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\"They say that if one consumes mermaid flesh, one can attain immortality. Unfortunately, the more likely results include becoming horribly deformed or turning into a vicious monster! Even if one were to gain eternal life, however, is such an anomaly a lucky blessing or a terrible curse? Yuta became immortal when he unwittingly ate mermaid flesh, and now he seeks a way to become human again. Hundreds of years later, he encounters a volatile and determined young lady named Mana while searching for a mermaid. Could this mysterious woman hold the key to saving Yuta's humanity?\"--Volume 1.

The presence of Fusobacterium nucleatum is associated with an immunosuppressive tumor immune microenvironment (TIM) in primary colorectal cancer (CRC), contributing to tumor progression. Its persistence in CRC liver metastasis tissues raises questions about its role in modulating local and systemic immune responses and influencing recurrence patterns. This retrospective cohort study of 218 patients with CRC liver metastasis investigated the association of F. nucleatum in CRC liver metastasis tissues with systemic inflammation, TIM alterations, and the number of metastatic organs involved in recurrence. Two‐step polymerase chain reaction (PCR), including digital PCR, detected F. nucleatum in 42% (92/218) of fresh‐frozen specimens of CRC liver metastases. Compared with the F. nucleatum‐none group, the F. nucleatum‐high group showed higher C‐reactive protein levels (0.82 vs. 0.22 mg/dL; Ptrend = 0.02), lower numbers of CD8+ cells (33.2 vs. 65.3 cells/mm2; Ptrend = 0.04) and FOXP3+ cells (11.3 vs. 21.7 cells/mm2; Ptrend = 0.01) in the TIM, and a greater number of metastatic organs involved in recurrence (1.6 vs. 1.1; p < 0.001). The presence of F. nucleatum in CRC liver metastasis tissues was associated with increased systemic inflammation, TIM alterations, and a greater number of metastatic organs involved in recurrence. These findings suggest a potential contribution of F. nucleatum to the metastatic propensity of CRC cells and could inform future research to enhance understanding of the interaction between tumor, host, and microbes in the metastatic process. In this retrospective cohort study of 218 patients with colorectal cancer (CRC) liver metastasis, Fusobacterium nucleatum was detected in liver metastasis tissues in 42% of cases and was associated with increased serum C‐reactive protein levels, reduced numbers of CD8+ cells and FOXP3+ cells in tumor tissues, and an increased number of metastatic organs involved in recurrence. F. nucleatum in CRC liver metastasis tissues might influence systemic and local immune responses and diversify the metastatic organs involved.

Background Indocyanine green (ICG)-fluorescence imaging has been developed for real-time identification of hepatic tumors and segmental boundaries during hepatectomy. Fusion ICG-fluorescence imaging (real-time visualization of pseudocolor-fluorescence signals on white-light color images) may serve as a reliable navigation tool especially in laparoscopic hepatectomy, in which gross inspection and palpation are limited. Methods The study population consisted of 41 patients undergoing laparoscopic hepatectomy. Hepatic tumors were identified by fluorescence imaging following the preoperative intravenous administration of ICG (0.5 mg/kg body weight). To visualize hepatic perfusion and segmental boundaries, ICG (1.25 mg) was injected intravenously during surgery, following closure of the proximal portal pedicle. A laparoscopic imaging system, which enabled superimposition of the pseudocolor-fluorescence images on white color images, was used for the fusion ICG-fluorescence imaging. Results Among the 53 malignant tumors resected, fusion ICG-fluorescence imaging revealed 45 nodules (85%), including three nodules of colorectal liver metastasis unidentifiable by white-light color images or intraoperative ultrasonography. It also delineated the segmental boundaries on the hepatic raw surfaces as well as on the phrenic/visceral surfaces in all 12 patients evaluated using this technique. Conclusions Fusion imaging enhances the feasibility of intraoperative ICG-fluorescence imaging in the identification of hepatic tumors and segmental boundaries. It may therefore help surgeons in the safe and accurate completion of laparoscopic hepatectomies.

In mouse studies, the results of behavioural experiments are greatly affected by differences in the experimental environment and handling methods. The Porsolt forced swim test and tail suspension test are widely used to evaluate predictive models of depression-like behaviour in mice. It has not been clarified how the results of these tests are affected by testing single or multiple mice simultaneously. Therefore, this study evaluated the differences between testing two mice simultaneously or separately. To investigate the effect of testing multiple mice simultaneously, the Porsolt forced swim test and tail suspension test were performed in three patterns: (1) testing with an opaque partition between two mice, (2) testing without a partition between two mice, and (3) testing a single mouse. In the Porsolt forced swim test, the mice tested simultaneously without a partition demonstrated increased immobility time as compared to mice tested alone. No difference in immobility time was observed between the three groups in the tail suspension test. Our results showed that the environment of behavioural experiments investigating depression-like behaviour in mice can cause a difference in depression-like behaviour. The results of this experiment indicated that it is necessary to describe the method used for behavioural testing in detail.

The increasing usage of proton pump inhibitors (PPIs) has been reported worldwide, but information on PPI use in East Asia is inadequate. This study aimed to examine the trends in PPI use in Japan, along with the changes in histamine H 2 receptor antagonist (H 2 RA) use, disease rate of reflux esophagitis, and the prevalence of upper gastrointestinal symptoms. We analyzed 217,712 healthy subjects (127,607 men and 90,105 women; 51.4 ± 9.7 years old) participating in the health check program from 2010 to 2019. Various upper gastrointestinal symptoms were evaluated using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire. Reflux esophagitis was diagnosed by esophageal erosion using the Los Angeles classification grades A, B, C, and D. From 2010 to 2019, the percentage of PPI users increased markedly from approximately 1.8% to 5.3%, whereas that of H 2 RA users decreased gradually from approximately 2.5% to 1.9%. The use of all classical types of PPIs (omeprazole, lansoprazole, rabeprazole, and esomerazole) and a new type of PPI, a potassium-competitive acid blocker (vonoprazan), greatly increased during the 10 years. An upward trend in the prevalence of reflux esophagitis was observed from 2010 to 2015, but not from 2016 to 2019, indicating that the monotonic rising prevalence of reflux disease stopped in the middle of the 2010s in Japan. In contrast, various upper gastrointestinal symptoms significantly improved between 2010 and 2019. All 12 FSSG symptoms of PPI users were significantly worse than those of non-PPI users, suggesting that PPIs still cannot completely control upper gastrointestinal symptoms. In conclusion, this study revealed a significant increase in PPI use and a slight decrease in H 2 RA use from 2010 to 2019. Despite a plateau in the prevalence of reflux esophagitis and considerable improvement in various upper gastrointestinal symptoms, PPI use has continued to increase in Japan.

BackgroundAutoimmune gastritis (AIG) is a chronic inflammatory condition in gastric mucosa and is associated with increased cancer risk, though not as high as that by Helicobacter pylori (H. pylori)-associated gastritis (HPG). Although aberrant DNA methylation is induced by HPG and the level correlates with the risk of gastric cancer, DNA methylation induction by AIG is unknown.MethodsGastric mucosa samples from the corpus were collected from 12 people with AIG without H. pylori infection, 10 people with HPG, and eight healthy volunteers. Genome-wide DNA methylation analysis was conducted using Infinium Methylation EPIC array. Gene expression was analyzed by quantitative RT-PCR.ResultsThe AIG samples had extensive aberrant DNA methylation but presented unique methylation profiles against the HPG samples after correction of leucocyte fractions. Comparison between the AIG and HPG samples showed that AIG induced methylation, but less than HPG, in overall CpG sites and also in promoter CpG islands. Promoter CpG islands of tumor-suppressor genes in the pathway of cell cycle, cell adhesion, p53, and WNT were highly methylated in the AIG samples, but more so in the HPG samples. The expression levels of IL1B and IL8, secreted by macrophage, were significantly lower in the AIG samples than in the HPG samples, suggesting that a difference in inflammatory response affected the degree and patterns of aberrant DNA methylation.ConclusionsAIG induced aberrant DNA methylation in gastric mucosa. However, the degree of DNA methylation was less than that by HPG, which reflected carcinogenic risk.

Organoids are regarded as physiologically relevant cell models and useful for compound screening for drug development; however, their applications are currently limited because of the high cost of their culture. We previously succeeded in reducing the cost of human intestinal organoid culture using conditioned medium (CM) of L cells co-expressing Wnt3a, R-spondin1, and Noggin. Here, we further reduced the cost by replacing recombinant hepatocyte growth factor with CM. Moreover, we showed that embedding organoids in collagen gel, a more inexpensive matrix than Matrigel, maintains organoid proliferation and marker gene expression similarly when using Matrigel. The combination of these replacements also enabled the organoid-oriented monolayer cell culture. Furthermore, screening thousands of compounds using organoids expanded with the refined method identified several compounds with more selective cytotoxicity against organoid-derived cells than Caco-2 cells. The mechanism of action of one of these compounds, YC-1, was further elucidated. We showed that YC-1 induces apoptosis through the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway, the mechanism of which was distinct from cell death caused by other hit compounds. Our cost-cutting methodology enables large-scale intestinal organoid culture and subsequent compound screening, which could expand the application of intestinal organoids in various research fields.

Background We describe the short- and long-term outcomes for PDAC patients after tailored mesopancreas dissection using supracolic artery-first approach followed by adjuvant therapy. Methods This study analyzed 233 consecutive patients who underwent artery-first pancreaticoduodenectomy for PDAC. Dissection extent for the superior mesenteric artery (SMA) was categorized into three levels: level 2 (LV2) including regional lymph nodes, level 3 (LV3) with hemicircumferential nerve plexus dissection, and extended-level 3 (E-LV3) including borderline resectable cases for the SMA. All clinical, pathological, and survival outcomes were reviewed. Results LV2/3/E-LV3 dissection was performed in 77/115/41 patients. The short-term outcomes were similar among groups without mortality. Although postoperative diarrhea requiring opioids was significantly more frequent in the E-LV3 group (76%) than other groups (vs. LV2 (21%), P  < .0001; vs. LV3 (34%), P  < .0001; LV2 vs. LV3, P  = 0.20), most cases of diarrhea were well controlled. Adjuvant chemotherapy was introduced similarly among groups (LV2, 76%; LV3, 81%; E-LV3, 88%, P  = 0.29). The 3- and 5-year overall survival rates in the LV2/3/E-LV3 groups were 42/33/42% and 27/22/26%, respectively, showing no significant difference among groups. Discussion Our tailored dissection and preemptive use of opioid antidiarrheal effectively prevents intractable diarrhea, increasing the success of adjuvant chemotherapy.