Current Status of Flow Cytometric Immunophenotyping of Hematolymphoid Neoplasms in Korea

Background@#Flow cytometric immunophenotyping of hematolymphoid neoplasms (FCIHLN) is essential for diagnosis, classification, and minimal residual disease (MRD) monitoring. FCI-HLN is typically performed using in-house protocols, raising the need for standardization. Therefore, we surveyed the current status of FCI-HLN in Korea to obtain fundamental data for quality improvement and standardization. @*Methods@#Eight university hospitals actively conducting FCI-HLN participated in our survey.We analyzed responses to a questionnaire that included inquiries regarding test items, reagent antibodies (RAs), fluorophores, sample amounts (SAs), reagent antibody amounts (RAAs), acquisition cell number (ACN), isotype control (IC) usage, positiveegative criteria, and reporting. @*Results@#Most hospitals used acute HLN, chronic HLN, plasma cell neoplasm (PCN), and MRD panels. The numbers of RAs were heterogeneous, with a maximum of 32, 26, 12, 14, and 10 antibodies used for acute HLN, chronic HLN, PCN, ALL-MRD, and multiple myeloma-MRD, respectively. The number of fluorophores ranged from 4 to 10. RAs, SAs, RAAs, and ACN were diverse. Most hospitals used a positive criterion of 20%, whereas one used 10% for acute and chronic HLN panels. Five hospitals used ICs for the negative criterion. Positiveegative assignments, percentages, and general opinions were commonly reported. In MRD reporting, the limit of detection and lower limit of quantification were included. @*Conclusions@#This is the first comprehensive study on the current status of FCI-HLN in Korea, confirming the high heterogeneity and complexity of FCI-HLN practices. Standardization of FCI-HLN is urgently needed. The findings provide a reference for establishing standard FCI-HLN guidelines.

Robotic surgeries in pediatric patients: an early experience in a single center

Purpose@#Robotic surgery (RS) has the advantages of 3-dimensional view, optical magnification, motional scaling, and improved ergonomics and degree of freedom. Although RS has widely been performed on pediatric patients lately, there are still numerous restrictions and ambiguous indications. The purpose of this study was to report our early experience with RS on pediatric patients at a single center. @*Methods@#Electronic medical records of patients who underwent RS with the da Vinci Xi surgical platform (Intuitive Surgical, Inc.) in Seoul National University Children Hospital from November 2019 to August 2021 were reviewed retrospectively. The median follow-up was 21.0 months (range, 12.3–31.8 months). An online survey was conducted to investigate satisfaction with robotic surgical scars. @*Results@#Fifty-four patients underwent robotic surgeries (median age at operation, 11.1 years [range, 0.1–17.8 years]). In our hospital, patients had 20 different kinds of robotic surgeries, including choledochal cyst excision with hepaticojejunostomy, ovarian mass excision, and others. Median operation time and console time were 157.5 minutes (range, 45–505 minutes) and 40 minutes (range, 11–360 minutes), respectively. All cases were done without conversion into open or laparoscopic methods. Postoperative complications were found in 5 patients. According to an online survey, over half of patients (60.9%) answered that they felt satisfied with scars. @*Conclusion@#Our early experience demonstrated the safety and feasibility of RS in children with a range of diagnoses and complicated procedures. With more experience, RS could be an alternative to traditional open or laparoscopic operations in pediatric patients. Further studies are needed to clarify indications of pediatric RS.

A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-κB pathway

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Suppressive role of vascular endothelial growth factor on intestinal apoptosis in induced necrotizing enterocolitis in rats

Purpose@#Necrotizing enterocolitis (NEC) is a devastating disease that can cause mortality in preterm babies. NEC may develop through an apoptotic pathway that is known to be inhibited by vascular endothelial growth factor (VEGF). This study determined whether VEGF exerted a protective effect against the development of NEC and apoptosis in rats. @*Methods@#To determine the effect of VEGF in NEC rats, neonatal rats were randomized into 4 groups: the control group, the NEC group, the NEC + intraperitoneal VEGF (50 ng/kg) group (NEC + VEGF IP group), and the NEC + oral VEGF (50 ng/ kg) group (NEC + VEGF OR group). NEC was induced by lipopolysaccharide/hypoxia and cold stress. The animals were sacrificed 72 hours later. After laparotomy, we obtained a region of the proximal small bowel from the ileocecal valve about 18 cm in length. @*Results@#The NEC histological grade, apoptosis histological score, and caspase-3 activity were lower in the NEC + VEGF IP and OR groups than in the NEC group. In the NEC + VEGF IP and OR groups, the messenger RNA expression of apoptotic and inflammatory genes, such as Bax, NF-κB, p53, Fas, FasL, and PAF-R, but not that of Bcl-2, was decreased, as was the Bax/Bcl-2 protein ratio. Histological analysis revealed that the apoptosis-blocking effect of VEGF was more effective in the NEC + VEGF IP group than in the NEC + VEGF OR group. @*Conclusion@#We identified apoptotic and inflammatory genes to confirm the preventive effect of VEGF pretreatment on NEC in rats. This study presents a novel approach to prevent apoptosis via VEGF pretreatment in rats with lipopolysaccharide/ hypoxia-induced NEC.

Efficacy and Tolerability of 14-Day Tegoprazan- versus Rabeprazole-Based Triple Therapy for Eradication of Helicobacter pylori: A Real-World Evidence Study

Background/Aims@#Tegoprazan, a new, fast, and strong potassium-competitive acid blocker, has been approved for the treatment of gastric acid-related diseases in Korea. However, realworld clinical data regarding this drug are scarce. We aimed to compare the Helicobacter pylori eradication rates of tegoprazan- and rabeprazole-based triple therapy. @*Methods@#We retrospectively reviewed data from patients who received first-line treatment for H. pylori infection using tegoprazan- or rabeprazole-based triple therapy for 2 weeks (50 mg tegoprazan or 20 mg rabeprazole+1,000 mg amoxicillin+500 mg clarithromycin twice daily). The primary endpoint was the eradication rate as determined by intention-to-treat analysis. @*Results@#Of the 677 patients included in our study, 344 and 333 received tegoprazan-based and rabeprazole-based triple therapy, respectively. The eradication rate from intention-to-treat analysis was 76.7% (95% confidence interval [CI], 72.1% to 81.0%) for tegoprazan-based triple therapy and 75.4% (95% CI, 70.5% to 79.8%) for rabeprazole-based triple therapy. There was no significant difference in the eradication rates between the two groups (p>0.999). Per-protocol analysis also revealed no significant difference between the eradication rates of the two groups (tegoprazan 83.4% [95% CI, 79.0% to 87.2%] vs rabeprazole 83.5% [79.0% to 87.4%], p>0.999).Furthermore, there was no significant difference in adverse event rates between the two groups (tegoprazan, 27.6%; rabeprazole, 25.8%; p=0.604). @*Conclusions@#The eradication rate of tegoprazan-based triple therapy was similar to that of rabeprazole-based triple therapy. Further studies on the dose-escalation effect of tegoprazan for H. pylori eradication and the efficacy of tegoprazan in regimens other than conventional triple therapy are needed.

Clinical course in children with equivocal appendicitis on computed tomography: a retrospective cohort study

Purpose@#Appendectomy is one of the most common surgeries in children. Although various radiological examinations are performed, they do not always reveal a definitive diagnosis of appendicitis. This study aimed to investigate the clinical course of equivocal appendicitis, identify the factors associated with appendectomy, and suggest appropriate management for these patients. @*Methods@#Patients younger than 19 years who visited Seoul National University Bundang Hospital with a differential diagnosis of appendicitis from January 2013 to December 2017 were included. All participants conducted ‘appendiceal CT’ with a scoring scale of 1–5. The higher the score, the higher the likelihood of a radiologic diagnosis of appendicitis. We defined the appendicitis CT score of 2–4 as equivocal appendicitis (n = 143). Medical records were reviewed retrospectively for demographics, further examination as abdominal ultrasonography, and appendectomy status (yes or no). The mean follow-up period was 15.6 ± 71 days. @*Results@#Equivocal appendicitis accounted for 16.7%. Additional ultrasonography test was performed in 24.5% (35 of 143). In total, 34 patients (23.8%) underwent appendectomy. Among the patients with appendiceal CT scores 2, 3, and 4, 4.9%, 50.0%, and 87.5% underwent appendectomy, respectively. Higher WBC count, higher appendicitis CT score, and readmission were significantly associated with appendectomy in patients with equivocal appendicitis. @*Conclusion@#Higher appendicitis CT score and WBC level were positively associated with appendectomy. Careful observation can be a treatment option in appendicitis CT score 2 or 3 groups. Appendectomy is the first-line treatment for patients with appendicitis score 4. Additional ultrasonography test is advisable to determine treatment modality for equivocal appendicitis.

Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL). @*Materials and Methods@#After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes. @*Results@#Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE. @*Conclusion@#Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.

Effects of Nurse Staffing Level on In-hospital Mortality and 30-day Mortality after Admission using Korean National Health Insurance Data / 임상간호연구

Purpose@#The purpose of this study is to investigate the association between the nurse staffing level and the patient mortality using Korean National Health Insurance data. @*Methods@#The data of 1,068,059 patients from 913 hospitals between 2015 and 2016 were analyzed. The nurse staffing level was categorized based on the bed-to-nurse ratio in general wards, intensive care units (ICUs), and hospitals overall. The x 2 test and generalized estimating equations (GEE) multilevel multivariate logistic regression analyses were used to explore in-hospital mortality and 30-day mortality after admission. @*Results@#The in-hospital mortality rate was 2.9% and 30-day mortality after admission rate was 3.0%. Odd Ratios (ORs) for in-hospital mortality were statistically lower in general wards with a bed-to-nurse ratio of less than 3.5 compared to that with 6.0 or more (OR=0.72, 95% CI=0.63~0.84) and in ICUs with a bed-to-nurse ratio of less than 0.88 compared to that with 1.25 or more (OR=0.78, 95% CI=0.66~0.92). ORs for 30-day mortality after admission were statistically lower in general wards with a bed-to-nurse ratio of less than 3.5 compared to that with 6.0 or more (OR=0.83, 95% CI=0.73~0.94) and in ICUs with a bed-to-nurse ratio of less than 0.63 compared to that with 1.25 or more (OR=0.85, 95% CI=0.72~1.00). @*Conclusion@#To reduce the patient mortality, it is necessary to ensure a sufficient number of nurses by improving the nursing fee system according to the nurse staffing level.

ACTG2 Variants in Pediatric Chronic Intestinal Pseudo-obstruction With Megacystis

Background/Aims@#Chronic intestinal pseudo-obstruction (CIPO) is a clinically heterogeneous syndrome characterized by compromised peristalsis and intestinal obstruction. Variants of actin gamma 2 (ACTG2), a protein crucial for correct enteric muscle contraction, have been found in CIPO patients. The aim of this study is to examine the clinical features and ACTG2 variants in Korean patients with CIPO. @*Methods@#From January 1995 to August 2020, 12 patients diagnosed with CIPO were included and genetic analysis testing of ACTG2 was performed. @*Results@#Heterozygous ACTG2 missense variants were found in 6 patients (50.0%). The p.Arg257Cys variant was found in 3 patients, and p.Arg63Gln and p.Arg178His variants were found in 1 patient each. A novel variant, p.Ile193Phe, was found in 1 patient. Three patients were diagnosed at birth, 2 at the age of 1 year, and 1 at 3 years of age. Abnormal prenatal genitourinary ultrasonographic findings were found in all 6 patients; microcolon was found in 4 patients (66.7%), and megacystis in all 6 patients. The pathology showed abnormal ganglion cells as well as myopathic findings. All patients are dependent on total parenteral nutrition and are to date alive. @*Conclusions@#ACTG2 variants are commonly found in Korean patients with CIPO. In CIPO patients with megacystis and abnormal prenatal ultrasonography, genetic testing of ACTG2 should be considered. Molecular diagnosis of CIPO is more important than pathologic diagnosis.

The protective effects of Aster yomena (Kitam.) Honda on high-fat diet-induced obese C57BL/6J mice

BACKGROUND/OBJECTIVES@#Aster yomena (Kitam.) Honda (AY) has remarkable bioactivities, such as antioxidant, anti-inflammation, and anti-cancer activities. On the other hand, the effects of AY against obesity-induced insulin resistance have not been reported. Therefore, this study examined the potential of AY against obesity-associated insulin resistance in highfat diet (HFD)-fed mice.MATERIALS/METHODS: An obesity model was established by feeding C57BL/6J mice a 60% HFD for 16 weeks. The C57BL6/When ethyl acetate fraction from AY (EFAY) at doses of 100 and 200 mg/kg/day was administered orally to mice fed a HFD for the last 4 weeks. Normal and control groups were administered water orally. The body weight and fasting blood glucose were measured every week. Dietary intake was measured every other day. After dissection, blood and tissues were collected from the mice. @*RESULTS@#The administration of EFAY reduced body and organ weights significantly compared to HFD-fed control mice. The EFAY-administered groups also improved the serum lipid profile by decreasing the triglyceride, total cholesterol, and low-density lipoprotein compared to the control group. In addition, EFAY ameliorated the insulin resistance-related metabolic dysfunctions, including the fasting blood glucose and serum insulin level, compared to the HFD-fed control mice. The EFAY inhibited lipid synthesis and insulin resistance by down-regulation of hepatic fatty acid synthase and up-regulation of the AMPactivated protein kinase pathway. EFAY also reduced lipid peroxidation in the liver, indicating that EFAY protected hepatic injury induced by obesity. @*CONCLUSIONS@#These results suggest that EFAY improved obesity-associated insulin resistance by regulating the lipid and glucose metabolism, suggesting that AY could be used as a functional food to prevent obesity and insulin resistance.

Genetics and genomics of bone marrow failure syndrome

Inherited bone marrow failure syndrome (IBMFS) is a group of clinically heterogeneous disorders characterized by significant hematological cytopenias of one or more hematopoietic cell lineages and is associated with an increased risk of cancer. The genetic etiology of IBMFS includes germline mutations impacting several key biological processes, such as DNA repair, telomere biology, and ribosome biogenesis, which may cause four major syndromes: Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Although the clinical features of some patients may be typical of a particular IBMFS, overlapping and atypical clinical manifestations and variable penetrance pose diagnostic challenges. Here, we review the clinical and genetic features of the major forms of IBMFS and discuss their molecular genetic diagnosis. Next-generation sequencing-based gene panel testing or whole exome sequencing will help elucidate the genetic causes and underlying mechanisms of this genetically heterogeneous group of diseases.

Protective effects of Populus tomentiglandulosa against cognitive impairment by regulating oxidative stress in an amyloid beta25–35 -induced Alzheimer's disease mouse model

BACKGROUND/OBJECTIVES@#Alzheimer's disease (AD) is one of the most representative neurodegenerative disease mainly caused by the excessive production of amyloid beta (Aβ).Several studies on the antioxidant activity and protective effects of Populus tomentiglandulosa (PT) against cerebral ischemia-induced neuronal damage have been reported. Based on this background, the present study investigated the protective effects of PT against cognitive impairment in AD.MATERIALS/METHODS: We orally administered PT (50 and 100 mg/kg/day) for 14 days in an Aβ 25–35-induced mouse model and conducted behavioral experiments to test cognitive ability. In addition, we evaluated the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and measured the production of lipid peroxide, nitric oxide (NO), and reactive oxygen species (ROS) in tissues. @*RESULTS@#PT treatment improved the space perceptive ability in the T-maze test, object cognitive ability in the novel object recognition test, and spatial learning/long-term memory in the Morris water-maze test. Moreover, the levels of AST and ALT were not significantly different among the groups, indicating that PT did not show liver toxicity. Furthermore, administration of PT significantly inhibited the production of lipid peroxide, NO, and ROS in the brain, liver, and kidney, suggesting that PT protected against oxidative stress. @*CONCLUSIONS@#Our study demonstrated that administration of PT improved Aβ25–35 -induced cognitive impairment by regulating oxidative stress. Therefore, we propose that PT could be used as a natural agent for AD improvement.

Inhibition of biofilm formation of periodontal pathogens by D-Arabinose

Periodontitis and periimplantitis are caused as a result of dental biofilm formation. This biofilm is composed of multiple species of pathogens. Therefore, controlling biofilm formation is critical for disease prevention. To inhibit biofilm formation, sugars can be used to interrupt lectin-involving interactions between bacteria or between bacteria and a host. In this study, we evaluated the effect of D-Arabinose on biofilm formation of putative periodontal pathogens as well as the quorum sensing activity and whole protein profiles of the pathogens. Crystal violet staining, confocal laser scanning microscopy, and scanning electron microscopy revealed that D-Arabinose inhibited biofilm formation of Porphyromonas gingivalis, Fusobacterium nucleatum, and Tannerella forsythia. D-Arabinose also significantly inhibited the activity of autoinducer 2 of F. nucleatum and the expression of representative bacterial virulence genes.Furthermore, D-Arabinose treatment altered the expression of some bacterial proteins. These results demonstrate that D-Arabinose can be used as an antibiofilm agent for the prevention of periodontal infections.

Neuroprotective Effects of GV1001 in Animal Stroke Model and Neural Cells Subject to Oxygen-Glucose Deprivation/Reperfusion Injury / 대한뇌졸중학회지

Background@#and Purpose Previous studies have revealed the diverse neuroprotective effects of GV1001. In this study, we investigated the effects of GV1001 on focal cerebral ischemia-reperfusion injury (IRI) in rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neural stem cells (NSCs) and cortical neurons. @*Methods@#Focal cerebral IRI was induced by transient middle cerebral artery occlusion (MCAO). Brain diffusion-weighted imaging (DWI) was performed 2 hours after occlusion, and a total of 37 rats were treated by reperfusion with GV1001 or saline 2 hours after occlusion. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging, immunohistochemistry, and neurobehavioral function analyses were performed. Additionally, OGD/R-injured NSCs and cortical neurons were treated with different GV1001 concentrations. Cell viability, proliferation, migration, and oxidative stress were determined by diverse molecular analyses. @*Results@#In the stroke model, GV1001 protected neural cells against IRI. The most effective dose of GV1001 was 60 μM/kg. The infarct volume on FLAIR 48 hours after MCAO compared to lesion volume on DWI showed a significantly smaller ratio in the GV1001-treated group. GV1001-treated rats exhibited better behavioral functions than the saline-treated rats. Treatment with GV1001 increased the viability, proliferation, and migration of the OGD/R-injured NSCs. Free radicals were significantly restored by treatment with GV1001. These neuroprotective effects of GV1001 have also been demonstrated in OGD/R-injured cortical neurons. Conclusions The results suggest that GV1001 has neuroprotective effects against IRI in NSCs, cortical neurons, and the rat brain. These effects are mediated through the induction of cellular proliferation, mitochondrial stabilization, and anti-apoptotic, anti-aging, and antioxidant effects.

Effects of the fermented Zizyphus jujuba in the amyloid β25-35 -induced Alzheimer's disease mouse model

RESULTS@#In behavioral tests, deterioration was revealed in the short- and long-term learning and memory functions in the Aβ25-35 -injected control group compared to the normal group, indicating that Aβ25-35 injection impairs cognitive functions. However, administration of Zj and Zj-Y improved cognitive function in mice, as compared to the Aβ25-35 -injected control mice. In addition, the Aβ25-35 induced elevations of MDA and NO in the brain, kidney, and liver were suppressed after exposure to Zj and Zj-Y. Especially, Zj-Y showed stronger scavenging effect against MDA and NO, as compared to Zj. @*CONCLUSIONS@#Results of the present study indicate that Zj-Y exerts a protective effect on cognitive impairment and memory dysfunction, which is exerted by attenuating the oxidative stress induced by Aβ25-35 .

Inhibition of biofilm formation of periodontal pathogens by D-Arabinose

Periodontitis and periimplantitis are caused as a result of dental biofilm formation. This biofilm is composed of multiple species of pathogens. Therefore, controlling biofilm formation is critical for disease prevention. To inhibit biofilm formation, sugars can be used to interrupt lectin-involving interactions between bacteria or between bacteria and a host. In this study, we evaluated the effect of D-Arabinose on biofilm formation of putative periodontal pathogens as well as the quorum sensing activity and whole protein profiles of the pathogens. Crystal violet staining, confocal laser scanning microscopy, and scanning electron microscopy revealed that D-Arabinose inhibited biofilm formation of Porphyromonas gingivalis, Fusobacterium nucleatum, and Tannerella forsythia. D-Arabinose also significantly inhibited the activity of autoinducer 2 of F. nucleatum and the expression of representative bacterial virulence genes.Furthermore, D-Arabinose treatment altered the expression of some bacterial proteins. These results demonstrate that D-Arabinose can be used as an antibiofilm agent for the prevention of periodontal infections.

Neuroprotective Effects of GV1001 in Animal Stroke Model and Neural Cells Subject to Oxygen-Glucose Deprivation/Reperfusion Injury / 대한뇌졸중학회지

Background@#and Purpose Previous studies have revealed the diverse neuroprotective effects of GV1001. In this study, we investigated the effects of GV1001 on focal cerebral ischemia-reperfusion injury (IRI) in rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neural stem cells (NSCs) and cortical neurons. @*Methods@#Focal cerebral IRI was induced by transient middle cerebral artery occlusion (MCAO). Brain diffusion-weighted imaging (DWI) was performed 2 hours after occlusion, and a total of 37 rats were treated by reperfusion with GV1001 or saline 2 hours after occlusion. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging, immunohistochemistry, and neurobehavioral function analyses were performed. Additionally, OGD/R-injured NSCs and cortical neurons were treated with different GV1001 concentrations. Cell viability, proliferation, migration, and oxidative stress were determined by diverse molecular analyses. @*Results@#In the stroke model, GV1001 protected neural cells against IRI. The most effective dose of GV1001 was 60 μM/kg. The infarct volume on FLAIR 48 hours after MCAO compared to lesion volume on DWI showed a significantly smaller ratio in the GV1001-treated group. GV1001-treated rats exhibited better behavioral functions than the saline-treated rats. Treatment with GV1001 increased the viability, proliferation, and migration of the OGD/R-injured NSCs. Free radicals were significantly restored by treatment with GV1001. These neuroprotective effects of GV1001 have also been demonstrated in OGD/R-injured cortical neurons. Conclusions The results suggest that GV1001 has neuroprotective effects against IRI in NSCs, cortical neurons, and the rat brain. These effects are mediated through the induction of cellular proliferation, mitochondrial stabilization, and anti-apoptotic, anti-aging, and antioxidant effects.

Clinical comparison between the presence and absence of protein plugs in pediatric choledochal cysts: experience in 390 patients over 30 years in a single center

Purpose@#The incidence of choledochal cyst (CC) with protein plugs is between 15.5%–40.4%. However, studies on CCs with protein plugs in children are limited. We aimed to analyze the clinical features, surgical findings, and complications of pediatric CCs with and without protein plugs. @*Methods@#We retrospectively analyzed 390 patients who underwent surgery for CCs between January 1987 and September 2017. The patients were divided into 2 groups: groups A (CC with protein plugs) and B (CC without protein plugs). The presence of protein plugs was evaluated using preoperative images or identified during surgery. @*Results@#One hundred forty-two (36.4%) patients had protein plugs in the pancreaticobiliary duct. The most common initial clinical presentation was abdominal pain, and its incidence was significantly higher in group A (66.2%) than in group B (54.8%) (P = 0.032). The incidence of accompanying pancreatitis was also significantly higher in group A (37.3% vs. 27.0%) (P = 0.040). Anomalous pancreaticobiliary ductal union (APBDU) was found in 261 patients (66.9%) and its incidence was significantly higher in group A (74.6% vs. 62.5%) (P = 0.014). Most protein plugs were found in the cyst (88.0%) and common channel (31.7%).The incidence of early complications was higher in group A; conversely, that of late complications did not differ. @*Conclusion@#Approximately 36.4% of the pediatric CC patients were accompanied by protein plugs. Abdominal pain, pancreatitis, and APBDU were more commonly observed among those with protein plugs than among those without; longterm complications did not differ between them.

Comparison of long-term biliary complications between open and laparoscopic choledochal cyst excision in children

Purpose@#Cyst excision with hepaticojejunostomy has been the classic procedure for treating choledochal cysts, and the use of laparoscopic treatment has been favored recently. The purpose of this study was to compare the long-term biliary complication of laparoscopic operation with open surgery for choledochal cyst presenting in children. @*Methods@#A retrospective study comparing the laparoscopic and open procedures was performed in 185 patients with choledochal cyst in a single children’s hospital. There were 109 patients who were operated with open surgery, and 76 patients operated with laparoscopic surgery. The primary outcome was long-term biliary complications and the secondary outcome included operative time, intraoperative transfusion, length of hospital stay, and other late postoperative complications. @*Results@#In the patient’s demographics, there was no significant difference between the 2 groups. Notably, it was shown that the operative time was longer in the laparoscopic group. The number of patients requiring blood transfusion intraoperatively was lower in the laparoscopic group. It was noted that the hospital stay was not statistically different. The duration to resumption of diet and duration of drainage were longer in the laparoscopic group. Biliary complications were shown to be significantly higher in the open group. The risk factor for long-term biliary complications was noted with the intraoperative transfusion. @*Conclusion@#The use of a laparoscopic choledochal cyst excision with hepaticojejunostomy is a safe and feasible technique in a young patient. The long-term biliary complication was lower compared to open surgery, rendering this a good option for pediatric patients.

Effects of the fermented Zizyphus jujuba in the amyloid β25-35 -induced Alzheimer's disease mouse model

RESULTS@#In behavioral tests, deterioration was revealed in the short- and long-term learning and memory functions in the Aβ25-35 -injected control group compared to the normal group, indicating that Aβ25-35 injection impairs cognitive functions. However, administration of Zj and Zj-Y improved cognitive function in mice, as compared to the Aβ25-35 -injected control mice. In addition, the Aβ25-35 induced elevations of MDA and NO in the brain, kidney, and liver were suppressed after exposure to Zj and Zj-Y. Especially, Zj-Y showed stronger scavenging effect against MDA and NO, as compared to Zj. @*CONCLUSIONS@#Results of the present study indicate that Zj-Y exerts a protective effect on cognitive impairment and memory dysfunction, which is exerted by attenuating the oxidative stress induced by Aβ25-35 .