The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms

Dangkwisoo-San (DS) is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO) production in human brain microvascular endothelial cells (HBMECs). DS (10–300 μg/mL) produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS) inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF), although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS) inhibitor, N5-(1-iminoethyl)-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation

Regional prevalence of non-alcoholic fatty liver disease in Seoul and Gyeonggi-do, Korea

Background/AimsThe prevalence of nonalcoholic fatty liver disease (NAFLD) in Korea has increased recently. The aim of the present study was to determine the regional differences in the prevalence and characteristics of NAFLD.MethodsFrom January 2009 to December 2010, 161,891 Seoul and Gyeonggi-do residents receiving a health examination at our institution were enrolled in this cross-sectional study. After applying exclusion criteria, the data of 141,610 subjects (80,943 males, 60,667 females) were analyzed. The presence of NAFLD was established by ultrasound examination.ResultsThe overall prevalence of NAFLD was 27.3% (38.3% in men, 12.6% in women). When standardized according to age, area, and sex, the prevalence of NAFLD was 25.2%. The age and area standardized prevalence of NAFLD was higher for men (34.4%) than for women (12.2%; P<0.001). The overall prevalence of NAFLD was higher in Gyeonggi-do (27.7%) than in Seoul (26.9%; P<0.001). Among the men, the prevalence of NAFLD was higher in Gyeonggi-do (39.2%) than in Seoul (37.4%; P<0.001), while for the women it was higher in Seoul (13.2%) than in Gyeonggi-do (12.0%; P<0.001).ConclusionsThe regional prevalence of NAFLD differed between Seoul and Gyeonggi-do. Further studies are needed to establish the etiology of this difference

Effects of Huang Bai (Phellodendri Cortex) and Three Other Herbs on GnRH and GH Levels in GT1–7 and GH3 Cells

The present study was to evaluate the effects of Huang Bai, Zhi Mu, Mai Ya, and Xia Ku Cao on hormone using the GT1–7 and GH3 cells. The GT1–7 and GH3 cell lines were incubated with DW; DMSO; and 30, 100, or 300 μg/mL of one of the four extract solutions in serum-free media for 24 hours. The MTT assay was performed to determine the cytotoxicity of the four herbs. The GT1–7 and GH3 cells were incubated in DW, estradiol (GT1–7 only), or noncytotoxic herb solutions in serum-free medium for 24 hours. A quantitative RT-PCR and western blot were performed to measure the GnRH expression in GT1–7 cells and GH expression in GH3 cells. Huang Bai, Zhi Mu, Xia Ku Cao, and Mai Ya inhibited the GnRH mRNA expression in GT1–7 cells, whereas Huang Bai enhanced GH mRNA expression in GH3 cells. Additionally, Xia Ku Cao inhibited GnRH protein expression in GT1–7 cells and Huang Bai promoted GH protein expression in GH3 cells. The findings suggest that Huang Bai can delay puberty by inhibiting GnRH synthesis in the hypothalamus while also accelerating growth by promoting GH synthesis and secretion in the pituitary

Comparison of the outcomes between sorafenib and lenvatinib as the first-line systemic treatment for HBV-associated hepatocellular carcinoma: a propensity score matching analysis

In a randomized controlled trial, lenvatinib was non-inferior to sorafenib in overall survival (OS) of patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to compare the effects of sorafenib and lenvatinib as first-line systemic therapy against uHCC with real-world data in chronic hepatitis B patients. This retrospective single-center study involved 132 patients with HBV-related uHCC. Propensity score matching (PSM) was used to balance the baseline characteristics, including age, sex, serum alpha-fetoprotein levels, Child–Pugh class, tumor size, and tumor stage. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), time to progression (TTP), and tumor response. After PSM, the final analysis included 44 patients treated with lenvatinib and 88 with sorafenib. The OS (7.0 vs 9.2months, p = 0.070) and PFS (4.6 vs 2.4months, p = 0.134) were comparable between the two drugs. Multivariable analysis showed that lenvatinib and sorafenib were not independent prognostic factors of OS (adjusted hazard ratio = 1.41, 95% confidence interval = 0.96–2.08, p = 0.077) after adjustment for baseline alpha-fetoprotein levels, total bilirubin levels, alanine aminotransferase level, performance status, tumor stage, and tumor size. However, the lenvatinib group had a significantly prolonged TTP (5.2 vs 2.5months, p = 0.018) and a higher objective response rate (18.2% vs 4.5%, p = 0.020) and disease control rate (77.3% vs 47.7%, p = 0.001) than the sorafenib group. Our study demonstrated that lenvatinib had a comparable OS and PFS but longer TTP and better tumor response compared to sorafenib in patients with HBV-related uHCC

Clinical features and long-term prognosis of acute fibrinous and organizing pneumonia histologically confirmed by surgical lung biopsy

Abstract Background Acute fibrinous and organizing pneumonia (AFOP) is a rare interstitial pneumonia characterized by intra-alveolar fibrin deposition and organizing pneumonia. The clinical manifestations and long-term prognosis of AFOP are unclear. Our objective was to investigate the clinical features and prognosis of AFOP. Methods We identified patients diagnosed with AFOP by surgical lung biopsy between January 2011 and May 2018 at Seoul National University Bundang Hospital. We retrospectively reviewed clinical and radiologic findings, treatment, and outcomes of AFOP. Results Fifteen patients with histologically confirmed lung biopsies were included. The median follow-up duration was 2.4 (range, 0.1–82) months. The median age was 55 (range, 33–75) years, and four patients were immunocompromised. Fever was the most common clinical presentation (86.7%). Patchy ground-glass opacities and/or consolidations were the most predominant findings on chest computed tomography images. Nine patients (60%) received mechanical ventilator care, and eight patients (53.3%) died. The non-survivors tended to have slightly higher body mass index (BMI) and a long interval between symptom onset and diagnosis than the survivors, but these findings were not statistically significant. Among seven survivors, five patients were discharged without dyspnea and oxygen supplement. Conclusions The clinical course of AFOP was variable. Although AFOP was fatal, most of the patients who recovered from AFOP maintained normal life without supplemental oxygen therapy and respiratory symptoms

Assessment of the Type D Personality Construct in the Korean Population: A Validation Study of the Korean DS14

This study aimed to develop a Korean version of the Type D Personality Scale-14 (DS14) and evaluate the psychiatric symptomatology of Korean cardiac patients with Type D personality. Healthy control (n = 954), patients with a coronary heart disease (n = 111) and patients with hypertension and no heart disease (n = 292) were recruited. All three groups completed DS14, the Eysenck Personality Questionnaire (EPQ), the state subscale of Spielberger State and Trait Anxiety Inventory (STAI-S), the Center for Epidemiologic Studies Short Depression Scale (CESD), and the General Health Questionnaire (GHQ). The Korean DS14 was internally consistent and stable over time. 27% of the subjects were classified as Type D. Type D individuals had significantly higher mean scores on the STAI-S, CESD, and GHQ compared to non-Type D subjects in each group. The Korean DS14 was a valid and reliable tool for identifying Type D personality. The general population and cardiovascular patients with Type D personality showed higher rate of depression, anxiety and psychological distress regarding their health. Therefore, identifying Type D personality is important in clinical research and practice in chronic medical disorders, especially cardiovascular disease, in Korea

A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids

Developing effective drugs for Alzheimer’s disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, we report an efficient, network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of AD with human iPSC-derived cerebral organoids (iCOs), including CRISPR-Cas9-edited isogenic lines. We use 1300 organoids from 11 participants to build a high-content screening (HCS) system and test blood–brain barrier-permeable FDA-approved drugs. Our study provides a strategy for precision medicine through the convergence of mathematical modeling and a miniature pathological brain model using iCOs. © 2021, The Author(s).1

Report of the key comparison CCQM-K88 : determination of lead in lead-free solder containing silver and copper

The CCQM-K88 key comparison was organised by the Inorganic Analysis Working Group of CCQM to test the abilities of the national metrology institutes to measure the mass fraction of lead in lead-free solder containing silver and copper. National Metrology Institute of Japan (NMIJ), National Institute of Metrology P. R. China (NIM) and Korea Research Institute of Standards and Science (KRISS) acted as the coordinating laboratories. The participants used different measurement methods, though most of them used inductively coupled plasma optical emission spectrometry (ICP-OES) or isotope-dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). Accounting for relative expanded uncertainty, comparability of measurement results was successfully demonstrated by the participating NMIs for the measurement of the mass fraction of lead in lead-free solder at the level of 200 mg/kg. It is expected that metals at mass fractions greater than approximately100 mg/kg in lead-free solder containing silver and copper can be determined by each participant using the same technique(s) employed for this key comparison to achieve similar uncertainties mentioned in the present report.Fil: Hioki, Akiharu. National Metrology Institute of Japan (NMIJ); JapónFil: Nonose, Naoko. National Metrology Institute of Japan (NMIJ); JapónFil: Liandi, Ma. National Institute of Metrology (NIM); ChinaFil: Jingbo, Chao. National Institute of Metrology (NIM); ChinaFil: Liuxing, Feng. National Institute of Metrology (NIM); ChinaFil: Chao, Wei. National Institute of Metrology (NIM); ChinaFil: Cho, Kyung Haeng. Korea Research Institute of Standards and Science (KRISS); Corea del SurFil: Suh, Jung Ki. Korea Research Institute of Standards and Science (KRISS); Corea del SurFil: Min, Hyung Sik. Korea Research Institute of Standards and Science (KRISS); Corea del SurFil: Lim, Youngran. Korea Research Institute of Standards and Science (KRISS); Corea del SurFil: Recknagel, Sebastian. Federal Institute for Materials Research and Testing (BAM); AlemaniaFil: Koenig, Maren. Federal Institute for Materials Research and Testing (BAM); AlemaniaFil: Vogl, Jochen. Federal Institute for Materials Research and Testing (BAM); AlemaniaFil: Caciano de Sena, Rodrigo. Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMetro); BrasilFil: dos Reis, Lindomar Augusto. Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMetro); BrasilFil: Borinsky, Mónica. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Puelles, Mabel. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Hatamleh, Nadia. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Acosta, Osvaldo. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Turk, Gregory. National Institute of Standards and Technology (NIST); Estados UnidosFil: Rabb, Savelas. National Institute of Standards and Technology (NIST); Estados UnidosFil: Sturgeon, Ralph. National Research Council (NRC); CanadáFil: Methven, Brad. National Research Council (NRC); CanadáFil: Rienitz, Olaf. Physikalisch-Technische Bundesanstalt (PTB); AlemaniaFil: Jaehrling, Reinhard. Physikalisch-Technische Bundesanstalt (PTB); AlemaniaFil: Konopelko, L. A. D. I. Mendeleev Institute for Metrology (VNIIM); RusiaFil: Kustikov, Yu. A. D. I. Mendeleev Institute for Metrology (VNIIM); RusiaFil: Kozyreva, S. B. D. I. Mendeleev Institute for Metrology (VNIIM); RusiaFil: Korzh, A. A. D. I. Mendeleev Institute for Metrology (VNIIM); Rusi

Nanostring-based multigene assay to predict recurrence for gastric cancer patients after surgery

10.1371/journal.pone.0090133PLoS ONE93-POLN

Hemo-metabolic impairment in patients with ST-segment elevation myocardial infarction: Data from the INTERSTELLAR registry

Background: Not only hemo-dynamic (HD) factors but also hemo-metabolic (HM) risk factors reflecting multi-organ injuries are considered as important prognostic factors in ST-segment elevation myocardial infarction (STEMI). However, studies regarding HM risk factors in STEMI patients are currently limited. Method: Under analysis were 1,524 patients with STEMI who underwent primary percutaneous coronary intervention in the INTERSTELLAR registry. Patients were divided into HM (≥ 2 risk factors) and non-HM impairment groups. The primary outcome was in-hospital all-cause mortality, and the secondary outcome was 1-year all-cause mortality. Results: Of 1,524 patients, 214 (14.0%) and 1,310 (86.0%) patients were in the HM and non-HM impairment groups, respectively. Patients with HM impairment had a higher incidence of in-hospital mortality than those without (24.3% vs. 2.7%, p &lt; 0.001). After adjusting for confounders, HM impairment was independently associated with in-hospital mortality (inverse probability of treatment weighting [IPTW]-adjusted odds ratio: 1.81, 95% confidence interval: 1.08–3.14). In the third door-to-balloon (DTB) time tertile (≥ 82 min), HM impairment was strongly associated with in-hospital mortality. In the first DTB time tertile ( &lt; 62 min), indicating relatively rapid revascularization, HM impairment was consistently associated with increased in-hospital mortality. Conclusions: Hemo-metabolic impairment is significantly associated with increased risk of in-hospital and 1-year mortality in patients with STEMI. It remains a significant prognostic factor, regardless of DTB time