Introduction: Carnosine can suppress secondary complications in diabetes and show robust neuroprotective activity against neurodegenerative diseases. Here, we report that carnosine ameliorates diabetes-associated cognitive decline in vivo through the modulation of autophagy. Methods: A high-fat diet (HFD) and one intraperitoneal injection of 30 mg/kg streptozotocin (STZ) were used to induce type 2 diabetes mellitus in Sprague-Dawley rats. The rats were randomly divided into five groups: control (CON), HFD/STZ, and three intragastric carnosine treatment groups receiving low (100 mg/kg), medium (300 mg/kg), and high (900 mg/kg) doses over 12 weeks. Body weight, blood glucose levels, and cognitive function were continuously monitored. From excised rat hippocampi, we determined superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels; carnosine concentration; protein expressions of Akt, mTOR and the autophagy markers LC3B and P62 and performed histopathological evaluations of the cornu ammonis 1 region. Results: The HFD/STZ group showed increased blood glucose levels and decreased body weight compared to the CON group. However, there were no significant differences in body weight and blood glucose levels between carnosine-treated and -untreated HFD-STZ-induced diabetic rats. Diabetic animals showed obvious learning and memory impairments in the Morris water maze test compared to the CON group. Compared to those in the HFD/STZ group, carnosine increased SOD activity and decreased MDA levels, increased hippocampal carnosine concentration, increased p-Akt and p-mTOR expression, decreased LC3B and P62 expression, alleviated neuronal injuries, and improved cognitive performance in a dose-dependent manner. Conclusion: Independent of any hyperglycemic effect, carnosine may improve mild cognitive impairments by mitigating oxidative stress, activating the Akt/mTOR pathway, and modulating autophagy in the hippocampus of type 2 diabetic rats.

Immune checkpoint blockade-based immunotherapy is a new modality of cancer treatment with a unique mechanism that has gained increased numbers of indication and is now used in several cancer types. However, immune-related adverse events (irAEs) emerge as a new entity of diseases involving one or multiple organ systems. irAEs could result in interruption of immunotherapy, morbidities or even death. Among various manifestations of irAEs, immune-mediated hypophysitis is rare but important, requiring prompt diagnosis and treatment to avoid life-threatening conditions. We report seven cases of immune-mediated hypophysitis in Taiwan. They suffered from various types of advanced cancer and received different regimens of immune checkpoint inhibitors. The time of onset after initiation of immunotherapy ranged from 5 to 36 weeks. All seven subjects were diagnosed of central adrenal insufficiency, while four of them had primary hypothyroidism. There was no typical finding of infiltrative hypophysitis on the pituitary MRI. There was no documented hormone recovery after diagnosis of hypophysitis, and the tumor responses to immunotherapy were variable in these seven patients. In conclusion, immune-mediated hypophysitis is often irreversible. Fortunately, it can be managed adequately with hormone replacements. Further investigations are warranted to unveil underlying mechanisms and ethnic differences to guide the solutions.

The spectral absorption of biomolecules holds immense potential for revealing molecular identity, biological functions, and clinical diagnostics. Here, we present color-resolved third harmonic generation microscopy (cTHGM), a noninvasive method for molecular imaging based on absorption-enhanced THG response. Leveraging one single broadband femtosecond laser beam, cTHGM captures subtle absorption variations, including ~2-nanometer shifts in the Soret band, enabling precise distinction of glycated hemoglobin (HbA1c) from hemoglobin with negligible phototoxicity. We demonstrate that cTHGM measures HbA1c fractions in single red blood cells (RBCs) in vivo and ex vivo, providing noninvasive HbA1c measurement and insights into HbA1c distribution at the cellular level. In addition, cTHGM reconstructs historical glycemic trajectories by decoding single-RBC HbA1c distributions, offering a retrospective view of glycemic variability over months. This innovative method combines label-free imaging, high spatial and spectral resolution, and noninvasive manners, making it a promising tool for diabetes management, glycemic variability monitoring, and broader applications in precision medicine.

Patients with Graves' disease who remain hyperthyroid under the treatment of antithyroid drugs (ATD) or cannot tolerate ATD usually receive radioactive iodine (RAI) to control disease activity. This pilot study aimed to identify predictors of prolonged euthyroidism > 12 months after receiving RAI. Demographic, clinical, and laboratory data from 117 patients receiving RAI were retrospectively collected, including age, gender, body surface area, smoking status, free thyroxine, thyrotropin, thyrotropin binding inhibiting immunoglobulin, microsomal antibody, thyroglobulin antibody, medication history, and thyroid volume. Only 85 patients without missing values were included in statistical analysis. The calculated RAI dose was the estimated thyroid volume × 0.4. The difference and ratio between the actual and calculated RAI doses were examined. A stepwise logistic regression analysis was conducted to identify important predictors of prolonged euthyroidism > 12 months. The cut-off values for discretizing continuous covariates were estimated by fitting generalized additive models. Among the 85 patients on RAI, 18 (21.2%) achieved prolonged euthyroidism > 12 months, 38 (44.7%) remained hyperthyroid with decreased ATD doses, but 29 (34.1%) suffered permanent hypothyroidism and needed long-term levothyroxine. Logistic regression analysis revealed that patients with age > 66 years, 33 < age ≤ 66 years, quitting smoking vs nonsmoking or current smoking, 600 < micorsomal antibody ≤ 1729 IU/mL, 47% < thyrotropin binding inhibiting immunoglobulin ≤ 81%, 7 < thyroglobulin antibody ≤ 162 IU/mL, 0.63 < ratio between actual and calculated RAI doses ≤ 1.96, or taking hydroxychloroquine would have a higher chance of reaching prolonged euthyroidism > 12 months after receiving RAI. Its area under the Receiver Operating Characteristic (ROC) curve was 0.932. Patients with Graves' disease who received an actual RAI dose close to the calculated RAI dose achieved prolonged euthyroidism > 12 months if they also took hydroxychloroquine during RAI treatment.

Introduction: Insulinoma is a rare pancreatic neuroendocrine tumor causing hypoglycemia. Surgery is the standard treatment, while endoscopic ultrasound (EUS)-guided ethanol ablation and medical therapy are alternatives in some patients. Methods: In this retrospective study, we recruited 19 patients with insulinoma treated between 2011 and 2025 at National Taiwan University Hospital. The final treatment strategies were surgery (n = 13), EUS-guided ethanol ablation (n = 3), and medical therapy (n = 3). The study outcomes included post-procedure stays (PPS), treatment-related complications, and follow-up results. New-onset diabetes and complete remission rates for insulinoma were examined and compared across treatment modalities. A Firth’s bias-reduced logistic regression analysis was performed to identify predictors of complete remission in 19 patients with insulinoma. Results: Patients could receive more than one treatment. Among the three final treatment modalities, surgical resection achieved the highest complete remission rate (13/13; 100%) but was associated with a longer PPS (mean ± standard deviation [SD] = 13.46 ± 7.59 days) and a higher incidence of new-onset diabetes (2/13, 15.38%). EUS-guided ethanol ablation demonstrated moderate efficacy (2/3; 66.67%) with a comparable PPS (18.33 ± 27.43 days). Lastly, medical therapy relieved symptoms but yielded no complete remissions in insulinoma (0/3; 0%). Paradoxical hypoglycemia occurred in 2 of 8 patients (25.0%) during octreotide testing or after direct octreotide treatment. One patient with insulin autoimmune syndrome improved after drug withdrawal and multimodal therapy. Logistic regression analysis identified a positive linear effect of baseline glucose levels (mg/dL) on insulinoma complete remission (estimated adjusted odds ratio [aOR] = 1.2140, p = 0.0461) and ever surgery (yes vs. no) as the most effective treatment for complete remission in insulinoma (aOR = 296.0707, p = 0.0015). Conclusion: Although surgery was the most effective treatment, it was associated with longer recovery times and potential metabolic risks. EUS-guided ethanol ablation provided a less invasive alternative with a moderate success rate, whereas medical therapy primarily offered symptomatic control rather than a definitive complete remission. Notably, lower baseline glucose levels were associated with treatment resistance, suggesting a potential role in guiding individualized therapeutic strategies.