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.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Background: Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency. Results: In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation ­(SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen ­(PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide ­(PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7. Conclusions This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

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.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.