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.

Anticancer treatment for acute lymphocytic leukemia is based on drugs such as methotrexate, 6-mercaptopurine, vincristine, and asparaginase. Asparaginase-related pancreatitis is known to have an incidence of up to 18%, and is a major cause of discontinuation of anticancer treatment for leukemia due to acute onset and chronic complications. There were various cases of treatment of peripancreatic fluid retention caused by anticancer drugs in leukemia patients. Use of lumen-apposing metal stents (LAMS) for walled-off necrosis (WON) drainage has recently increased. The electrocautery-enhanced delivery system allowed simpler and faster stent placement, streamlining the overall procedure and potentially reducing procedure time. Therefore, favorable outcomes have been reported with the use of LAMS for endoscopic drainage of various conditions. In this paper, we discuss a case in which hot-system LAMS was performed to treat L-asparaginase-induced acute pancreatitis and pancreatic pseudocyst in an adult patient with acute lymphoblastic leukemia.

Objective: To establish local diagnostic reference levels (DRLs) for pediatric neck CT based on age, weight, and water-equivalent diameter (WED) across multiple university hospitals in South Korea. Materials and Methods: This retrospective study analyzed pediatric neck CT examinations from nine university hospitals, involving patients aged 0–18 years. Data were categorized by age, weight, and WED, and radiation dose metrics, including volume CT dose index (CTDIvol) and dose length product, were recorded. Data retrieval and analysis were conducted using a commercially available dose-management system (Radimetrics, Bayer Healthcare). Local DRLs were established following the International Commission on Radiological Protection guidelines, using the 75th percentile as the reference value. Results: A total of 1159 CT examinations were analyzed, including 169 scans from Institution 1, 132 from Institution 2, 126 from Institution 3, 129 from Institution 4, 128 from Institution 5, 105 from Institution 6, 162 from Institution 7, 127 from Institution 8, and 81 from Institution 9. Radiation dose metrics increased with age, weight, and WED, showing significant variability both within and across institutions. For patients weighing less than 10 kg, the DRL for CTDIvol was 5.2 mGy. In the 10–19 kg group, the DRL was 5.8 mGy; in the 20–39 kg group, 7.6 mGy; in the 40–59 kg group, 11.0 mGy; and for patients weighing 60 kg or more, 16.2 mGy. DRLs for CTDIvol by age groups were as follows: 5.3 mGy for infants under 1 year, 5.7 mGy for children aged 1–4 years, 7.6 mGy for ages 5–9 years, 11.2 mGy for ages 10–14 years, and 15.6 mGy for patients 15 years or older. Conclusion Local DRLs for pediatric neck CT were established based on age, weight, and WED across nine university hospitals in South Korea.

BACKGROUND/OBJECTIVES: Rosa hybrida has been demonstrated to exert biological effects on several cell types. This study investigated the efficacy of the edible ethanol extract of R.hybrida (EERH) against human colorectal carcinoma cell line (HCT116) cells.MATERIALS/METHODS: HCT116 cells were cultured with different concentrations of EERH (0, 400, 600, 800, and 1,000 µg/mL) in Dulbecco’s modified Eagle medium. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide and viable cell counting assays. Cell cycle pattern was observed by flow cytometry analysis. The wound-healing migration assay, invasion assay, and zymography were used to determine the migratory and invasive level of HCT116 cells treated with EERH. The protein expression and binding ability level of HCT116 cells following EERH treatment were analyzed via immunoblotting and the electrophoretic mobility shift assay. RESULTS: EERH suppressed HCT116 cell proliferation, thus arresting the G1-phase cell cycle.It also reduced cyclin-dependent kinases and cyclins, which are associated with p27KIP1 expression. Additionally, EERH differentially regulated the phosphorylation of extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase, p38, and protein kinase B. Moreover, EERH treatment inhibited the enzymatic activity of matrix metalloproteinase-9 (MMP-9) and MMP-2, resulting in HCT116 cell migration and invasion. The EERH-induced inhibition of MMP-9 and MMP-2 was attributed to the reduced transcriptional binding of activator protein-1, specificity protein-1, and nuclear factor-κB motifs in HCT116 cells. Kaempferol was identified as the main compound contributing to EERH's antitumor activity. CONCLUSION EERH inhibits HCT116 cell proliferation and metastatic potential. Therefore, it is potentially useful as a preventive and curative nutraceutical agent against colorectal cancer.

Objectives: We analyzed the demographic and clinical characteristics of patients diagnosedwith coronavirus disease 2019 (COVID-19), focusing specifically on severe/critical cases, andassessed the trends and rates of severity and fatality among these patients in the Republic of Korea. Methods: Clinical data on patients with COVID-19 from January 20, 2020 to August 30, 2023were collected from the Korea Disease Control and Prevention Agency’s database. We identified patients who progressed to severe/critical conditions and analyzed their demographic and clinical profiles. Severity and fatality rates were calculated and compared annually to track thedisease progression over time. Results: During the surveillance period, 34,572,554 COVID-19 cases were confirmed, among whom 38,112 (0.11%) progressed to severe/critical conditions. Most severe/critical cases occurred in individuals aged ≥60 years, with a notable increase in patients aged ≥80 years from 2022.The overall severity rate was 0.19%, with a fatality rate of 0.10%. However, the severity of cases gradually diminished during the study period. In 2022, the severity and fatality rates decreased to 0.14% and 0.09%, respectively. In 2023, while the severity rate remained stable at 0.15%, thefatality rate further decreased to 0.06%. Notably, throughout the study period, individuals aged ≥80 years had a significantly higher severity rate (2.44%), with a fatality rate of 1.75%. Conclusion These findings underscore the importance of prioritizing protection and management strategies for older adults and high-risk groups to mitigate the impact ofCOVID-19. Continued surveillance and analysis are essential to effectively control COVID-19 and minimize its burden on public health.

Objective: This study aimed to validate the reliability and validity of the Diagnostic Interview for the Internet Addiction Scale (DIA) among Korean children and adolescents in the clinical setting. Methods: We collected the clinical data from university hospitals in South Korea and 194 children and adolescents (aged 7–18 years) completed the questionnaire. The content validity was conducted on 10 items of the DIA and an internal consistency test was performed for the verification of reliability. Results: Participants on average, aged 13.17 years (standard deviation=2.46), and 75.3% (n=146) were boys. The DIA was highly correlated with the scores of the Korean scale for Internet addiction for adolescents, Young’s Internet Addiction Test, Internet addiction proneness scale for children and adolescents. The overall sampling suitability of the 10-item scale was tested using the Kaiser–Meyer–Olkin, resulting in a high value of 0.861. The DIA revealed a two-factor structure and the Cronbach’s alpha correlation coefficient for the total scale was 0.806. Confirmatory factor analysis showed an acceptable model fit (root-mean square error of approximation=0.058, comparative fit index=0.950, and Tucker-Lewis Index=0.919). Conclusion The DIA may suggest in-depth-scale examinations of the factors that influence Internet addiction. We may expect that DIA would be used efficiently for the diagnosing of Internet addiction and further studies for the assessment.

Objective: The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism. Methods: We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test. Results: Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness). Conclusion This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.

Background/Aims: Cardiovascular disease is the leading cause of death worldwide. This study aimed to investigate the recent nationwide trends in major dietary risk factors for dyslipidemia and atherosclerosis. Methods: We estimated age-standardized mean intakes of fresh fruits, fresh vegetables, whole grains, dietary fiber, and sugar-sweetened beverages (SSBs); and mean percentage of energy intake from protein, total fat, saturated fat, and polyunsaturated fat using nationally representative samples from the Korean National Health Examination and Nutrition Survey 2013–2022. To assess overall diet quality, we calculated mean Korean Healthy Eating Index (KHEI) (range 0–100, higher scores indicating greater diet quality). Results: In 2013–2022, there were overall decreasing trends in age-standardized mean KHEI score and intakes of fresh fruits and vegetables, whole grains, and dietary fiber; and overall increasing trends in mean intakes of SSBs, protein, and dietary fat among both male and female. The KHEI score increased in older adults aged ≥ 60 years, whereas it decreased among younger adults. Throughout the study period, younger adults tended to have lower intakes of fresh fruits, fresh vegetables, and whole grains; higher intakes of SSBs, protein, and dietary fat; and lower KHEI score. The mean KHEI score was lower in male (vs. female) and lower (vs. higher) income groups. Conclusions Our data suggest that, from 2013 to 2022, there was a trend toward an unhealthy diet in Korean adults. Our findings also suggest dietary inequalities among age, sex, and income groups, suggesting the need for more intense interventions targeting the vulnerable populations.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

Auricular vagus nerve stimulation (aVNS) is one of the promising neuromodulation techniques due to its non-invasiveness, convenience, and effectiveness. aVNS has been suggested as a potential treatment for neurodegenerative diseases showing impaired cerebrospinal fluid (CSF) dynamics. Improving CSF flow has been proposed as a key mechanism of the therapeutic effect on neurodegenerative diseases. However, aVNS parameters have been set empirically and the effective parameter that maximize the effect remains elusive. Here we show that 30 minutes of low-frequency aVNS increased arterial vasomotion events and enhanced cortical CSF influx along the branches of middle cerebral arteries. By using in vivo two photon imaging or widefield fluorescence microscopy with plasma and CSF tracers for visualizing blood vessels and perivascular spaces, arterial vasomotion and cortical CSF influx dynamics were acquired. The low-frequency (2 Hz) aVNS, but not middleand high-frequency (40 and 100 Hz) aVNS, significantly increased the number of vasomotion events compared to the sham group. Accordingly, in the CSF imaging, 2 Hz of aVNS markedly enhanced the CSF influx. Our findings demonstrate that lowfrequency aVNS is the effective parameter in respect to modulating vasomotion and CSF influx, resulting in brain clearance effect.