• Journal of Korean Medical classics
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• v.23 no.2
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• pp.235-270
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• 2010

This paper studies the main treatment methods, Ikgi(益氣) and Seung-yang(升陽) applied frequently by Lee Jema(李濟馬) on the exterior disease of So-eumin(少陰人), one of the four constitutions. The methodology of this paper is to understand the pharmacology of "Dong-uisusebowon(東醫壽世保元)" by examining the formulas applied by Lee Jema. I have examined the organization of formulas in "Dong-uisusebowon(東醫壽世保元)" beforehand to categorize the formulas applicable in this study according to an objective standard. I have analyzed the prescriptions applied to So-eumin exterior disease. As a result, I could see that in the case of Ulgwang(鬱狂) syndrome, Ikgi(益氣) and Seung-yang(升陽) methods were mainly applied, but as the disease progressed, Seung-yang(升陽) was withdrawn while Ikgi(益氣) was stressed. Likewise, in the case of Mang-yang(亡陽), both methods were mainly adopted, but as the patients got worse, the level of Seung-yang(升陽) was maintained and that of Ikgi(益氣) was elevated with the addition of Buja(附子). Through this process, we could verify the overall action of Ikgi(益氣), Seung-yang(升陽) and Buja(附子). Originally, the two methods of Ikgi(益氣) and Seung-yang(升陽) are intimately related, but by analyzing the overall functions of the two methods, we could see that Seung-yang(升陽) and Buja(附子) support the Yang gi of the interior of So-eumin, while Ikgi(益氣) resolves inner stagnation of Yang gi and emits the cold pathogen of the exterior. Also, in the course of treatment, Ikgi(益氣) could only be realized after securing Seung-yang(升陽).

• Genomics & Informatics
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• v.12 no.4
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• pp.187-194
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• 2014

Metabolic syndrome (METS) is a disorder of energy utilization and storage and increases the risk of developing cardiovascular disease and diabetes. To identify the genetic risk factors of METS, we carried out a genome-wide association study (GWAS) for 2,657 cases and 5,917 controls in Korean populations. As a result, we could identify 2 single nucleotide polymorphisms (SNPs) with genome-wide significance level p-values (< $5{\times}10^{-8}$), 8 SNPs with genome-wide suggestive p-values ($5{\times}10^{-8}{\leq}$ p < $1{\times}10^{-5}$), and 2 SNPs of more functional variants with borderline p-values ($5{\times}10^{-5}{\leq}$ p < $1{\times}10^{-4}$). On the other hand, the multiple correction criteria of conventional GWASs exclude false-positive loci, but simultaneously, they discard many true-positive loci. To reconsider the discarded true-positive loci, we attempted to include the functional variants (nonsynonymous SNPs [nsSNPs] and expression quantitative trait loci [eQTL]) among the top 5,000 SNPs based on the proportion of phenotypic variance explained by genotypic variance. In total, 159 eQTLs and 18 nsSNPs were presented in the top 5,000 SNPs. Although they should be replicated in other independent populations, 6 eQTLs and 2 nsSNP loci were located in the molecular pathways of LPL, APOA5, and CHRM2, which were the significant or suggestive loci in the METS GWAS. Conclusively, our approach using the conventional GWAS, reconsidering functional variants and pathway-based interpretation, suggests a useful method to understand the GWAS results of complex traits and can be expanded in other genomewide association studies.

• Genomics & Informatics
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• v.6 no.3
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• pp.153-156
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• 2008

Complex diseases such as stroke and cancer have two or more genetic loci and are affected by environmental factors that contribute to the diseases. Due to the complex characteristics of these diseases, identifying candidate genes requires a system-level analysis of the following: gene ontology, pathway, and interactions. A database and user interface, termed StrokeBase, was developed; StrokeBase provides queries that search for pathways, candidate genes, candidate SNPs, and gene networks. The database was developed by using in silico data mining of HGNC, ENSEMBL, STRING, RefSeq, UCSC, GO, HPRD, KEGG, GAD, and OMIM. Forty candidate genes that are associated with cerebrovascular disease were selected by human experts and public databases. The networked cerebrovascular disease gene maps also were developed; these maps describe genegene interactions and biological pathways. We identified 1127 genes, related indirectly to cerebrovascular disease but directly to the etiology of cerebrovascular disease. We found that a protein-protein interaction (PPI) network that was associated with cerebrovascular disease follows the power-law degree distribution that is evident in other biological networks. Not only was in silico data mining utilized, but also 250K Affymetrix SNP chips were utilized in the 320 control/disease association study to generate associated markers that were pertinent to the cerebrovascular disease as a genome-wide search. The associated genes and the genes that were retrieved from the in silico data mining system were compared and analyzed. We developed a well-curated cerebrovascular disease-associated gene network and provided bioinformatic resources to cerebrovascular disease researchers. This cerebrovascular disease network can be used as a frame of systematic genomic research, applicable to other complex diseases. Therefore, the ongoing database efficiently supports medical and genetic research in order to overcome cerebrovascular disease.

• Genomics & Informatics
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• v.11 no.2
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• pp.83-92
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• 2013

Genetic studies on facial morphology targeting healthy populations are fundamental in understanding the specific genetic influences involved; yet, most studies to date, if not all, have been focused on congenital diseases accompanied by facial anomalies. To study the specific genetic cues determining facial morphology, we estimated familial correlations and heritabilities of 14 facial measurements and 3 latent factors inferred from a factor analysis in a subset of the Korean population. The study included a total of 229 individuals from 38 families. We evaluated a total of 14 facial measurements using 2D digital photographs. We performed factor analysis to infer common latent variables. The heritabilities of 13 facial measurements were statistically significant (p < 0.05) and ranged from 0.25 to 0.61. Of these, the heritability of intercanthal width in the orbital region was found to be the highest ($h^2$ = 0.61, SE = 0.14). Three factors (lower face portion, orbital region, and vertical length) were obtained through factor analysis, where the heritability values ranged from 0.45 to 0.55. The heritability values for each factor were higher than the mean heritability value of individual original measurements. We have confirmed the genetic influence on facial anthropometric traits and suggest a potential way to categorize and analyze the facial portions into different groups.

• Genomics & Informatics
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• v.11 no.4
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• pp.245-253
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• 2013

A radioresistant cell line was established by fractionated ionizing radiation (IR) and assessed by a clonogenic assay, flow cytometry, and Western blot analysis, as well as zymography and a wound healing assay. Microarray was performed to profile global expression and to search for differentially expressed genes (DEGs) in response to IR. H460R cells demonstrated increased cell scattering and acidic vesicular organelles compared with parental cells. Concomitantly, H460R cells showed characteristics of increased migration and matrix metalloproteinase activity. In addition, H460R cells were resistant to IR, exhibiting reduced expression levels of ionizing responsive proteins (p-p53 and ${\gamma}$-H2AX); apoptosis-related molecules, such as cleaved poly(ADP ribose) polymerase; and endoplasmic reticulum stress-related molecules, such as glucose-regulated protein (GRP78) and C/EBP-homologous protein compared with parental cells, whereas the expression of anti-apoptotic X-linked inhibitor of apoptosis protein was increased. Among DEGs, syntrophin beta 2 (SNTB2) significantly increased in H460R cells in response to IR. Knockdown of SNTB2 by siRNA was more sensitive than the control after IR exposure in H460, H460R, and H1299 cells. Our study suggests that H460R cells have differential properties, including cell morphology, potential for metastasis, and resistance to IR, compared with parental cells. In addition, SNTB2 may play an important role in radioresistance. H460R cells could be helpful in in vitro systems for elucidating the molecular mechanisms of and discovering drugs to overcome radioresistance in lung cancer therapy.

• Journal of Korean Medical classics
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• v.20 no.1
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• pp.65-74
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• 2007

"The Golden Mirror of Medicine(醫宗金鑑)" was compiled by the medical officers of the Qing government, headed by Wu-Qian(吳謙)."The Elimination &Supplement about the Famous Prescription Comments(刪補名醫方論)", a collection of notes written by famous scholars, is one part of "The Golden Mirror of Medicine(醫宗金鑑)" . Through the translation and comparative study of invigorative prescription(補氣方劑) in "The Elimination & Supplement about the Famous Prescription Comments(刪補名醫方論)" of "The Golden Mirror of Medicine(醫宗金鑑)" with "The Famous Prescription Comments on Ancient and Modem Times(古今名醫方論)" , we confirmed that many sentences of "The Famous Prescription Comments on Ancient and Modern Times(古今名醫方論)" were quoted, but that most of the text was not quoted as the same: it was revised and supplemented. In organization, invigoration prescriptions are placed at the head of the chapter, indicating their importance. In classification, prescriptions for reinforcing middle-jiao(中焦) and replenishing qi(補中益氣湯類 方劑) were usually included in the invigoration prescriptions(補氣方劑), which is explained in chapter II, thereby clearly distinguishing between treatments of deficiency of qi(氣虛) and combining it with the sinking of qi of middle-jiao(中氣下陷).

• Neonatal Medicine
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• v.28 no.3
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• pp.124-132
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• 2021

Purpose: Neonatal near miss (NNM) allows for the detection of risk factors associated with serious newborn complications and death, the prevention of which could reduce neonatal mortality. This study was conducted with the objective of identifying predictors for NNM in a tertiary hospital in Bangalore city. Methods: This was an unmatched case-control study involving 120 NNM cases and 120 controls. NNM was determined using Pileggi-Castro's pragmatic and management criteria. Data was collected from in-patient hospital records and interviews of postpartum mothers. Multiple logistic regression of exposure variables was performed to calculate adjusted odds ratio (AOR) with 95% confidence interval (CI). Results: Significant predictors were maternal age ≥30 years (AOR, 5.32; 95% CI, 1.12 to 9.29; P=0.041), inadequate antenatal care (ANC) (AOR, 8.35; 95% CI, 1.98 to 51.12; P=0.032), <3 ultrasound scans during pregnancy (AOR, 12.5; 95% CI, 1.60 to 97.27; P=0.016), maternal anaemia (AOR, 18.96; 95% CI, 3.10 to 116.02; P=0.001), and any one obstetric complication (hypertensive disorder in pregnancy, diabetes in pregnancy, preterm premature rupture of membranes, prolonged labour, obstructed labour, malpresentation) (AOR, 4.34; 95% CI, 1.26 to 14.95; P=0.02). Conclusion: The predictors of NNM identified has important implications for public health policy and practice whose modifications can improve NNM. These include expanding essential ANC package to include ultrasound scans, ensuring World Health Organization recommendations of eight ANC visits, capacity building at all levels of health care to strengthen routine ANC and obstetric care for effective screening, referral and management of obstetric complications.

• Genomics & Informatics
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• v.19 no.4
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• pp.38.1-38.7
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• 2021

Kawasaki disease (KD) is an acute pediatric vasculitis that affects genetically susceptible infants and children. To identify coding variants that influence susceptibility to KD, we conducted whole exome sequencing of 159 patients with KD and 902 controls, and performed a replication study in an independent 586 cases and 732 controls. We identified five rare coding variants in five genes (FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10) associated with KD (odds ratio [OR], 1.18 to 4.41; p = 0.0027-0.031). We also performed association analysis in 26 KD patients with coronary artery aneurysms (CAAs; diameter > 5 mm) and 124 patients without CAAs (diameter < 3 mm), and identified another five rare coding variants in five genes (FGFR4, IL31RA, FNDC1, MMP8, and FOXN1), which may be associated with CAA (OR, 3.89 to 37.3; p = 0.0058- 0.0261). These results provide insights into new candidate genes and genetic variants potentially involved in the development of KD and CAA.

• Genomics & Informatics
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• v.21 no.1
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• pp.9.1-9.13
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• 2023

Matrix metalloproteinase-9 (MMP-9) is a zinc and calcium-dependent proteolytic enzyme involved in extracellular matrix degradation. Overexpression of MMP-9 has been confirmed in several disorders, including cancers, Alzheimer's disease, autoimmune diseases, cardiovascular diseases, and dental caries. Therefore, MMP-9 inhibition is recommended as a therapeutic strategy for combating various diseases. Cinnamic acid derivatives have shown therapeutic effects in different cancers, Alzheimer's disease, cardiovascular diseases, and dental caries. A computational drug discovery approach was performed to evaluate the binding affinity of selected cinnamic acid derivatives to the MMP-9 active site. The stability of docked poses for top-ranked compounds was also examined. Twelve herbal cinnamic acid derivatives were tested for possible MMP-9 inhibition using the AutoDock 4.0 tool. The stability of the docked poses for the most potent MMP-9 inhibitors was assessed by molecular dynamics (MD) in 10 nanosecond simulations. Interactions between the best MMP-9 inhibitors in this study and residues incorporated in the MMP-9 active site were studied before and after MD simulations. Cynarin, chlorogenic acid, and rosmarinic acid revealed a considerable binding affinity to the MMP-9 catalytic domain (ΔG_binding < -10 kcal/ mol). The inhibition constant value for cynarin and chlorogenic acid were calculated at the picomolar scale and assigned as the most potent MMP-9 inhibitor from the cinnamic acid derivatives. The root-mean-square deviations for cynarin and chlorogenic acid were below 2 Å in the 10 ns simulation. Cynarin, chlorogenic acid, and rosmarinic acid might be considered drug candidates for MMP-9 inhibition.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.2
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• pp.172-179
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• 2023

Backgrounds/Aims: Cancer stigma (CS), a self-inflicted sense of hopelessness, has been identified as a major factor affecting cancer patients' outcomes. However, few studies have investigated the CS-related outcomes in hepatobiliary and pancreatic (HBP) cancer. Thus, the aim of this study was to investigate effects of CS on quality of life (QoL) of HBP cancer. Methods: From 2017 to 2018, 73 patients who underwent curative surgery for HBP tumor at a single intuitive were enrolled prospectively. The QoL was measured using the European Organization for Research and Treatment of Cancer QoL score, and CS was evaluated in three categories, "impossibility of recovery," "cancer stereotypes," and "social discrimination." the stigma was defined by higher scores of attitudes compared with the median value. Results: The stigma group showed a lower QoL (-17.67, 95% confidence interval [CI]: -26.75 to 8.60, p < 0.001) than the no stigma group. Similarly, most function and symptoms of the stigma group showed worse results than the no stigma group. The difference in function scores between the two groups according to CS was highest in cognitive function (-21.20, 95% CI: -30.36 to 12.04, p < 0.001). Fatigue showed the largest difference between the two groups at 22.84 (95% CI: 12.88-32.07, p < 0.001) and was the most severe symptom in stigma group. Conclusions: CS was an important negative factor affecting the QoL, function, and symptoms of HBP cancer patients. Therefore, appropriate management of CS is crucial for improved postoperative QoL.