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Hwangryunhaedok-tang induces the depolarization of pacemaker potentials through 5-HT3 and 5-HT4 receptors in cultured murine small intestine interstitial cells of Cajal

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World Journal of Gastroenterology 2017年第29期23卷 5313-5323页

作者： Hyun Jung Kim guem san lee Hyungwoo Kim Byung Joo Kim Division of Longevity and Biofunctional Medicine Healthy Aging Korean Medical Research Center School of Korean Medicine Pusan National University Wonkwang University College of Korean Medicine Division of Pharmacology School of Korean Medicine Pusan National University Division of Longevity and Biofunctional Medicine School of Korean Medicine Pusan National University

AIM To investigate the effects of a water extract of Hwangryunhaedok-tang(HHTE) on the pacemaker potentials of mouse interstitial cells of Cajal(ICCs).METHODS We dissociated ICCs from small intestines and cultured. ICCs were immunologically identified using an antic-kit antibody. We used the whole-cell patch-clamp configuration to record the pacemaker potentials generated by cultured ICCs under the current clamp mode(I = 0). All experiments were performed at 30 ℃-32 ℃RESULTS HHTE dose-dependently depolarized ICC pacemaker potentials. Pretreatment with a 5-HT_3 receptor anta-gonist(Y25130) or a 5-HT_4 receptor antagonist(RS39604) blocked HHTE-induced pacemaker potential depolarizations, whereas pretreatment with a 5-HT7 receptor antagonist(SB269970) did not. Intracellular GDPβS inhibited HHTE-induced pacemaker potential depolarization and pretreatment with a Ca^(2+)-free solution or thapsigargin abolished the pacemaker potentials. In the presence of a Ca^(2+)-free solution or thapsigargin, HHTE did not depolarize ICC pacemaker potentials. In addition, HHTE-induced pacemaker potential depolarization was unaffected by a PKC inhibitor(calphostin C) or a Rho kinase inhibitor(Y27632). Of the four ingredients of HHT, Coptidis Rhizoma and Gardeniae Fructus more effectively inhibited pacemaker potential depolarization.CONCLUSION These results suggest that HHTE dose-dependently depolarizes ICC pacemaker potentials through 5-HT_3 and 5-HT_4 receptors via external and internal Ca^(2+) regulation and via G protein-, PKC-and Rho kinase-independent pathways.

关键词： Hwangryunhaedok-tang Interstitial cells of Cajal Pacemaker potentials Gastrointestinal tract Motility

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Effects of Hwangryunhaedok-tang on gastrointestinal motility function in mice

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World Journal of Gastroenterology 2017年第15期23卷 2705-2715页

作者： Hyoyeon Kim Iksung Kim Min Cheol lee Hyun Jung Kim guem san lee Hyungwoo Kim Byung Joo Kim Division of Longevity and Biofunctional Medicine Healthy Aging Korean Medical Research CenterSchool of Korean MedicinePusan National University Wonkwang University College of Korean Medicine Division of Pharmacology School of Korean MedicinePusan National University

AIM To investigate the effects of Hwangryunhaedok-tang(HHT) on gastrointestinal(GI) motility in mice.METHODS The effects of a boiling water extract of HHT(HHTE) on GI motility were investigated by calculating percent intestinal transit rates(ITR%) and gastric emptying(GE) values using Evans Blue and phenol red, respectively, in normal mice and in mice with experimentally induced GI motility dysfunction(GMD). In addition, the effects of the four components of HHT, that is, Gardeniae Fructus(GF), Scutellariae Radix(SR), Coptidis Rhizoma(CR), and Phellodendri Cortex(PC), on GI motility were also investigated.RESULTS In normal ICR mice, ITR% and GE values were significantly and dose-dependently increased by the intragastric administration of HHTE(0.1-1 g/kg). The ITR% values of GMD mice were significantly lower than those of normal mice, and these reductions were significantly and dose-dependently inhibited by HHTE(0.1-1 g/kg). Additionally, GF, CR, and PC dosedependently increased ITR% and GE values in normal and GMD mice.CONCLUSION These results suggest that HHT is a novel candidate for the development of a gastroprokinetic agent for the GI tract.

关键词： Hwangryunhaedok-tang 胃肠的活动性肠的运输率胃的倒空 Gastroprokinetic

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Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben Chung-Lap Chan Grace Gar-lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man Tsang Clara Bik-san Lau Ping-Chung Leung Chun-Kwok Wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary glands.Sixty-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat pads.Starting from the day of tumor cell inoculation,tumors were grown for 6 days.The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,respectively.The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week.The control group received daily oral gavage of 0.2 mL double-distilled water.The treatment period was 30 days.At the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota analysis.Results Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological activities.Moreover,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective in activating the anti-tumor immune response(P<

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

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Effects of Banxia Xiexin Decoction (半夏泻心汤) on Cisplatin-Induced Apoptosis of Human A549 Lung Cancer Cells

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Chinese Journal of Integrative Medicine 2018年第6期24卷 436-441页

作者： Ha-Rim Kim guem-san lee Mi-Seong Kim Do-Gon Ryu Hong-Seob So Hyoung-Chul Moon Young-Rae lee Sei-Hoon Yang Kang-Beom Kwon Center for Metabolic Function Regulation Wonkwang University School of Medicine Iksan Jeonbuk 54538 South Korea Department of Herbology Wonkwang University School of Korean Medicine Iksan Jeonbuk 54538 South Korea Department of Korean Physiology Wonkwang University School of Korean Medicine Iksan Jeonbuk 54538 South Korea Institute of Customized Physical Therapy Gwanju 62279 South Korea Department of Oral Biochemistry Wonkwang University School of Dentistry Iksan Jeonbuk 54538 South Korea Department of Internal Medicine Wonkwang University School of Medicine Iksan Jeonbuk 54538 South Korea

Objective： To examinie the synergistic effects of Banxia Xiexin Decoction （半夏泻心汤, Known as Banhasasim-tang in Korean） extract （BXDE） on cisplatin-induced cytotoxicity in the A549 human lung cancer ceil lines. Methods： A549 cells were treated with varying concentrations （50-200μg/mL） of cisplatin and BXDE alone or in combination for 96 h. We used 1-（4,5-dimethylthiazol-2-yl）-3,5-diphenylformazan assay and flow cytometry to analyze cell viability and apoptosis, respectively. Results： The exposure of cells to cispiatin and BXDE alone or in combination decreased ceil viability dose- and time-dependently （P〈0.05）, which was found to be mediated by the apoptotic pathway as confirmed by the increase in the annexin V^＋/propidium iodide stained cell population and a ladder pattern of discontinuous DNA fragments. Furthermore, the apoptosis was inhibited by the pan-caspase inhibitor, benzyloxycarbonyI-Val-Ala-Asp （OMe） fluoromethylketone （z-VAD-FMK）. Conclusions： BXDE significantly potentiated apoptotic effects of cisplatin in A549 cells. Moreover, apoptosis induced by BXDE might be the pivotal mechanism mediating its chemopreventative action against cancer.

关键词： Banxia Xiexin Decoction cisplatin A549 cells apoptosis anticancer synergism Chinese medicine

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臺灣地區廟宇楹聯中的中華文化與風土特色

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中国文化 2024年第1期 99-105页

作者：李淑珍臺北市立大學歷史與地理學系

臺灣地區保存的中華文化,除了文人大傳統之外,更有庶民之小傳統,寺廟就是其中之一;而寺廟楹聯馬文人馬地方信徒所撰寫,具有教化作用,則可謂大傳統與小傳統之間的媒介。清代臺灣地區號稱難治,官方遭遇的挑戰至少有三:其一是如何使南島語... 详细信息

臺灣地區保存的中華文化,除了文人大傳統之外,更有庶民之小傳統,寺廟就是其中之一;而寺廟楹聯馬文人馬地方信徒所撰寫,具有教化作用,則可謂大傳統與小傳統之間的媒介。清代臺灣地區號稱難治,官方遭遇的挑戰至少有三:其一是如何使南島語族部落林立的島嶼逐漸漢化;其二是如何使偷渡來壼的羅漢脚接受文教;其三則是如何面對反清復明傳統、消解官民對立。本文以明清時代堂南地區為例,討論廟宇楹聯如何反映當時的士紳心態,特别是他們如何透過這個公共載體來教化百姓、或傳遞官方意識形態。全國性信仰放在臺灣地區的歷史脉絡中,孔廟象徵中華文教的移植,玄天大帝代表對明代正統的懷念,關公則被清代官方用來獎勵忠節。而表現地方特色的神衹,海神媽祖與醫藥神保生大帝都與渡海來壹的移民有地緣關聯性;至於王爺信仰及鄭成功崇拜,更是暗藏了臺灣地區民間抗衡清代官方的社會力量,清廷最終必須退讓,與這些信仰妥協。總之,堂南地區的廟宇,一方面反映了中華文化在此地開始扎根,另一方面也反映了此地强烈的風土特色。

关键词：清代臺灣地區廟宇楹聯中華文化风土特色

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Tensorial tomographic Fourier ptychography with applications to muscle tissue imaging

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Advanced Photonics 2024年第2期6卷 50-60页

作者： Shiqi Xu Xi Yang Paul Ritter Xiang Dai Kyung Chul lee Lucas Kreiss Kevin C.Zhou Kanghyun Kim Amey Chaware Jadee Neff Carolyn Glass Seung Ah lee Oliver Friedrich Roarke Horstmeyer Duke University DurhamNorth CarolinaUnited States Friedrich-Alexander University ErlangenGermany UC san Diego La JollaCaliforniaUnited States Yonsei University SeoulRepublic of Korea UC Berkeley BerkeleyCaliforniaUnited States Duke University Medical Center DurhamNorth CarolinaUnited States

We report tensorial tomographic Fourier ptychography(T^(2)oFu),a nonscanning label-free tomographic microscopy method for simultaneous imaging of quantitative phase and anisotropic specimen information in 3D.Built upon Fourier ptychography,a quantitative phase imaging technique,T^(2)oFu additionally highlights the vectorial nature of light.The imaging setup consists of a standard microscope equipped with an LED matrix,a polarization generator,and a polarization-sensitive camera.Permittivity tensors of anisotropic samples are computationally recovered from polarized intensity measurements across three dimensions.We demonstrate T^(2)oFu’s efficiency through volumetric reconstructions of refractive index,birefringence,and orientation for various validation samples,as well as tissue samples from muscle fibers and diseased heart tissue.Our reconstructions of healthy muscle fibers reveal their 3D fine-filament structures with consistent orientations.Additionally,we demonstrate reconstructions of a heart tissue sample that carries important polarization information for detecting cardiac amyloidosis.

关键词： computational imaging three-dimensional imaging phase retrieval microscopy polarization-sensitive imaging labelfree imaging

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Toward Data-Driven Digital Therapeutics Analytics:Literature Review and Research Directions

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IEEE/CAA Journal of Automatica Sinica 2023年第1期10卷 42-66页

作者： Uichin lee Gyuwon Jung Eun-Yeol Ma Jin san Kim Heepyung Kim Jumabek Alikhanov Youngtae Noh Heeyoung Kim Korea Advanced Institute of Science and Technology Daejeon 34141Republic of Korea Inha University Incheon 402-751Republic of Korea KENTECH Naju-siRepublic of Korea

With the advent of digital therapeutics(DTx),the development of software as a medical device(SaMD)for mobile and wearable devices has gained significant attention in recent years.Existing DTx evaluations,such as randomized clinical trials,mostly focus on verifying the effectiveness of DTx products.To acquire a deeper understanding of DTx engagement and behavioral adherence,beyond efficacy,a large amount of contextual and interaction data from mobile and wearable devices during field deployment would be required for analysis.In this work,the overall flow of the data-driven DTx analytics is reviewed to help researchers and practitioners to explore DTx datasets,to investigate contextual patterns associated with DTx usage,and to establish the(causal)relationship between DTx engagement and behavioral adherence.This review of the key components of datadriven analytics provides novel research directions in the analysis of mobile sensor and interaction datasets,which helps to iteratively improve the receptivity of existing DTx.

关键词： Causal inference data-driven analytics framework digital therapeutics(DTx) mobile and wearable data technical and behavioral engagement

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Secular trends of intrahepatic cholangiocarcinoma in a high endemic area:A population-based study

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World Journal of Gastroenterology 2022年第28期28卷 3695-3705页

作者： Chun-Ru Lin Yu-Kwang lee Chun-Ju Chiang Ya-Wen Yang Hung-Chuen Chang san-Lin You School of Medicine College of MedicineFu Jen Catholic UniversityNew Taipei City 242008Taiwan Department of Surgery National Taiwan University HospitalTaipei 100229Taiwan Graduate Institute of Epidemiology and Preventive Medicine College of Public HealthNational Taiwan UniversityTaipei 10055Taiwan Division of Gastroenterology Department of Internal MedicineShin Kong Wu Ho-Su Memorial HospitalTaipei 111045Taiwan School of Medicine and Data Science Center Fu Jen Catholic UniversityNew Taipei City 242008Taiwan

BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is one of the most aggressive malignancies.However,because of its scarcity there are limited population-based data available for investigations into its epidemiologic characteristics.In Taiwan,we have a national cancer registry database that can be used to evaluate the secular trends of ICC.AIM To evaluate secular trends of ICC according to age,sex,and risk factors in Taiwan.METHODS In this population-based study,we used the national Taiwan Cancer Registry database.Age-standardized and relative percent changes in incidence rates were used to describe secular trends in incidence rates and sex ratios of ICC in Taiwan.RESULTS The age-standardized ICC incidence rate among males increased from 1.51 per 100000 in 1993-1997 to 4.07 per 100000 in 2013-2017 and among female from 1.73 per 100000 to 2.95 per 100000.The incidence in females tended to plateau after 2008-2012.For males,the ICC incidence increased as age increased.In the long-term incidence trend of ICC in females,the incidence of the four age groups(40-44,45-49,50-54 and 55-59 years)remained stable in different years;although,the incidence of the 60-64 group had a peak in 2003-2007,and the peak incidence of the 65-69 and 70-74 groups occurred in 2008-2012.Among males,beginning at the age of 65,there were increases in the incidence of ICC for the period of 2003-2017 as compared with females in the period of 2003-2017.CONCLUSION Increased incidence of ICC occurred in Taiwan over the past two decades.The increased incidence has progressively shifted toward younger people for both males and females.

关键词： Intrahepatic cholangiocarcinoma Incidence Secular trend Sex ratio Risk factor

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Pancreatic lymphangioma:two case reports from an institutional experience with a rare entity and review of literature

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Journal of Pancreatology 2022年第2期5卷 98-109页

作者： Alfonso Tan-Garcia Ser Yee lee Jen san Wong Thomas W.T.Ho Keng Sin Ng Kiat Hon Tony Lim Division of Pathology Department of Anatomical PathologySingapore General HospitalSingapore Surgical Associates Mount Elizabeth Medical CentreSingapore Department of Hepatopancreatobiliary and Transplant Surgery Singapore General HospitalSingapore Hepatobiliary and Pancreatic Surgery Centre Mount Elizabeth Medical CentreSingapore Digestive Surgical Oncology Department of Diagnostic Imaging Mount Alvernia HospitalSingapore

Pancreatic lymphangiomas are very rare benign cystic lesions that pose a diagnostic dilemma due to their resemblance to other non-neoplastic and neoplastic pancreatic cystic lesions.As such,pancreatic lymphangiomas are frequently diagnosed only after histological examination of the excised lesion.We present 2 cases of pancreatic lymphangioma,determine its prevalence at our institution and perform a detailed review of published literature since 2010.Case 1 is a 36-year-old male and case 2 is a 35-year-old female,both of which presented with abdominal pain.These were the only cases of pancreatic lymphangiomas reported at our institution since 2010.We reviewed 69 cases of pancreatic lymphangiomas from 52 publications.It affects predominantly females with a median age of 43 and such patients typically present with abdominal pain(58.8%)or are asymptomatic(27.9%).The median size is 8.6 cm,the most common location is the head of pancreas and the most common imaging finding is that of a multilocular cyst.Majority of patients underwent surgical resection(69.6%).Endoscopic ultrasound-guided fine-needle aspiration features of pancreatic lymphangiomas include chylous cyst fluid,elevated fluid triglyceride levels(15/16 cases)and numerous lymphocytes on cytology.The majority of patients with elevated fluid triglyceride levels(13/15 cases)were managed conservatively.Pancreatic lymphangiomas are rare pancreatic cystic lesions that may be diagnosed preoperatively using a multidisciplinary and multimodal approach involving clinical,radiological,biochemical and cytological features,allowing greater confidence in the selection of patients who can be managed conservatively.

关键词： Case report Cystic Diagnostic features Literature review Lymphangioma management Pancreas Prevalence

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Macroscopic Ag nanostructure array patterns with high-density hotspots for reliable and ultra-sensitive SERS substrates

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Nano Research 2019年第10期12卷 2554-2558页

作者： Taeksu lee Soongeun Kwon san ghee Jung Hyungjun Lim Jae-Jong lee Department of Nano Manufacturing Technology Korea Institute of Machinery and Materials(KIMM)156 Gajeongbuk-RoYuseong-GuDaejeon 34103Republic of Korea

Syn thesis of metal nano structures arrays with large amounts of small nano-gaps on a homoge nous macroscale is of significant in terest and importa nee in chemistry,biotech no logy,physics,and nan otech no logy because of their enhan ced properties.However,the fabricatio n of uncovered nano-gaps with high-density and uniformity is rather difficult due to the complex and multiple synthetic steps.In this research,a facile and low-cost approach is demonstraind for the synthesis of high-density small nano-gaps(about 3.4 nm)between silver nanostructure array patter ns(SNAPs)over a large area.Uniform nan o?hole patter ns were periodically gen erated over an entire substrate using nano-impri nt lithography.Electrochemical reacti on at the high over-potential produced multiple silver nano crystals inside the nano-hole patter ns,gen erati ng a high-de nsity of small and un covered nano-gaps.Finally,we fully dem on strate their applicati on in the rapid detectio n of rhodamine 6G(R6G)molecules by surface-enhaneed Raman scattering(SERS)spectroscopy with a very low detection limit(1 fM)as well as excellent signal uniformity(RSD<8.0%±2.5%),i ndicati ng an extra ordinary capability for single-molecule detecti on.

关键词： nanoImprint lithography surface-enhanced Raman scattering(SERS)spectroscopy electrodeposition nano patterning gold silver

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