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.

PURPOSE: The purpose of this study was to compare the surface characteristics and healing patterns after implantation of implants treated with SLA and those treated with both SLA and femtosecond laser. MATERIALS AND METHODS: A total of 10 male New Zealand white rabbits were used to compare recovery levels between implants treated with SLA (SLA group) and those treated with both SLA and femtosecond laser (SF group). The implants’ surface characteristics were determined through topographic evaluation, element analysis, surface roughness, and wettability evaluation. In total, 4 implants were placed in each rabbit (2 in each tibia), with 20 implants per treatment group. Using the implant stability quotient (ISQ), marginal bone volume, and histological analysis (bone-to-implant contact (BIC), bone volume/tissue volume (BV/TV)), and post implantation outcomes were assessed. Outcome data were analyzed using independent t-tests, Mann-Whitney U tests, Wilcoxon signed-rank tests, and one-way ANOVA (α = 0.05). RESULTS: No significant differences were noted between SLA and SF groups in terms of ISQ, marginal bone volume, BIC, and BV/TV (P > .05). However, significant differences in ISQ were observed within each group over time (P < .05). Furthermore, significant differences were noted in the marginal bone volume of the SF group (P < .05) and the BV/TV of the SLA group between weeks 4 and 6 (P < .05). CONCLUSION Surface treatment via SLA and femtosecond laser is feasible compared with SLA treatment alone in terms of ISQ, marginal bone volume, BIC, and BV/TV. However, further clinical research is warranted.

Tooth wear is a physiologic process, but when accelerated by specific factors, it is considered pathologic wear, leading various issues that require prosthodontic intervention. Full-mouth prosthetic rehabilitation is often considered to restore adequate vertical dimension and esthetics for patients with severely worn dentition.However, a minimally invasive prosthodontic approach through multidisciplinary collaboration may be feasible for patients with localized anterior or posterior wear. This clinical case addressed the treatment for excessive anterior deep bites and pathologic wear of the anterior teeth, leading to deteriorated esthetics and function. Orthodontic extrusion was employed in the posterior teeth to increase the vertical dimension of occlusion and secure adequate space for the anterior restorations. A minimally invasive treatment was possible by limiting the scope of treatment to the anterior region. As a result, function and esthetics were improved by restoring only the teeth with pathologic wear without removing healthy tooth structure.

Crossbite refers to a condition where there are remaining teeth, but none of the teeth are in occlusal contact, resulting in the loss of vertical support. When posterior vertical stop is lost, it is important to appropriately restore this support and create a harmonious occlusal plane. In this case, the patient had lost posterior support but declined surgical intervention due to a history of osteoporosis and the associated risk of medication-related osteonecrosis of the jaw (MRONJ). To restore the vertical space required for prosthetic rehabilitation, the vertical dimension was increased. The missing posterior teeth were replaced using removable partial dentures. Cross-mounting was performed, and the metal copings of the surveyed crowns and the framework of the final removable partial denture were 3D printed. After the treatment was completed, the patient expressed satisfaction with both functions and aesthetics. Regular follow-ups were conducted to monitor oral hygiene and occlusal stability.

Background/Aims: Cholecystectomy for gallbladder (GB) polyps is performed primarily based on preoperative images. This study examined the accuracy of surgical indications commonly used in clinical practice for detecting neoplastic polyps and investigated further clues for predicting neoplastic polyps. Methods: This retrospective study included 385 patients who underwent a cholecystectomy for GB polyps. The predictive performances of seven surgical indications were compared by fitting the receiver operating characteristic curves. Logistic regression analysis was used to identify the candidate variables associated with predicting neoplastic polyps. Results: Neoplastic polyps were identified in 18.9% (n=62) of the 385 patients assessed. The neoplastic group contained more females than males, larger polyps, more frequent solitary lesions, and lower platelet counts than the non-neoplastic group. Current surgical indications revealed an unsatisfactory prediction for neoplastic polyps. The optimal cutoff polyp size for neoplastic polyps by ultrasound (US) was larger than by computed tomography (CT) (12 mm vs. 10 mm). The proportion of pathologic neoplastic polyps was higher when both US and CT images were used than that predicted using a single test. Logistic regression analysis revealed larger polyps, increasing age, female sex, and lower platelet count to be associated with neoplastic polyps. Conclusions The current indications for cholecystectomy in GB polyps have a low predictive value for neoplastic lesions that can lead to overtreatment. Combining the polyp size from US and CT images may reduce unnecessary surgery. In addition, knowledge of the patient's age, sex, and platelet count could help make more selective surgical decisions for neoplastic polyps.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms that mainly occur in the stomach and small intestine; those arising in the esophagus are rarer. A 54-year-old woman was referred to our hospital with a one-month history of dysphagia. Esophagogastroduodenoscopy (EGD), performed approximately five months earlier, had not revealed any specific findings. However, an EGD performed in our hospital showed the presence of a round, protruding lesion (approximately 40×30 mm in size), with a normal overlying mucosal surface, 35–39 cm from the upper incisor. Chest computed tomography (CT) revealed a large esophageal mass. Enucleation was performed on the esophageal mass, and a GIST was diagnosed using immunochemical staining. Imatinib mesylate administration was initiated two months postoperatively. The patient was stable, without any evident recurrence in the 8-month postoperative follow-up EGD and chest CT examinations. Therefore, physicians should consider that patients with worsening dysphagia may have an underlying organic condition, such as an acute increase in size of an esophageal GIST, even if recent examinations were unremarkable.

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.

Background/Aims: Psoriasis is a common inflammatory skin disorder following non-specific triggers. Involvement of immune system is widely accepted for pathogenesis studies have demonstrated importance of gut microbiota in pathogenesis of inflammatory skin diseases. Proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) are acid-suppressive drugs widely used for acid related gastrointestinal diseases, and prolonged use has been associated with altered gut microbiota. This study aimed to investigate association between psoriasis and acid suppressing drugs in Korean population. Methods: This study was conducted with 3,662 patients diagnosed with psoriasis between 2002 and 2013 in NHIS-NSC. A total of 14,648 controls were matched at 1:4 based on sex, age, and gastrointestinal disease. ORs were estimated to determine the association between acid suppressing drug use and psoriasis. Results: Our study found a statistically significant association between the prolonged use of acid-suppressive drugs and the development of psoriasis in the Korean population. Specifically, patients with gastrointestinal diseases who used histamine-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI) for extended periods exhibited a higher risk of developing psoriasis. The adjusted odds ratio for psoriasis was 1.89 (95% CI, 1.66–2.17) with long-term use, indicating a clear dose-response relationship. Conclusions Results from our study indicate that prolonged use of H2RA or PPI is associated with the risk of psoriasis among patients with gastrointestinal diseases in Korean population. The risk was increased in dose-response trend after adjusting for confounding variables. Clinicians should be aware of risks associated with prolonged use of acid suppressing drugs.

Background/Aims: Adiponectin, a hormone primarily produced by adipocytes, typically shows an inverse relationship with body mass index (BMI). However, some studies have reported a positive correlation between the two. Thus, this study aimed to examine the relationship between adiponectin level and BMI in diabetic patients, focusing on the impact of past obesity on current adiponectin levels. Methods: We conducted an observational study analyzing data from 323 diabetic patients at Kyungpook National University Hospital. Based on past and current BMIs, participants were categorized into never-obese (nn, n = 106), previously obese (on, n = 43), and persistently obese (oo, n = 73) groups based on a BMI threshold of 25 kg/m2. Adiponectin level and BMI were key variables. Kaplan–Meier analysis assessed their impact on all-cause mortality up to August 2023, with survival differences based on adiponectin quartiles and follow-up starting from patient enrollment (2010–2015). Results: The analysis revealed a significant inverse correlation between adiponectin level and past maximum BMI. The on group exhibited approximately 10% lower adiponectin levels compared to the nn group. This association remained significant after adjusting for current BMI, age, and sex, highlighting the lasting influence of previous obesity on adiponectin levels. Furthermore, survival analysis indicated that patients in the lowest adiponectin quartile had reduced survival, with a statistically significant trend (p = 0.062). Conclusions Findings of this study suggest that lower adiponectin levels, potentially reflecting past obesity, are associated with decreased survival in diabetic patients, underscoring a critical role of adiponectin in long-term health outcomes.

Background/Aims: Krebs von den Lungen-6 (KL-6) is associated with prognosis in patients with COVID-19. However, there is limited data on the correlation between the prognosis of COVID-19 and varying KL-6 levels at different time points. We investigated the optimal cutoff values of the initial and peak serum KL-6 levels to predict mortality and evaluated their correlation with mortality. Methods: This retrospective cohort study collected data on serially collected serum KL-6 levels in patients hospitalized with COVID-19 between October 2020 and January 2022 at a single tertiary hospital in South Korea. The area under the receiver operating characteristic curve and Youden index were used to determine the cutoff points for the initial and peak KL-6 levels that best predicted 30-day mortality. The association between the initial and peak KL-6 values was assessed by univariate and multivariate logistic regression models. Results: A total of 349 patients were included in this study. The mean initial and peak KL-6 levels were significantly higher in the non-survivor group than in the survivor group. The initial and peak KL-6 values that best predicted 30-day mortality were 491.85 U/mL and 660.05 U/mL, respectively. An initial KL-6 level greater than 491.85 U/mL and a peak KL-6 level greater than 660.05 U/mL were significantly associated with 30-day mortality. Conclusions The initial and peak levels of KL-6 were significantly associated with 30-day mortality in hospitalized patients with COVID-19. These findings suggest that serially monitoring blood KL-6 levels could be a valuable prognostic indicator for COVID-19.