Search Results (987)

Background/Objectives: Anti-mGluR1 encephalitis is a rare form of autoimmune encephalitis predominantly manifesting as acute/subacute cerebellar ataxia. We describe a newly diagnosed case series from our center and conduct a comprehensive review of reported cases worldwide to compare clinical manifestations, treatment options, and outcomes. Methods: We consecutively identified 11 patients at Peking Union Medical College Hospital, and additionally extracted clinical data from 42 previously published cases identified via PubMed and Google Scholar (search updated to 1 August 2025). Demographics, phenotypes, laboratory findings, imaging, treatment, and outcomes were systematically summarized. This pooled review was not prospectively registered, and extracted data from 21 published articles were analyzed alongside our 11 newly diagnosed cases. Results: The integrated cohort comprised 53 patients with anti-mGluR1 encephalitis, including 29 males and 24 females, with patients reported from Asia (n = 18), North America (n = 11), and Europe (n = 24). The median age at onset was 50 years (IQR 29.5–58.5; range 3–81), with North American patients presenting later than their Asian and European counterparts (median 60 vs. 48 and 45 years, respectively; all p < 0.05). Disease onset was subacute in most cases (58.7%). Comorbid tumors were present in nine patients, most commonly lymphomas. Clinical phenotypes were classified as pure cerebellar syndrome (n = 31), cerebellar ataxia with encephalitic features (n = 20), and non-cerebellar presentations (n = 2). Baseline severity differed across phenotypes (χ² = 35.7, p < 0.001). Regional variability in severity was observed but did not reach significance. CSF analyses revealed pleocytosis in 59% (23/39), elevated protein in 31.3% (5/16), and oligoclonal bands in 52.2% (12/23). MRI abnormalities were detected in 34.7% (17/49) of patients, with 21.9% (7/32) developing cerebellar atrophy on follow-up. Therapeutic strategies varied significantly across regions (p = 0.041), with Asian cohorts more frequently receiving long-term immunosuppression, European cohorts favoring combined regimens, and North American cases relying predominantly on first-line therapies. Overall, 65.9% (29/44) of patients clinically improved, 13.6% (6/44) relapsed and 20.5% (9/44) remained unaffected. Conclusions: Anti-mGluR1 encephalitis presents with significant clinical heterogeneity, ranging from cerebellar-dominant ataxia to neuropsychiatric or non-cerebellar phenotypes, and demonstrates differences in reported age of onset, disease severity, and therapeutic approaches across publication regions. Our findings underscore the importance of early recognition, sustained immunotherapy, and international collaboration to establish standardized, evidence-based management for this rare but disabling disorder. Full article

Astroviruses are non-enveloped, positive-sense single-stranded RNA viruses known to infect various mammals and birds, including humans, often causing gastrointestinal disorders. In recent years, astroviruses have also been linked to neurological and respiratory diseases across several species, including ruminants, mink, deer, and other mammals. Notably, astrovirus infections in goats have been documented in countries such as Switzerland and China, where novel genotypes have been identified in fecal samples. However, their role in the context of disease remains unclear, and reports focusing solely on goat astrovirus in the United States have not been published. A necropsy case of a Boer goat kid with a history of diarrhea was submitted for investigation following death in January 2025. Fresh tissues were received and used for histopathology and enteric pathogen testing, including parasitic, bacterial, and viral workups. Metagenomic-based next-generation sequencing (mNGS) was also applied for this case. Histological examination revealed severe necrotizing enterocolitis. The small intestine exhibited epithelial ulcerations, villus atrophy, hyperplastic and dilated crypts with necrotic debris, few intraenterocytic coccidian parasites, and increased inflammatory cells in the lamina propria. The large intestine showed similar findings with pleomorphic crypt enterocytes. Standard enteric pathogen tests were negative except for aerobic culture that identified Escherichia.coli and Enterococcus hirae. mNGS and bioinformatic analysis identified a novel astrovirus in the intestinal content that showed the highest nucleotide identity (86%) to the sheep strain Mamastrovirus 13 sheep/HA3 from China based on BLAST analysis. Phylogenetic analysis indicated that the newly identified caprine astrovirus IL90175 clustered with astrovirus strains from small ruminants in Asia and Europe. This research reports the discovery, histopathologic features, and genetic characteristics of a gastrointestinal disease-causing astrovirus in a goat kid, which had not been previously described in the United States. Full article

Determination of the right price is vital for the success of newly developed food products. This study examined the market prices and their determinants for five ready-to-cook catfish products: Panko-Breaded Standard Strips (PBSS), Panko-Breaded Standard Fillet (PBSF), Panko-Breaded Delacata Fillet (PBDF), Sriracha-Marinated Delacata Fillet (SMDF), and Sesame-Ginger-Marinated Delacata Fillet (SGMDF). Market prices were derived using Vickrey’s second-price auction, where the second-highest bid represents the market price. We analyzed experimental auction data from 121 consumers using a logit model to estimate the probability of offering the market price based on product sensory attributes, socio-demographic characteristics of the participants, and the level of competition (panel size). Consumers’ willingness-to-pay (WTP) was elicited in two rounds: before tasting (visual evaluation) and after tasting (organoleptic evaluation) the products. Breaded products received higher market prices than marinated products, with PBDF ranked highest. Sensory traits, especially taste, along with income, education, and grocery shopping involvement, significantly influenced the formation of market price. Increased competition elevated the market prices. Both product features and consumer characteristics significantly affect market price outcomes, and experimental auctions provide a robust tool for understanding consumer behavior toward newly developed food products. Full article

Background and Objectives: Cognitive deficits are common in obstructive sleep apnea (OSA), and both intermittent hypoxemia and cardiovascular comorbidity may contribute to poorer outcomes. Arterial hypertension (HTN) has been suggested as a potential modifier of cognitive function in OSA, but findings remain inconsistent. This study examined whether HTN influences baseline cognition or cognitive improvement after continuous positive airway pressure (CPAP) therapy in moderate-to-severe OSA and identified predictors of poorer post-treatment cognitive status. Materials and Methods: This prospective study involved 71 adults with newly diagnosed moderate-to-severe OSA (AHI ≥ 15). Participants underwent baseline polysomnography, Montreal Cognitive Assessment (MoCA) testing, and P300 assessments. Cognitive impairment was defined as MoCA < 26 and HTN by antihypertensive therapy, documented diagnosis, or repeatedly elevated blood pressure. All participants initiated auto-adjusting CPAP and were reassessed after three months for adherence, residual respiratory indices, MoCA, and P300 parameters. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were used to identify independent predictors of poorer cognitive outcomes. Results: CPAP therapy significantly improved apnea severity, daytime sleepiness, global cognition, and P300 latency, while P300 amplitude did not change significantly. After three months, hypertensive and normotensive patients showed similar MoCA scores, respiratory outcomes, and P300 amplitude; P300 latency remained marginally longer in hypertensive individuals. Across multivariate models, lower mean nocturnal oxygen saturation and reduced CPAP adherence independently predicted poorer cognitive outcome at follow-up. CPAP adherence demonstrated greater discriminative ability than mean nocturnal oxygenation. Conclusions: In adequately treated moderate-to-severe OSA, HTN did not significantly affect baseline cognition or short-term cognitive recovery with CPAP. Although P300 latency remained slightly prolonged in hypertensive individuals, this difference was marginal and not accompanied by cognitive deficits. Nocturnal oxygenation and CPAP adherence emerged as the strongest predictors of post-treatment cognitive status, underscoring the importance of sustained and effective therapy. These findings suggest that effective CPAP adherence and improved nocturnal oxygenation are crucial for cognitive recovery in OSA patients, regardless of hypertensive status. Full article

Circulating irisin, a myokine implicated in energy expenditure and adipose tissue regulation, has been increasingly studied as a potential biomarker of metabolic dysfunction. This study evaluated the relationship between serum irisin and metabolic indices, including the atherogenic index of plasma (AIP), the lipid accumulation product (LAP), and hypertriglyceridemic-waist (HTGW) phenotype in individuals with prediabetes (PreDM) and newly diagnosed type 2 diabetes mellitus (T2DM). A total of 138 participants (48 PreDM, 90 T2DM) were assessed for anthropometric, glycemic, and lipid parameters. Serum irisin levels were measured by enzyme-linked immunosorbent assay (ELISA) and correlated with insulin resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI)), glycemic control (glycosylated hemoglobin A1c (HbA1c)), and composite lipid markers (total triglycerides-to-high-density lipoprotein cholesterol (TG/HDL-C)). Group differences were evaluated using non-parametric tests; two-way ANOVA assessed interactions between phenotypes and markers; multiple linear regression (MLR) and logistic regression models explored independent associations with metabolic indices and HTGW; receiver operating characteristic (ROC) analyses compared global and stratified model performance. Serum irisin was significantly lower in T2DM than in PreDM (median 140.4 vs. 230.7 ng/mL, p < 0.0001). Irisin levels remained comparable between males and females in both groups. Post hoc analysis shows that lipid indices and irisin primarily distinguish HTGW phenotypes, especially in T2DM. In both groups, irisin correlated inversely with HOMA-IR, AIP, and TG/HDL-C, and positively with QUICKI, indicating a possible compensatory role in early insulin resistance. MLR analyses revealed no independent relationship between irisin and either AIP or LAP in PreDM, while in T2DM, waist circumference remained the strongest negative predictor of irisin. Logistic regression identified age, male sex, and HbA1c as independent predictors of the HTGW phenotype, while irisin contributed modestly to overall model discrimination. ROC curves demonstrated good discriminative performance (AUC = 0.806 for global; 0.794 for PreDM; 0.813 for T2DM), suggesting comparable predictive accuracy across glycemic stages. In conclusion, irisin levels decline from prediabetes to overt diabetes and are inversely linked to lipid accumulation and insulin resistance but do not independently predict the HTGW phenotype. These findings support irisin’s role as an integrative indicator of metabolic stress rather than a stand-alone biomarker. Incorporating irisin into multi-parameter metabolic panels may enhance early detection of cardiometabolic risk in dysglycemic populations. Full article

Background: Effective preoperative patient counseling is essential to shared decision-making. In thyroid surgery, patient communication can be complicated by the complex anatomy and variable surgical approaches, which may not be fully conveyed through conventional verbal explanations or schematic drawings. Virtual three-dimensional (3D) thyroid models may provide an intuitive tool to enhance patient comprehension. Methods: We conducted a randomized controlled trial at Peking Union Medical College Hospital with 94 newly-diagnosed thyroid cancer patients scheduled for thyroidectomy. Participants were assigned to either the control group (n = 47), which received preoperative drawing-based counseling, or the intervention group (n = 47), which utilized a virtual 3D model for communication. The Thyroid Navigator app, developed by Kuma Hospital, was used to provide dynamic 3D representation of the thyroid gland, surrounding structures, and potential surgical procedures. After standardized preoperative consultations, patients were surveyed to assess their understanding in pertinent anatomy and postoperative complications. Results: Patients in the 3D model group demonstrated similar correct response rates in lesion localization (p = 0.536) or parathyroid gland recognition (p = 0.071), but significantly higher accuracy in identifying the recurrent laryngeal nerve and the extent of lymph node dissection compared with the control group (p < 0.05). Moreover, comprehension of the causes of major postoperative complications—including hoarseness (recurrent laryngeal nerve injury, p = 0.004), hypocalcemia (parathyroid gland impairment, p = 0.015), and bleeding (inadequate hemostasis, p = 0.008)—was significantly improved in the 3D model group. Conclusions: Use of a virtual 3D thyroid model significantly improves patient comprehension of thyroid anatomy, surgical procedures, and potential complications, thereby enhancing clinician–patient communication. Virtual 3D models represent a practical and cost-effective supplement to conventional counseling in thyroid surgery, offering clear benefits in patient education and shared decision-making. Full article

Background: Atherosclerosis and its associated chronic inflammation of the arterial wall disrupt fatty acid metabolism, leading to changes in plasma fatty acid composition. These alterations can be used to improve disease diagnosis and risk stratification by the development and application of specific lipidomic indices. Objectives: The objectives of this study are to evaluate the performance of conventional fatty acid indices and enhance diagnostic efficiency in atherosclerosis by introducing novel index based on plasma PUFA n-6 and n-3 content (Omega-6/3 Balance Index, O6/3-BI), as well as the perspective SFA/MUFA ratio (stearic/oleic acid ratio, C18:0/C18:1n-9) and a logit function combining PUFA and SFA/MUFA biomarkers. Methods: Plasma fatty acids were quantified by LC-MS/MS in healthy controls (n = 50) and patients with carotid atherosclerosis (n = 52), stratified by atorvastatin, rosuvastatin, or no statin therapy. The conventional indices (the Omega-3 Status (EPA + DHA), AA/EPA, and the omega-6/omega-3 ratio), and pathway ratios (C18:0/C18:1n-9; and C20:4n-6/C22:4n-6), as well as the newly introduced PUFA index and combined PUFA-SFA/MUFA logit function, were calculated. Their diagnostic performance for distinguishing atherosclerosis was assessed by a receiver operating characteristic (ROC) analysis with the cross-validation and calculation of Cliff’s Δ effect size. Results: The conventional parameters demonstrated a poor to low discrimination ability of the atherosclerosis patients’ groups from healthy controls (area under the ROC curve, AUC 0.548–0.711). In statin-treated patients, these conventional markers lost significance. The newly introduced PUFA index and SFA/MUFA ratio demonstrated improved patients’ discrimination with AUC 0.734–0.780 for the former and strong predictive power with AUC 0.831–0.858 for the latter marker and maintained their diagnostic value under statin therapy. The most significant positive effect size was observed for the SFA/MUFA ratio with Cliff’s Δ = 0.67–0.71. The combined PUFA-SFA/MUFA logit function also demonstrated a strong predictive power with AUC = 0.880 (Cliff’s Δ = −0.76), outperforming any single index. Conclusions: The newly introduced lipidomic index based on the PUFA content, SFA/MUFA ratio, and a logit function combining PUFA-SFA/MUFA biomarkers demonstrated a substantially better discrimination of atherosclerosis-related fatty acid metabolic disturbances than conventional fatty acid biomarkers. Full article

Background/objectives: Improvements in esophageal adenocarcinoma (EAC) treatment have reduced mortality. While chemoradiation before surgery was previously a standard of care, updated guidelines recommend peri-operative chemotherapy without chemoradiation. Continued investigation into optimal non-operative treatment paradigms for patients who defer surgery or are not candidates for surgery and certain chemotherapy regimens is needed. The impact of induction chemotherapy prior to chemoradiation on survival and surgical outcomes remains unclear. This study assessed survival and surgical outcomes in a real-world cohort of EAC patients receiving induction chemotherapy before chemoradiation. Methods: This single-institution, IRB-approved, retrospective cohort study included patients with newly diagnosed stage II-IVb (oligometastatic for IVb) EAC who received definitive chemoradiation (radiation ≥ 40 Gy and two cycles of chemotherapy) +/− esophagectomy from 2007 to 2022. Patients receiving induction chemotherapy were compared to those who did not. Endpoints included survival and surgical outcomes. Results: A total of 141 EAC patients received definitive chemoradiation; 83 received induction chemotherapy before chemoradiation. Patients receiving induction chemotherapy were younger (p < 0.01) with slightly lower performance status (p = 0.27) and presented at a more advanced stage (p < 0.001). Median OS was 3.5 years in the induction chemotherapy group compared to 2.2 years (p = 0.10). There was no difference in pathologic complete response (p = 0.81), esophagectomy frequency (p = 0.87), or surgical downstaging between treatment groups (p = 0.84). Conclusions: In this real-world, single-institutional patient cohort investigating induction chemotherapy prior to chemoradiation in EAC, patients receiving induction chemotherapy did well but did not have a statistically significant improvement in survival outcomes or surgical outcomes. This study showed that significant numbers of real-world patients may not receive esophagectomy. Thus, prospective, randomized clinical trials are warranted to better delineate the efficacy and selection of patients for induction chemotherapy when non-operative approaches are favored. Full article

Background: As a newly recognized type of cell death implicated in cancer, ferroptosis plays multiple roles in tumor biology. Here, we sought to construct a prognostic framework for EC on the basis of ferroptosis-related long non-coding RNAs (FerlncRNAs), microRNAs (FermiRNAs), and mRNAs (FRGs) for endometrial cancer (EC). Methods: Transcriptomic profiles of tumors and matched clinical data for 544 EC patients were retrieved from TCGA-UCEC. A prognostic framework was generated through Cox regression, integrating ferroptosis-linked lncRNAs, miRNAs, and mRNAs. EC cases were stratified into groups with high or low predicted risk based on ferroptosis-related gene expression. The model’s prognostic utility was examined through Kaplan–Meier (K–M) analysis and receiver operating characteristic curves. Results: A prognostic model based on 16 RNAs, including 10 FerlncRNAs, 2 FermiRNAs, and 4 FRGs, was developed. Analysis using K–M plots showed that high-risk patients experienced shorter overall survival than their low-risk counterparts (p < 0.001). The model’s area under curve (AUC) values were 0.731, 0.749, and 0.768 at 1-, 3-, and 5-year time points, surpassing those of standard clinical parameters. Furthermore, in an external validation cohort, these signature RNAs were associated with EC prognosis. Conclusions: The novel ferroptosis-related lncRNA–miRNA–mRNA prognostic model provides a basis to assess clinical prognosis in EC patients. Full article

Ecological compensation is an important policy tool for coordinating ecological protection and economic development and narrowing regional disparities. In China, Linyi, for the first time, applied a cap-and-trade policy to the forestry sector by implementing the Intergovernmental Forest Ecological Indicator Trading Policy (IFEITP)—a new ecological compensation policy—to increase the city’s overall forest coverage. However, the compensation standard for this policy was formulated solely by referring to provincial afforestation subsidy standards, resulting in excessively low indicator trading prices and making the policy difficult to sustain. This paper proposes a technical framework for ecological compensation based on the ecosystem service spillover value (ESSV), aiming to optimize the IFEITP. The results revealed that during the policy implementation period, Linyi’s total ecosystem service value (ESV) increased, and the proportion of ESV provided by forests in each district and county also increased. Under the new framework, there were minor changes in the ecosystem service supply zones and payment zones. The compensation received by supply zones increased by 116.2%, whereas the payments made by payment zones accounted for less than 0.2% of local fiscal revenue. The newly calculated indicator trading price under this framework not only reflects the value of ecosystem services but also remains within the acceptable range of government finances, demonstrating high operability and providing a basis for optimizing the IFEITP. This study offers broader insights for regions with similar ecological and socioeconomic conditions, enabling the application of analogous ecological compensation policies to maintain environmental justice and promote sustainable development. Full article

Background/Objectives: Multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs) are at increased risk of venous thromboembolism (VTE). Standard prophylaxis typically involves aspirin or low-molecular-weight heparin (LMWH), guided by risk assessment tools such as SAVED and IMPEDE-VTE. However, these models have practical limitations, and real-world evidence supporting novel oral anticoagulants (NOACs) as primary prophylaxis remains limited. Methods: In this retrospective, single-center study, we analyzed 101 MM patients treated with IMiD-based therapy between January 2020 and December 2024. All patients received NOAC prophylaxis (apixaban 2.5 mg twice daily or rivaroxaban 10–20 mg once daily), irrespective of baseline thrombotic risk. Clinical characteristics, comorbidities, and treatment details were collected. The primary outcome was objectively confirmed VTE, while secondary outcomes included bleeding events and treatment feasibility, assessed by treatment continuation without clinically significant bleeding. Results: Median age was 63 years (range 35–89); 36.6% were female. Lenalidomide and pomalidomide were used in 86.1% and 13.9%, respectively. Twenty-eight patients (27.7%) had relapsed/refractory disease, while 72.3% were newly diagnosed. Over a median NOAC exposure of 6 months, two patients (2.0%) developed VTE (both deep vein thrombosis). One major bleeding event (1.0%) occurred. Conclusions: Universal NOAC prophylaxis in MM patients receiving IMiD-based therapy was associated with a low incidence of thromboembolic events and an acceptable safety profile. These real-world findings suggest that NOACs may represent a practical and effective alternative to aspirin or LMWH, potentially overcoming the limitations of score-based prophylaxis strategies. Full article

Bone regeneration remains a clinical challenge, particularly in critical-size defects, motivating the investigation of biomaterials and adjuvant therapies that may support tissue repair. This experimental study evaluated bone healing in critical-size calvarial defects created in rats, using different combinations of regenerative strategies, including heterologous fibrin biopolymer gel, bovine cortical bone biological membrane, and photobiomodulation. Standardized 5.0 mm calvarial defects were surgically created in sixty Wistar rats, which were randomly allocated into six experimental groups according to the filling material and the application or absence of photobiomodulation. The treatments included clot alone, fibrin biopolymer gel, biological membrane, photobiomodulation, or their respective combinations. Animals were euthanized at 14 or 42 days, and bone repair was evaluated by histomorphometric analysis. At 14 days, differences in the extent of newly formed bone were observed among the experimental groups, with higher bone formation values detected in groups receiving combined treatments and lower values in groups treated with fewer regenerative components. At 42 days, all groups showed progression of bone repair, with greater bone formation observed in groups in which a biological membrane was used, regardless of photobiomodulation. Overall, the findings indicate that the association of different regenerative approaches was related to variations in bone repair patterns over time, suggesting that photobiomodulation, when applied in combination with biomaterials, may be associated with differences in early bone healing, without implying a direct causal effect. Full article

Background/Objectives: Although Tumor-Treating Fields (TTFields) therapy is an established treatment modality for adult glioblastoma, clinical data on its efficacy in pediatric brain tumors are extremely scarce. The present study aimed to evaluate the safety of TTFields therapy for pediatric diffuse high-grade glioma (HGG) and to conduct an exploratory analysis of its efficacy. Methods: A prespecified, interim analysis was performed to determine whether the study should be continued on the basis of safety and feasibility data on the first three patients. The target population was children aged 5 to 17 years with newly diagnosed, supratentorial HGG or its first recurrence following frontline therapy. After completion of initial, local treatment for the tumor (surgical removal and/or radiotherapy), all patients received TTFields therapy using Optune^TM for 28 days per course for up to 26 courses until disease progression. Results: The interim analysis, which was completed in October 2022, included three female patients aged 14, 17, and 9 years. All had a histological grade 4 tumor, two of which were radiation-induced, secondary HGG. No serious, treatment-related toxicities or device-related issues were observed. All three patients were able to continue using the device for 75% or more of the time in accordance with the protocol, suggesting that the treatment was feasible. The MRI findings of two patients indicated that the treatment has a potential antitumor effect. Based on these results, the study was resumed and is currently being continued at multiple centers. Conclusions: The initial results of the prespecified, interim analysis demonstrated that TTFields therapy was safe and feasible for children with HGG. This study was funded by the Japan Agency for Medical Research and Development (AMED) and was registered with the Japan Registry of Clinical Trials (jRCTs032200423). Full article

Background: Decitabine efficacy in acute myeloid leukemia (AML) may be enhanced by the pharmacologic upregulation of microRNA miR-29b, a regulator of DNA methyltransferase (DNMT) expression. Bortezomib and sorafenib have been shown preclinically to increase miR-29b levels, providing a biologically informed strategy to sensitize leukemic blasts to DNMT inhibition. Objectives: To evaluate the safety, tolerability, biological activity, and preliminary efficacy of combining bortezomib and sorafenib followed by decitabine in patients with newly diagnosed or relapsed/refractory AML. Methods: This phase I, dose-escalation study enrolled 15 patients (11 untreated, 4 relapsed/refractory) who received fixed-dose bortezomib and sorafenib across three dose levels prior to decitabine. Dose escalation was guided by dose-limiting toxicities (DLTs) and an increase in miR-29b expression. Results: The regimen was generally well tolerated with the most frequent grade ≥3 adverse events of hypertension and febrile neutropenia. At the highest dose level, a ≥2-fold increase in miR-29b expression was observed in two of the six evaluable patients. The overall response rate was 33.3%, with clinical responses observed in both newly diagnosed and relapsed/refractory patients. However, changes in miR-29b expression did not consistently correlate with clinical response. Conclusions: Sequential treatment with bortezomib and sorafenib followed by decitabine is feasible and demonstrates acceptable safety in AML. Although the biologic modulation of miR-29b was variable, this trial provides a proof of concept for pharmacodynamic-guided dose finding in epigenetic therapy combinations. Full article

Background: Gastrointestinal (GI) mucosal injury is a frequent complication of long-term nonsteroidal anti-inflammatory drug (NSAID) use. Effective mucosal healing requires coordinated epithelial migration, proliferation, and angiogenesis, which may be influenced by focal adhesion kinase (FAK). This study aimed to determine whether our newly developed FAK activators promote intestinal mucosal healing by enhancing angiogenesis and whether FAK activation increases resistance to reinjury. Methods: Ischemic jejunal ulcers were induced in C57BL/6 mice. After 24 h, mice received intraperitoneal injections of the FAK activator ZINC40099027 (ZN27, 900 µg/kg every 6 h) or vehicle for 2, 4, or 14 days. Ulcer areas were quantified, and liver and kidney function were assessed. Ulcer and adjacent tissues were analyzed by immunofluorescence staining for angiogenesis and proliferation markers. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with ZN27 to evaluate proliferation, migration, angiogenesis, and intracellular signaling. In a reinjury model, male C57BL/6J mice received continuous infusion of the FAK activator M64HCl (25 mg/kg/day) or vehicle for 7 days, with a single subcutaneous injection of indomethacin (10 mg/kg) on day 1 to induce GI injury. Fourteen days after the first dose of indomethacin, the mice received a second indomethacin challenge, and one day later, total ulcer areas in the pyloric opening and small intestine were quantified. Results: Ulcer areas were significantly smaller in ZN27-treated mice compared with vehicle-treated controls at 3 and 5 days, accompanied by increased expression of angiogenesis and proliferation markers. In vitro, ZN27 enhanced HUVEC migration via FAK activation in an ERK1/2-dependent manner and increased the number of angiogenic sprouts. In the reinjury model, treatment with M64HCl during the initial indomethacin-induced injury resulted in significantly smaller ulcer areas in both the pyloric opening and small intestine after the second indomethacin challenge compared with controls. Conclusions: FAK activation accelerates ischemic ulcer healing, in part by enhancing angiogenesis. Moreover, FAK activation during an initial injury reduces susceptibility to recurrent NSAID-induced intestinal injury, perhaps because it promotes initial higher-quality ulcer repair. Full article