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Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients

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World Journal of Gastroenterology 2021年第42期27卷 7340-7349页

作者： Min-Woo chung Moon-Ju Kim eun Jeong Won Yu Jeong Lee Yong-Woon Yun Sung Bum Cho Young-eun Joo Jun-Eul Hwang Woo Kyun Bae Ik-Joo chung Myung Geun Shin Jong Hee Shin Department of Internal Medicine Chonnam National University Hospital and College of MedicineHwasun 58128Jeollanam-doSouth Korea Department of Parasitology and Tropical Medicine Chonnam National University Medical SchoolHwasun 58128Jeollanam-doSouth Korea Department of Laboratory Medicine Chonnam National University Hwasun HospitalHwasun 58128Jeollanam-doSouth Korea Department of Preventive Medicine Chonnam National University Medical SchoolHwasun-eupHwasun 58128Jeollanam-doSouth Korea Department of Laboratory Medicine Chonnam National University HospitalGwangju 61469South Korea

BACKGROUND Immunotherapy has revolutionized the clinical outcomes of intractable cancer *** is known about the intestinal nonpathogenic bacterial composition of hepatocellular carcinoma(HCC)patients treated by *** To determine whether there is a correlation between gut bacterial composition and prognosis in HCC *** From September 2019 to March 2020,we prospectively collected fecal samples and examined the gut microbiome of 8 advanced HCC patients treated with nivolumab as a second-or third-line systemic *** samples were collected before the start of *** samples of patients with progression during treatment were collected at the time of progression,and fecal samples of patients who showed good response to nivolumab were collected after 5-7 mo as *** data from 16S ribosomal RNA sequencing were analyzed using CLC Genomics *** data were analyzed according to therapeutic *** All 8 patients were male,of which 6 had underlying chronic hepatitis B.A higher Shannon index was found in the responders than in the non-responders after nivolumab therapy(P=0.036).The unweighted beta diversity analysis also showed that the overall bacterial community structure and phylogenetic diversity were clearly distinguished according to therapeutic *** was no significant difference in the diversity or composition of the patient gut microbiome according to the immunotherapy *** taxa specific to therapeutic response were designated as follows:Dialister pneumosintes,Escherichia coli,Lactobacillus reteri,Streptococcus mutans,Enterococcus faecium,Streptococcus gordonii,Veillonella atypica,Granulicatella sp.,and Trchuris trichiura for the nonresponders;Citrobacter freundii,Azospirillum *** Enterococcus durans for the *** note,a skewed Firmicutes/Bacteroidetes ratio and a low Prevotella/Bacteroides ratio can serve as predictive markers of non-response,wh

关键词： Microbiome Nivolumab Firmicutes/Bacteroidetes ratio Prevotella/Bacteroides ratio Hepatocellular carcinoma Prognosis

Hwangryunhaedoktang exerts anti-inflammation on LPS-induced NO production by suppressing MAPK and NF-κB activation in RAW264.7 macrophages

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Journal of Integrative Medicine 2017年第4期15卷 326-336页

作者： Byung hyuk Han Yun Jung Lee Jung Joo Yoon eun Sik Choi Seung Namgung Xian Jun Jin Da Hye Jeong Dae Gill Kang Ho Sub Lee College of Oriental Medicine and Professional Graduate School of Oriental Medicine Wonkwang University Hanbang Body-fluid Research Center Wonkwang University

OBJECTIVE： This study aimed to evaluate whether Hwangryunhaedoktang （HHT）, a herbal compound, has an inhibitory effect on lipopolysaccharide （LPS）-induced inflammation in RAW264.7 macrophages. METHODS： The effects of HHT were evaluated by confirming nitric oxide （NO） production and expression of inducible NO synthase （iNOS） and mitogen-activated protein kinases （MAPKs） in LPS-stimulated RAW264.7 macrophages via the Griess assay, Western blotting, and real-time reverse transcription quantitative polymerase chain reaction. Western blot analyses and luciferase assays were used to evaluate whether HHT has an effect on the phosphorylation and translocation of nuclear factor-κB （NF-κB）. The secretion and expression of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were determined via enzyme-linked immunosorbent assay and Western blot analyses. RESULTS： HHT suppressed LPS-induced NO production and expression of iNOS in a dose-dependent manner. Additionally, MAPKs activation was also attenuated via inhibition of phosphorylation of extracellular signal-regulated kinases 1/2, c-Jun N-terminal kinase and p38 which were related to inflammatory pathway. Furthermore, HHT also effectively attenuated NF-κB activation and its translocation to the nucleus, a process that is closely linked to inflammation. LPS normally induced the expression of inflammatory cytokines such as TNF-α and IL-6, but the secretion and expression of TNF-α and IL-6 were significantly attenuated by pretreating the cells with HHT. CONCLUSION： HHT suppressed LPS-induced NO production by blocking the activation of NF-κB and MAPK signaling pathways in RAW264.7 macrophages. Furthermore, HHT may have an anti-inflammatory effect by suppressing the LPS-induced secretion of TNF-α and IL-6. Therefore, the traditional herbal formula HHT might be a useful potential therapeutic agent for inflammation.

关键词： medicine, Chinese traditional lipopolysaccharide nitric oxide nuclear factor-κB mitogen-activatedprotein kinases tumor necrosis factor-a inflammation

Involvement of heme oxygenase-1 induction in anti-vascular inflammation effects of Xanthoceras sorbifolia in human umbilical vein endothelial cells

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Journal of Traditional Chinese Medicine 2018年第6期38卷 803-814页

作者： Jung Joo Yoon Byung hyuk Han eun Sik Choi Seung Namgung Da Hye Jeong Song Nan Jin Yun Jung Lee Dae Gill Kang Ho Sub Lee College of Oriental Medicine and Professional Graduate School of Oriental Medicine Wonkwang University Hanbang Cardio-Renal Syndrome Research Center Wonkwang University Institute of Materia Medica Taishan Medical University

OBJECTIVE: To define the effects of Xanthoceras sorbifolia(EXS) on vascular inflammation and the mechanisms in endothelial ***: Vascular protective effects of an ethanol extract of seeds from EXS(1-50 μg/mL) against tumor necrosis factor-α(TNF-α)-induced vascularinflammation were examined in human umbilical vein endothelial cells(HUVECs).RESULTS: EXS significantly decreased TNF-α-induced expression of cell adhesion molecules, such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial cell selectin,in a dose-dependent manner. Pre-treatment with EXS significantly inhibited translocation and transcriptional activity of nuclear factor-κB(NF-κB) increased by TNF-α. EXS also significantly inhibited formation of intracellular reactive oxygen species(ROS). Moreover, the vascular protective effects of EXS were linked to up-regulation of heme oxygenase-1(HO-1) and nuclear factor E2-related factor-2(Nrf-2) expression. EXS-induced HO-1 expression was significantly decreased in SnPP(HO-1 inhibitor)-and HO-1 siRNA-treated cells, whereas an increase was found in cobalt protoporphyrin IX(CoPP)(HO-1 inducer)-treated cells. In addition, pretreatment with EXS increased HO-1 and Nrf-2 expression under TNF-α stimulation with or without N-acetyl-L-cysteine. Furthermore, the inhibitory effects of EXS on TNF-α-induced vascular inflammation were partially reversed in SnPP-and of HO-1siRNA-treated cells but increased by ***: These results suggest that EXS may have important implications for prevention of vascular complications associated with vascular inflammation by inhibition of the NF-κB/ROS pathway and activation of the Nrf-2/HO-1 pathway.

关键词： Sapindaceae Vascular disease inflammation Human umbilical vein endothelial cells Cell adhesion molecules NF-kappa B Heme oxy-genase-1

Risk factors for metachronous gastric carcinoma development after endoscopic resection of gastric dysplasia: Retrospective, single-center study

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World Journal of Gastroenterology 2017年第24期23卷 4407-4415页

作者： Hee Seok Moon Gee Young Yun Ju Seok Kim hyuk Soo eun Sun Hyung Kang Jae Kyu Sung Hyun Yong Jeong Kyu-Sang Song Department of Internal Medicine Chungnam National University Hospital Chungnam National University School of Medicine Department of Pathology Chungnam National University Hospital Chungnam National University School of Medicine

To determine the gastric adenocarcinoma (GAC) occurrence rate and related factors, we evaluated the follow-up results of patients confirmed to have gastric dysplasia after endoscopic resection (ER). METHODSWe retrospectively analyzed the medical records, endoscopic examination records, endoscopic procedure records, and histological records of 667 cases from 641 patients who were followed-up for at least 12 mo, from among 1273 patients who were conformed to have gastric dysplasia after Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of gastric mucosal lesions between January 2007 and August 2013 at the chungnam National University Hospital. RESULTSThe mean follow-up period was 33.8 mo, and the median follow-up period was 29 mo (range: 12-87). During the follow-up period, the occurrence of metachronous GAC was 4.0% (27/667). The mean and median interval periods between the occurrence of metachronous GAC and endoscopic treatment of gastric dysplasia were 36.3 and 34 mo, respectively (range: 16-71). The factors related to metachronous GAC occurrence after ER for gastric dysplasia were male sex (5.3% vs 1.0%), open-type atrophic gastritis (9.5% vs 3.4%), intestinal metaplasia (6.8% vs 2.4%), and high-grade dysplasia (HGD; 8.4% vs 3.2%). Among them, male sex [OR: 5.05 (1.18-21.68), P = 0.029], intestinal metaplasia [OR: 2.78 (1.24-6.23), P = 0.013], and HGD [OR: 2.70 (1.16-6.26), P = 0.021] were independent related factors in multivariate analysis. Furthermore, 24 of 27 GAC cases (88.9%) occurred at sites other than the previous resection sites, and 3 (11.1%) occurred at the same site as the previous resection site. CONCLUSIONMale sex, intestinal metaplasia, and HGD were significantly related to the occurrence of metachronous GAC after ER of gastric dysplasia, and most GACs occurred at sites other than the previous resection sites.

关键词： Gastric dysplasia Neoplasms Second primary Endoscopic mucosal resection Stomach neoplasms

Differential risk of 23 site-specific incident cancers and cancer-related mortality among patients withmetabolic dysfunction-associated fatty liver disease:a population-based cohort study with 9.7 million Korean subjects

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Cancer Communications 2023年第8期43卷 863-876页

作者： Goh eun chung Su Jong Yu Jeong-Ju Yoo Yuri Cho Kyu-na Lee Dong Wook Shin Yoon Jun Kim Jung-Hwan Yoon Kyungdo Han eun Ju Cho Department of Internal Medicine and Healthcare Research Institute Seoul National University Hospital Healthcare System Gangnam CenterSeoulRepublic of Korea Department of Internal Medicine and Liver Research Institute Seoul National University College of MedicineSeoulRepublic of Korea Department of Gastroenterology and Hepatology Soonchunhyang University Bucheon HospitalBucheonGyeonggi-doRepublic of Korea Center for Liver and Pancreatobiliary Cancer National Cancer CenterGoyangGyeonggi-doRepublic of Korea Department of Biomedicine&Health Science Catholic University of KoreaSeoulRepublic of Korea Department of Family Medicine/Supportive care center Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea Department of Clinical Research Design and Evaluation/Department of Digital Health Samsung Advanced Institute for Health ScienceSeoulRepublic of Korea Department of Statistics and Actuarial Science Soongsil UniversitySeoulRepublic of Korea

Introduction:Although an association between metabolic dysfunctionassociated fatty liver disease(MAFLD)and cardiovascular disease or overall mortality has been reported,it is unclearwhether there is an association between MAFLD and cancer incidence or *** aimed to investigate the differential risk of all-and site-specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver ***:Using the Korean National Health Insurance Service database,we stratified the participants into three groups:(1)single-etiology MAFLD(SMAFLD)or MAFLD of pure metabolic origin;(2)mixed-etiology MAFLD(M-MAFLD)or MAFLD with additional etiological factor(s)(i.e.,concomitant liver diseases and/or heavy alcohol consumption);and(3)*** steatosis and fibrosiswere defined using the fatty liver index and the BARDscore,*** proportional hazards regression was performed to estimate the risk of cancer ***:Among the 9,718,182 participants,the prevalence of S-MAFLD and M-MAFLD was 29.2%and 6.7%,*** the median 8.3 years of follow-up,510,330(5.3%)individuals were newly diagnosed with cancer,and 122,774(1.3%)cancer-related deaths occurred among the entire *** with the non-MAFLD group,the risk of all-cancer incidence and mortality was slightly higher among patients in the S-MAFLD group(incidence,adjusted hazard ratio[aHR]=1.03;95%confidence interval[CI]:1.02−1.04;mortality,aHR=1.06;95%CI:1.04−1.08)and highest among patients with M-MAFLD group(incidence,aHR=1.31;95%CI:1.29−1.32;mortality,aHR=1.45;95%CI:1.42−1.48,respectively).The M-MAFLD with fibrosis group(BARD score≥2)showed the highest relative risk of all-cancer incidence(aHR=1.38,95%CI=1.36–1.39),followed by the M-MAFLD without fibrosis group(aHR=1.09,95%CI=1.06–1.11).Similar trends were observed for cancer-related ***:MAFLD classification,by applying additional etiologies other than pure metabolic origi

关键词： cancer etiology metabolic mortality steatosis

Nontarget screening using passive air and water sampling with a level Ⅱ fugacity model to identify unregulated environmental contaminants

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Journal of Environmental Sciences 2017年第12期29卷 84-91页

作者： In-Young chung Yu-Mi Park Hyun-Jeoung Lee hyuk Kim Dong-Hoon Kim Il-Gyu Kim Sang-Min Kim Young-Sun Do Kwang-Seol Seok Jung-Hwan Kwon Chemical Research Division Environmental Health Research Department National Institute of Environmental ResearchIncheon Division of Environmental Science and Ecological Engineering Korea University

It is thought that there are many unregulated anthropogenic chemicals in the *** risk assessment of chemicals, it is essential to estimate the predicted environmental concentrations. As an effort of identifying residual organic contaminants in air and water in Korea, nontarget screening using two-dimensional gas chromatography time-of-flight mass spectrometry（GC × GC-TOFMS） was conducted at 10 sites using polyurethane foam passive air sampler and at 6 sites using polydimethyl siloxane（PDMS） passive water sampler in three different seasons in 2014. More than 600 chemical peaks were identified satisfying the identification criteria in air and water samples, respectively, providing a list for further investigation. Chemical substances with reported national emission rates in2014（n = 149） were also screened for potential existence in the environment using a level Ⅱ fugacity model. Most of chemical substances classified as not detectable were not identified with detection frequency greater than 20% by nontarget screening, indicating that a simple equilibrium model has a strong potential to be used to exclude chemicals that are not likely to remain in the environment after emissions from targeted monitoring.

关键词： Nontarget screening GC × GC-TOFMS Passive sampling Pollutant release and transfer register(PRTR) Fugacity model

Endoscopic en bloc resection of an exophytic gastrointestinal stromal tumor with suction excavation technique

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World Journal of Gastroenterology 2016年第23期22卷 5454-5458页

作者： hyuk Soon Choi Hoon Jai Chun Kyoung-Oh Kim eun Sun Kim Bora Keum Yoon-Tae Jeen Hong Sik Lee Chang Duck Kim Division of Gastroenterology and Hepatology Department of Internal MedicineInstitute of Gastrointestinal Medical Instrument ResearchKorea University College of MedicineKorea University Medical Center Department of Internal Medicine Gachon University Gil Medical CenterGachon University of Medicine and Science

Here, we report the first successful endoscopic resection of an exophytic gastrointestinal stromal tumor (GIST) using a novel perforation-free suction excavation technique. A 49-year-old woman presented for further management of a gastric subepithelial tumor on the lesser curvature of the lower body, originally detected via routine upper gastrointestinal endoscopy. Abdominal computed tomography and endoscopic ultrasound showed a 4-cm extraluminally protruding mass originating from the muscularis propria layer. The patient firmly refused surgical resection owing to potential cardiac problems, and informed consent was obtained for endoscopic removal. Careful dissection and suction of the tumor was repeated until successful extraction was achieved without serosal injury. We named this procedure the suction excavation technique. The tumor’s dimensions were 3.5 cm × 2.8 cm × 2.5 cm. The tumor was positive for C-KIT and CD34 by immunohistochemical staining. The mitotic count was 6/50 high-power fields. The patient was followed for 5 years without tumor recurrence. This case demonstrated the use of endoscopic resection of an exophytic GIST using the suction excavation technique as a potential therapy without surgical resection.

关键词： Gastrointestinal stromal tumor Endoscopic resection Submucosal tumor Subepithelial tumor En bloc resection

Delayed diagnosis of imperforate hymen with huge hematocolpometra:A case report

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World Journal of Clinical Cases 2021年第29期9卷 8901-8905页

作者： eunbi Jang Kyeong A So Bomin Kim A Jin Lee Nae Ri Kim eun Jung Yang Seung-hyuk Shim Sun Joo Lee Tae Jin Kim Department of Obstetrics and Gynecology Konkuk University School of MedicineSeoul 05030South Korea

BACKGROUND Imperforate hymen is a rare obstructive anomaly of the female reproductive *** is associated with complications,such as cyclical abdominal pain,urinary retention,and pelvic *** SUMMARY A 13-year-old girl presented several times to the emergency room with lower abdominal pain for a *** received conservative treatment,such as pain control,at each *** visited our gynecological clinic for worsening pain,and a 14-cm hematocolpos was found on *** was finally diagnosed with an imperforate hymen with *** was performed,which resulted in event-free regular cyclical *** Imperforate hymen should be considered in a premenarcheal adolescent girl with periodic abdominal pain.

关键词： Hematocolpos Imperforate hymen Abdominal pain Amenorrhea Case report

Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization

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International Journal of Ophthalmology(English edition) 2016年第11期9卷 1541-1548页

作者： Jin Woo Kwon Jin A Choi eun Young Shin Tae Yoon La Dong Hyun Jee Yeon Woong chung Yang Kyung Cho Department of Ophthalmology St.Vincent's HospitalCollege of Medicinethe Catholic University of Korea Research Institute of Medical Science St.Vincent's Hospitalthe Catholic University of Korea

AIM： To evaluate whether trapping vascular endothelial growth factor-A（VEGF-A） would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture ***： We established two groups of animals, one with non-dry eyes and the other with induced dry *** both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I（aflibercept）,subgroup II（dexamethasone） and subgroup III（phosphate buffered saline, PBS）. Corneas were harvested and immunohistochemical staining was performed to compare the extents of neovascularization and CD11b＋ cell infiltration. Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and VEGF-A in the ***： Trapping VEGF-A with aflibercept resulted in significantly decreased angiogenesis and inflammation compared with the dexamethasone and PBS treatments in the dry eye corneas（all P 〈0.05）, but with no such effects in non-dry eyes. The anti-inflammatory and antiangiogenic effects of VEGF-A trapping were stronger than those of dexamethasone in both dry eye and non-dry eye corneas（all P 〈0.05）. The levels of RNA expression of VEGF-A, TNF-alpha, and IL-6 in the aflibercept subgroup were significantly decreasedcompared with those in the PBS subgroup in the dry eye ***： Compared with non-dry eye corneas,dry eye corneas have greater amounts of inflammation and neovascularization and also have a more robust response to anti-inflammatory and anti-angiogenic agents after ocular surface surgery. Trapping VEGF-A is effective in decreasing both angiogenesis and inflammation in dry eye corneas after ocular surface surgery.

关键词： dry eye aflibercept neovascularization inflammation dexamethasone