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We report a case of inguinal hernia that contained the entire uterus and both adnexa, presenting with an irreducible soft mass in the left groin and asymmetric labia majora, in a 2-month-old, full-term girl who visited the emergency department. Ultrasonography was performed immediately, and urgent surgical repair was performed without complications. Although inguinal hernia is a common surgical disease, it is rare that the hernia contains the uterus with its adnexa, and presents as a mass of the labia majora. Unlike the bowel herniation, the entity can be complicated by strangulation of the ovary, leading to infertility. To preserve fertility, rapid and accurate diagnosis using ultrasonography should be considered in an infant with an irreducible inguinal mass and asymmetric labia majora.

Button battery ingestion requires emergency endoscopic removal since severe complications, such as esophageal perforation, can develop within 4 hours of the ingestion. Given that guardians do not witness the children’s foreign body ingestion 40% of the time, physicians can only guess what was swallowed based on plain radiography. We report a case of a 45-month-old-boy who visited the emergency department after swallowing an unknown foreign body and whose radiographs showed “circle-within-a-circle appearance” on the anteroposterior view and “step-off appearance” on the lateral view, suggesting button battery ingestion. We conducted emergency endoscopic removal, and found stacked coins mimicking a button battery on the radiographs. The coins were pushed into the stomach and came out through defecation 3 weeks later without further complications. Distinguishing between stacked coins and a button battery through radiography may help avoid unnecessary emergency endoscopy.

Recurrent pregnancy loss (RPL) affects 1% to 5% of women, with devastating effects on both reproductive health and psychological well-being. Homeobox (

As a disease with high mortality and prevalence rates worldwide, colorectal cancer (CRC) has been thoroughly investigated. Mucins are involved in the induction of CRC and regulation of intestinal homeostasis. However, the role of MUC4, which is a member of the mucin gene family, is controversial because it shows an association with either decreased susceptibility to or a worse prognosis of CRC. In our study, the multifunctional aspects of MUC4 were elucidated by genetic polymorphism analysis in a case-control study of 420 controls and 464 CRC patients. The MUC4 rs1104760 A>G polymorphism had a protective effect on CRC risk (AG, AOR = 0.537; GG, AOR = 0.297; dominant model, AOR = 0.493; recessive model, AOR = 0.382). In addition, the MUC4 rs2688513 was associated with an increased mortality rate of CRC (5 years, GG, adjusted HR = 6.496; recessive model, adjusted HR = 5.848). Furthermore, a significant synergistic effect was observed between MUC4 rs1104760 A>G and low-density lipoprotein cholesterol (LDL-C) indicating a high potential as a biomarker for CRC susceptibility. This is the first study to indicate a significant association between MUC4 genetic polymorphisms and CRC prevalence, suggesting a functional genetic variant with the LDL-C level, for CRC prevention.

To identify predictors of failed enema reduction in children with intussusception. PubMed and EMBASE were searched for all studies published over a 20-year time frame, prior to March 25, 2020. Original articles that reported predictors of failed enema reduction were included. The pooled odds ratio (OR) for successful enema reduction according to various features was calculated. The combined estimates were meta-analytically pooled by random-effects modeling. The risk of bias was assessed using the National Institute of Health Quality Assessment Tool. This review was registered to the PROSPERO (CRD42020190178). A total of 38 studies, comprising 40,133 cases, were included. The shorter duration of symptoms (< 24 h; combined OR, 3.812; 95% CI, 2.150–6.759) and abdominal pain (combined OR, 2.098; 95% CI, 1.405–3.133) were associated with the success (all p < 0.001). Age < 1 year (combined OR, 0.385; 95% CI, 0.166–0.893; p = 0.026), fever (combined OR, 0.519; 95% CI, 0.371–0.725; p < 0.001), rectal bleeding (combined OR, 0.252; 95% CI, 0.165–0.387; p < 0.001), and vomiting (combined OR, 0.497; 95% CI, 0.372–0.664; p < 0.001) were associated with the failed reduction. The ascites (combined OR, 0.127; 95% CI, 0.044–0.368; p = 0.001), left-sided intussusception (combined OR, 0.121; 95% CI, 0.058–0.252; p < 0.001), and trapped fluid (combined OR, 0.179; 95% CI, 0.061–0.525; p = 0.017) on US were associated with the failed reduction. Successful predictors for intussusception reduction have been summarized. This evidence can help identify patients who are more likely to fail non-operative reduction and could be potential surgical candidates. • A shorter duration of symptoms and presence of abdominal pain were associated with increased probability of success. • Age (less than 1 year), presence of fever, rectal bleeding, vomiting, and presence of ascites, left-sided intussusception, or trapped fluid on ultrasonography were associated with decreased probability of success. • This study suggests that various clinical and ultrasonography predictors would help identify patients who are more likely to fail nonoperative reduction and identify potential preoperative candidates.

Stroke is the second leading cause of death in the world. Approximately 80% of strokes are ischemic in origin. Many risk factors have been linked to stroke, including an increased level of plasminogen activator inhibitor-1 (PAI-1). PAI-1 levels increase and remain elevated in blood during the acute phase of ischemic stroke, which can impair fibrinolytic activity, leading to coronary artery disease and arterial thrombotic disorders. Here, we present a case-control study of 574 stroke patients and 425 controls seen for routine health examination or treatment for nonspecific dizziness, nonorganic headache, or anxiety for positive family history of stroke at the Bundang Medical Center in South Korea. Polymorphisms in PAI-1 were identified by polymerase chain reaction/restriction fragment length polymorphism analysis using genomic DNA. Specifically, three variations (−675 4G>5G, 10692T>C, and 12068G>A) were linked to a higher overall prevalence of stroke as well as a higher prevalence of certain stroke subtypes. Haplotype analyses also revealed combinations of these variations (−844G>A, −675 4G>5G, 43G>A, 9785A>G, 10692T>C, 11053T>G, and 12068G>A) that were significantly associated with a higher prevalence of ischemic stroke. To the best of our knowledge, this is the first strong evidence that polymorphic sites in PAI-1 promoter and 3′-UTR regions are associated with higher ischemic stroke risk. Furthermore, the PAI-1 genotypes and haplotypes identified here have potential as clinical biomarkers of ischemic stroke and could improve the prognosis and future management of stroke patients.

BackgroundFever in infants under 90 days of age is highly likely to be caused by a severe bacterial infection (SBI) and it accounts for a large number of patients visiting the pediatric emergency room. In order to predict the bacterial infection and reduce unnecessary treatment, the classic classification system is based on white blood cell (WBC) count, urinalysis, and x-ray, and it is modified and applied at each center by incorporating recently studied biomarkers such as c-reactive protein (CRP) or procalcitonin (PCT). This study analyzed the usefulness of PCT in predicting SBI when applied along with the existing classification system, including CRP, among infants less than 90 days old who visited with a fever at a single institution pediatric emergency center.MethodsWe retrospectively reviewed the medical records of patients younger than 3 months of age who presented with fever at the Seoul Asan Medical Center pediatric emergency room between July 2017 and October 2018.ResultsA total of 317 patients were analyzed, and 61 were diagnosed with SBI, among which urinary tract infection (UTI) accounted for the largest proportion (55/61, 90.2%). There were differences in WBC, neutrophil proportion, CRP, and PCT between the SBI group and the non-SBI group, and the AUC values of WBC, CRP, and PCT were 0.651, 0.804, and 0.746, respectively. When using the cut-off values of CRP and PCTs as 2.0 mg/dL and 0.3 ng/mL, respectively, the sensitivity and specificity for SBI were 49.2/89.5, and 54.1/87.5, respectively. WBC, CRP, and PCT were statistically significant for predicting SBI in multivariate analysis (odds ratios 1.066, 1.377, and 1.291, respectively). When the subjects were classified using the existing classification criteria, WBC and CRP, the positive predictive value (PPV) and negative predictive value (NPV) were 29.3 and 88.7%, respectively, and when PCT was added, the PPV and NPV were 30.7 and 92%, respectively, both increased.ConclusionPCT is useful for predicting SBI in children aged 3 months or less who visit the emergency room with a fever. It is useful as a single biomarker, and when used in conjunction with classic biomarkers, its diagnostic accuracy is further increased.

Large artery disease (LAD), cardioembolism (CE), and small vessel disease (SVD) are well-established causes of ischemic stroke. Although a founder variant of RNF213 has been regarded a genetic susceptibility for Moyamoya disease (MMD) and certain types of intracranial atherosclerotic stenosis (ICAS), correlations between RNF213 variants and ischemic stroke with SVD remain largely unknown. This study aimed to characterize the associations of four RNF213 polymorphisms (4448G>A, 4810G>A, 4863G>A, and 4950G>A) with ischemic stroke subtypes in Koreans. Genetic data from 529 stroke patients were analyzed and compared to 424 age- and sex-matched controls. Genetic variants of RNF213, as obtained from the Human Gene Mutation Database, were analyzed in the study subjects using the polymerase chain reaction restriction fragment length polymorphism assay. We investigated four single-nucleotide polymorphisms of RNF213 to elucidate their association with ischemic stroke [LAD, (n = 192), SVD (n = 145) and CE (n = 51)]. The RNF213 4950G>A genotype was observed more frequently in cerebral stroke patients and was more strongly associated with SVD than LAD (P = 0.014). RNF213 4448/4950 in combination with G–A was higher in SVD patients. However, the RNF213 4863/4950 allele combination was associated with increased risk of SVD and LAD. These results confirmed that RNF213 4950GA+AA variants were more frequent in ischemic stroke, especially in SVD, and that RNF213 G–G–G–A and G–G–G–A (4448/4810/4863/4950) haplotype sequences play a role in LAD and CE as well as SVD. Our data reported that the RNF213 4950G>A genotypes and several RNF213 (4448/4810/4863/4950) haplotypes were associated with ischemic stroke in Koreans.

(1) Background: First-pass success (FPS) of endotracheal intubation is more challenging in children than in adults. We aimed to identify factors associated with FPS of intubation in acute care settings. (2) Methods: We analyzed data of children aged

Recurrent pregnancy loss (RPL) is the loss of two or more consecutive pregnancies before 20 weeks of gestational age. Our study investigated whether mucin 4 (MUC4) polymorphisms are associated with RPL. MUC polymorphisms (rs882605 C>A, rs1104760 A>G, rs2688513 A>G, rs2258447 C>T, and rs2291652 A>G) were genotyped in 374 women with RPL and 239 controls of Korean ethnicity using polymerase chain reaction-restriction fragment length polymorphism analysis and the TaqMan probe SNP genotyping assay. Differences in genotype frequencies between cases of RPL and the controls were compared. MUC4 rs882605 C>A and rs1104760 A>G polymorphisms were associated with increased incidence of RPL in three and four or more pregnancy loss patients. The haplotype analyses showed a tendency for the allelic effect including the association of MUC4 rs882605 A and rs1104760 G alleles with increased incidence of RPL. In addition, the MUC4 rs882605 CA/MUC4 rs2258447 CC genotype combination was associated with increased RPL prevalence. The two exonic polymorphisms lead to amino acid changes of protein and may act as pathogenic variants for RPL. In conclusion, the MUC4 rs882605 C>A and MUC4 rs1104760 A>G polymorphisms were associated with the susceptibility of RPL and we considered them as potential biomarkers for RPL.

Coronary artery disease (CAD), a leading cause of death worldwide, has a complex etiology comprising both traditional risk factors (type 2 diabetes, dyslipidemia, arterial hypertension, and cigarette smoking) and genetic factors. Vascular endothelial growth factor (VEGF) notably contributes to angiogenesis and endothelial homeostasis. However, little is known about the relationship between CAD and VEGF polymorphisms in Koreans. The aim of this study is to investigate the associations of 2 VEGF promoter region polymorphisms (−1154G>A [rs1570360], −1498T>C [rs833061]) and 4 VEGF 3′-UTR polymorphisms (+936C>T [rs3025039], +1451C>T [rs3025040], +1612G>A [rs10434], and +1725G>A [rs3025053]) with CAD susceptibility in Koreans. We studied 885 subjects: 463 CAD patients and 422 controls. Genotyping was conducted with polymerase chain reaction-restriction fragment length polymorphism analysis and TaqMan allelic discrimination assays, and the genotype frequencies were calculated. We then performed haplotype and genotype combination analyses and measured the associations between VEGF polymorphisms and clinical variables in both the CAD patients and control subjects. We detected statistically significant associations between CAD and certain VEGF allele combinations. In the haplotypes of 5 single-nucleotide polymorphisms, the VEGF allele combination −1154A/+936T was associated with a decreased prevalence of CAD (A-T-T-G-G of VEGF −1154G>A/−1498T>C/+936C>T/+1612G>A/+1725G>A, AOR = 0.077, p = 0.021). In contrast, the VEGF allele combinations −1498T/+1725A and −1498T/+1612A/+1725A were associated with an increased prevalence of CAD (G-T-C-C-A of VEGF −1154G>A/−1498T>C/+936C>T/+1451C>T/+1725G>A, AOR = 1.602, p = 0.047; T-C-C-A-A of VEGF −1498T>C/+936C>T/+1451C>T/+1612G>A/+1725G>A, AOR = 1.582, p = 0.045). Gene–environment combinatorial analysis showed that the combination of the VEGF +1725AA genotype and several clinical factors (e.g., body mass index, hemoglobin A1c, and low-density lipoprotein cholesterol) increased the risk of CAD. Therefore, we suggest that VEGF polymorphisms and clinical factors may impact CAD prevalence.

Recurrent pregnancy loss (RPL) is typically defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation. Although the causes of idiopathic RPL are not completely understood, vascular development and glucose concentration were reported to correlate with the pregnancy loss. The TGF-β signaling pathway which plays a significant role in pregnancy is activated by the interaction between high glucose and SMAD signaling and affects the vascular cells.

Rapid sequence intubation (RSI) using sedatives and neuromuscular blocking agents (NMBAs) is recommended for pediatric emergency endotracheal intubation (ETI), but is not frequently performed in Korea. This study aimed to verify factors associated with the underuse of RSI medications.This multicenter retrospective study reviewed patients aged under 18 years who underwent an ETI within 24 hours of arrival at the emergency department between 2016 and 2019. Any cases of ETI during cardiopulmonary resuscitation were excluded. We investigated the characteristics of the patients, intubators, RSI medications, and outcomes. The study cases were classified into no-medication, sedative-only, and sedative-with-NMBA groups. Multivariable logistic regression analysis of RSI medication use was conducted.A total of 334 cases with a median age of 3.4 years were included in this study. Sedatives and NMBAs were used in 63.8% and 32.9%, respectively. In comparing the no-medication (n=121), sedative-only (n=103), and sedative-with-NMBA (n=110) groups, patient age (median; 1.0 year vs. 2.8 years vs. 11.3 years;RSI accounted for 32.9% of pediatric emergency ETI in Korea. The underuse of RSI medications is associated with younger patient age, underlying medical conditions, and pediatricians as intubators.

OBJECTIVES This study aimed to investigate the feasibility of point-of-care ultrasound (POCUS) for diagnosing hypertrophic pyloric stenosis (HPS) in the emergency department (ED). METHODS A retrospective study was conducted in infants aged younger than 90 days who were brought to the ED due to vomiting between January 2015 and December 2019. Of these, infants who were clinically suspected of having HPS and underwent ultrasound were included and categorized into 3 groups: POCUS only, POCUS followed by radiologist-performed ultrasound (RADUS), and RADUS only. All confirmative diagnoses of HPS were made by RADUS. The diagnostic performance of POCUS was analyzed, and the ED patient flow was compared between the POCUS-performed (POCUS only or POCUS followed by RADUS) and RADUS-only groups. RESULTS Overall, 171 patients with a median age of 34 days were included. Of these, 79 patients (46.2%) underwent POCUS only, and none had HPS; 50 patients (29.2%) underwent POCUS followed by RADUS; and 42 patients (24.5%) underwent RADUS only. Overall, 41 patients (24.0%) were diagnosed with HPS, and POCUS showed a sensitivity of 96.6% and specificity of 94.0%. In the total cohort, length of stay in the ED (EDLOS) was shorter in the POCUS-performed group than in the RADUS-only group (2.6 vs 3.8 hours, P = 0.015). Among non-HPS patients, time to disposition (1.8 vs 2.7 hours, P = 0.005) and EDLOS (2.0 vs 3.0 hours, P = 0.004) were shorter in the POCUS-performed group than in the RADUS-only group. Performing POCUS followed by RADUS did not significantly delay the treatment among HPS patients. CONCLUSIONS Point-of-care ultrasound is accurate and useful for diagnosing HPS and improved the ED patient flow by reducing EDLOS and door-to-disposition time in non-HPS patients.

The aim of this study was to re-validate the changes in natural killer (NK) cell cytotoxicity and cytokines related to T cells after Sil-Q1 (SQ, silk peptide) supplementation in a larger pool of Korean adults with minimized daily dose of SQ and controlling seasonal influence compared to the previous study. A total of 130 subjects were randomly assigned (1:1) to consume either 7.5 g of SQ or placebo for 8 weeks. NK cell cytotoxicity and cytokines were measured at T0 (baseline) and T8 (follow-up). Comparing the NK cell cytotoxicity values at T0 and T8 within each group, the cytotoxicity at all effector cell (E) to target cell (T) ratios of 10:1, 5:1, 2.5:1, and 1.25:1 was significantly increased in the SQ group at T8. Additionally, significant differences in the changed value (Δ, subtract baseline values from follow-up values) comparison between the groups at E:T = 10:1, 5:1, and 2.5:1 were found. As a secondary endpoint, the interleukin (IL)-12 level in the SQ group was significantly increased for 8 weeks, and Δ IL-12 in the SQ group was greater than in the placebo group. In conclusion, the present study showed considerable practical implications of SQ supplementation. Thus, SQ is an effective and safe functional food supplement for enhancing immune function.

Objectives: Coronavirus disease 2019 (COVID-19) changed the epidemiology of various diseases. The present study retrospectively investigated the epidemiologic and clinical changes of intussusception from before to after the COVID-19 outbreak, when communicable diseases other than COVID-19 have dramatically decreased due to social lockdown.Methods: The incidence of intussusception and the total monthly visits, including communicable and non-communicable diseases, aged ≤7 years, were investigated from February 2019 to January 2021 in a single pediatric emergency department of a university-affiliated tertiary hospital. The relationship between the incidence of communicable disease and intussusception was analyzed. The clinical characteristics of patients with intussusception were compared for the one-year periods before (February 2019–January 2020) and after (February 2020–January 2021) social lockdown due to COVID-19.Results: Incidence of communicable disease, non-communicable disease, and intussusception is decreased after COVID-19 outbreak (15,932 to 3,880 [24.4%], 12,994 to 8,050 [62.0%], and 87 to 27 [31.0%], respectively). The incidence of intussusception correlated significantly with the change in incidence of communicable diseases (Poisson log-linear regression, Odds ratio=2.15, 95% CI=1.08–4.26, P=0.029). Compared with non-pandemic period, patients of pandemic period showed higher proportions of pathologic leading point and hospitalization (14.8% vs. 2.3%, 18.5% vs. 4.6%, respectively), lower base excess (-4.8 mmol/L vs. -3.6 mmol/L), and higher lactate concentration (1.7 mmol/L vs. 1.5 mmol/L).Conclusions: The incidence of pediatric intussusception decreased after the COVID-19 pandemic. This reduced incidence may be related to the reduced incidence of communicable diseases. However, the proportions of more severe disease and PLPs were higher after the COVID-19 pandemic.

BACKGROUND AND PURPOSE The pathophysiologic mechanisms underlying benign convulsions with mild gastroenteritis (CwG) in children remain unclear. We investigated the incidence of ketosis in CwG and whether this is related to seizures. METHODS This retrospective study included children aged from 6 months to 6 years who visited our emergency department and were diagnosed as CwG between June 2015 and December 2018. The clinical and laboratory data were analyzed for these cases. Ketosis and severe ketosis were defined as blood β-hydroxybutyrate levels of ≥0.6 and ≥4.5 mmol/L, respectively. RESULTS We enrolled 42 pediatric CwG patients aged 21.0±11.5 months (mean±SD) whose blood β-hydroxybutyrate level was 3.65±1.51 mmol/L. Ketosis was observed in 95.2% of these children, while 35.7% had severe ketosis. Compared to the non-severe-ketosis group (n=27), the severe-ketosis group (n=15) demonstrated significantly lower blood glucose levels (68.8 vs. 82.6 mg/dL, p=0.020) and sodium levels (134.2 vs. 135.6 mEq/L, p=0.018), and included a larger proportion of low-body-weight children (defined as adjusted weight

Objectives The aim of the study was to investigate the diagnostic efficacy of C-reactive protein (CRP) in predicting serious bacterial infection (SBI) in febrile children aged 3 to 36 months with extreme leukocytosis (EL), defined as a peripheral white blood cell count of 25,000 to 49,999/mm. Methods The presence of SBI was reviewed in previously healthy children aged 3 to 36 months with a fever of 39°C or higher and EL, who visited a tertiary care hospital emergency department between September 2010 and August 2015. We measured cutoff values of CRP with corresponding likelihood ratios (LRs) and posttest probabilities (PPs). Results Of 9989 febrile children, 4252 (42.6%) underwent assays for white blood cell and CRP. Of 233 (5.5%) children with EL, 133 (3.1%) were enrolled, of whom 43 (32.3%; 95% confidence interval [CI], 25.0%-40.7%) had SBI, including 33 pyelonephritis, 5 deep abscesses, 3 lobar pneumonia, and 2 soft tissue infections. With the cutoff of 7.8 mg/dL, the sensitivity of CRP in predicting SBI was 81.4% (95% CI, 67.4%-90.3%); the specificity, 80.0% (95% CI, 70.6%-87.0%); the positive predictive value, 66.0% (95% CI, 52.6%-77.3%); the negative predictive value, 90.0% (95% CI, 81.5%-94.9%); the positive LR, 4.1; and the PP, 66.0% (95% CI, 55.6%-75.0%). A CRP concentration of 16.1 mg/dL or higher yielded an LR of 11.2 and a PP of 84.2% (95% CI, 62.1%-94.5%). A CRP concentration of lower than 3.4 mg/dL yielded an LR of 0.05 and a PP of 2.4% (95% CI, 0.3%-14.6%). Conclusions High concentration of CRP is strongly associated with the presence of SBI in febrile children with EL.

In this study, we evaluated the immunostimulatory effect of silk peptide in subjects with peripheral blood leukocyte levels of 4–8 × 103/μl by a randomized, double-blind, placebo-controlled clinical trial. The subjects were randomly assigned to one of two groups, the placebo control or silk peptide intervention group, for 8 weeks. As a result, evaluation of efficacy in 97 subjects showed no significant difference between the groups in immunostimulatory parameters. However, after separate analysis of 61 non-season influenza vaccine subjects, the natural killer cell activity (%) with an effector cell: target cell (E: T) ratio of 10:1 was increased significantly from 30.7 ± 2.28% at week 0 to 41.8 ± 2.71% at week 8 (p

Context: Silk peptide from cocoons of silkworm (Bombyx mori L., Bombycidae) has been employed as a biomedical material and exhibits various bioactivities, including immune-modulating activity. Objective: We analyzed whether silk peptide exerts direct modulating effects on NK cells using an NK cell line in vitro and ex vivo splenocytes. We also attempted to delineate the mechanism underlying the modulation. Material and methods:In vitro activity of silk peptide on NK cells was determined by measurement of cytolytic activity against K562 cells at an effector-to-target ratio of 5:1 after incubation of NK-92MI cells with silk peptide (0–2000 μg/mL) for 48 and 72 h. Ex vivo activity of silk peptide on mouse splenic NK cells was determined similarly by using YAC-1 cells. Results: Treatment of NK-92MI NK cells with silk peptide (500–2000 μg/mL) significantly increased cytolytic activity on target cells by 2- to 4-fold. The same concentrations (500–2000 μg/mL) of silk peptide treatment also significantly enhanced the cytolytic activity of splenic NK cells against YAC-1 cells. Silk peptide treatment of IL-2-stimulated splenocytes induced enhanced expression of Th1, 2 and 17 cytokines including TNF-α, IFN-γ, IL-6, IL-4 and IL-17. Finally, ex vivo treatment with silk peptide on mouse splenocytes significantly enhanced the degree of NK cell maturation in a dose-dependent manner from 3.49 to 23.79%. Discussion and conclusions: These findings suggest that silk peptide stimulates NK cells, thereby influencing systemic immune functions and improving natural immunity. Thus, silk peptide could be useful as a complementary therapy in cancer patients.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related mortality in Western countries. Polymorphisms in one-carbon metabolism and angiogenesis-related genes have been shown to play important roles in tumor development, progression, and metastasis for many cancers, including CRC. Moreover, recent studies have reported that polymorphisms in specific microRNA (miRNA)-binding regions, which are located in the 3′-untranslated region (UTR) of miRNA-regulated genes, are present in a variety of cancers. Here, we investigated the association between two thymidylate synthase (TYMS or TS) 3′-UTR polymorphisms, 1100T&gt, C [rs699517] and 1170A&gt, G [rs2790], and CRC susceptibility and progression in Korean patients. A total of 450 CRC patients and 400 healthy controls were enrolled in this study, and genotyping at the TS locus was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) or TaqMan allelic discrimination assays. We found that TS 1170A&gt, G genotypes, as well as the TS 1100T-1170G and 1100C-1170A haplotypes, are strongly associated with CRC. The TS 1100TC+CC type was associated with a poor survival (OS and RFS) rate. In addition, levels of the TS 1100C and TS 1170G allele were found to be significantly increased in CRC tissue. Our study provides the first evidence for 3′-UTR variants in TS genes as potential biomarkers of CRC prognosis and prevention.

Recurrent implantation failure (RIF) refers to the occurrence of more than two failed in vitro fertilization–embryo transfers (IVF-ETs) in the same individual. RIF can occur for many reasons, including embryo characteristics, immunological factors, and coagulation factors. Genetics can also contribute to RIF, with some single-nucleotide variants (SNVs) reported to be associated with RIF occurrence. We examined SNVs in a long non-coding RNA, homeobox (HOX) transcript antisense RNA (HOTAIR), which is known to affect cancer development. HOTAIR regulates epigenetic outcomes through histone modifications and chromatin remodeling. We recruited 155 female RIF patients and 330 healthy controls, and genotyped HOTAIR SNVs, including rs4759314, rs920778, rs7958904, and rs1899663, in all participants. Differences in these SNVs were compared between the patient and control groups. We identified significant differences in the occurrence of heterozygous genotypes and the dominant expression model for the rs1899663 and rs7958904 SNVs between RIF patients and control subjects. These HOTAIR variants were associated with serum hemoglobin (Hgb), luteinizing hormone (LH), total cholesterol (T. chol), and blood urea nitrogen (BUN) levels, as assessed by analysis of variance (ANOVA). We analyzed the four HOTAIR SNVs and found significant differences in haplotype patterns between RIF patients and healthy controls. The results of this study showed that HOTAIR is not only associated with the development of cancer but also with pregnancy-associated diseases. This study represents the first report showing that HOTAIR is correlated with RIF.

Background Pediatric sedation in the emergency department (ED) is widely performed in Korea; thus exploring the trends of its use is necessary. This study aimed to investigate the characteristics of patients and sedatives use in the ED and verify their changes over recent years. Methods A nationwide population-based retrospective study was conducted including pediatric patients aged ≤ 15 years who received sedative medication in the ED and were discharged during 2007–2018, using the Korean Health Insurance Review and Assessment Service database. Patient characteristics (age, sex, level of ED, and diagnosis) and type of sedative used were analyzed. Results Sedation was performed in total 468,221 visits during 2007–2018 (399,320 visits, at least 3.8% of overall ED visits during 2009–2018). Among these, 71.0% were children aged 1–3 years and 93.5% were sedated to support diagnosis of injury. An increase in total sedation was observed in patients aged 4–6 years during the study period (from 13.8% to 21.8%). A gradual decrease in the use of chloral hydrate (CH) compared with an increase in ketamine use was observed (CH, from 70.6% to 28.6%; ketamine, from 23.8% to 60.7%). Therefore, ketamine was the most used sedative since 2014. The most frequently used sedatives over the study period differed according to age groups (CH in, Graphical Abstract

BackgroundFever in infants under 90 days of age is highly likely to be caused by a severe bacterial infection (SBI) and it accounts for a large number of patients visiting the pediatric emergency room. In order to predict the bacterial infection and reduce unnecessary treatment, the classic classification system is based on white blood cell (WBC) count, urinalysis, and x-ray, and it is modified and applied at each center by incorporating recently studied biomarkers such as c-reactive protein (CRP) or procalcitonin (PCT). This study analyzed the usefulness of PCT in predicting SBI when applied along with the existing classification system, including CRP, among infants less than 90 days old who visited with a fever at a single institution pediatric emergency center.MethodsWe retrospectively reviewed the medical records of patients younger than 3 months of age who presented with fever at the Seoul Asan Medical Center pediatric emergency room between July 2017 and October 2018.ResultsA total of 317 patients were analyzed, and 61 were diagnosed with SBI, among which urinary tract infection (UTI) accounted for the largest proportion (55/61, 90.2%). There were differences in WBC, neutrophil proportion, CRP, and PCT between the SBI group and the non-SBI group, and the AUC values of WBC, CRP, and PCT were 0.651, 0.804, and 0.746, respectively. When using the cut-off values of CRP and PCTs as 2.0 mg/dL and 0.3 ng/mL, respectively, the sensitivity and specificity for SBI were 49.2/89.5, and 54.1/87.5, respectively. WBC, CRP, and PCT were statistically significant for predicting SBI in multivariate analysis (odds ratios 1.066, 1.377, and 1.291, respectively). When the subjects were classified using the existing classification criteria, WBC and CRP, the positive predictive value (PPV) and negative predictive value (NPV) were 29.3% and 88.7%, respectively, and when PCT was added, the PPV and NPV were 30.7% and 92%, respectively, both increased.ConclusionPCT is useful for predicting SBI in children aged 3 months or less who visit the emergency room with a fever. It is useful as a single biomarker, and when used in conjunction with classic biomarkers, its diagnostic accuracy is further increased.

Background: Pediatric patients undergoing diagnostic tests in the pediatric emergency room are frequently sedated. Although efforts are made to prevent adverse events, no sedation protocol has specified the optimal regimen, dosage, and interval of medication to prevent adverse events. This study analyzed the safety and efficacy of sequential pediatric sedation protocols for pediatric patients undergoing diagnostic tests in the pediatric emergency room of a single tertiary medical center.Methods: The medical records of patients aged Results: Of the 289 included patients, 20 (6.9%) experienced adverse events, none serious, and nine (3.1%) failed to reach the depth of sedation required to complete the test. The regimen (P=0.622) and dosage (P=0.777) of the sedatives were unrelated to the occurrence of adverse events when sedation was performed according to protocol.Conclusion: The sedation protocol used in these patients, consisting of sequential administration of minimum dosages, achieved a sufficient depth of sedation with relatively few adverse events, indicating that this protocol can be used safely and effectively for painless sedation in pediatric patients undergoing diagnostic testing.

The most common type of cardiovascular disease is coronary artery disease (CAD), in which a plaque builds up inside the coronary arteries that can lead to a complete blockage of blood flow to the heart, resulting in a heart attack. The CAD may be affected by various factors including age, gender, and lipoprotein disposition as well as genetic factors and metabolic syndrome. In this study, we investigated whether three PAI-1 polymorphisms (-844 G&gt, A, -675 4G&gt, 5G, and +43 G&gt, A) and CAD-related clinical parameters are associated with CAD susceptibility. Genotyping of 463 CAD patients and 401 controls was performed using polymerase chain reaction restriction fragment length polymorphism analysis. We report that the 4G5G genotype (crude odds ratio(COR), 1.392, 95% confidence interval (CI), 1.036&ndash, 1.871, p = 0.028) and dominant model (4G4G vs. 4G5G + 5G5G, COR, 1.401, 95% CI, 1.060&ndash, 1.850, p = 0.018, adjust odds ratio, 1.371, 95% CI, 1.027&ndash, 1.831, p = 0.032) of PAI-1 -675 polymorphisms were associated with increased CAD risk. Haplotype and genotype combinations of PAI-1 -675 and +43 polymorphisms show an increased risk of CAD according to alterations of the -675 polymorphism allele or genotype. Moreover, the PAI-1 -675 polymorphisms show a synergistic effect with the metabolic syndrome component of CAD risk. This study suggests that polymorphisms in the PAI-1 genes along with the metabolic syndrome component of CAD can be useful biomarkers for CAD diagnosis and treatment.

The authors wish to make a correction to the published version of their paper [...]

Anti-aging research suggests that immunosenescent cells can play deleterious roles in the immune system. Here, young (2 months old) and old (14 months old) C57BL/6 mice received a daily oral dose (100 or 750 mg/kg/day) of acid-hydrolyzed silk peptide (SP) for a period of 5 weeks. Mouse spleen, lymph node, and serum were analyzed to determine the immune homeostasis of SP by flow cytometry, Western blotting, ELISA, and qRT-PCR. The results suggest that SP ameliorates age-related dysfunction of T and B cells. Amelioration of B cell dysfunction improved the immunoglobulin response in aged mice. Taken together, the results suggest that SP restores immune homeostasis with respect to immunosenescent cells.

Background Intussusception decreases blood flow to the bowel, and tissue hypoperfusion results in increased lactic acid levels. We aimed to determine whether lactic acid levels are associated with pediatric intussusception outcomes. Methods The electronic medical records of our emergency department pediatric patients diagnosed with intussusception, between January 2015 and October 2018, were reviewed. An outcome was considered poor when intussusception recurred within 48 h of reduction or when surgical reduction was required due to air enema failure. Results A total of 249 patients were included in the study, including 39 who experienced intussusception recurrence and 11 who required surgical reductions; hence, 50 patients were included in the poor outcome group. The poor and good outcome groups showed significant differences in their respective blood gas analyses for pH (7.39 vs. 7.41, P = .001), lactic acid (1.70 vs. 1.30 mmol/L, P P = .036). Multivariable logistic regression analyses showed that pH and lactic acid levels were the two factors significantly associated with poor outcomes. When the lactic acid level cutoff values were ≥ 1.5, ≥2.0, ≥2.5, and ≥ 3.0 mmol/L, the positive predictive values for poor outcomes were 30.0, 34.6, 50.0, and 88.9%, respectively. Conclusion Lactic acid levels affect outcomes in pediatric patients with intussusception; higher lactic acid levels are associated with higher positive predictive values for poor outcomes.

The aim of this study was to identify novel genetic markers related to coronary artery disease (CAD) using a whole-exome sequencing (WES) approach and determine any associations between the selected gene polymorphisms and CAD prevalence. CUBN, HNF1A and LIPC gene polymorphisms related to CAD susceptibility were identified using WES screening. Possible associations between the five gene polymorphisms and CAD susceptibility were examined in 452 CAD patients and 421 control subjects. Multivariate logistic regression analyses indicated that the CUBN rs2291521GA and HNF1A rs55783344CT genotypes were associated with CAD (GG vs. GA; adjusted odds ratio [AOR] = 1.530; 95% confidence interval [CI] 1.113–2.103; P = 0.002 and CC vs. CT; AOR = 1.512; 95% CI 1.119–2.045; P = 0.007, respectively). The CUBN rs2291521GA and HNF1A rs55783344CT genotype combinations exhibited a stronger association with CAD risk (AOR = 2.622; 95% CI 1.518–4.526; P = 0.001). Gene-environment combinatorial analyses indicated that the CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotype combination and several clinical factors (fasting blood sugar (FBS), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels) were associated with increased CAD risk. The CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotypes in conjunction with abnormally elevated cholesterol levels increase the risk of developing CAD. This exploratory study suggests that polymorphisms in the CUBN, HNF1A, and LIPC genes can be useful biomarkers for CAD diagnosis and treatment.

Acid-hydrolyzed silk peptide (SP) is a valuable material that has been used traditionally to treat various diseases, however, the mechanism by which it affects inflammatory responses is unknown. To examine the effects of SP on inflammatory responses, we used macrophages as a vehicle for examining signaling via toll-like receptor 4 (TLR4), which plays an important role in innate immune responses to pathogenic infections and pathogen-derived molecules such as lipopolysaccharide (LPS). We then confirmed the anti-inflammatory effects of SP by examining lymph node, spleen, and serum samples from C57BL/6 mice injected with LPS. We also used LPS-induced bone marrow-derived macrophages and RAW264.7 cells (a murine macrophage cell line) to identify the mechanism by which SP modulates immune responses via the TLR4 signaling pathway. In addition, we showed that SP prevents LPS-induced production of nitric oxide and reactive oxygen species. In summary, SP inhibits LPS-induced inflammatory responses by modulating the TLR4 signaling pathway.

Recurrent pregnancy loss (RPL), which is defined as two pregnancy losses that occur before 20 weeks of gestation, is relatively common, occurring in approximately 1−5% of women. The underlying cause is often unclear, although numerous factors may contribute to RPL, including environmental and immunological factors, blood coagulation disorders, and genetics. In particular, single nucleotide variants have been associated with RPL, including those found in microRNAs (miRNAs). We investigated the association between four miRNA polymorphisms, miR-25T>C, miR-32C>A, miR-125aC>T, and miR-222G>T, and RPL in a cohort consisting of 361 RPL patients and 272 controls. Subjects were genotyped at miRNA loci by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, and genotype frequencies were calculated. We then performed allele and genotype combination analyses and measured the association between miRNA polymorphisms and clinical variables in both RPL patients and controls. We detected a statistically significant association between RPL and the miR-25T/miR-32C/miR-125aT/miR-222T allele combination (adjusted odds ratio (AOR), 4.361; 95% confidence interval (CI), 1.496−12.72; P=0.003). Three-gene combinations, including miR-32C/miR-125aT/miR-222T (AOR, 3.085; 95% CI, 1.254−7.588; P=0.010) and miR-25T/miR-125aT/miR-222T (AOR, 2.929; 95% CI, 1.183−7.257; P=0.015), and the two-gene combination miR-125aT/miR-222T (AOR, 2.417; 95% CI, 1.084−5.386; P=0.026) were also associated with RPL. Analysis of variance (ANOVA) revealed that platelet counts and blood urea nitrogen levels were significantly different in RPL patients expressing different miR-125aC>T and miR-25T>C genotypes, respectively (PC and miR-32C>A. We investigated miRNAs (miR-25, miR-32, miR-125a, miR-222) in RPL patients and healthy controls. Significantly different allele frequencies were detected by ANOVA. We suggest that miRNAs and clinical factors can impact RPL occurrence.

In colorectal carcinogenesis, the unique molecular and genetic changes that occur within cells result in specific CRC phenotypes. The involvement of the long non-coding RNA, HOTAIR, in cancer development, progression, and metastasis is well-established. Various studies have reported on the contribution of HOTAIR to cancer pathogenesis. Therefore, we selected four HOTAIR polymorphisms (rs7958904G>C, rs1899663G>T, rs4759314A>G, and rs920778T>C) to evaluate the association of each variant with CRC prevalence and prognosis. We conducted a case–control study of 850 individuals to identify the genotype frequencies of each polymorphism. The study population included 450 CRC patients and 400 control individuals that were randomly selected following a health screening. Notably, rs7958904 and rs1899663, their hetero genotype, and the dominant model were significantly different when compared to the healthy control group (rs7958904; AOR = 1.392, 95% CI = 1.052–1.843, P = 0.021). To evaluate the effect of HOTAIR polymorphisms on the survival rate, we analyzed patient mortality and relapse occurrence within 3 and 5 years with Cox-regression analysis. The rs7958904 CC polymorphism mortality rate was significantly higher than the GG polymorphism mortality rate (adjusted HR = 2.995, 95% CI = 1.189–7.542, P = 0.021). In addition, the rs920778 CC genotype was significantly different than the TT genotype (adjusted HR = 3.639, 95% CI = 1.435–9.230, P = 0.007). In addition, this study confirmed that genetic variants of HOTAIR alter the mRNA expression level (P < 0.01). We suggest that HOTAIR rs7958904G>C which is associated with CRC prevalence and mortality is a potential biomarker for CRC. The association between HOTAIR gene polymorphisms and CRC prevalence were reported for the first time.

Background: To investigate the clinical features of coinfection due to Mycoplasma pneumoniae ( M. pneumoniae ), a common copathogen in influenza, in influenza pneumonia patients. Methods: We reviewed 4,465 patients with influenza who visited a tertiary care hospital emergency department in Seoul (Korea) from 2010 through 2016, and underwent immunoglobulin M (IgM) serology or polymerase chain reaction (PCR) for M. pneumoniae . Influenza pneumonia was defined as laboratory-confirmed influenza plus radiographic pneumonia. Patients with healthcare-associated pneumonia or non-mycoplasma bacterial coinfection were excluded. Clinical, laboratory, and radiographic findings and outcomes of the influenza pneumonia patients with and without M. pneumoniae coinfection were compared. Multivariable logistic regression analysis was performed to identify factors associated with the coinfection. Results: Of 244 influenza pneumonia patients, 41 (16.8%) had M. pneumoniae coinfection. These patients were younger with a higher frequency of age of 5–10 years, and had higher white blood cell (WBC) and lymphocyte counts; lower concentration of C-reactive protein (CRP). The coinfection had no association with specific radiographic findings and poor outcome. Multivariable analysis showed the age of 5–10 years (adjusted odds ratio, 18.83; 95% confidence interval, 5.899–60.08; P

To evaluate the diagnostic performance of reduced-dose CT for suspected appendicitis. A systematic search of the MEDLINE and EMBASE databases was carried out through to 10 January 2017. Studies evaluating the diagnostic performance of reduced-dose CT for suspected appendicitis in paediatric and adult patients were selected. Pooled summary estimates of sensitivity and specificity were calculated using hierarchical logistic regression modelling. Meta-regression was performed. Fourteen original articles with a total of 3,262 patients were included. For all studies using reduced-dose CT, the summary sensitivity was 96 % (95 % CI 93–98) with a summary specificity of 94 % (95 % CI 92–95). For the 11 studies providing a head-to-head comparison between reduced-dose CT and standard-dose CT, reduced-dose CT demonstrated a comparable summary sensitivity of 96 % (95 % CI 91–98) and specificity of 94 % (95 % CI 93–96) without any significant differences (p=.41). In meta-regression, there were no significant factors affecting the heterogeneity. The median effective radiation dose of the reduced-dose CT was 1.8 mSv (1.46–4.16 mSv), which was a 78 % reduction in effective radiation dose compared to the standard-dose CT. Reduced-dose CT shows excellent diagnostic performance for suspected appendicitis. • Reduced-dose CT shows excellent diagnostic performance for evaluating suspected appendicitis. • Reduced-dose CT has a comparable diagnostic performance to standard-dose CT. • Median effective radiation dose of reduced-dose CT was 1.8 mSv (1.46–4.16). • Reduced-dose CT achieved a 78 % dose reduction compared to standard-dose CT.

Coronavirus disease 2019 (COVID-19) changed the epidemiology of various diseases. The present study retrospectively investigates the epidemiologic and clinical changes in pediatric intussusception for ages ≤ 7 years before (February 2019–January 2020) and after (February 2020–January 2021) the COVID-19 outbreak in a single pediatric emergency department of a university-affiliated tertiary hospital. The incidence of communicable diseases—defined as infectious diseases with the potential for human-to-human transmission via all methods, non-communicable diseases, and intussusception were decreased following the COVID-19 outbreak (15,932 to 3880 (24.4%), 12,994 to 8050 (62.0%), and 87 to 27 (31.0%), respectively). The incidence of intussusception correlated significantly with the change in incidence of communicable diseases (Poisson log-linear regression, odds ratio = 2.15, 95% CI = 1.08–4.26, and p = 0.029). Compared with the pre-pandemic period, patients of the pandemic period showed higher proportions of pathologic leading point (PLP) and hospitalization (14.8% vs. 2.3% and 18.5% vs. 4.6%, respectively), lower base excesses (−4.8 mmol/L vs. −3.6 mmol/L), and higher lactate concentrations (1.7 mmol/L vs. 1.5 mmol/L). The incidence of pediatric intussusception decreased after the COVID-19 pandemic. This reduced incidence may be related to the reduced incidence of communicable diseases. However, the proportions of more severe diseases and PLPs were higher after the COVID-19 pandemic.

Careful modulation of surficial and interfacial properties of electrode materials is a critical factor for determining overall electrochemical characteristics. Recent studies have indicated that metal oxide nanocoating layer (such as titanium (IV) oxide (TiO2)) on metal oxide anodes (such as tin (IV) oxide (SnO2)) exhibited superior electrochemical properties, but fundamental research on the effect and role of TiO2 layer thickness has been limited. Here we have successfully conducted in-depth study on how the thickness of TiO2 overlayer on SnO2 can have significant influence in the overall parameters of electrochemistry. It is revealed that TiO2 overlayer with 12 nm shows good cycle retention (75.8%) even after 80 cycles and retains capacity of 438.3 mAh g−1 even at high current density (5000 mA g−1). Surprisingly, it was further discovered that TiO2 layer not only alleviates the volume expansion but also helps to facilitate Li ion transport compared with SnO2. The improvements in both ionic and electrical conductivity of TiO2 layer are main factors in better cycle retention and rate capabilities. Finally, in situ transmission electron microscopy analysis was adopted to observe the growth dynamics of solid electrolyte interphase layer on TiO2@SnO2, which demonstrates that TiO2 overlayer results in homogeneous and thinner interphase layer compared with SnO2 NTs.

Sb 2 Se 3 is an emerging material among alternative light absorbers for photovoltaic applications. Unlike typical chalcogenides, Sb 2 Se 3 is particularly appealing due to its single stable crystal phase, layered structure with loose binding of no dangling bonds. Nevertheless, a cost-effective electrochemical approach for the synthesis of Sb 2 Se 3 compounds has not been identified, and the Sb 2 Se 3 film with the most favorable [001] preferred orientation has only just been developed. In this study, Sb-rich precursors were prepared electrochemically at −950 mV (vs. Ag/AgCl), and homogeneous Sb 2 Se 3 thin films were produced using a pre-thermal treatment process prior to the typical selenization process with additional Se coating. This novel procedure notably suppresses potential Sb dissolution into liquid Se due to the formation of polycrystalline Sb-related crystals. As a result, the Sb-rich precursor was successfully transformed into Sb 2 Se 3 thin films with an enhanced perpendicular orientation of the [001] direction. Unfortunately, a high density of voids was produced in the precursor film with two distinguishable layers, and their size increased after selenization. The voids were formed through evolution of H 2 Se gas after the initial electrochemical reaction. The resulting photovoltaic cells demonstrated an energy conversion efficiency of 1.8% in a substrate structure consisting of Mo/Sb 2 Se 3 /CdS/ZnO/ITO.

The conversion reaction is important in lithium-ion batteries because it governs the overall battery performance, such as initial Coulombic efficiency, capacity retention, and rate capability. Here, we have demonstrated in situ observation of the complete conversion reaction and agglomeration of nanoparticles (NPs) upon lithiation by using graphene liquid cell transmission electron microscopy. The observation reveals that the Sn NPs are nucleated from the surface of SnO2, followed by merging with each other. We demonstrate that the agglomeration has a stepwise process, including rotation of a NP, formation of necks, and subsequent merging of individual NPs.