Ameliorative Effect of Ginsenoside Rg6 in Periodontal Tissue Inflammation and Recovering Damaged Alveolar Bone.

Periodontal disease is a chronic disease with a high prevalence, and in order to secure natural materials to prevent oral diseases, new materials that protect periodontal tissue from inflammation are being sought. Genes were identified using real-time quantitative polymerase chain reaction (RT-qPCR), and proteins were confirmed using Western blot. Dichlorodihydrofluorescein diacetate (DCF-DA) analysis was used, and the antibacterial effects were confirmed through Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) analysis. To confirm this effect in vivo, Sprague-Dawley rats, in which periodontitis was induced using ligation or Lipopolysaccharide of Porphyromonas gingivalis (PG-LPS), were used. In vitro experiments using human periodontal ligament (HPDL) cells stimulated with PG-LPS showed that Ginsenoside Rg6 (G-Rg6) had anti-inflammatory, antibacterial, antioxidant, and osteoblast differentiation properties. In vivo, G-Rg6 was effective in Sprague-Dawley rats in which periodontitis was induced using ligation or PG-LPS. Therefore, Ginsenoside Rg6 shows potential effectiveness in alleviating periodontitis.

[The Effect of COVID-19 on Pediatric Intussusception: A Retrospective Study of a Single Center in South Korea with 10-Year Experience]. / 코로나바이러스감염증­2019 ìœ í–‰ 후 소아 장중첩증의 변화: 단일기관 10ë „ 의무 기록을 이용한 연구.

Purpose: To evaluate the effect of the emergence of coronavirus disease-19 (COVID-19) on pediatric intussusception. Materials and Methods: Patients (< 18 years) who were diagnosed with intussusception and received enema reduction from 2011 to 2020 were included. We reviewed the demographics, yearly/monthly/seasonal incidence of intussusception, method and failure rate of enema reduction, recurrence rate of intussusception, surgical record, and pathologic report. Subsequently, we investigated the differences in mean age, failure rate of enema reduction, and recurrence rate of intussusception between the cases in 2020 and those in the period from 2011 to 2019. Results: A total of 859 enema reductions were performed during the past decade, more in males and in the age < 1 year (mean age, 22.2 months). The yearly incidence was highest in 2014 and lowest in 2020, and the monthly incidence was highest on December and September. The cases in 2020 (n = 27) had a lower mean age (18.1 months vs. 22.8 months), higher failure rate of enema reduction (7.4% vs. 2.4%), and higher recurrence rate of intussusception (14.8% vs 7.3%) compared with those that occurred between 2011 and 2019 (n = 832). However, these results did not show statistical significance (p = 0.07, p = 0.15, p = 0.14, respectively). Conclusion: With the emergence of COVID-19, the number of enema reductions was remarkably decreased with a lower mean age, higher failure rate, and higher recurrence rate.

New sedatives and analgesic drugs for gastrointestinal endoscopic procedures.

Procedural sedation has become increasingly common in endoscopy. Sedatives and analgesics induce anxiolysis and amnesia. In addition, an appropriate level of sedation is necessary for safe procedures including therapeutic endoscopy. Midazolam and propofol are the most commonly used drugs in sedative endoscopy. In recent years, the need to ascertain the safety and effectiveness of sedation has increased in practice. Therefore, new sedatives and analgesic drugs for optimal sedative endoscopy, have recently emerged. This article reviews the characteristics of sedatives and analgesics, and describes their clinical use in gastrointestinal endoscopy.

Real-World Analysis of Rapid-Acting Insulin Analog Use and Its Blood Glucose Lowering Effect in Patients with Type 2 Diabetes Mellitus: Results from PASSION Disease Registry in Korea.

Purpose: Although rapid-acting insulins (RAIs) are used frequently in Korean clinical settings, evidence on their use is limited. This study explores the pattern and clinical effectiveness of the use of RAIs in Korean patients with type 2 diabetes mellitus (T2DM). Patients and Methods: This non-interventional, observational study enrolled patients (aged >18 years) with T2DM who were prescribed RAIs. The pattern of use and effectiveness of RAI analogs were evaluated over 6 months. Results: A total of 299/451 patients were analyzed. Approximately 90% (n/N=270/299) of the patients received insulin glulisine, which significantly reduced their levels of glycated hemoglobin (HbA1c: n=270, mean± standard deviation [SD]; -1.16±6.02%, p=0.0017), fasting plasma glucose (n=40; mean±SD: -54.9±90.89 mg/dl, p=0.0005), and post prandial blood glucose (n=35, mean±SD: -89.46± 105.68 mg/dl, p<0.0001) at 6 months, with a corresponding increase in body weight (BW) (n=197, mean±SD:1.45±3.64 kg, p<0.0001). At 6 months, more patients receiving an intensive regimen (basal insulin+≥2 RAI injections/day) had HbA1c <7% than those receiving a non-intensive regimen (basal insulin+1 RAI injection/day) (20.69% vs 7.46%; p=0.0333); the corresponding reduction in HbA1c was also higher in patients receiving the intensive regimen (p<0.0001). About one-fourth patients (n/N=22/95) were switched to the intensive regimen (from 1 to ≥2 RAI injections/day), and only 4.41% (n/N=9/204) of the patients were switched to 1 RAI injection/day. The patients receiving the intensive regimen showed higher levels of HbA1c reductions (mean±SD: -1.27±1.96%) compared with the maintenance group-1 RAI injection/day (mean±SD: -0.72±1.66%) (p=0.0459), without a significant increase in BW and body mass index. Conclusion: The insulin glulisine intensification regimen showed glycemic target achievement and can be considered a therapeutic tool in the management of T2DM patients.

2021 Korean Society of Gastrointestinal Endoscopy Clinical Practice Guidelines for Endoscopic Sedation.

Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Such cardiopulmonary complications are usually temporary, and most patients recover without sequelae. However, these events may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk.

[2021 Korean Society of Gastrointestinal Endoscopy Clinical Practice Guidelines for Endoscopic Sedation].

Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Cardiopulmonary complications are usually temporary. Most patients recover without sequelae. However, they may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk.

2021 Korean Society of Gastrointestinal Endoscopy Clinical Practice Guidelines for Endoscopic Sedation.

Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Cardiopulmonary complications are usually temporary. Most patients recover without sequelae. However, they may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk.

Suppressive activity of RGX-365 on HMGB1-mediated septic responses

Abstract RGX-365 is the main fraction of black ginseng conmprising protopanaxatriol (PPT)-type rare ginsenosides (ginsenosides Rg4, Rg6, Rh4, Rh1, and Rg2). No studies on the antiseptic activity of RGX-365 have been reported. High mobility group box 1 (HMGB1) is recognized as a late mediator of sepsis, and the inhibition of HMGB1 release and recovery of vascular barrier integrity have emerged as attractive therapeutic strategies for the management of sepsis. In this study, we examined the effects of RGX-365 on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. RGX-365 was administered to the mice after HMGB1 challenge. The antiseptic activity of RGX-365 was assessed based on the production of HMGB1, measurement of permeability, and septic mouse mortality using a cecal ligation and puncture (CLP)-induced sepsis mouse model and HMGB1-activated human umbilical vein endothelial cells (HUVECs). We found that RGX-365 significantly reduced HMGB1 release from LPS- activated HUVECs and CLP-induced release of HMGB1 in mice. RGX-365 also restored HMGB1-mediated vascular disruption and inhibited hyperpermeability in the mice. In addition, treatment with RGX-365 reduced sepsis-related mortality in vivo. Our results suggest that RGX- 365 reduces HMGB1 release and septic mortality in vivo, indicating that it is useful in the treatment of sepsis.

Ginsenoside Rg4 Enhances the Inductive Effects of Human Dermal Papilla Spheres on Hair Growth Via the AKT/GSK-3ß/ß-Catenin Signaling Pathway.

Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 µg/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3ß, which activates the WNT/ß-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of ß-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/ß-catenin pathway including WNT5A, ß-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3ß/ß-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.

PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer.

PURPOSE: Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS: Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS: Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION: PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

PEGylated nanoparticle albumin-bound steroidal ginsenoside derivatives ameliorate SARS-CoV-2-mediated hyper-inflammatory responses.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm.

Suspecting Intussusception and Recurrence Risk Stratification Using Clinical Data and Plain Abdominal Radiographs.

PURPOSE: Although ultrasonography is the gold standard of diagnosing intussusception, plain abdomen radiograph (AXR) is often used to make differential diagnosis for pediatric patients with abdominal pain. In intussusception patients, we aimed to analyze the AXR and clinical data to determine the characteristics of early AXR findings associated with diagnosis of intussusception and recurrence after reduction. METHODS: Between January 2011 and June 2018, 446 patients diagnosed with intussusception based on International Classification of Diseases-10 code of K56.1 were admitted. We retrospectively reviewed medical records of 398 patients who received air reduction; 51 of them have recurred after initial reduction. We evaluated six AXR features including absent ascending colon gas, absent transverse colon gas, target sign, meniscus sign, mass, and ileus. Clinical data and AXR features were compared between single episode and recurrence groups. RESULTS: Two groups did not show significant differences regarding clinical data. Mean time to recurrence from air reduction was 3.4±3.2 days. Absent ascending colon gas (63.9%) was the most common feature in intussusception, followed by mass (29.1%). All of six AXR features were observed more frequently in the recurrence group. Absent transverse colon gas was the most closely associated AXR finding for recurrence (odds ratio, 2.964; 95% confidence interval, 1.327-6.618; p=0.008). CONCLUSION: In our study, absence of ascending colon gas was the most frequently seen AXR factor in intussusception patients. Extended and careful observation after reduction may be beneficial if such finding on AXR is found in intussusception patients.

Appropriate Number of Treatment Sessions in Virtual Reality-Based Individual Cognitive Behavioral Therapy for Social Anxiety Disorder.

Virtual reality (VR) was introduced to maximize the effect of cognitive behavioral therapy (CBT) by efficiently performing exposure therapy. The purpose of this study was to find out whether VR-based individual CBT with relatively few treatment sessions is effective in improving social anxiety disorder (SAD). This therapy was applied to 115 patients with SAD who were retrospectively classified into 43 patients who completed the nine or 10 sessions normally (normal termination group), 52 patients who finished the sessions early (early termination group), and 20 patients who had extended the sessions (session extension group). The Brief Fear of Negative Evaluation Scale (BFNE) scores tended to decrease in all groups as the session progressed, and the slope of decrease was the steepest in the early termination group and the least steep in the session extension group. Severity of social anxiety in the last session and symptom reduction rate showed no significant group difference. Our findings suggest that short-term VR-based individual CBT of nine to 10 sessions may be effective. When the therapeutic effect is insufficient during this period, the additional benefit may be minimal if the session is simply extended. The improvement in the early termination group suggests that even shorter sessions of five or six can also be effective.

Neutrophil-derived trail is a proinflammatory subtype of neutrophil-derived extracellular vesicles.

Aims: Extracellular vesicles (EVs) are membrane-derived vesicles that mediate intercellular communications. Neutrophils produce different subtypes of EVs during inflammatory responses. Neutrophil-derived trails (NDTRs) are generated by neutrophils migrating toward inflammatory foci, whereas neutrophil-derived microvesicles (NDMVs) are thought to be generated by neutrophils that have arrived at the inflammatory foci. However, the physical and functional characteristics of neutrophil-derived EVs are incompletely understood. In this study, we aimed to investigate the differences between NDTRs and NDMVs. Methods: The generation of neutrophil-derived EVs were visualized by live-cell fluorescence images and the physical characteristics were further analyzed using nanotracking analysis assay, scanning electron microscopic analysis, and marker expressions. Functional characteristics of neutrophil-derived EVs were analyzed using assays for bactericidal activity, monocyte chemotaxis, phenotype polarization of macrophages, and miRNA sequencing. Finally, the effects of neutrophil-derived EVs on the acute and chronic inflammation were examined in vivo. Results: Both EVs share similar characteristics including stimulators, surface marker expression, bactericidal activity, and chemoattractive effect on monocytes via MCP-1. However, the integrin-mediated physical interaction was required for generation of NDTRs whereas NDMV generation was dependent on PI3K pathway. Interestingly, NDTRs contained proinflammatory miRNAs such as miR-1260, miR-1285, miR-4454, and miR-7975, while NDMVs contained anti-inflammatory miRNAs such as miR-126, miR-150, and miR-451a. Although both EVs were easily uptaken by monocytes, NDTRs enhanced proinflammatory macrophage polarization whereas NDMVs induced anti-inflammatory macrophage polarization. Moreover, NDTRs showed protective effects against lethality in a murine sepsis model and pathological changes in a murine chronic colitis model. Conclusion: These results suggest that NDTR is a proinflammatory subtype of neutrophil-derived EVs distinguished from NDMV.

Familial Risk of Inflammatory Bowel Disease: A Population-Based Cohort Study in South Korea.

BACKGROUND & AIMS: Despite the rapid increase in inflammatory bowel disease (IBD), population-level familial risk estimates of IBDs still are lacking in Asian-Pacific countries. We aimed to quantify the familial risk of incident IBD among first-degree relatives (FDRs) of individuals with IBD according to age, sex, and familial relationship. METHODS: Using the South Korea National Health Insurance database (2002-2017), which has complete population coverage and confirmed accuracy of both FDR information and IBD diagnoses, we constructed a cohort of 21,940,795 study subjects comprising 12 million distinct families. We calculated incidence risk ratios of ulcerative colitis (UC) or Crohn's disease (CD) in individuals of affected FDRs compared with individuals without affected FDRs. RESULTS: Of 45,717 individuals with UC and 17,848 individuals with CD, 3.8% and 3.1% represented familial cases, respectively. Overall, there was a 10.2-fold (95% CI, 9.39-11.1) and a 22.1-fold (95% CI, 20.5-24.5) significantly higher adjusted risk of UC and CD among FDRs of individuals with vs without IBD. Familial risk was highest among twins, followed by nontwin siblings, and then offspring of affected parents. Familial risk generally was higher within generations (sibling-sibling) vs between generations (parent-offspring). Familial risk also increased with the increasing number of affected FDRs. CONCLUSIONS: According to this population-based analysis, there is a substantially increased risk of IBD among FDRs of affected individuals, with the highest risk among siblings and for CD. These findings might help with an earlier diagnosis and appropriate therapeutic intervention in FDRs of individuals with IBD. Dedicated studies are needed to evaluate the contributions of shared early-in-life environmental exposures and genetic factors.

Incisive canal remodelling following maximum anterior retraction reduces apical root resorption.

INTRODUCTION: The objectives were to visualize the incisive canal (IC) remodelling following maximum incisor retraction and to evaluate its impact on canal-invasion-associated apical root resorption. METHODS: Pre- and post-treatment CBCT images of 34 adult orthodontic patients (age 18-47 years) with a large amount of maxillary incisor retraction (>4 mm) using temporary anchorage devices (TADs) were retrospectively evaluated. Maxillary regional superimpositions and 3D models of the IC along with central incisors were used to measure the changes in IC dimension, IC invasion by the roots and IC remodelling. In addition, the association of the amount of apical root resorption with the root-IC relationship and IC remodelling were evaluated. RESULTS: IC invasion by the incisor roots following maximum retraction was seen in 53% (18 out of 34) of the cases. IC with larger volume and area showed more invasions compared with those with smaller volume and area (P < .01). The amount of root resorption was significantly higher with IC invasion than without invasion (2.39 mm vs 0.82 mm, P < .0001). IC remodelling following maximum retraction was seen in 24% of the subjects. IC remodelling group demonstrated less apical root resorption than the non-remodelling group (0.98 mm vs 3.27 mm, P < .0001). CONCLUSION: IC with larger volume and surface area before treatment were more likely to show canal invasion by the incisor roots after maximum retraction. IC invasion resulted in apical root resorption. However, approximately one-fourth of cases showed remodelling of the IC, which reduced the amount of root resorption.

Association between Self-Reported Sleep Duration and Dietary Nutrients in Korean Adolescents: A Population-Based Study.

(1) Background: Adolescence is a transient period from childhood to adulthood, which is characterized by rapid physical growth and psychological changes, including sleep. Because the relationship between insufficient sleep and obesity has been observed in children and adults, the potential links between sleep, dietary intake, and nutrition have received increased attention. We aimed to examine the association of sleep duration with dietary nutrients intake in South Korean adolescents; (2) Methods: This population-based, cross-sectional study analyzed the data obtained from the Korea National Health and Nutrition Examination Survey between 2013 and 2015. Data related to 1422 adolescents aged 12-18 years (741 males and 681 females) were included in the analysis. Sleep duration was assessed using a self-reported questionnaire. Nutrient intake, including daily total energy intake, was assessed with a 24-h dietary recall questionnaire; (3) Results: Most males (84.4%) and females (86.4%) reported < 9 h of sleep per night. Short sleep duration was inversely associated with body mass index and obesity in both sexes. We found that higher intake of fiber and lower intake of sodium were associated with longer sleep duration (P < 0.05). When comparing the intake above and below the estimated average requirements (EAR), the difference in sleep duration was significant in the group that consumed vitamins B1 and C below EAR; (4) Conclusions: The findings of this study indicate that sleep duration can be associated with intake of some nutrients, which may also be associated with obesity in adolescents. Therefore, it is possible to prevent obesity and its complications by controlling the sleep duration and intake of nutrients of adolescents.

Expression of the Long Noncoding RNA GAS5 Correlates with Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Advanced liver fibrosis is the most important prognostic factor in nonalcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA), growth arrest-specific transcript 5 (GAS5), is associated with the inhibition of liver fibrogenesis, and its levels are decreased in cirrhotic liver. METHODS: We analyzed 51 patients with NAFLD, the diagnosis of which was confirmed by liver biopsy. Expression of GAS5 in both the liver and plasma of the patients was analyzed using a quantitative real-time polymerase chain reaction according to the fibrosis stage. RESULTS: Plasma GAS5 expression was significantly higher in patients with advanced fibrosis than in those without. As the fibrosis progressed, GAS5 expression in plasma increased, with the exception of that in cirrhotic livers. Plasma levels of GAS5 were lower in patients with cirrhosis than in those with advanced fibrosis. CONCLUSION: Elevated circulating levels of the lncRNA GAS5 are associated with the progression of liver fibrosis prior to the development of cirrhosis.