In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

Background/Aims: Elevated troponin levels predict in-hospital mortality and influence decisions regarding thrombolytic therapy in patients with acute pulmonary embolism (PE). However, the usefulness of high-sensitivity troponin T (hsTnT) regarding PE remains uncertain. We aimed to establish the optimal cut-off level and compare its performance for precise risk stratification. Methods: 374 patients diagnosed with acute PE were reviewed. PE-related adverse outcomes, a composite of PE-related deaths, cardiopulmonary resuscitation incidents, systolic blood pressure < 90 mmHg, and all-cause mortality within 30 days were evaluated. The optimal hsTnT cut-off for all-cause mortality, and the net reclassification index (NRI) was used to assess the incremental value in risk stratification. Results: Among 343 normotensive patients, 17 (5.0%) experienced all-cause mortality, while 40 (10.7%) had PE-related adverse outcomes. An optimal hsTnT cut-off value of 60 ng/L for all-cause mortality (AUC 0.74, 95% CI 0.61–0.85, p < 0.001) was identified, which was significantly associated with PE-related adverse outcomes (OR 4.07, 95% CI 2.06–8.06, p < 0.001). Patients with hsTnT ≥ 60 ng/L were older, hypotensive, had higher creatinine levels, and right ventricular dysfunction signs. Combining hsTnT ≥ 60 ng/L with simplified pulmonary embolism severity index ≥1 provided additional prognostic information. Reclassification analysis showed a significant shift in risk categories, with an NRI of 1.016 ± 0.201 (p < 0.001). Conclusions We refined troponin’s predictive value in patients with acute PE, proposing a new cut-off value of hsTnT ≥ 60 ng/L. Validation through large-scale studies is essential to offer clinically useful guidance for managing patient population.

Ketone bodies produced by sodium-glucose cotransporter 2 (SGLT2) inhibitors can be advantageous, providing an efficient and stable energy source for the brain and muscles. However, in patients with diabetes, ketogenesis induced by SGLT2 inhibitors may be harmful, potentially resulting in severe diabetic ketoacidosis (DKA). During fasting, ketone body production serves as an alternative and efficient energy source for the brain by utilizing stored fat, promoting mental clarity, and reducing dependence on glucose. The concurrent use of SGLT2 inhibitors during perioperative fasting may further elevate the risk of euglycemic DKA. We describe a case of DKA that occurred during perioperative fasting in a patient receiving empagliflozin, an SGLT2 inhibitor. This case underscores the importance of recognizing the potential risk of DKA in patients with diabetes using SGLT2 inhibitors during perioperative fasting.

Fecal impaction (FI) is a potentially fatal condition characterized by the accumulation of large, hardened fecal masses in the large intestine, resulting in mechanical obstruction. This condition is commonly observed in older adults but can also affect younger populations, particularly patients with psychiatric conditions who face increased risk due to medication side effects, autonomic dysfunction, and inadequate bowel management. This report describes two forensic autopsy cases of fatal FI in patients with neuropsychiatric disorders. The first case involved a 52-year-old man with mild intellectual disability who had received long-term psychiatric treatment. Autopsy findings included marked colonic dilation (maximum diameter >10 cm), ischemic mucosal changes, and a large fecal mass (~2,200 g) obstructing the sigmoid and descending colon. The second case involved a 25-year-old man with severe intellectual disability. Autopsy revealed severe colonic dilation (maximum diameter of 12 cm), extensive FI along rectum and descending colon, and no evidence of alternative causes of death. In both cases, death was attributed to mechanical intestinal obstruction secondary to FI. These cases highlight the forensic significance of FI as a cause of sudden death in patients with neuropsychiatric disorders. Symptoms such as paradoxical diarrhea may be misinterpreted, and the inadvertent use of contraindicated medications (e.g., antidiarrheals) can worsen the condition, contributing to fatal outcomes. Furthermore, forensic evaluation must assess whether inadequate medical intervention or neglect played a role in the progression of FI. Early recognition, proactive bowel management, and interdisciplinary collaboration are critical to preventing fatal events in high-risk patients with neuropsychiatric disorders.

Objective: This study aimed to quantitatively assess abnormalities in the talar dome cartilage using MRI T2 mapping, with additional analyses based on the Lauge-Hansen (LH) classification and anatomical locations. Materials and Methods: This retrospective study analyzed 78 patients who underwent ankle MRI with T2 mapping for acute ankle trauma between January 2021 and October 2022. Patients were classified into the supination (S) and pronation (P) groups based on the LH classification, and then divided into subgroups based on posterior malleolus (PM) involvement. The T2 values for the talar cartilage were quantitatively measured in six anatomical regions defined by the combination of medial vs.lateral and anterior vs. central vs. posterior. The T2 mapping values in each region of the talus were compared between the S and P groups and between the PM and non-PM injury groups using t-tests. The T2 values were also compared between the medial and lateral sides within each group. Results: Among the 78 patients (mean age, 38.62 ± 14.82 years; 47 male), 53 and 25 were in the S and P groups, respectively, and 53 patients showed PM involvement. In comparison with the P group, the S group exhibited higher T2 values in the medial portion (61.27 ± 8.30 vs. 54.03 ± 6.96; P < 0.001) and lower T2 values in the lateral talus (54.95 ± 8.47 vs. 64.15 ± 7.31; P < 0.001). The PM injury group showed higher T2 values in the posterior region than the non-PM injury group (P ≤ 0.011). Within the PM injury group, T2 values were higher in the anteromedial and posterolateral regions than on the opposite sides (P= 0.037 and 0.011, respectively). Conclusion MRI T2 values demonstrated significant regional variations in the talar dome cartilage in acute ankle trauma, and the T2 values may reflect different ankle trauma mechanisms and PM involvement. Thus, T2 mapping can facilitate evaluation of talar cartilage alterations.

Objective: The upper lumbar region has distinctive anatomical characteristics that contribute to the challenges of performing discectomy. We introduce far-lateral transforaminal unilateral biportal endoscopic (UBE) lumbar discectomy for central or paracentral disc herniations in the upper lumbar region. Methods: We conducted retrospective review of the patients who underwent a far-lateral transforaminal UBE lumbar discectomy at our institution from January 2018 to September 2024. The electronic medical records, operative records, and radiologic images of the patients were reviewed. Results: A total of 27 patients underwent far-lateral transforaminal UBE lumbar discectomy for central or paracentral disc herniations in the upper lumbar region. The patient had a mean age of 54.0 ± 13.7 years. Operation was performed at the L1–2 level in 3 patients (11.1%), L2–3 in 9 patients (33.3%), and L3–4 in 15 patients (55.6%). The patients were followed-up for a mean of 27.7 ± 19.3 months. The Oswestry Disability Index was significantly decreased from 36.3 ± 6.8 preoperatively to 3.7 ± 3.3 at last follow-up (p < 0.001). The visual analogue scale (VAS) back was significantly decreased from 7.8 ± 0.9 preoperatively to 3.1 ± 0.6 postoperative day 2 (p < 0.001). The VAS leg was significantly decreased from 8.1 ± 0.8 preoperatively to 2.3 ± 0.7 postoperative day 2 (p < 0.001). Conclusion The far-lateral transforaminal UBE lumbar discectomy would be a viable surgical option for upper lumbar disc herniations.

Background/Aims: Elevated troponin levels predict in-hospital mortality and influence decisions regarding thrombolytic therapy in patients with acute pulmonary embolism (PE). However, the usefulness of high-sensitivity troponin T (hsTnT) regarding PE remains uncertain. We aimed to establish the optimal cut-off level and compare its performance for precise risk stratification. Methods: 374 patients diagnosed with acute PE were reviewed. PE-related adverse outcomes, a composite of PE-related deaths, cardiopulmonary resuscitation incidents, systolic blood pressure < 90 mmHg, and all-cause mortality within 30 days were evaluated. The optimal hsTnT cut-off for all-cause mortality, and the net reclassification index (NRI) was used to assess the incremental value in risk stratification. Results: Among 343 normotensive patients, 17 (5.0%) experienced all-cause mortality, while 40 (10.7%) had PE-related adverse outcomes. An optimal hsTnT cut-off value of 60 ng/L for all-cause mortality (AUC 0.74, 95% CI 0.61–0.85, p < 0.001) was identified, which was significantly associated with PE-related adverse outcomes (OR 4.07, 95% CI 2.06–8.06, p < 0.001). Patients with hsTnT ≥ 60 ng/L were older, hypotensive, had higher creatinine levels, and right ventricular dysfunction signs. Combining hsTnT ≥ 60 ng/L with simplified pulmonary embolism severity index ≥1 provided additional prognostic information. Reclassification analysis showed a significant shift in risk categories, with an NRI of 1.016 ± 0.201 (p < 0.001). Conclusions We refined troponin’s predictive value in patients with acute PE, proposing a new cut-off value of hsTnT ≥ 60 ng/L. Validation through large-scale studies is essential to offer clinically useful guidance for managing patient population.

Purpose: Cognitive behavioral therapy (CBT) has long been recognized as an effective treatment for depression and suicidality.Virtual reality (VR) technology is widely used for cognitive training for conditions such as anxiety disorder and post-traumatic stress disorder, but little research has considered VR-based CBT for depressive symptoms and suicidality. We tested the effectiveness and safety of a VR-based CBT program for depressive disorders. Materials and Methods: We recruited 57 participants from May 2022 through February 2023 using online advertisements. This multi-center, assessor-blinded, randomized, controlled exploratory trial used two groups: VR treatment group and treat as usual (TAU) group. VR treatment group received a VR mental health training/education program. TAU group received standard pharmacotherapy. Assessments were conducted at baseline, immediately after the 6-week treatment period, and 4 weeks after the end of the treatment period in each group. Results: Depression scores decreased significantly over time in both VR treatment and TAU groups, with no differences between the two groups. The suicidality score decreased significantly only in VR group. No group differences were found in the remission or response rate for depression, perceived stress, or clinical severity. No adverse events or motion sickness occurred during the VR treatment program. Conclusion VR CBT treatment for major depressive disorder has the potential to be equivalent to the gold-standard pharmacotherapy in reducing depressive symptoms, suicidality, and related clinical symptoms, with no difference in improvement found in this study. Thus, VR-based CBT might be an effective alternative to pharmacotherapy for depressive disorders.

Purpose: Hair disorders, which are often attributed to conditions associated with a shortened anagen growth phase, oxidative stress, and hormonal dysregulation, especially during aging, have profound psychological implications. Currently, only minoxidil has been approved as a topical hair growth solution; thus, alternative therapies for treating hair loss and promoting hair health are urgently needed. Herein, we aimed to develop and assess a novel method to promote hair growth and health using mastic (Pistacia lentiscus) gum and peppermint (Mentha piperita L.) extracts. Materials and Methods: After determining the optimal ratio of mastic gum and peppermint extracts, we performed in vitro and in vivo experiments to verify the efficacy of the 7:3 mastic gum-peppermint mixture (MP73; FHH-MG) for enhancing hair growth and health. Results: Mastic gum significantly promoted cell proliferation and demonstrated synergistic benefits when combined with peppermint extract. In vitro, FHH-MG increased human dermal follicle papilla cell proliferation and demonstrated anti-inflammatory and antioxidant effects. In vivo, treatment with FHH-MG dose-dependently enhanced hair growth and gloss and increased the expression of vascular endothelial growth factor, epidermal growth factor, β-catenin, and insulin-like growth factor-1 in C57BL/6 mice compared to the negative control. Conclusion The novel mixture exhibited hair growth-promoting effects in C57BL/6 mice; thus, FHH-MG may serve as a botanical alternative for hair growth and health promotion.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.