma (SRCC, n = 9). Based on the expression profile of the mucin core protein, DGAs were classified into a gastrointestinal phenotype showing either MUC5AC or MUC6 expression and MUC2 or CD10 expression simultaneously (n = 5), and a gastric phenotype (n = 11) showing either MUC5AC or MUC6 expression. All DGAs with a gastrointestinal phenotype shared similar endoscopic characteristics, such as reddish depressed lesions in the antrum. In contrast, DGAs with a gastric phenotype exhibited several distinct endoscopic features, including a raspberry-shaped appearance and whitish flat-elevated appearance; the former expressed only MUC5AC and the latter exhibited co-expression of MUC5AC and MUC6. Among 16 HP-uninfected DGAs, seven were subjected to NGS. APC was recurrently mutated in DGA (42.9%) and was enriched in DGAs with a gastrointestinal phenotype (75%).Overall, HP-uninfected gastric adenocarcinomas showed distinct clinicopathologic and endoscopic characteristics. Furthermore, HP-uninfected DGAs, especially those with a gastrointestinal phenotype, may be characterized by recurrent APC mutations.

Objectives: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. Methods: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Results: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogenously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HP and PPI-L were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Conclusion: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

Hollow PC-girders are hollow along the length of the girder; because of this, the possibility of developing horizontal cracking at their ends at the prestressing time is high. In this paper, a numerical analysis was performed to examine the effects of strand-debonding and end-zone reinforcements on the principal stresses, which is the leading cause to develop horizontal cracks at the ends of the hollow PC-girders. First, the length of the selected PC-girder was reduced to 4 m span which is necessary for enough prestressing; after that, with the help of the Midas FEA software, a detailed prestressing analysis was conducted. This study indicated that debonding four PC-strands at the ends of the girder and placing end-zone reinforcements could decrease the magnitude of principal stresses to the level to be less than the tensile strength of concrete, and therefore, horizontal cracks were eliminated at the ends of the hollow PC-girder.

This study aimed to investigate the association between changes in FABP4 concentration and hormone and metabolite levels during and after acute low- and moderate-intensity aerobic exercise in healthy men. Eleven healthy men (24.4±1.4 years) were administered three trials in random order: 1) low-intensity aerobic exercise trial (LE trial; acute exercise at 40% peak oxygen uptake [Vo2peak]+bed rest), 2) moderate-intensity aerobic exercise trial (ME trial: acute exercise at 60%Vo2peak+bed rest), and 3) bed rest (Con trial). Expired gas and venous blood samples were collected at baseline, and immediately, 30 and 60 min after exercise, and substrate oxidation and hormone, metabolite, and FABP4 concentrations were measured. FABP4 concentration did not increase during aerobic exercise in LE and ME trials (p>0.05). However, FABP4 concentration significantly increased after the acute aerobic exercise in both the LE and ME trials (p≤0.003). Increased FABP4 concentration after acute exercise was not correlated with adrenaline, noradrenaline, other hormone, and metabolite concentration changes. These findings suggest that FABP4 concentration increases after acute aerobic exercise independently of exercise intensity. Furthermore, increased FABP4 concentration after acute aerobic exercise may not be involved in the magnitude of adrenaline, noradrenaline, and lipolytic response.

A mediastinal thoracic duct cyst that originates from the thoracic duct is a very rare disease in the mediastinum. There have been no reports of mediastinal thoracic duct cyst infection caused by endoscopic treatment. This is the first case of mediastinal thoracic duct cyst infection after endoscopic submucosal dissection for early esophageal cancer. We herein report a 75-year-old man with mediastinal thoracic duct cyst infection caused by esophageal endoscopic submucosal dissection. In cases where a mediastinal thoracic duct cyst is found before performing endoscopic esophageal treatment, we should carefully consider the potential risk of post-treatment cyst infection.

The incidence of gastric cancer in Okinawa Prefecture is the lowest in Japan, which is attributed to differences in strains of

Background/Objectives: To professionally meet bridge load demands, hollow PC-girders are recently considered for bridge construction, particularly in Japan. Hollow girders are pretensioned girders, which can be a good alternative for ordinary PC-girders by having lightweight, using less material than other beams, and spanning long distances. Hollow PC-girders can be vulnerable to horizontal end cracking at the time of prestressing strand release. Methods: In this study, a nonlinear finite element analysis was performed to investigate the occurrence of horizontal cracks at the time of prestressing at the ends of hollow PC-girders. First, the selected hollow girder was miniaturized to a span length of 4 m required for sufficiently prestressing; then, a standard static prestressing analysis was performed using a finite element analysis software Midas FEA. This software is an analysis tool with standard FEM analysis functions in the construction field and can perform detailed analysis for reinforcements and concrete crack analysis. The software was used to model the girder and investigate the temporal changes of principal stresses at hollow PC-girders’ ends. Findings: The study showed that placing only end-zone reinforcements cannot reduce principal stresses to the level to be less than the concrete’s tensile strength. However, debonding four PC-strands at the ends of the girder alongside the placement of end-zone reinforcements could sufficiently reduce principal stresses to the level to be less than the tensile strength of concrete, and consequently, horizontal cracks were eliminated at the ends of the hollow PC-girder., 論文

Bile acids are strongly associated with the pathogenesis of functional gastrointestinal diseases. In recent years, blue laser imaging (BLI) endoscopy has emerged as a novel image-enhanced endoscopic method, which illustrates bile as a reddish hue. The present study investigated the factors that affect the area of bile in duodenal bulbs using BLI. For this purpose, patients (356 cases) who underwent upper endoscopy with BLI between April, 2017 and December, 2019, and completed patient background and symptom questionnaires [Constipation Scoring System (CSS), Bristol Stool Form Scale (BSFS) and Frequency Scale for Symptoms of gastroesophageal reflux disease (FSSG)], were retrospectively investigated. Each BLI bile score was calculated as a percentage of bile area in a field of view in the duodenal bulb using a KS400 image analysis system, and the association with abdominal symptoms was examined using multiple regression analysis. The patient characteristics included the following: Age (in years), 69.9±11.3; male/female ratio, 146/210; body mass index, 23.0±3.8; reflux esophagitis (M/A/B/C), 143/19/3/3; atrophic gastritis (C-0/C1-3/O1-3), 132/100/124; proton pump inhibitor potassium competitive acid blocker/aspirin/ursodeoxycholic acid/gall bladder stones/cholecystectomy, 105/27/18/43/18; BLI bile score, 7.10 (±14.34); CSS score, 3.55 (±3.80); BSFS score, 3.91 (±1.02); and FSSG score, 4.80 (±5.76). Correlation coefficients (P0.05) for the BLI bile score were found for cholecystectomy (Rho=0.137) and aspirin use (Rho=0.118). In multiple regression analysis, independent predictors of the BLI bile score were cholecystectomy [standardized partial regression coefficient (β)=0.169, P=0.001] and the BSFS score (β=0.107, P=0.042). On the whole, the present study demonstrates that the duodenal bile area in BLI upper endoscopy is associated with cholecystectomy and fecal characteristics.

Background: Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics. Summary: From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy.

[Purpose] Square-stepping exercise is recommended for elderly people, as it has a positive effect on cognitive and physical functions; however, few studies have examined the exercise intensity of square-stepping exercise. Therefore, we aimed to examine the exercise intensity of square-stepping exercise in community-dwelling late elderly females. [Participants and Methods] Study 1: The participants, constituting 12 community-dwelling late elderly females (age: 78.7 ± 3.8 years), performed the three target step patterns. Exhaled gas, heart rate, and rating of perceived exertion using the Borg Scale were measured during square-stepping exercise. Study 2: Participants were 57 community-dwelling elderly females (81.2 ± 4.3 years old). The exercise intensity, heart rate, and rating of perceived exertion using the Borg Scale during square-stepping exercise were measured. [Results] Study 1: The average METs of the 3 target step patterns was 3.6 ± 0.7, and the %heart rate reserve and rating of perceived exertion were 54.3 ± 20.0% and 11.4 ± 1.9%, respectively. Study 2: The average METs during the square-stepping exercise program was 2.1 ± 0.2, and the %heart rate reserve and rating of perceived exertion were 19.6 ± 10.2% and 11.3 ± 1.4%, respectively. [Conclusion] Square-stepping exercise was confirmed to be a low to moderate intensity exercise program and is expected to improve health and physical fitness.

The incidence of gastric cancer in Okinawa Prefecture is the lowest in Japan, which is attributed to differences in strains of Helicobacter pylori in Okinawa and other prefectures in Japan. Our aim was to compare the endoscopic findings of H. pylori-infected gastric mucosa in Okinawa and Tokyo. Patients who underwent upper gastrointestinal endoscopy (UGI) at Northern Okinawa Medical Center (Okinawa group) and Juntendo University Hospital (Tokyo group) from April 2019 to March 2020 were included. Patients diagnosed with H. pylori-infected gastric mucosa were retrospectively compared between the Okinawa and Tokyo groups according to the Kyoto Classification of Gastritis. The numbers of subjects (Okinawa/Tokyo) were 435/352, male/female ratio was 247:188/181:171, and age was 53.3 ± 14.7/64.6 ± 14.3 (mean ± standard deviation) years. Regarding the Kyoto Classification of Gastritis, the prevalence (Okinawa/Tokyo) of the closed type of atrophic gastritis was 73%/37% (p < 0.001), diffuse redness 80%/84% (p = 0.145), mucosal swelling 46%/46% (p = 0.991), enlarged fold 26%/32% (p = 0.048), spotty redness 77%/68% (p = 0.002), sticky mucus 17%/36% (p < 0.001), and intestinal metaplasia 32%/42% (p < 0.001). Age analysis also revealed that closed-type atrophy and spotty redness were more frequent in the Okinawa group than in the Tokyo group. There may be regional differences in endoscopic findings of H. pylori-infected gastric mucosa between Okinawa and Tokyo.

Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency and skin disorders. Various cells including mast cells release Zn-containing granules when activated; however, the biological role of the released Zn is currently unclear. Here we report our findings that Zn transporter ZnT2 is required for the release of Zn from mast cells. In addition, we found that Zn and mast cells induce IL-6 production from inflammatory cells such as skin fibroblasts and promote wound healing, a process that involves inflammation. Zn induces the production of a variety of pro-inflammatory cytokines including IL-6 through signaling pathways mediated by the Zn receptor GPR39. Consistent with these findings, wound healing was impaired in mice lacking IL-6 or GPR39. Thus, our results show that Zn and mast cells play a critical role in wound healing through activation of the GPR39/IL-6 signaling axis.

The trace element zinc is essential for the immune system, and its dysregulation and deficiency results in impaired immune function. Recent studies have shown that zinc can behave as an intracellular signaling molecule in immune cells. We have previously demonstrated that L-type calcium channel (LTCC) is involved in the regulation of zinc signaling, Zinc wave and cytokine production by stimulating Fc epsilon receptor for immunoglobulin E (IgE) in mast cells. However, it is not known whether LTCC-mediated Zinc wave is required for cytokine production by stimulation of toll-like receptors and cytokine receptors in mast cells. Here we report that stimulation of toll-like receptors and cytokine receptors can induce Zinc wave in mast cells and regulate the expression of cytokine genes. The LTCC antagonist nicardipine inhibited lipopolysaccharide (LPS)- and interleukin-33 (IL-33)-mediated Zinc wave and the induction of cytokine genes such as IL-6. Consistent with these results, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) also inhibited LPS- and IL-33-induced cytokine gene expression. Furthermore, LPS induced Zinc wave not only in mast cells but also in dendritic cells. Together, these observations show that Zinc wave is activated by various stimuli and is linked to cytokine gene induction in immune cells.

Mast cells play a pivotal role in allergic reactions and inflammations. Aggregation of the high affinity IgE receptor (FceRI) eventually leads to the release of granule components such as histamine, as well as the de novo synthesis of inflammatory cytokines and lipid mediators. These substances are involved in the development of allergy and inflammation. Therefore, efficient inhibitors of mast cell activation would be therapeutically beneficial. We previously demonstrated that the synthetic peptide derived from the NH2-terminal region (2-17: GNIFANLFKGLFGKKE) of a small GTPase ARF1 (ADP-ribosylation factor1) inhibited FceRI-induced mast cell degranulation. However, detailed structure-activity relationship study of NH2-terminal portion of ARF1 peptide has not been done. In addition, it is still unclear whether the NH2-terminal peptide of ARF1 suppresses FceRI-induced production of cytokines and lipid mediators such as leukotriene C4 (LTC4) from mast cells. Here we show that amino acid residues K10-K16 are necessary for ARF1 peptide to efficiently inhibit FceRI-induced activation of bone marrow-derived mast cells (BMMCs), indicated by decreased mast cell degranulation, cytokine secretion and leukotriene release. Furthermore, we show that ARF1 peptide inhibits IgE-mediated passive cutaneous anaphylaxis reaction. Our results suggest that the peptide derived from ARF1 could be developed into a novel anti-allergic agent for therapeutic intervention in allergy and mast cell-related pathologies.

Background Circulating fatty acid-binding protein 4 (FABP4) is a marker for various diseases. It would be highly useful to have simple and less invasive techniques for the assessment of FABP4 concentrations in the clinical research setting. The purpose of the present study was to assess the concordance of circulating FABP4 concentrations in venous and capillary blood both at rest and immediately after acute exercise in healthy young males. Results Thirty-eight healthy young male adults aged from 19 to 25 years (mean age, 20.8 ± 1.2 years) were recruited. Paired blood samples were taken from the cubital vein (venous) and fingertip (capillary) blood at rest (resting state) and immediately after incremental exercise (exercising state). Blood samples were analyzed to determine the circulating FABP4 concentration using an enzyme-linked immunosorbent assay. Pearson’s correlation coefficients for circulating FABP4 concentrations between venous and capillary blood samples indicated a strong positive correlation in both the resting and exercising state (resting state: r = 0.982, exercising state: r = 0.989, both p p = 0.178), whereas it was significantly higher in capillary blood than in venous blood in the exercising state (p p = 0.453) in the resting state, whereas a significant bias (− 0.45 ± 0.61 ng/mL, p Conclusions These results indicate that capillary blood sampling can slightly overestimate circulating FABP4 concentrations under a physiologically dynamic state. However, the association between the venous and capillary blood in terms of FABP4 concentration was very strong, suggesting that capillary blood sampling can detect changes in FABP4 concentration in both physiologically steady and dynamic states.

Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics.From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy.

Jabara (Citrus jabara Hort. ex Y. Tanaka) is a type of citrus fruit known for its beneficial effect against seasonal allergies. Jabara is rich in the antioxidant narirutin whose anti-allergy effect has been demonstrated. One of the disadvantages in consuming Jabara is its bitter flavor. Therefore, we fermented the fruit to reduce the bitterness and make Jabara easy to consume. Here, we examined whether fermentation alters the anti-allergic property of Jabara. Suppression of degranulation and cytokine production was observed in mast cells treated with fermented Jabara and the effect was dependent on the length of fermentation. We also showed that 5-hydroxymethylfurfural (5-HMF) increases as fermentation progresses and was identified as an active component of fermented Jabara, which inhibited mast cell degranulation. Mast cells treated with 5-HMF also exhibited reduced degranulation and cytokine production. In addition, we showed that the expression levels of phospho-PLC&gamma, 1 and phospho-ERK1/2 were markedly reduced upon Fc&epsilon, RI stimulation. These results indicate that 5-HMF is one of the active components of fermented Jabara that is involved in the inhibition of mast cell activation.

Mast cells are hematopoietic-lineage cells that participate in immunoglobulin E (IgE)-associated immune responses, including allergic reactions and parasite resistance. Recent studies have shown that zinc (Zn) ion can behave as an intracellular signaling molecule and that Zn is involved in mast cell activation. We demonstrated that mast cells stimulated through the high-affinity IgE receptor (FcεRI) rapidly release intracellular Zn from the endoplasmic reticulum (ER), and we named this phenomenon the "Zn wave". Furthermore, we found that the L-type calcium channel (LTCC) is the gatekeeper for the Zn wave. LTCC antagonists inhibited the Zn wave, and an agonist was sufficient to induce it. Notably, LTCC was mainly localized to the ER rather than to the plasma membrane in mast cells, and the Zn wave was impaired by LTCC knockdown. We also found that the LTCC-mediated Zn wave positively controlled inflammatory cytokine gene induction by enhancing the DNA-binding activity of nuclear factor-kappa B (NF-κB). These findings indicated that the LTCC has a novel function as a gatekeeper for the Zn wave, which is involved in regulating NF-κB signaling. In this review, we describe our current understanding of Zn signaling, especially with regard to the Zn wave and the role of Zn signaling in mast cells.