• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.246-256
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• 2022

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 µM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7r-NLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

• Nutrition Research and Practice
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• v.16 no.5
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• pp.604-615
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• 2022

BACKGROUND/OBJECTIVES: This study aimed to investigate cancer-specific survival (CSS) and associated risk factors in elderly gastric cancer (EGC) patients. SUBJECTS/METHODS: EGC patients (≥ 70 yrs) who underwent curative gastrectomy between January 2013 and December 2017 at our hospital were included. Clinicopathologic characteristics and survival data were collected. Receiver operating characteristic (ROC) analysis was used to extract the best cutoff point for body mass index (BMI). A Cox proportional hazards model was used to determine the risk factors for CSS. RESULTS: In total, 290 EGC patients were included, with a median age of 74.7 yrs. The median follow-up time was 31 (1-77) mon. The postoperative 1-yr, 3-yr and 5-yr CSS rates were 93.7%, 75.9% and 65.1%, respectively. Univariate analysis revealed risk factors for CSS, including age (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 1.01-1.15), intensive care unit (ICU) admission (HR = 1.73; 95% CI, 1.08-2.79), nutritional risk screening (NRS 2002) score ≥ 5 (HR = 2.33; 95% CI, 1.49-3.75), and preoperative prognostic nutrition index score < 45 (HR = 2.06; 95% CI, 1.27-3.33). The ROC curve showed that the best BMI cutoff value was 20.6 kg/m². Multivariate analysis indicated that a BMI ≤ 20.6 kg/m² (HR = 2.30; 95% CI, 1.36-3.87), ICU admission (HR = 1.97; 95% CI, 1.17-3.30) and TNM stage (stage II: HR = 5.56; 95% CI, 1.59-19.43; stage III: HR = 16.20; 95% CI, 4.99-52.59) were significantly associated with CSS. CONCLUSIONS: Low BMI (≤ 20.6 kg/m²), ICU admission and advanced pathological TNM stages (II and III) are independent risk factors for CSS in EGC patients after curative gastrectomy. Nutrition support, better perioperative management and early diagnosis would be helpful for better survival.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.755-765
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• 2023

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca²⁺ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca²⁺ ([Ca²⁺]_i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca²⁺]_i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca²⁺]_i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca²⁺]_i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca²⁺ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca²⁺]_i.

• Korean Journal of Radiology
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• v.22 no.7
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• pp.1213-1224
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• 2021

Objective: To develop a machine learning (ML) pipeline based on radiomics to predict Coronavirus Disease 2019 (COVID-19) severity and the future deterioration to critical illness using CT and clinical variables. Materials and Methods: Clinical data were collected from 981 patients from a multi-institutional international cohort with real-time polymerase chain reaction-confirmed COVID-19. Radiomics features were extracted from chest CT of the patients. The data of the cohort were randomly divided into training, validation, and test sets using a 7:1:2 ratio. A ML pipeline consisting of a model to predict severity and time-to-event model to predict progression to critical illness were trained on radiomics features and clinical variables. The receiver operating characteristic area under the curve (ROC-AUC), concordance index (C-index), and time-dependent ROC-AUC were calculated to determine model performance, which was compared with consensus CT severity scores obtained by visual interpretation by radiologists. Results: Among 981 patients with confirmed COVID-19, 274 patients developed critical illness. Radiomics features and clinical variables resulted in the best performance for the prediction of disease severity with a highest test ROC-AUC of 0.76 compared with 0.70 (0.76 vs. 0.70, p = 0.023) for visual CT severity score and clinical variables. The progression prediction model achieved a test C-index of 0.868 when it was based on the combination of CT radiomics and clinical variables compared with 0.767 when based on CT radiomics features alone (p < 0.001), 0.847 when based on clinical variables alone (p = 0.110), and 0.860 when based on the combination of visual CT severity scores and clinical variables (p = 0.549). Furthermore, the model based on the combination of CT radiomics and clinical variables achieved time-dependent ROC-AUCs of 0.897, 0.933, and 0.927 for the prediction of progression risks at 3, 5 and 7 days, respectively. Conclusion: CT radiomics features combined with clinical variables were predictive of COVID-19 severity and progression to critical illness with fairly high accuracy.

• Korean Journal of Radiology
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• v.24 no.4
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• pp.338-348
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• 2023

Objective: Patients with a history of ischemic stroke are at risk for a second ischemic stroke. This study aimed to investigate the relationship between carotid plaque enhancement on perfluorobutane microbubble contrast-enhanced ultrasonography (CEUS) and future recurrent stroke, and to determine whether plaque enhancement can contribute to risk assessment for recurrent stroke compared with the Essen Stroke Risk Score (ESRS). Materials and Methods: This prospective study screened 151 patients with recent ischemic stroke and carotid atherosclerotic plaques at our hospital between August 2020 and December 2020. A total of 149 eligible patients underwent carotid CEUS, and 130 patients who were followed up for 15-27 months or until stroke recurrence were analyzed. Plaque enhancement on CEUS was investigated as a possible risk factor for stroke recurrence and as a possible adjunct to ESRS. Results: During follow-up, 25 patients (19.2%) experienced recurrent stroke. Patients with plaque enhancement on CEUS had an increased risk of stroke recurrence events (22/73, 30.1%) compared to those without plaque enhancement (3/57, 5.3%), with an adjusted hazard ratio (HR) of 38.264 (95% confidence interval [CI]:14.975-97.767; P < 0.001) according to a multivariable Cox proportional hazards model analysis, indicating that the presence of carotid plaque enhancement was a significant independent predictor of recurrent stroke. When plaque enhancement was added to the ESRS, the HR for stroke recurrence in the high-risk group compared to that in the low-risk group (2.188; 95% CI, 0.025-3.388) was greater than that of the ESRS alone (1.706; 95% CI, 0.810-9.014). A net of 32.0% of the recurrence group was reclassified upward appropriately by the addition of plaque enhancement to the ESRS. Conclusion: Carotid plaque enhancement was a significant and independent predictor of stroke recurrence in patients with ischemic stroke. Furthermore, the addition of plaque enhancement improved the risk stratification capability of the ESRS.

• The Journal of Dong Guk Oriental Medicine
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• v.10
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• pp.41-61
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• 2008

The outline and characteristics of the important doctors of the 'Zhe Zhong Pai'(折衷派) are as follows. Part 1. In the late Edo(江戶) period The 'Zhe Zhong Pai', which tried to take the theory and clinical treatment of the 'Hou Shi Pai (後世派)' and the 'Gu Fang Pai(古方派)' and get their strong points to make treatments perfect, appeared. Their point was 'The main part is the art of the ancients, The latter prescriptions are to be used'(以古法爲主, 後世方爲用) and the "Shang Han Lun(傷寒論)" was revered for its treatments but in actual use it was not kept at that. As mentioned above The 'Zhe Zhong Pai' viewed treatments as the base, which was the view of most doctors in the Edo period. However, the reason the 'Zhe Zhong Pai' is not valued as much as the 'Gu Fang Pai' by medical history books in Japan is because the 'Zhe Zhong Pai' does not have the substantiation or uniqueness of the 'Gu Fang Pai', and also because the view of 'gather as well as store up'(兼收並蓄) was the same as the 'Kao Zheng Pai'. Moreover, the 'compromise'(折衷) point of view was from taking in both Chinese and western medical knowledge systems(漢蘭折衷). Generally the pioneer of the 'Zhe Zhong Pai' is seen as Mochizuki Rokumon(望月鹿門) and after that was Fukui Futei(福井楓亭), Wadato Kaku(和田東郭), Yamada Seichin(山田正珍) and Taki Motohiro(多紀元簡). Part 2. The lives of Wada Tokaku(和田東郭), Nakagame Kinkei(中神琴溪), Nei Teng Xi Zhe(內藤希哲), the important doctors of the 'Zhe Zhong Pai', are as follows. First Wada Tokaku(和田東郭, 1743-1803) was born when the 'Hou Shi Pai' was already declining and the 'Gu Fang Pai' was flourishing and learned medicine from a 'Hou Shi Pai' doctor, Hu Tian Xu Shan(戶田旭山) and a 'Gu Fang Pai' doctor, Yoshimasu Todo(吉益東洞). He was not hindered by 'the old ways(古方)' and did not lean towards 'the new ways(後世方)' and formed a way of compromise that 'looked at hardness and softness as the same'(剛柔相摩) by setting 'the cure of the disease' as the base, and said that to cure diseases 'the old way' must be used, but 'the new way' was necessary to supplement its shortcomings. His works include "Dao Shui Suo Yan(導水瑣言)", "Jiao Chiang Fang Yi Je(蕉窗方意解)" and "Yi Xue Sho(醫學說)". Second. Nakagame Kinkei(中神琴溪, 1744-1833) was famous for leaving Yoshimasu Todo(吉益東洞) and changing to the 'Zhe Zhong Pai', and in his early years used qing fen(輕粉) to cure geisha(妓女) of syphilis. His argument was "the "Shang Han Lun" must be revered but needs to be adapted", "Zhong Jing can be made into a follower but I cannot become his follower", "the later medical texts such as "Ru Men Shi Qin(儒門事親)" should only be used for its prescriptions and not its theories". His works include "Shang Han Lun Yue Yan(傷寒論約言)". Third, Nei Teng Xi Zhe(內藤希哲, 1701-1735) learned medicine from Qing Shui Xian Sheng(淸水先生) and went out to Edo. In his book "Yi Jing Jie Huo Lun(醫經解惑論)" he tells of how he went from 'learning'(學) to 'skepticism'(惑) and how skepticism made him learn in 'the six skepticisms'(六惑). In the latter years Xi Zhe(希哲) combines the "Shen Nong Ben Cao Jing(神農本草經)", the main text for herbal medicine, "Ming Tang Jing(明堂經)" of accupuncture, basic theory texts "Huang Dui Nei Jing(皇帝內經)" and "Nan Jing(難經)" with the "Shang Han Za Bing Lun", a book that the 'Gu Fang Pai' saw as opposing to the rest, and became 'an expert of five scriptures'(五經一貫). Part 3. Asada Showhaku(淺田宗伯, 1815-1894) started medicine at Zhong Cun Zhong Zong(中村中倧) and learned 'the old way'(古方) from Yoshimasu Todo and got experience through Ouan Yue(川越) and Fu Jing(福井) and received teachings in texts, history and Wang Yangmin's principles(陽明學) fmm famous teachers. Showhaku(倧伯) meets a medical official of the makufu(幕府), Ben Kang Zong Yuan(本康宗圓), and receives help from the 3 great doctors of the Edo period, Taki Motokato(多紀元堅), Xiao Dao Xue Gu(小島學古) and Xi Duo Cun Kao(喜多村栲窻) and further develops his arts. At 47 he diagnoses the general Jia Mao(家茂) with 'heart failure from beriberi'(脚氣衡心) and becomes a Zheng Shi(徵土), at 51 he cures a minister from France and received a present from Napoleon, at 65 he becomes the court physician and saves Ming Gong(明宮) Jia Ren Qn Wang(嘉仁親王, later the 大正天皇) from bodily convulsions and becomes 'the vassal of merit who saved the national polity(國體)' At the 7th year of the Meiji(明治) he becomes the 2nd owner of Wen Zhi She(溫知社) and takes part in the 'kampo continuation movement'. In his latter years he saw 14000 patients a year, so we can estimate the qualjty and quantity of his clinical skills. Showhaku(宗伯) wrote over 80 books including the "Ju Chuang Shu Ying(橘窻書影)", "Wu Wu Yao Shi Fang Han(勿誤藥室方函)", "Shang Han Biang Shu(傷寒辨術)", "Jing Qi Shen Lun(精氣神論)", "Hunag Guo Ming Yi Chuan(皇國名醫傳)" and the "Xian Jhe Yi Hua(先哲醫話)". Especially in the "Ju Chuang Shu Ying(橘窻書影) he says "the old theories are the main, and the new prescriptions are to be used"(以古法爲主, 後世方爲用), stating the 'Zhe Zhong Pai' way of thinking, In the first volume of "Shang Han Biang Shu(傷寒辨術)" and "Za Bing Lun Shi(雜病論識)", 'Zong Ping'(總評), He discerns the parts that are not Zhang Zhong Jing's writings and emphasizes his theories and practical uses.

• Journal of Korean Medical classics
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• v.20 no.3
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• pp.121-141
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• 2007

The outline and characteristics of the important doctors of the 'Zhe Zhong Pai'(折衷派) are as follows. Part 1. In the late Edo(江戶) period The 'Zhe Zhong Pai', which tried to take the theory and clinical treatment of the 'Hou Shi Pai (後世派)' and the 'Gu Fang Pai (古方派)' and get their strong points to make treatments perfect, appeared. Their point was 'The main part is the art of the ancients, The latter prescriptions are to be used'(以古法爲主, 後世方爲用) and the "Shang Han Lun(傷寒論)" was revered for its treatments but in actual use it was not kept at that. As mentioned above The 'Zhe Zhong Pai ' viewed treatments as the base, which was the view of most doctors in the Edo period, However, the reason the 'Zhe Zhong Pai' is not valued as much as the 'Gu Fang Pai' by medical history books in Japan is because the 'Zhe Zhong Pai' does not have the substantiation or uniqueness of the 'Gu Fang Pai', and also because the view of 'gather as well as store up' was the same as the 'Kao Zheng Pai', Moreover, the 'compromise'(折衷) point of view was from taking in both Chinese and western medical knowledge systems(漢蘭折衷), Generally the pioneer of the 'Zhe Zhong Pai' is seen as Mochizuki Rokumon(望月鹿門) and after that was Fukui Futei(福井楓亭), Wadato Kaku(和田東郭), Yamada Seichin(山田正珍) and Taki Motohiro(多紀元簡), Part 2. The lives of Wada Tokaku(和田東郭), Nakagame Kinkei(中神琴溪), Nei Teng Xi Zhe(內藤希哲), the important doctors of the 'Zhe Zhong Pai', are as follows First. Wada Tokaku(和田東郭, 1743-1803) was born when the 'Hou Shi Pai' was already declining and the 'Gu Fang Pai' was flourishing and learned medicine from a 'Hou Shi Pai' doctor, Hu Tian Xu Shan(戶田旭山) and a 'Gu Fang Pai' doctor, Yoshimasu Todo(吉益東洞). He was not hindered by 'the old ways(古方), and did not lean towards 'the new ways(後世方)' and formed a way of compromise that 'looked at hardness and softness as the same'(剛柔相摩) by setting 'the cure of the disease' as the base, and said that to cure diseases 'the old way' must be used, but 'the new way' was necessary to supplement its shortcomings. His works include "Dao Shui Suo Yan", "Jiao Chiang Fang Yi Je" and "Yi Xue Sho(醫學說)" Second. Nakagame Kinkei(中神琴溪, 1744-1833) was famous for leaving Yoshirnasu Todo(吉益東洞) and changing to the 'Zhe Zhong Pai', and in his early years used qing fen(輕粉) to cure geisha(妓女) of syphilis. His argument was "the "Shang Han Lun" must be revered but needs to be adapted", "Zhong jing can be made into a follower but I cannot become his follower", "the later medical texts such as "Ru Men Shi Qin(儒門事親)" should only be used for its prescriptions and not its theories". His works include "Shang Han Lun Yue Yan(傷寒論約言) Third. Nei Teng Xi Zhe(內藤希哲, 1701-1735) learned medicine from Qing Shui Xian Sheng(淸水先生) and went out to Edo. In his book "Yi Jing Jie Huo Lun(醫經解惑論)" he tells of how he went from 'learning'(學) to 'skepticism'(惑) and how skepticism made him learn in 'the six skepticisms'(六惑). In the latter years Xi Zhe(希哲) combines the "Shen Nong Ben Cao jing(神農本草經)", the main text for herbal medicine, "Ming Tang jing(明堂經)" of accupuncture, basic theory texts "Huang Dui Nei jing(黃帝內徑)" and "Nan jing(難經)" with the "Shang Han Za Bing Lun", a book that the 'Gu Fang Pai' saw as opposing to the rest, and became 'an expert of five scriptures'(五經一貫). Part 3. Asada Showhaku(淺田宗伯, 1815-1894) started medicine at Zhong Cun Zhong(中村中倧) and learned 'the old way'(古方) from Yoshirnasu Todo and got experience through Chuan Yue(川越) and Fu jing(福井) and received teachings in texts, history and Wang Yangmin's principles(陽明學) from famous teachers. Showhaku(宗伯) meets a medical official of the makufu(幕府), Ben Kang Zong Yuan(本康宗圓), and recieves help from the 3 great doctors of the Edo period, Taki Motokato(多紀元堅), Xiao Dao Xue GU(小島學古) and Xi Duo Cun Kao Chuang and further develops his arts. At 47 he diagnoses the general Jia Mao(家茂) with 'heart failure from beriberi'(脚氣衝心) and becomes a Zheng Shi(徵I), at 51 he cures a minister from France and received a present from Napoleon, at 65 he becomes the court physician and saves Ming Gong(明宮) jia Ren Qn Wang(嘉仁親王, later the 大正犬皇) from bodily convulsions and becomes 'the vassal of merit who saved the national polity(國體)' At the 7th year of the Meiji(明治) he becomes the 2nd owner of Wen Zhi She(溫知社) and takes part in the 'kampo continuation movement'. In his latter years he saw 14000 patients a year, so we can estimate the quality and quantity of his clinical skills Showhaku(宗伯) wrote over 80 books including the "Ju Chuang Shu Ying(橘窓書影)", "WU Wu Yao Shi Fang Han(勿誤藥室方函)", "Shang Han Biang Shu(傷寒辨術)", "jing Qi Shen Lun(精氣神論)", "Hunag Guo Ming Yi Chuan(皇國名醫傳)" and the "Xian Jhe Yi Hua(先哲醫話)". Especially in the "Ju Chuang Shu Ying(橘窓書影)" he says "the old theories are the main, and the new prescriptions are to be used"(以古法爲主, 後世方爲用), stating the 'Zhe Zhong Pai' way of thinking. In the first volume of "Shung Han Biang Shu(傷寒辨術) and "Za Bing Lun Shi(雜病論識)", 'Zong Ping'(總評), He discerns the parts that are not Zhang Zhong Jing's writings and emphasizes his theories and practical uses.