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Abstract Background The interactions between cancer cells and tumor‐associated macrophages (TAMs) via microRNAs (miRNAs) play crucial roles in malignant potential and drug resistance. However, it remains unclear how lenvatinib‐resistant hepatocellular carcinoma (LR HCC) promotes TAM tumor biology. Here we investigated the crosstalk between LR HCC cells and TAMs for cancer progression and lenvatinib resistance, focusing on an exosomal miRNA. Methods We used two bioinformatics software programs to identify miRNAs that target PTEN in gastrointestinal cancers, then investigated exosomal miRNA expression in LR HCC conditioned medium (CM). After modifying TAMs with LR HCC CM (LR TAM), macrophage phenotype and PTEN‐Nrf2 signaling pathway component expression were analyzed in LR TAMs. The malignant potential and drug resistance were investigated in naïve HCC cells cultured with LR TAM CM. Results LR HCC cells highly induced M2‐like properties in macrophages compared with naïve HCC cells. Exosomal miR‐301a‐3p expression was increased in LR HCC CM, with higher activation of the PTEN/PI3K/GSK3β/Nrf2 signaling pathway in LR TAMs. Naïve HCC cells were educated with LR TAM CM to promote malignant potential and lenvatinib resistance. Inhibition of exosomal miR‐301a‐3p prevented the malignant potential of LR TAMs. Activation of Nrf2 signaling by LR HCC cell‐derived exosomal miR‐301a‐3p skewed the transformation of macrophages to the M2 phenotype. Conclusion Our study provides new findings on the role of miR‐301a‐3p, suggesting it is a promising therapeutic target to improve HCC lenvatinib resistance.

Introduction Needle‐track seeding of prostate cancer into the rectal wall following transrectal prostate biopsy is exceedingly rare. We report a case of mucinous prostate cancer recurrence in the rectal wall due to biopsy needle seeding, discovered after robot‐assisted radical prostatectomy. Case presentation A 67‐year‐old man underwent robot‐assisted radical prostatectomy for mucinous prostate cancer (clinical stage T2cN0M0, Gleason score of 4 + 4, and initial prostate‐specific antigen level of 8.8 ng/mL). Five years postoperatively, endoscopy revealed a rectal tumor, which was diagnosed as needle‐track seeding from the previous transrectal prostate biopsy. Following resection of this rectal tumor, the patient's prostate‐specific antigen level fell to

Glycerophospholipids, a primary component of cellular membranes, play important structural and functional roles in cells. In the remodelling pathway (Lands' cycle), the concerted actions of phospholipase As and lysophospholipid acyltransferases (LPLATs) contribute to the incorporation of diverse fatty acids in glycerophospholipids in an asymmetric manner, which differ between cell types. In this study, the role of LPLATs in osteoblastic differentiation of C2C12 cells was investigated. Gene and protein expression levels of lysophosphatidylcholine acyltransferase 2 (LPCAT2), one of the LPLATs, increased during osteoblastic differentiation in C2C12 cells. LPCAT2 knockdown in C2C12 cells downregulated the expression of osteoblastic differentiation markers and the number and size of lipid droplets (LDs) and suppressed the phosphorylation of Smad1/5/9. In addition, LPCAT2 knockdown inhibited Snail1 and the downstream target of Runx2 and vitamin D receptor (VDR). These results suggest that LPCAT2 modulates osteoblastic differentiation in C2C12 cells through the bone morphogenetic protein (BMP)/Smad signalling pathway.

Abstract Burning mouth syndrome (BMS) is characterized by burning sensations in the oral region without corresponding abnormalities and is often accompanied by uncomfortable sensations. Herein, we present cases of BMS in which the remaining uncomfortable sensations improved with perospirone augmentation with clonazepam. Case 1: A 61‐year‐old man complained of a burning pain in his tongue, a sensation of dryness and discomfort as if his tongue was sticking to a palatal plate. With the diagnosis of BMS, psychopharmacotherapy was initiated with amitriptyline. At the dose of amitriptyline 50 mg, the pain lessened but uncomfortable sensations persisted. Further attempts to alleviate symptoms by combining aripiprazole with amitriptyline, aripiprazole with mirtazapine, or aripiprazole with clonazepam were limited; however, nearly all symptoms were relieved by a combination of perospirone 8.0 mg with clonazepam 1.5 mg. Case 2: A 51‐year‐old woman complained of a burning sensation along with oral dryness and crumb‐like feeling on her tongue. She was diagnosed with BMS and began treatment with amitriptyline. Her burning sensation improved at the dose of 25 mg, but uncomfortable sensations persisted. Augmentation of amitriptyline with aripiprazole, aripiprazole either with valproate, mirtazapine, or clonazepam failed to produce a significant improvement. However, a regimen of perospirone 6.0 mg and clonazepam 1.5 mg relieved the crumb‐like sensation and pain and culminated in a stabilized condition. The reported cases suggested that multiple approaches targeting the dopaminergic circuit in basal ganglia involving the serotoninergic and GABA systems, through the administration of perospirone with clonazepam is an effective adjunctive treatment for the remaining uncomfortable sensations in patients with BMS.

Abstract Background and Aim Neutrophil gelatinase‐associated lipocalin (NGAL) is characterized by increased expression before the rise in serum creatinine and has been used as a biomarker for the early prediction of acute kidney injury (AKI). However, there have been no comprehensive analyses of its significance in gastrointestinal diseases. This study aimed to analyze the usefulness of measuring urinary NGAL levels in patients with gastrointestinal diseases. Methods This study included 171 patients with a wide range of gastrointestinal diseases. Urinary NGAL levels were measured in all patients within 24 h of admission and 72 h later. Results Urinary NGAL levels were higher in patients with acute pancreatitis and acute cholangitis/cholecystitis than in those with other diseases. Although lower than in these diseases, urinary NGAL tends to be higher in inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, as well as in acute and chronic liver diseases, and is higher in liver cirrhosis as the Child–Pugh grade increases. Furthermore, we found that the group with higher urinary NGAL levels, which continued to increase over time, had worse hospital stays and prognosis. Conclusion Urinary NGAL could be used as an indicator of infectious diseases rather than an indicator of AKI in inflammatory bowel diseases and cirrhosis, and could predict the prognosis of patients with gastrointestinal diseases.

Abstract Background and aim Ulcerative colitis (UC) is characterized by repeated relapse and remission. Because no fundamental therapeutic strategy has been established, the treatment goal is generally to maintain the remission phase for a long period after rapid remission induction. Granulocyte and monocyte adsorption (GMA) for UC is reportedly quite safe because it does not affect immunosuppression. Moreover, it is useful in combination with other remission induction therapy. The aim of this study was to evaluate the difference in efficacy by the timing of the addition of GMA with corticosteroids, calcineurin inhibitors, and anti‐cytokine therapy for active UC. Methods The study included 59 patients. Patients who started GMA of 5–11 days were in the early GMA combination group. Patients who started GMA 12 days or more were in the late GMA combination group. The primary endpoint was difference in the effect of additional GMA according to the timing of the intervention. The secondary endpoint was difference in the time to remission induction between the two groups. Results Of the 32 early GMA group patients, 24 achieved remission induction. Of the 27 late group patients, 18 achieved remission induction. No significant difference in induction rates was found (P = 0.481). The early group had shorter mean time to remission induction (P

Abstract The nonselective calcium‐permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo‐electron microscopy (cryo‐EM) structures of human TRPV4 are presented in‐complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage‐sensing‐like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4 to undergo an apparent fourfold to twofold symmetry transition. Moreover, it is demonstrated that one of the antagonists binds to the VSLD extended pocket, which differs from the canonical VSLD pocket. Complemented with functional and molecular dynamics simulation results, this study provides crucial mechanistic insights into TRPV4 regulation by small‐molecule antagonists, which may facilitate future drug discovery targeting TRPV4.

Introduction Prostatic urethral lift is a treatment option for benign prostatic hyperplasia, yet information on surgeries following this procedure is scarce. Case presentation A 71‐year‐old man with persistent urinary retention following prostatic urethral lift underwent a secondary holmium laser enucleation of the prostate. The morcellation procedure, complicated by the presence of implants from the previous surgery, broke the morcellator blade. The fragmented blade was successfully retrieved without any organ damage. Postoperatively, the patient encountered no complications and showed improvement in his urinary symptoms. Conclusion This case highlights the potential risk of device breakage when a secondary surgery, specifically the morcellation process, is performed following prostatic urethral lift. Care must be taken to prevent interaction between the implants and the morcellator. Our case demonstrates the efficacy of holmium laser enucleation of the prostate as a salvage surgical intervention for patients in whom prostatic urethral lift has failed.

Key Clinical Message An 89‐year‐old patient with fenitrothion toxicity received sublingual atropine eye drops, reducing the intravenous atropine requirement. This alternative method enabled rapid rehabilitation, and he walked unaided, leading to discharge.

Abstract Endoscopic ultrasound (EUS)‐guided coil deployment (EUS‐coiling) has been newly developed for treating isolated gastric varices (iGV). This report describes three cases of EUS‐coiling for iGV using a 0.035‐inch hydrocoil (Azur; Terumo Corp., Tokyo, Japan). When used for EUS‐coiling, this hydrocoil provides the following benefits: Its electrically detachable system allows pull back. It has smooth and dense deployment. Moreover, it has a strong blood‐flow blocking effect because of its long length and large diameter with internal swelling functions of the hydrogel. Technical success of coiling was achieved in all cases. After coiling, additional treatments such as cyanoacrylate and sclerosant injection were performed as deemed appropriate. All iGVs were obliterated successfully. No adverse event occurred during the procedure or during the mean follow‐up of six months. Our findings indicate that this 0.035‐inch hydrocoil can be used to treat iGV safely and effectively.

Abstract Background and Aim While short and long attachment caps are available for colonoscopy, it is unclear which type is more appropriate for stigmata of recent hemorrhage (SRH) identification in acute hematochezia. This study aimed to compare the performance of short versus long caps in acute hematochezia diagnoses and outcomes. Methods We selected 6460 patients who underwent colonoscopy with attachment caps from 10 342 acute hematochezia cases in the CODE BLUE‐J study. We performed propensity score matching (PSM) to balance baseline characteristics between short and long cap users. Then, the proportion of definitive or presumptive bleeding etiologies found on the initial colonoscopy and SRH identification rates were compared. We also evaluated rates of blood transfusions, interventional radiology, or surgery, as well as the rate of rebleeding and mortality within 30 days after the initial colonoscopy. Results A total of 3098 patients with acute hematochezia (1549 short cap and 1549 long cap users) were selected for PSM. The rate of colonic diverticular bleeding (CDB) diagnosis was significantly higher in long cap users (P = 0.006). While the two groups had similar rates of the other bleeding etiologies, the frequency of unknown etiologies was significantly lower in long cap users (P

Abstract Cryptococcosis typically manifests as pulmonary lesions, with endobronchial lesions occurring rarely. Inhaled corticosteroids (ICS) may be a risk factor for cryptococcosis of the larynx but not of the bronchi. Here, we report a case involving a 73‐year‐old Japanese man who developed endobronchial cryptococcosis during ICS treatment for asthma. Chest computed tomography showed right mainstem bronchial stenosis and asthma control worsening when he received adequate asthma treatments. Bronchoscopy revealed multiple elevated lesions with white slough from the trachea to the right mainstem bronchus and the right mainstem bronchus lumen entrance narrowing. Bronchial lavage culture revealed Cryptococcus neoformans. Combination treatment with the antifungal agent, mepolizumab, and bronchodilation surgery successfully controlled cryptococcosis and asthma. Attention should be paid to central airway lesions during ICS treatment for uncontrolled asthma.

Abstract Purpose Anastomotic leakage (AL) is a serious postoperative complication that affects short‐ and long‐term outcomes. The use of a trans‐anal drainage tube (TDT) is reported to prevent AL in rectal cancer patients, but its value in sigmoid colon cancer patients is unknown. Methods Admitted to the study were 379 patients who underwent surgery for sigmoid colon cancer between 2016 and 2020. Patients were divided into two groups according to the placement (n = 197) or nonplacement of a TDT (n = 182). To determine the factors affecting the association between TDT placement and AL, we estimated average treatment effects by stratifying each factor using the inverse probability of treatment weighting method. The association between prognosis and AL was evaluated in each identified factor. Results Factors associated with postsurgical insertion of a TDT were advanced age, male sex, high body mass index (BMI), poor performance status, and presence of comorbidities. TDT placement was associated with a significantly lower AL in male patients (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.07–0.73; P = .013) and for BMI ≥ 25 kg/m2 (OR, 0.13; 95% CI, 0.02–0.65; P = .013). In addition, there was a significant association of AL with poor prognosis in patients with BMI ≥ 25 kg/m2 (P = .043), age > 75 y (P = .021), and pathological node‐positive disease (P = .015). Conclusion Sigmoid colon cancer patients with BMI ≥ 25 kg/m2 are the most appropriate candidates for postoperative TDT insertion, in terms of reduced incidence of AL and improved prognosis.

Abstract We find at fast‐ and intermediate‐spreading seafloor that their ridge‐parallel bathymetric profiles between two neighboring fracture zones, excluding the part of the seafloor inward to fracture zone (FZ) valley, are predominantly upward concave. The temporal evolution of the bathymetric profiles from the lithosphere formed at the Chile Rise is characterized by (a) the rapid growth of the middle deflection to about 200 m relative to the ends for the first few millions of years and (b) a steady state afterward. We show that these characteristics and the upward‐concave sense of bending can be reasonably explained as the flexure of a thin elastic plate contracting thermally from the top while cooling. The best‐fitting model needs only about 10% of the thermal bending moment based on the half‐space cooling model and the free‐end assumption. Our model is consistent with the recent observations that oceanic lithosphere is cut open at a FZ valley, which disprove the previous assumption that ocean floor is bent down forming the valley walls.

Key Clinical Message We found an extremely rare case of PVG after a barium swallow examination. This may be related to vulnerable intestinal mucosa in the patient undergoing prednisolone treatment. Conservative therapy should be considered for patients with PVG without bowel ischemia or perforation. Caution should be exercised during barium examination undergoing prednisolone treatment.

Abstract We address in situ serpentinization and mineral carbonation processes in oceanic lithosphere using integrated field magnetic measurements, rock magnetic analyses, superconducting quantum interference device (SQUID) microscopy, microtextural observations, and energy dispersive spectroscopy phase mapping. A representative suite of ultramafic rock samples were collected, within the Atlin ophiolite, along a 100‐m long transect across a continuous outcrop of mantle harzburgite with several alteration fronts: serpentinite, soapstone (magnesite + talc), and listvenite (magnesite + quartz). Strong correlations between changes in magnetic signal strengths and amount of alteration are shown with distinctive contrasts between serpentinite, transitional soapstone, and listvenite that are linked to the formation and breakdown of magnetite. While previous observations of the Linnajavri ultramafic complex indicated that the breakdown of magnetite occurred during listvenite formation from the precursor soapstone (Tominaga et al., 2017, https://doi.org/10.1038/s41467-017-01610-4), results from our study suggest that magnetite destabilization already occurred during the replacement of serpentinite by soapstone (i.e., at lower fluid CO2 concentrations). This difference is attributed to fracture‐controlled flow of sulfur‐bearing alteration fluid at Atlin, causing reductive magnetite dissolution in thin soapstone zones separating serpentinite from sulfide‐mineralized listvenite. We argue that magnetite growth or breakdown in soapstone provides insight into the mode of fluid flow and the composition, which control the scale and extent of carbonation. This conclusion enables us to use magnetometry as a viable tool for monitoring the reaction progress from serpentinite to carbonate‐bearing assemblages in space and time with a caution that the three‐dimensionality of magnetic sources impacts the scalability of measurements.

Abstract A woman in her 60s underwent endoscopic sphincterotomy for choledocholithiasis. Unfortunately, post‐endoscopic retrograde cholangiopancreatography pancreatitis occurred. In addition, huge walled‐off necrosis (WON) appeared as a late complication. For the infected WON, endoscopic ultrasound‐guided fistuloplasty and endoscopic necrosectomy were performed, and a double pigtail plastic stent (PS) (7Fr, 7 cm) was placed to prevent a recurrence. Plain computed tomography conducted two years later showed that the stent implanted for WON had deviated. The distal end of the stent was found to have migrated into the bile duct. In addition, common bile duct stones with stents as nuclei were observed. Upon performing endoscopic retrograde cholangiography, it was revealed that the stent tip perforated the distal bile duct just above the papilla. After removal of the stent using grasping forceps, we made an incision between the duodenal – bile duct fistula and bile duct orifice using a sphincterotome. Then, the stone was removed by a balloon catheter. Although such late adverse events are rare occurrences, placement of long‐term PS after treatment of WON should be followed up regularly with imaging examination, and if there is no recurrence for several months, removal of the PS at that point may be considered.

Abstract The patient, a 73‐year‐old woman, had been taking acid‐suppressive therapy for refractory reflux esophagitis for 10 years. A potassium‐competitive acid blocker was administered to strengthen acid‐suppressive therapy for worsening symptoms of gastroesophageal reflux disease. Esophagogastroduodenoscopy showed an increase in the number and size of fundic gland polyposis (FGPs). When acid‐suppressive therapy was changed from potassium‐competitive acid blocker to proton pump inhibitor, the FGPs showed reduced size 1 year later. Furthermore, when acid‐suppressive therapy was changed from proton pump inhibitor to histamine‐2 receptor antagonist, FGPs were even smaller after 1 and 2 years. The patient, who had no flare‐up of gastroesophageal reflux disease symptoms, continues to be treated medically with histamine‐2 receptor antagonist. This case report describes changes in endoscopic findings of a patient with FGPs caused by acid‐suppressive therapy for refractory gastroesophageal reflux disease.

Abstract Endoscopic ultrasound (EUS) is widely recognized for its non‐invasiveness and for its usefulness in chronic pancreatitis (CP) diagnosis, including early CP. Although it is desirable to obtain a definitive diagnosis of CP by tissue sampling with EUS‐guided fine needle aspiration, histopathological changes in CP are heterogeneous in terms of the extent and the distribution of lesions. Therefore, histopathological diagnosis of appropriate tissue sampling by EUS‐fine needle aspiration is expected to be difficult. Furthermore, it is virtually impossible to match EUS images with pathological sections, making direct contrast between EUS findings and pathology difficult. This narrative review presents a discussion of the diagnosis of CP/early CP by EUS, particularly assessing the association between ultrasound and pathological findings. Recently, the histological corroboration and correlation of EUS findings related to CP have been clarified by surgical specimens, including those obtained from animal studies. Furthermore, remarkable advances have occurred in the objective and quantitative diagnosis of pancreatic fibrosis by EUS‐elastography. Future technological advances in EUS are expected to improve the accuracy of diagnosis of pancreatic fibrosis at earlier stages.

Abstract A 38‐year‐old woman was admitted to our hospital for a detailed examination of jaundice. Three years before, she had undergone a right total mastectomy and axillary lymph node dissection of her right breast because of cancer. Histopathological evaluation revealed invasive ductal carcinoma. Postoperatively, because multiple bone metastases were found, she underwent chemoradiotherapy. Endoscopic retrograde cholangiopancreatography was performed, which revealed widespread multiple stenoses with a smooth surface from the intrahepatic to the extrahepatic bile duct. A transpapillary biliary biopsy was performed. Histopathological examination revealed adenocarcinoma extending into the subepithelium of the bile duct. The obtained cancer cells were similar to those of the earlier invasive breast cancer. This rare case demonstrates bile duct metastasis of breast cancer with specific endoscopic retrograde cholangiopancreatography findings.

Abstract In patients with the Chilaiditi sign, pulmonary lower lobes collapse occurs because of interposition of the bowel between diaphragm and liver. When such patients suffer from COVID‐19 pneumonia, clinicians should carefully monitor respiratory status.

Abstract Background Spinal epidural hematoma (SEH), which may develop into an emergency condition, is a rare disease. Here, we present the case of a patient with SEH caused by cervical massage using a commercial massage tool. Case Presentation A 75‐year‐old man was brought to our hospital with a chief complaint of posterior neck pain during sleep. He had used a commercial massage tool before going to bed. Upon arrival, hypotension and respiratory failure were observed. His muscle strength in both the upper and lower extremities rated 0 on the manual muscle test, and sensory loss below the papillae was observed. His symptoms resolved spontaneously after 2 h. Magnetic resonance imaging suggested a spinal cord epidural hematoma at the C2/C3 to C3/C4 level. On day 6, the patient was discharged without any impairment. Conclusion Fatal complications could occur by cervical massage using a commercial massage tool.

Abstract We present a case of a 55‐year‐old woman complaining of abdominal distension owing to acute gastric dilatation. Her localized skin mottling had spread from the lower abdomen to both knees. The skin mottling in the area affected by gastric dilatation improved immediately after stomach emptying using a gastric tube and upper endoscopy.

Abstract New seismic reflection data collected and processed as part of early career scientist training at sea and in classroom projects fill gaps in seismic coverage of the Cascadia subduction zone and provide new insights into anomalous subduction behavior and mass wasting along the south‐central Cascadia Subduction Zone (CSZ) between 42°20’N and 44°15’N. The data reveal at least six distinct buried horizons of folded and faulted sediments similar to strata recently interpreted to result from in situ deformation induced by the load imposed by a large blocky mass transport deposit known as the 44°N slide. Although our results support prior studies indicating that the south‐central CSZ has experienced large slope instabilities, they indicate that the slides were more frequent but volumetrically smaller than previously thought. Similar strata have not been observed elsewhere beneath the abyssal plain adjacent to the Cascadia subduction zone. The structure of the deformation front along this segment is also indistinct, in contrast to the clear frontal faults outboard of folded trench strata observed immediately to the north and south (and generally throughout the rest of Cascadia). We attribute the anomalous nature of this segment of the margin to past subduction of shallow and rough seafloor, which resulted in greater uplift of the forearc than elsewhere along the margin. A consequence of this postulated history would be the shedding of older, more consolidated blocks onto the Juan de Fuca plate, resulting in the observed distinctive stratigraphy offshore southern Oregon.

Abstract Objectives Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota. Methods Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 ± 8.3 years) with DC. They underwent double‐ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method. Results All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2–3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased α‐diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae, in the diverted colon decreased after autologous FMT. Conclusions This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment.

Abstract This report highlights the easy peeling of the esophageal epithelium with Nikolsky phenomenon after swallowing the foreign body and the healing status of the esophagus only 3 days later in a patient of pemphigus vulgaris.