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.

Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Background/Aims: Functional dyspepsia (FD) has long been regarded as a syndrome because its pathophysiology is multifactorial. However, recent reports have provided evidence that changes in the duodenal ecosystem may be the key. This study aimed to identify several gastrointestinal factors and biomarkers associated with FD, specifically changes in the duodenal ecosystem that may be key to understanding its pathophysiology. Methods: In this case-control study, 28 participants (12 with FD and 16 healthy control individuals) were assessed for dietary nutrients, gastrointestinal symptom severity, immunological status of the duodenal mucosa, and microbiome composition from oral, duodenal, and fecal samples. Integrated data were analyzed using immunohistochemistry, real-time polymerase chain reaction, 16S rRNA sequencing, and network analysis. Results: Duodenal mucosal inflammation and impaired expression of tight junction proteins were confirmed in patients with FD. The relative abundance of duodenal Streptococcus (p=0.014) and reductions in stool Butyricicoccus (p=0.047) were confirmed. These changes in the gut microbiota were both correlated with symptom severity. Changes in dietary micronutrients, such as higher intake of valine, were associated with improved intestinal barrier function and microbiota. Conclusions This study emphasizes the relationships among dietary nutrition, oral and gut microbiota, symptoms of FD, impaired function of the duodenal barrier, and inflammation. Assessing low-grade inflammation or increased permeability in the duodenal mucosa, along with changes in the abundance of stool Butyricicoccus, is anticipated to serve as effective biomarkers for enhancing the objectivity of FD diagnosis and monitoring.

Background/Aims: Acute pancreatitis (AP) is a leading cause of emergency hospitalization. We present the current diagnostic and therapeutic status of AP as revealed by analysis of a large multicenter dataset. Methods: The medical records of patients diagnosed with AP between 2018 and 2019 in 12 tertiary medical centers in Korea were retrospectively reviewed. Results: In total, 676 patients were included, of whom 388 (57.4%) were male, and the mean age of all patients was 58.6 years. There were 355 (52.5%), 301 (44.5%), and 20 (3.0%) patients with mild, moderate, and severe AP, respectively, as assessed by the revised Atlanta classification. The most common etiologies of AP were biliary issues (41.6%) and alcohol consumption (24.6%), followed by hypertriglyceridemia (6.8%). The etiology was not identified in 111 (16.4%) patients at the time of initial admission. The overall mortality rate was 3.3%, increasing up to 45.0% among patients with severe AP. Notably, 70.0% (14/20) of patients with severe AP and 81.5% (154/189) of patients with systemic inflammatory response syndrome had received <4 L per day during the initial 24 hours of admission. Only 23.8% (67/281) of acute biliary pancreatitis patients underwent cholecystectomy during their initial admission. In total, 17.8% of patients experienced recurrent attacks during follow-up. However, none of the patients with acute biliary pancreatitis experienced recurrent attacks if they had undergone cholecystectomy during their initial admission. Conclusions This study provides insights into the current status of AP in Korea, including its etiology, severity, and management. Results reveal disparities between clinical guidelines and their practical implementation for AP treatment.

Acute pancreatitis can range from a mild, self-limiting disease requiring no more than supportive care, to severe disease with life-threatening complications. With the goal of providing a recommendation framework for clinicians to manage acute pancreatitis, and to contribute to improvements in national health care, the Korean Pancreatobiliary Association (KPBA) established the Korean guidelines for acute pancreatitis management in 2013. However, many challenging issues exist which often lead to differences in clinical practices. In addition, with newly obtained evidence regarding acute pancreatitis, there have been great changes in recent knowledge and information regarding this disorder. Therefore, the KPBA committee underwent an extensive revision of the guidelines. The revised guidelines were developed using the Delphi method, and the main topics of the guidelines include the following: diagnosis, severity assessment, initial treatment, nutritional support, convalescent treatment, and the treatment of local complications and necrotizing pancreatitis. Specific recommendations are presented, along with the evidence levels and recommendation grades.

Tinea capitis is an infection of the scalp hair follicles and surrounding skin that primarily occurs in prepubertal children. Microsporum canis remains the most common pathogen causing tinea capitis in Asian countries, including South Korea, although the causative organism of this condition varies across geographical regions and time periods. Systemic antifungal agents are the mainstay treatments for tinea capitis; however, the therapeutic responses to antifungal drugs may vary depending on the causative species, and treatment failure may occur owing to drug resistance. Although dermatophytosis resistant to clinical treatment have been increasingly encountered, recalcitrant tinea capitis cases have rarely been reported. Herein, we report three cases of tinea capitis caused by M. canis in children. All three patients showed unsatisfactory clinical responses to prolonged courses of oral terbinafine or itraconazole without achieving mycological cure; however, they were successfully treated with oral griseofulvin. Although griseofulvin is not currently available or licensed for use in many countries, including South Korea, it is one of the most effective agents against Microsporum species and remains the most widely used first-line treatment for tinea capitis in children, based on dermatology textbooks and reliable treatment guidelines.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been acknowledged as an effective mean of preventing infection and hospitalization.However, the emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) has led to substantial increase in infections among children and adolescents. Vaccineinduced immunity and longevity have not been well defined in this population. Therefore, we aimed to analyze humoral and cellular immune responses against ancestral and SARSCoV-2 variants after two shots of the BNT162b2 vaccine in healthy adolescents. Although vaccination induced a robust increase of spike-specific binding Abs and neutralizing Abs against the ancestral and SARS-CoV-2 variants, the neutralizing activity against the Omicron variant was significantly low. On the contrary, vaccine-induced memory CD4+ T cells exhibited substantial responses against both ancestral and Omicron spike proteins.Notably, CD4+ T cell responses against both ancestral and Omicron strains were preserved at 3 months after two shots of the BNT162b2 vaccine without waning. Polyfunctionality of vaccine-induced memory T cells was also preserved in response to Omicron spike protein.The present findings characterize the protective immunity of vaccination for adolescents in the era of continuous emergence of variants/subvariants.

Subclinical hypothyroidism (SCH), characterized by elevated serum thyroid-stimulating hormone (TSH) levels and normal free thyroxine levels, usually presents without symptoms, and is often discovered incidentally during routine blood test. The Task Force of the Korean Thyroid Association Committee of Clinical Practice Guidelines has established a guideline to evaluate and manage SCH; the guideline emphasizes the implementation of diagnostic criteria based on the TSH reference range for Koreans and focuses on the proven health benefits of levothyroxine (LT4) treatment. Based on the Korea National Health and Nutrition Examination Survey (2013-2015), serum TSH level of 6.8 mIU/L is considered the reference value for SCH. SCH can be categorized as mild (TSH 6.8-10.0 mIU/L) or severe (TSH ＞10.0 mIU/L), and patients are classified as adults (age ＜70 years) or elderly patients (age ≥70years) depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, along with the thyroid peroxidase antibody test, preferably 2-3 months after the initial evaluation. Usually, LT4 treatment is not recommended for mild SCH in adults; however, treatment is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and can be considered for coexisting dyslipidemia. LT4 treatment is not recommended for mild or even severe SCH in elderly patients, in general. Patients with SCH who receive LT4 treatment, the LT4 dosage should be personalized, and serum TSH levels should be monitored to ensure optimal LT4 dosage (dosage that is neither excessive nor insufficient). Patients with SCH who do not receive LT4 treatment require periodic follow-up at appropriate testing intervals determined by disease severity. The guideline also provides several educational points applicable in clinical settings.