Background: Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden. Methods: We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease. Results: The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100. Conclusion CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.

Background: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). Methods: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. Results: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. Conclusion VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test.

Purpose: This study evaluates the potential protective effects of hemp (Cannabis sativa L.) seed oil supplementation in rats fed a high-cholesterol diet. Methods: Rats were fed a 1.25% cholesterol diet for 8 weeks, followed by oral administration of either of the two doses of hemp seed oil (HO) (0.5 mL/kg (HOL group) or 1 mL/kg (HOH group) body weight/day) or simvastatin at 10 mg/kg body weight/day. Oxidative stress, lipids, liver enzymes, and renal markers were measured in the serum. Western blot analysis was applied for evaluating the expressions of inflammatory makers. Results: Except for HDL-cholesterol, the altered levels of lipoproteins, aminotransferases, urea, and creatine kinases in hypercholesterolemic rats were significantly corrected by HO administration. Especially, compared to the HOH group, HOL treatment further reduced AST, ALT, creatinine, TC, and LDL-cholesterol levels. Moreover, both the atherogenic index and cardiac risk factor (CRF) in the HOL group were more restrained compared to the HOH group. Increased levels of p-AMPK coincided with the inhibition of SREBP-2 activation which subsequently suppressed the expression of HMGCR. Nuclear factor (NF)-κB activation coincided with the PI3K/Akt pathway activation and the increased phosphorylation of p38;these levels were significantly suppressed by HO treatment. In addition, HO treatment markedly reversed the changes in chemokines such as ICAM-1, VCAM-1, and MCP-1.Histological alterations induced by cholesterol overload in cardiac and hepatic tissues were ameliorated by HO supplementation. Conclusion Taken together, our results indicate a low concentration of HO demonstrates improved dysfunctions caused by a high-cholesterol diet via inhibition of the PI3K/Akt/NF-κB signaling pathway.

Background and Objectives: The de novo serine biosynthetic pathway from glucose has emerged as one of cancer metabolism; however, it is not explored the interplay between papillary thyroid cancer and metabolic flux of de novo serine synthesis. In this study, we explored the interplay between glucose utilization via GLUT1 expression and phosphoglycerate dehydrogenase (PHGDH). Materials and Methods: The Cancer Genome Atlas (TCGA) database was used to determine the association between glucose importation and the serine metabolic pathway. The effects of glucose on serine biosynthesis and the role of PHGDH were investigated in papillary thyroid cancer cell lines. PHGDH and GLUT1 expression in 230 patients with papillary thyroid cancer (PTC) was explored using immunohistochemistry to explore the impact of the de novo serine biosynthetic pathway from glucose. Results: Glucose importation was significantly correlated with the serine biosynthetic and L-serine metabolic processes. Glucose uptake and serine synthesis were significantly increased and mitochondrial complex expression was upregulated in PTC cell lines grown in high-glucose media. Knockdown and inhibition of PHGDH decreased cell migration associated with glucose utilization. High PHGDH expression is significantly related with tumor aggressiveness and GLUT1 expression in patients with PTC. Conclusion In this study, we demonstrated that de novo serine biosynthesis from glucose is highly expressed in papillary thyroid cancer and associated with cancer cell metastasis through glucose utility. Our findings suggest the link between glucose utilization PHGDH to regulate tumor aggressiveness in PTC.

Organized hematoma of maxillary sinus is a rare pathologically benign mass in which pressure in the hematoma increases as it undergoes a process of organization, causing the deformation of the surrounding tissue, mimicking malignancies. The midfacial degloving approach can be used when extensive exposure is required in the treatment of lesions or traumas in the midfacial area with intranasal and intraoral incisions. We report a surgical excision case of organized hematoma of maxillary sinus using midfacial degloving approach without major complications and recurrence after one-year follow up.

Objective: Methamphetamine (MA), cocaine, and heroin cause severe public health problems as well as impairments in neural plasticity and cognitive function in the hippocampus. This study aimed to identify the genes differentially expressed in the hippocampi of cynomolgus monkeys in response to these drugs. Methods: After the monkeys were chronically exposed to MA, cocaine, and heroin, we performed large-scale gene expression profiling of the hippocampus using RNA-Seq technology and functional annotation of genes differentially expressed. Some genes selected from RNA-Seq analysis data were validated with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). And the expression changes of ADAM10 protein were assessed using immunohistochemistry. Results: The changes in genes related to axonal guidance (PTPRP and KAL1), the cell cycle (TLK2), and the regulation of potassium ions (DPP10) in the drug-treated groups compared to the control group were confirmed using RT-qPCR. Comparative analysis of all groups showed that among genes related to synaptic long-term potentiation, CREBBP and GRIN3A were downregulated in both the MA- and heroin-treated groups compared to the control group. In particular, the mRNA and protein expression levels of ADAM10 were decreased in the MA-treated group but increased in the cocaine-treated group compared to the control group. Conclusion These results provide insights into the genes that are upregulated and downregulated in the hippocampus by the chronic administration of MA, cocaine, or heroin and basic information for developing novel drugs for the treatment of hippocampal impairments caused by drug abuse.

Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal tract, which is often accompanied by altered gut microbial composition. Gut dysbiosis in IBD is considered to be the reason for the high risk of Clostridioides difficile infection (CDI) in patients with IBD. Therefore, CDI should be evaluated in IBD patients with a symptom flare. Medical treatment of non-severe CDI in IBD is similar to that in non-IBD patients and includes oral vancomycin or fidaxomicin. The risk of recurrent CDI in IBD is higher than in non-IBD patients and this could be mitigated by fecal microbiota transplantation. As CDI may worsen the clinical outcomes of IBD, patients should be carefully monitored and an escalation of IBD therapy needs to be considered when there is no improvement seen with the antimicrobial treatment of CDI. This review discusses the risk, pathophysiology, diagnosis, and management of CDI in IBD.

Background: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. Methods: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. Results: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P= 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). Conclusion Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

Background: People are generally considered overweight and obese if their body mass index (BMI) is above 25 kg/m 2 and 30.0 kg/m 2 , respectively. The World Health Organization proposed stricter criteria for Asians (≥ 23 kg/m2 : overweight, ≥ 25 kg/m2 : obese). We aimed to verify whether this criteria could predict adverse pregnancy outcomes in Korean women. Methods: We included 7,547 Korean women from 12 institutions enrolled between June 2016 and October 2018. Women with no pre-pregnancy BMI data, not Korean, or lost to followup were excluded, leaving 6,331. The subjects were categorized into underweight, normal, overweight, class I obesity, and class II/III obesity based on a pre-pregnancy BMI of < 18.5, 18.5–22.9, 23.0–24.9, 25.0–29.9, and ≥ 30.0 kg/m2 , respectively. Results: Overall, 13.4%, 63.0%, 11.8%, 9.1%, and 2.6% of women were underweight, normal, and overweight and had class I obesity and class II/III obesity, respectively. In the multivariable analysis adjusted for maternal age, a higher BMI significantly increased the risk of preeclampsia, gestational diabetes, preterm delivery caused by maternal-fetal indications, cesarean section, large for gestational age, and neonatal intensive care unit admission. Conclusion Adverse pregnancy outcomes started to increase in those with a pre-pregnancy BMI ≥ 23.0 kg/m2 after adjusting for maternal age. The modified obesity criteria could help predict adverse pregnancy outcomes in Koreans.

Purpose: Paeonia Radix Alba is a traditional herbal medicine used to treat the liver and the spleen. Many studies have reported that Paeonia Radix Alba extract (PR) affects liver injury, but there has been no study on liver injuries induced by thioacetamide (TAA). Therefore, we aimed at evaluating the effect of PR on a TAA-induced acute liver injury (ALI) model. Methods: The antioxidant activity of PR was assayed by the content of total polyphenol, total flavonoid, 1,1-diphenyl-2′-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonicacid) (ABTS) radical scavenging activities in vitro test. ALI was induced via-intraperitoneal injection of TAA (200 mg/kg body weight) for three consecutive days. Also, silymarin (100 mg/ kg body weight) and PR (100 or 200 mg/kg body weight) were administered at 1 hours 30 minutes prior to TAA treatment. The levels of ammonia, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were analyzed using an assay kit. The expressions of antioxidant proteins including Nrf2, Keap1, HO-1, SOD, catalase, and GPx-1/2 and oxidative stressrelated proteins including NOX2, p47 phox , and p22 phox were evaluated by the western blot analysis. Results: PR showed excellent antioxidant activity in vitro. TAA administration increased the levels of ammonia, GOT, and GPT in the ALI control group compared to the normal group, whereas it was significantly reduced by PR pretreatment. Moreover, NADPH oxidase protein expressions were upregulated after TAA treatment, while the elevated expressions were inhibited by PR pretreatment. The expressions of antioxidant protein were downregulated in the ALI control group, whereas Nrf2 activation in the PR group was accompanied by increased levels of antioxidant enzymes. Conclusion PR administration increased the antioxidant enzymes via activation of the Keap1/Nrf2 pathway and inhibited the protein levels of NADPH oxidase factors. Taken together, these results showed that PR treatment may be considered to ameliorate acute liver injury induced by TAA.