Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Objectives: . This study investigated age-related differences in nasal morphometry and the degree of changes within an individual over at least a 10-year period by pairing previous and recent three-dimensional reconstructed computed tomography (CT) images. Methods: . Forty-eight adult Korean patients who underwent at least two CT scans of the nasal region with an interval of at least 10 years were selected. Patients were categorized into six subgroups according to sex and age (20–39 years, 40–49 years, and ≥50 years) at the time of initial imaging. Eight nasal parameters were measured on the initial and recent images, and paired comparisons between the two images were performed based on the data. The differences in the degree of change by age were also analyzed. Results: . Over an average image interval of 12 years, men exhibited an increase in the nasofrontal angle (3.2°±5.4°, P=0.041), profile nasal length (1.7±1.7 mm, P=0.002), and nasal bridge height (1.2±1.6 mm, P=0.002). Conversely, they showed a decrease in the nasofacial angle (–2.3°±2.9°, P=0.010). Women also demonstrated an increase in the nasofrontal angle (2.5°±5.2°, P=0.010), profile nasal length (1.4±1.9 mm, P<0.001), and nasal bridge height (1.3±1.6 mm, P<0.001). However, they exhibited a decrease in the nasofacial angle (–2.0°±2.1°, P<0.001), glabella angle (–9.1°±9.8°, P<0.001), and pyriform angle (–8.5°±10.1°, P<0.001). With the exception of the nasal bridge height (P=0.036) and pyriform angle (P=0.022), the degree of changes in most parameters did not show significant differences across age groups. Conclusion . Our findings indicate that the aging nose exhibits a greater nasal length with inferior angulation of the nasal tip, with an increase in the nasofrontal angle, profile nasal length, and nasal bridge height, along with a decrease in the nasofacial angle. The degree of most nasal morphologic changes demonstrated no significant differences by specific age group.

Background/Aims: Potassium channel tetramerization domain containing 17 (KCTD17) protein, an adaptor for the cullin3 (Cul3) ubiquitin ligase complex, has been implicated in various human diseases; however, its role in hepatocellular carcinoma (HCC) remains elusive. Here, we aimed to elucidate the clinical features of KCTD17, and investigate the mechanisms by which KCTD17 affects HCC progression. Methods: We analyzed transcriptomic data from patients with HCC. Hepatocyte-specific KCTD17 deficient mice were treated with diethylnitrosamine (DEN) to assess its effect on HCC progression. Additionally, we tested KCTD17-directed antisense oligonucleotides for their therapeutic potential in vivo. Results: Our investigation revealed the upregulation of KCTD17 expression in both tumors from patients with HCC and mouse models of HCC, in comparison to non-tumor controls. We identified the leucine zipper-like transcriptional regulator 1 (Lztr1) protein, a previously identified Ras destabilizer, as a substrate for KCTD17-Cul3 complex. KCTD17-mediated Lztr1 degradation led to Ras stabilization, resulting in increased proliferation, migration, and wound healing in liver cancer cells. Hepatocyte-specific KCTD17 deficient mice or liver cancer xenograft models were less susceptible to carcinogenesis or tumor growth. Similarly, treatment with KCTD17-directed antisense oligonucleotides (ASO) in a mouse model of HCC markedly lowered tumor volume as well as Ras protein levels, compared to those in control ASO-treated mice. Conclusions KCTD17 induces the stabilization of Ras and downstream signaling pathways and HCC progression and may represent a novel therapeutic target for HCC.

Switch/sucrose non-fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)-deficient sinonasal carcinoma is a rare subtype of sinonasal undifferentiated carcinoma (SNUC). Due to the highly aggressive nature of the disease course, it is important to diagnose early and use multimodal treatments in the course of the disease. Two main morphologic patterns are commonly identified under the microscope: plasmacytoid/rhabdoid and basaloid. Furthermore, it demonstrates a total absence of integrase interactor 1 expression upon immunohistochemical staining. Here, we present two cases of SMARCB1-deficient sinonasal carcinoma with contrasting outcomes.

Objectives: . A crooked nose is frequently caused by nasal bony vault deviation, and proper management of the bony vault is an integral part of rhinoplasty. Conventional osteotomy to correct a deviated nose favors simultaneous medial and lateral osteotomies, which allows the free independent movement of each nasal bone. However, patient satisfaction with deviated nose surgery is sometimes low. In the present study, we introduce a one-unit osteotomy procedure that combines bilateral and root osteotomies with unilateral triangular bony wedge resection to allow symmetry of both nasal bones. Methods: . Twenty consecutive patients who presented with bony vault deviation and underwent one-unit osteotomy were enrolled in this retrospective single-center study. The Nasal Obstruction Symptom Evaluation (NOSE) questionnaire was used to evaluate each patient’s functional outcome. The angle of bony vault deviation before and after one-unit osteotomy was measured using a protractor and compared with the results of 14 patients who had undergone conventional osteotomy. The improvement in dorsal deviation was evaluated using facial photography preoperatively and 3 months postoperatively. Results: . NOSE values improved from 8.4±6.4 to 4.1±4.2 (P =0.021). The angle of bony vault deviation improved from 6.9°±2.2° to 2.1°±1.2° (P <0.001) in one-unit osteotomy and from 7.3°±4.0° to 2.7°±1.2° (P =0.001) in conventional osteotomy. The preoperative deviation angle improved by 70.3% in one-unit osteotomy compared with 56.6% in conventional osteotomy, which was a significant difference (P =0.033). The mean grade of the postoperative esthetic outcomes for the remaining deviation was 1.6±0.5, which was similar to that in the conventional osteotomy group. Conclusion . One-unit osteotomy is a relatively simple procedure that balances the width of both lateral walls by removing excessive bony fragments from the wider bony wall and providing better structural integrity. This technique improves functional outcomes and has equivalent esthetic results to those of the traditional procedure.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Background: Obstructive sleep apnea (OSA) is closely related to maternal obesity in pregnant women, and the association increases with later pregnancy. Obesity and OSA are risk factors of pregnancy-related complications, including gestational hypertension, gestational diabetes mellitus (GDM), and fetal morbidities. We aimed to determine the prevalence of OSA and to assess the impact of OSA on pregnancy-related disorders in overweight pregnant women. Methods: Eligible participants who were overweight [body mass index (BMI) ≥ 23 kg/m 2 ] in gestational age 30 weeks or more, assessed OSA using a portable polysomnography at home.Clinical data were collected from pregnant women and their babies. Results: The average age of 51 participants was 34.5 years (27–44 years). The number of primipara was 25 (49%) and that of multipara was 26 (51%). Eight cases of GDM (15.7%) and five cases of preeclampsia (9.8%) were reported, and six patients (11.8%) experienced preterm delivery. In results of polysomnography, 14 patients (27.5%) were diagnosed as OSA. Apnea-hypopnea index moderately correlated with BMI (r = 0.515, P < 0.001). The BMI (P < 0.005) and preeclampsia rate (P < 0.017) were higher in the OSA group compared to the control group. Odds ratios (ORs) adjusting age, BMI, parity, and abortion history were calculated. The presence of OSA increased OR of preeclampsia (OR, 13.1; 95% confidence interval, 1.1–171.3). The majority of preeclampsia patients (4/5, 80%) underwent preterm delivery. Conclusion OSA is an important risk factor for preeclampsia, resulting in preterm delivery.For overweight pregnant women, an OSA evaluation should be mandatory.

Background: Enlarged perivascular space (ePVS) is recently reported to be associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD). The topographical location of ePVS may relate to the underlying pathology; basal ganglia (BG)-ePVS has been associated with cerebral vascular diseases and centrum semi-ovale (CSO)-ePVS associated with cerebral amyloid angiopathy (CAA). However, the effects of ePVS on various neurological conditions remain still controversial. To investigate the clinical relevance of ePVS in neurodegenerative diseases, we tested relationships between ePVS and cognition, markers of SVD, vascular risk factors, or amyloid pathology. Methods: We retrospectively reviewed 292 patients (133 AD dementia, 106 mild cognitive impairment, 39 other neurodegenerative diseases, 14 subjective cognitive decline) who underwent both amyloid positron emission tomography and brain magnetic resonance imaging. Vascular risk factors and cognitive tests results were collected. The ePVS in the BG and CSO, SVD markers and the volume of white matter hyperintensities were measured. Results: There were no significant differences in the severity and distribution of ePVS among clinical syndromes. Both BG- and CSO-ePVS were not related to cognitive function. Patients with lacunes were more likely to have high-degree BG-ePVS. High degree CSO-ePVS had an odds ratio (OR) for amyloid positive of 2.351, while BG-ePVS was a negative predictor for amyloid pathology (OR, 0.336). Conclusions Our findings support that ePVS has different underlying pathologies according to the cerebral topography. BG-ePVS would be attributed to hypertensive angiopathy considering the relation with SVD markers, whereas and CSO-ePVS would be attributed to CAA considering the association with amyloid pathology.