Background: Vitiligo is a skin disorder characterized by the loss of melanocytes (MCs), leading to depigmentation.While the exact mechanisms are unclear, the transcription factor Ets-1, known for its role in regulating matrix metalloproteinase expression and MC migration, is suspected to play a part. Ets-1 gene-deficient mice exhibit a vitiligo-like phenotype with spontaneous skin depigmentation, suggesting a direct link between Ets-1 deficiency and MC dysfunction. This study aimed to characterize the molecular and histological features of Ets-1 gene knockout (KO) mice to understand the underlying mechanisms of this depigmentation. Results: Transcriptomic analysis of depigmented and normal skin from Ets-1 KO and wild-type mice revealed significant differentially expressed genes (DEGs). KEGG pathway enrichment analysis demonstrated alterations in metabolic and signal transduction pathways, notably the downregulation of melanogenesis-related genes. RT-qPCR and immunohistochemistry confirmed reduced tyrosinase expression at both transcript and protein levels in the depigmented skin of KO mice. Protein-protein interaction network analysis of the DEGs highlighted a central network involving keratin proteins and discrete interactions regulating melanogenesis, stress response, and cellular signaling pathways. Conclusions These findings demonstrate that Ets-1 deficiency in mice leads to significant molecular and histological changes consistent with MC dysfunction and depigmentation. The observed downregulation of melanogenesisrelated genes and alterations in key signaling pathways provide valuable insights into the molecular basis of Ets-1’s role in MC maintenance and suggest potential therapeutic targets for skin pigmentation disorders, including vitiligo.

Background/Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE). Methods: A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE). Results: We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%. Conclusions In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Background/Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE). Methods: A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE). Results: We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%. Conclusions In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Background/Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE). Methods: A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE). Results: We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%. Conclusions In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.

Background: Chemoradiotherapy is the standard treatment for esophageal cancer, but the optimal radiation dose remains undetermined. A dose of 50.4 Gy is commonly used in both neoadjuvant and definitive settings. This study evaluates the outcomes of using 50.4 Gy in neoadjuvant chemoradiotherapy (nCRT). Methods: Patients with esophageal cancer who underwent nCRT with 50.4 Gy radiation followed by surgery between 2010 and 2023 were retrospectively analyzed. They were categorized as achieving pathological complete response (pCR patients) or not (non-pCR patients). Oncological outcomes, including overall survival (OS) and recurrence-free survival (RFS), were assessed. Results: Among 258 patients treated with nCRT, 96.5% completed the treatment protocol, and 74.4% (n=192) proceeded to surgery. These 192 patients formed the analysis cohort. The overall complication rate was 70.3%, with 19.3% classified as major complications. The 30-day and 90-day postoperative mortality rates were both 0.5%. The pCR rate was 45%. Patients with pCR had a 3-year OS rate of 72.7% and a median survival of 125 months, whereas non-pCR patients had a 3-year OS rate of 49.6% and a median survival of 35 months (p=0.002). Additionally, pCR patients had a 3-year RFS rate of 62.0% and a median RFS of 68 months, compared to 33.6% and 20 months, respectively, for non-pCR patients (p<0.001). Conclusion This study reports the outcomes of using 50.4 Gy in nCRT for locally advanced esophageal cancer. The findings affirm the efficacy of 50.4 Gy neoadjuvant chemoradiotherapy in achieving favorable long-term outcomes, particularly among patients with complete pathological response.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: The relationship between adverse childhood experiences and methamphetamine use disorder (MUD) has been shown in previous studies; nevertheless, the underlying neural mechanisms remain elusive. Childhood trauma is associated with aberrant functional connectivity (FC) within the default-mode network (DMN). Furthermore, within the DMN, FC may contribute to impaired self-awareness in addiction, while cross-network FC is critical for relapse.We aimed to investigate whether childhood trauma was associated with DMN-related resting-state FC among healthy controls and patients with MUD and to examine whether DMN-related FC affected the effect of childhood trauma on the symptom load of MUD diagnosis. Methods: Twenty-seven male patients with MUD and 27 male healthy controls were enrolled and completed the Childhood Trauma Questionnaire. DMN-related resting-state FC was examined using functional magnetic resonance imaging. Results: There were 47.1% healthy controls and 66.7% MUD patients in this study with adverse childhood experiences.Negative correlations between adverse childhood experiences and within-DMN FC were observed in both healthy controls and MUD patients, while within-DMN FC was significantly altered in MUD patients. The detrimental effects of adverse childhood experiences on MUD patients may be attenuated through DMN-executive control networks (ECN) FC. Conclusion Adverse childhood experiences were negatively associated with within-DMN FC in MUD patients and healthy controls. However, DMN-ECN FC may attenuate the effects of childhood trauma on symptoms load of MUD.