1.Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression
Sumin OH ; Yang-Hyun BAEK ; Sungju JUNG ; Sumin YOON ; Byeonggeun KANG ; Su-hyang HAN ; Gaeul PARK ; Je Yeong KO ; Sang-Young HAN ; Jin-Sook JEONG ; Jin-Han CHO ; Young-Hoon ROH ; Sung-Wook LEE ; Gi-Bok CHOI ; Yong Sun LEE ; Won KIM ; Rho Hyun SEONG ; Jong Hoon PARK ; Yeon-Su LEE ; Kyung Hyun YOO
Clinical and Molecular Hepatology 2024;30(2):247-262
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression.
Methods:
Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD.
Results:
After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort.
Conclusions
We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.
2.The Sagittal Balance of Cervical Spine : Comprehensive Review of Recent Update
Sang Hoon LEE ; Tae Hwan KIM ; Seok Woo KIM ; Hyun Take RIM ; Heui Seung LEE ; Ji Hee KIM ; In Bok CHANG ; Joon Ho SONG ; Yong Kil HONG ; Jae Keun OH
Journal of Korean Neurosurgical Society 2023;66(6):611-617
The cervical spine plays a critical role in supporting the skull, maintaining horizontal gaze, and facilitating walking. Its unique characteristics, including the widest range of motion among spinal segments, have led to extensive research on cervical sagittal alignment. Various parameters have been proposed to evaluate cervical alignment, with studies investigating their clinical significance, correlation with symptoms, and implications for surgical interventions. Recent findings suggest that cervical sagittal alignment not only impacts the cervical spine but also influences global spine-pelvic alignment through compensatory mechanisms. This comprehensive review examines classical and new parameters of cervical sagittal alignment and considers the dynamic and muscular factors associated with it.
3.Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET
Jin-Young LEE ; Bok Yun KANG ; Sang-Jin JUNG ; Ah-Won KWAK ; Seung-On LEE ; Jin Woo PARK ; Sang Hoon JOO ; Goo YOON ; Mee-Hyun LEE ; Jung-Hyun SHIM
Biomolecules & Therapeutics 2023;31(2):200-209
Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive muta-tions initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resis-tance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunc-tion, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.
4.Workload in Emergency Rooms among Clinical Specialties and Overburdened Neurologists
Daeyoung KIM ; Nathan JO ; Jae-Kwan CHA ; Hojin CHOI ; Sang Wuk JEONG ; Im Seok KOH ; Kwang Ik YANG ; Kwang-Yeol PARK ; Kyung-Bok LEE ; Woong-woo LEE ; Dong Hoon SHIN ; Dong Jin SHIN
Journal of the Korean Neurological Association 2022;40(2):127-136
Background:
To evaluate workload in emergency rooms (ERs) among clinical specialties including neurology and investigate characteristics of neurological consultations in ER.
Methods:
A nationwide survey was conducted to evaluate the number of specialists, resident physicians/surgeons, and emergency consultations of each clinical specialty in Korean tertiary referral hospitals from 2018 to 2019. Characteristics of neurological emergency consultations during the same period were investigated in one of the hospitals that participated.
Results:
A total of 23 hospitals were included. Four irrelevant clinical specialties were excluded. The number of neurology specialists and resident physicians were 12.5/hospital (4.1% of all specialists) and 6.4/hospital (3.4% of all resident physicians/surgeons), respectively, while the mean numbers of specialists and resident physicians or surgeons per clinical specialty were 13.7/hospital and 8.6/hospital, respectively. Neurological consultations accounted for 11.0% of all ER consultations for severe patients (Korean Triage and Acuity Scale level 1-3). Annual ER consultations for severe patients per neurology specialist was 274.1, which was only second to pediatrics (290.0). Annual ER consultations for severe patients per resident physician was 406.6 which was 1.6 times higher than the second highest (internal medicine, 247.0). Frequent conditions for neurological ER consultation were dizziness (24.8%), motor weakness (23.9%), headache (10.6%), dysarthria (9.9%), and seizures (7.7%). Frequent primary diagnoses were cerebrovascular diseases (29.0%) and episodic and paroxysmal disorders (24.9%).
Conclusions
Workloads of neurology specialists for ER consultation were significantly heavy, and the workload of neurology resident physicians was the heaviest among all specialties. This should be considered in health care policies.
5.The Investigation on the Burden of Neurology Residents to Manage the Patient who Received Thrombolytic Treatment in the Emergency Department with Hyperacute Stroke
Hyun Joon LEE ; Dong Hoon SHIN ; Kwang Ik YANG ; Im-Seok KOH ; Kyung Bok LEE ; Woong-Woo LEE ; Daeyoung KIM ; Kwang-Yeol PARK ; Sang Wuk JEONG ; Hojin CHOI ; Jae-Kwan CHA ; Dong Jin SHIN
Journal of the Korean Neurological Association 2021;39(4):305-311
Background:
Because Korea is the fastest aging country, the stroke incidence is increasing rapidly. We investigate the trend of the number of patients with acute stroke in recent years and estimate the burden of the neurologist to treat the acute stroke patient visited the emergency department.
Methods:
We requested a questionnaire survey to all teaching hospitals on the number of hospital beds, the number of stroke patients who visited the emergency department, the number of stroke patients in charge of the neurologist, and the number of days on duty of residents from 2016 to 2019.
Results:
Of 69 teaching hospitals, 41 hospitals answered the survey. The average hospital beds per hospital were increased annually from 909 to 916. The average patients who visited the emergency department with stroke and were in charged to neurologists were rapidly increased from 799 to 867 per hospital. In particular, the number of patients with hyperacute cerebral infarction requiring the thrombolytic administration or mechanical thrombectomy were rapidly increased from 105 to 131. On the other hand, the average number of residents per hospital was decreased from 5.1 to 4.8. Therefore, the days on duty per resident were increased from 74 to 77.
Conclusions
The number of acute stroke patients, especially, hyperacute stroke required the rapid cooperation and high labor were increasing rapidly in recent years. However, because the number of residents were decreased, the burden was increasing. To improve the quality of acute stroke treatment, it is necessary to increase the number of residents.
6.Colon Polyp Detection in Primary Health Care Institutions of Korea: Detection Rate and Issues with Following the Guidelines
Sang Hyun PARK ; Kwang Il HONG ; Hyun Chul PARK ; Young Sun KIM ; Gene Hyun BOK ; Kyung Ho KIM ; Dong Suk SHIN ; Jae Yong HAN ; Young Kwan KIM ; Yeun Jong CHOI ; Soo Hoon EUN ; Byung Hoon LIM ; Kyeong Kun KWACK ; The Korean Society of Digestive Endoscopy (KSDE) Polyp Study Workgroup
The Korean Journal of Gastroenterology 2021;78(6):328-336
Background/Aims:
There have been few multicenter studies on colonic polyps conducted by primary medical institutions. This study examined the detection rate of colonic polyps in primary health care institutions and the related factors while following the guidelines.
Methods:
The medical records of 14,029 patients who underwent colonoscopy between January-June 2020 at 40 primary medical institutions in Korea were analyzed. High-risk adenoma was defined as advanced adenoma, carcinoma, or ≥3 adenomas.
Results:
Most patients (71.2%) aged ≥50 years underwent re-colonoscopy within 5 years (51.3%) for diagnostic purposes (61.3%) in Korean primary medical institutions. The detection rates of colon polyps, adenoma, advanced adenoma, high-risk adenoma, and carcinoma was 59.9%, 38.9%, 5.9%, 11.4%, and 0.3% in all subjects and 59.8%, 37.5%, 8.5%, 12.9%, and 0.3% in average-risk patients, respectively. The incidences of adenoma in average-risk patients increased significantly with age (30s/40s/50s: 20.1%/29.4%/43% for adenoma, 4.4%/6.7%/10.3% for advanced adenoma, and 5.6%/9.5%/14.6% for high-risk adenoma; p<0.05). Before 50 years of age, high-risk adenoma was detected in 9.1% of patients in the first-time screening group, and the significant risk factors were being male and ≥40 years of age. The detection rate of high-risk adenoma in the normal index colonoscopy group within 5 years was 9.0%. The significant risk factors included older age, male sex, positive fecal occult blood test, stool form changes, and nonspecific symptoms (gas and indigestion).
Conclusions
More colonic adenoma studies targeting real-world clinical practice will be needed to revise the Korean guidelines for colorectal cancer screening and surveillance.
7.The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management
Woo-Jung SONG ; Mira CHOI ; Dong Hun LEE ; Jae-Woo KWON ; Gun-Woo KIM ; Myung Hwa KIM ; Mi-Ae KIM ; Min-Hye KIM ; Byung-Keun KIM ; Sujeong KIM ; Joung Soo KIM ; Jung Eun KIM ; Ju-Young KIM ; Joo-Hee KIM ; Hyun Jung KIM ; Hye One KIM ; Hyo-Bin KIM ; Joo Young ROH ; Kyung Hee PARK ; Kui Young PARK ; Han-Ki PARK ; Hyunsun PARK ; Jung Min BAE ; Ji Yeon BYUN ; Dae Jin SONG ; Young Min AHN ; Seung Eun LEE ; Young Bok LEE ; Joong Sun LEE ; Ji Hyun LEE ; Kyung-Hwan LIM ; Young-Min YE ; Yoon-Seok CHANG ; You Hoon JEON ; Jiehyun JEON ; Mihn-Sook JUE ; Sun Hee CHOI ; Jeong-Hee CHOI ; Gyu-Young HUR ; Young Min PARK ; Dae Hyun LIM ; Sang Woong YOUN
Allergy, Asthma & Immunology Research 2020;12(4):563-578
Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.
8.The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management
Woo-Jung SONG ; Mira CHOI ; Dong Hun LEE ; Jae-Woo KWON ; Gun-Woo KIM ; Myung Hwa KIM ; Mi-Ae KIM ; Min-Hye KIM ; Byung-Keun KIM ; Sujeong KIM ; Joung Soo KIM ; Jung Eun KIM ; Ju-Young KIM ; Joo-Hee KIM ; Hyun Jung KIM ; Hye One KIM ; Hyo-Bin KIM ; Joo Young ROH ; Kyung Hee PARK ; Kui Young PARK ; Han-Ki PARK ; Hyunsun PARK ; Jung Min BAE ; Ji Yeon BYUN ; Dae Jin SONG ; Young Min AHN ; Seung Eun LEE ; Young Bok LEE ; Joong Sun LEE ; Ji Hyun LEE ; Kyung-Hwan LIM ; Young-Min YE ; Yoon-Seok CHANG ; You Hoon JEON ; Jiehyun JEON ; Mihn-Sook JUE ; Sun Hee CHOI ; Jeong-Hee CHOI ; Gyu-Young HUR ; Young Min PARK ; Dae Hyun LIM ; Sang Woong YOUN
Allergy, Asthma & Immunology Research 2020;12(4):563-578
Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.
9.Efficacy and Safety of Letibotulinum Toxin A for the Treatment of Essential Blepharospasm
Ji Hyun KIM ; Doh Hoon CHUNG ; Sung Eun KIM ; Ji Sun PAIK ; Namju KIM ; Tae Yoon LA ; Jun Hyuk SON ; Hee Bae AHN ; Jae Wook YANG ; Kyung In WOO ; Helen LEW ; Jin Sook YOON ; Sang Un LEE ; Sung Bok LEE ; Jeong Kyu LEE ; Jae Woo JANG ; Ho Kyung CHOUNG ; Mijung CHI ; Suk Woo YANG
Journal of the Korean Ophthalmological Society 2020;61(3):227-234
PURPOSE: To evaluate the efficacy and safety of BOTULAX® in subjects with essential blepharospasm.METHODS: In this study, a total of 250 subjects with essential blepharospasm were enrolled at 15 investigational sites and a total of 220 subjects completed the study. The efficacy and safety were evaluated at weeks 4 and 16 after treatment compared with baseline. In total, 240 subjects were enrolled, treated with the investigational product, and evaluable for the primary efficacy assessment at week 4 after treatment; these subjects were included in the intention-to-treat (ITT) population. With the ITT set as the main efficacy set, efficacy assessment included Jankovic rating scale (JRS), functional disability score, investigator evaluation of global response and quality of life. Safety assessment including the incidence of adverse events was also performed.RESULTS: In terms of the primary efficacy endpoint (i.e., change in JRS total score at week 4 after treatment from baseline [ITT set]), mean change indicated a statistically significant reduction (p < 0.0001) and demonstrated the non-inferiority of the test drug to similar drugs. In terms of the secondary efficacy endpoints, mean change in JRS total score at week 16 after treatment and mean change in functional disability score at weeks 4 and 16 after treatment both exhibited a statistically significant reduction compared with baseline (p < 0.0001 for all). Among the 249 subjects treated with the investigational product in this study, 44 (17.67%) experienced 76 treatment emergent adverse events but no serious adverse events were observed.CONCLUSIONS: Based on the study results, BOTULAX® is considered to be an effective and safe treatment for essential blepharospasm.
10.Detection and genetic analysis of zoonotic hepatitis E virus, rotavirus, and sapovirus in pigs
Eu Lim LYOO ; Byung-Joo PARK ; Hee-Seop AHN ; Sang-Hoon HAN ; Hyeon-Jeong GO ; Dong-Hwi KIM ; Joong-Bok LEE ; Seung-Yong PARK ; Chang-Seon SONG ; Sang-Won LEE ; In-Soo CHOI
Korean Journal of Veterinary Research 2020;60(2):61-68
The zoonotic transmission of viral diseases to humans is a serious public health concern. Pigs are frequently a major reservoir for several zoonotic viral diseases. Therefore, periodic surveillance is needed to determine the infection rates of zoonotic diseases in domestic pigs. Hepatitis E virus (HEV), rotavirus, sapovirus (SaV), and norovirus (NoV) are potential zoonotic viruses. In this study, 296 fecal samples were collected from weaned piglets and growing pigs in 13 swine farms, and the viral RNA was extracted. Partial viral genomes were amplified by reverse transcription-polymerase chain reaction (PCR) or nested-PCR using virusspecific primer sets under different PCR conditions. HEV-3, rotavirus A, and SaV genogoup 3 were detected from 11.5, 2.7, and 3.0% of the samples, respectively. On the other hand, NoV was not detected in any of the samples. Genetic analysis indicated that the nucleotide sequences of swine HEV-3 and rotavirus A detected in this study were closely related to those of human isolates. However, swine SaV was distant from the human strains. These results suggest that HEV-3 and rotavirus A can be transmitted from pigs to humans. Therefore, strict preventive measures should be implemented by workers in the swine industry to prevent infections with HEV-3 and rotavirus A excreted from pigs.

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