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: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global health, exacerbated metabolic health issues, and altered lifestyle behaviors. This study examined the sex-specific impact of the COVID-19 outbreak on the incidence of metabolic syndrome using data from the Korea National Health and Nutrition Examination Survey (KNHANES). Methods: Data from the KNHANES VII (2018) and VIII (2019–2021), including 15,499 participants, were analyzed. The study population was stratified by sex, and further subdivisions were conducted based on the timeframe relative to the COVID-19 outbreak. Variables such as age, education level, household income, smoking status, and high-risk drinking were analyzed to assess their influence on the prevalence of metabolic syndrome. Results: The overall prevalence of metabolic syndrome significantly increased from 28.11% before the outbreak to 29.69% after the outbreak. Both males and females reported significant increases in waist circumference and fasting glucose levels. Age and education level differentially influenced the prevalence of metabolic syndrome between the sex. Smoking was significantly associated with increased prevalence in males, whereas high-risk drinking was associated with increased prevalence in males and decreased prevalence in females. Conclusions The COVID-19 pandemic has significantly increased the prevalence of metabolic syndrome with notable sex-specific differences. These findings highlight the need for sex-specific public health interventions to mitigate the impact of the pandemic on metabolic health.

Background/Aims: This nationwide cohort study aimed to evaluate (1) whether primary Sjogren’s syndrome (pSS) can contribute to the development of dementia and (2) whether the use of hydroxychloroquine (HCQ) can decrease the incidence of dementia in patients with pSS using the Health Insurance Review and Assessment database. Methods: We established a cohort between 2008 and 2020 of 20,160 patients with pSS without a history of dementia. The control group comprised sex- and age-matched individuals with no history of autoimmune disease or dementia. Cox proportional hazard analyses were performed to identify the association between pSS and dementia development. We also assessed the hazard ratio (HR) of dementia in early users of HCQ (within 180 days of the diagnosis of pSS) compared to non-users, adjusted for age, sex, and comorbidities. Results: The incidence of dementia was 0.68 (95% CI 0.64–0.72) cases per 100 person-years in pSS, and it was 0.58 (0.56–0.60) in the controls. The adjusted HR (aHR) of developing dementia was 1.16 (1.09–1.25) times greater in the pSS group than in the controls. The risk of dementia did not increase in HCQ users (aHR 1.07 [0.94–1.21]), but HCQ non-users had a 1.22 (1.12–1.33) higher risk of developing dementia than the matched controls. The use of HCQ lowered the risk of dementia in comparison with non-users in patients with pSS (aHR 0.82 [0.71–0.94]). Conclusions Our results suggest that pSS is associated with an increased risk of dementia. HCQ may prevent dementia in patients with pSS.

Objective: This study aimed to investigate the prevalence and characteristics of impacted teeth (ITs) in orthodontic patients at university dental hospitals in Korea. Methods: This study included 14,774 patients who visited the Department of Orthodontics at 10 university dental hospitals in Korea between 2020 and 2022 and underwent orthodontic diagnosis. The prevalence and characteristics of ITs were investigated using orthodontic diagnostic records, radiographs, and diagnostic casts. Results: The prevalence of ITs, excluding third molar impaction, in Korean orthodontic patients was 13.6% (n = 2,014).The prevalence of ITs in pediatric orthodontic patients was 24.5% (n = 1,614).Of these patients, 68.2% had one IT, 27.5% had two ITs, 24.3% had bilateral IT, and 75.7% had unilateral IT. The most frequent IT was the maxillary canine (50.1%), followed by the mandibular second molar (11.7%), and maxillary second premolar (9.6%). An abnormal eruption path (46.5%) was the most frequent etiology. Orthodontic traction after surgical exposure (70.6%) was the most frequent treatment option. Among the patients with ITs, 29.8% had other dental anomalies, such as tooth agenesis (8.7%), microdontia (8.0%), and supernumerary teeth (5.1%). Furthermore, 50.8% had complications such as cystic lesions (18.3%), transposition (17.7%), and root resorption (14.8%).Among the patients with maxillary canine impaction, 62.2% had labial maxillary canine impaction and 21.1% had palatal maxillary canine impaction. Conclusions The prevalence of ITs in Korean orthodontic patients at university dental hospitals was high, particularly in pediatric orthodontic patients.

Purpose: Persistent postoperative stiffness is a common complication after arthroscopic rotator cuff repair (ARCR).We hypothesized that a subacromial steroid injection (SAI) may improve the early outcomes in patients with persistent stiffness without increasing steroid-associated complications. Therefore, we evaluated the effectiveness and safety of SAI in patients with persistent stiffness 3 months after ARCR. Methods: We retrospectively analyzed 300 ARCR cases performed between January 2012 and May 2014, in which repair integrity was confirmed at postoperative 3 months. Patients were divided into SAI and control groups. The SAI group received a single SAI (triamcinolone 40 mg and ropivacaine 52.5 mg) to address postoperative stiffness, with no additional SAI thereafter. The control group did not receive any injections until the final follow-up. Functional and radiological outcomes were compared between the two groups. Results: The mean follow-up period was 18.1±4.7 months (range, 12.1–37.2 months), with no difference between groups (p=0.731). At the time of injection, the range of motion was significantly lower in the SAI (all p＜0.001). However, functional outcomes were comparable between the two groups at 3 months after injection and the final follow-up (all p＞ 0.05). The healing failure rate at the final follow-up also did not differ between the SAI and control groups (14.9% vs. 13.2%, p=0.671). Conclusion This short-term follow-up study suggests that the administration of a single SAI to treat persistent stiffness at 3 months after ARCR may improve functional recovery without increasing the risk of healing failure.

Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44–1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67–1.14; p=0.310). Conclusions Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

BACKGROUND: Osteoporosis, characterized by decreased bone mineral density due to an imbalance between osteoblast and osteoclast activity, poses significant challenges in bone healing, particularly in postmenopausal women. Current treatments, such as bisphosphonates, are effective but associated with adverse effects like medication-related osteonecrosis of the jaw, necessitating safer alternatives. METHODS: This study investigated the use of L-serine-incorporated gelatin sponges for bone regeneration in calvarial defects in an ovariectomized rat model of osteoporosis. Thirty rats were divided into three groups: a control group, a group treated with a gelatin sponge containing an amino acid mixture, and a group treated with a gelatin sponge containing L-serine. Bone regeneration was assessed using micro-computed tomography (micro-CT) and histological analyses. RESULTS: The L-serine group showed a significant increase in bone volume (BV) and bone area compared to the control and amino acid groups. The bone volume to total volume (BV/TV) ratio was also significantly higher in the L-serine group.Immunohistochemical analysis demonstrated that L-serine treatment suppressed the expression of cathepsin K, a marker of osteoclast activity, while increasing serine racemase activity. CONCLUSION These findings suggest that L-serine-incorporated gelatin sponges not only enhance bone formation but also inhibit osteoclast-mediated bone resorption, providing a promising and safer alternative to current therapies for osteoporosis-related bone defects. Further research is needed to explore its clinical applications in human patients.

Lichen amyloidosis is characterized by coalescent hyperpigmented papules with a predilection for the extremities and is accompanied by severe chronic pruritus. Various therapies have been attempted; however, there is no uniformly recognized effective treatment. In the first case, a 60-year-old man with a 37-year history of intractable itching presented with hyperkeratotic brown papules and coalescing plaques on the trunk and extensor surfaces of the extremities. The second case involved a 31-year-old man who presented with brownish macules and papules with a rippled pattern on the upper back and lower extremities. Histological examination of the lesions from both patients revealed epidermal hyperplasia and amorphous material deposited in the papillary dermis, which tested positive on Congo red staining. Although both patients were diagnosed with lichen amyloidosis, several treatment modalities showed limited efficacy. Subsequently, dupilumab, a treatment for severe pruritus, was administered to both patients, resulting in significant improvements.

Background: Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker. Methods: A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely “0–2 breakfasts per week” and “3–7 breakfasts per week”; hs-CRP concentrations were measured through blood tests. Results: Comparing between the “infrequent breakfast consumption (0–2 breakfasts per week)” and “frequent breakfast consumption (3–7 breakfasts per week)” groups, the mean hs-CRP was found to be significantly higher in the “infrequent breakfast consumption” group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036). Conclusion Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.