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An apoptosis-independent role of TRAIL in suppressing joint inflammation and inhibiting T-cell activation in inflammatory arthritis

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Cellular & Molecular Immunology 2018年第9期15卷 846-857页

作者： I-Tsu Chyuan Hwei-Fang Tsai hsiu-Jung Liao Chien-Sheng Wu Ping-Ning Hsu Department of Internal Medicine Cathay General HospitalTaipeiTaiwanChina graduate Institute of Clinical Medicine College of MedicineNational Taiwan UniversityTaipeiTaiwanChina graduate Institute of Clinical Medicine College of MedicineTaipei Medical UniversityTaipeiTaiwanChina Department of Internal Medicine Taipei Medical University Shuang Ho HospitalTaipeiTaiwanChina graduate Institute of Immunology College of MedicineNational Taiwan UniversityTaipeiTaiwanChina Division of Rheumatology Department of Internal MedicineFar Eastern Memorial HospitalTaipeiTaiwanChina Department of Internal Medicine National Taiwan University HospitalTaipeiTaiwanChina

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been implicated in the regulation ofinflammation in rheumatoid arthritis (RA), primarily due to its ability to promote apoptosis in synoviocytes andinfiltrating lymphocytes. The aim of this study was to investigate the immunomodulatory mechanism and role ofTRAIL in inflammatory arthritis. We created an animal model of inflammatory arthritis and demonstrated that TRAILsignificantly inhibited joint inflammation and reduced the severity of arthritis. The suppression of joint inflammationwas not due to the TRAIL-mediated induction of apoptosis in T cells, macrophages or synovial fibroblasts. Incontrast, TRAIL directly inhibited T-cell proliferation and suppressed the production of cytokines, which indicatedthat TRAIL exerted its anti-inflammatory effects by direct inhibition of T-cell activation. Moreover, TRAIL receptor(TRAIL-R)-knockout mice developed more severe disease, and the protective effects of TRAIL were abolished in theexperimental arthritis model in TRAIL-R knockout mice. From these results, we conclude that TRAIL suppressesjoint inflammation via an apoptosis-independent pathway and directly inhibits T-cell activation. Our results providea novel apoptosis-independent, immune regulatory role for TRAIL in suppressing inflammatory arthritis and shedlight on the development of effective new therapies for autoimmune inflammatory diseases.

关键词： collagen-induced arthritis T-cell activation TRAIL

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Hepatobiliary Surgery and Nutrition 2019年第1期8卷 1-9页

作者： Li-Chueh Weng hsiu-Li Huang Wei-Chen Lee yu-Hsia Tsai Woan-Shyuan Wang Kang-HuaChen School of Nursing College of MedicineChang Gung UniversityTaoyuanTaiwan Department of general Surgery Transplantation CenterChang Gung Memorial Hospital LinkouTaoyuanTaiwan Department of Long-Term Care College of Health TechnologyNational Taipei University of Nursing and Health ScienceTaipeiTaiwan Department of Cardiovascular Medicine Chang Gung Memorial Hospital LinkouTaoyuanTaiwan Department of Nursing Chang Gung Memorial Hospital LinkouTaoyuanTaiwan

background:Improving the health-related quality of life(HRQOL)of living liver donors post-donation is an important aspect of care *** the HRQOL of living liver donors prospectively could help improve our understanding of the recovery of HRQOL and help improve the quality of donor *** this study,we examined the HRQOL of living liver donors at pre-donation and at 1-year post-donation and analyzed the effect of pre-and post-donation factors on the donors'physical and mental ***:This was a prospective *** the enrollment period(August 2013 to December 2015),68 living liver donors completed the study questionnaires 5 times:at pre-donation and at 1,3,6,and 12 months *** Medical Outcomes Study Questionnaire Short Form-36,which yields both physical(PCS)and mental(MCS)component summary scores,was used to measure the *** pre-and post-donation factors included donation ambivalence,recipients'physical condition,post-donation complications,and recipients'survival ***:Participants'mean PCS scores were 43.59 and 56.50 at 1 and 12 months after donation,respectively,whereas their mean MCS scores were 46.89 and 46.28,*** mean PCS score was worse at 1 month after donation but improved significantly over time(Py,the MCS was quite stable over time(P>0.05).A good PCS score was associated with no surgical complications of donation(coefficient=2.87,P=0.02),whereas a poor MCS score was associated with an education of less than a bachelor's degree(coefficient=?3.60,P=0.004),a higher Model for End-Stage Liver Disease(MELD)score in the recipient(coefficient=?0.13,P=0.03),and recipient death(coefficient=?3.48,P=0.03).Pre-donation ambivalence and sense of coherence were not significant predictors of the PCS or MCS ***:The impact of living liver donation on HRQOL was strongest in the early stages of the post-surgery period for the physical ***-care professionals should carefull

关键词： Ambivalence living-donor liver transplantation(LDLT) long term medical outcome quality of life

LipoCol Forte capsules reduce the risk of liver cancer:A propensity score-matched,nationwide,population-based cohort study

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World Journal of gastrointestinal Oncology 2023年第5期15卷 828-842页

作者： Hsiang-Chun Lai Hung-Jen Lin ying-hsiu Shih Jen-Wei Chou Kuan-Wen Lin Long-bin Jeng Sheng-Teng Huang graduate Institute of Chinese Medicine School of Chinese MedicineCollege of Chinese MedicineChina Medical UniversityTaichung 40447Taiwan School of Post-baccalaureate Chinese Medicine College of Chinese MedicineChina Medical UniversityTaichung 40402Taiwan Management Office for Health Data China Medical University HospitalTaichung 40447Taiwan Department of Internal Medicine China Medical University HospitalTaichung 40447Taiwan Department of Surgery China Medical University HospitalTaichung 40447Taiwan Organ Transplantation Center China Medical University HospitalTaichung 40447Taiwan Department of Chinese Medicine China Medical University HospitalTaichung 40447Taiwan Cancer Research Center for Traditional Chinese Medicine Department of Medical ResearchChina Medical University HospitalTaichung 40447Taiwan An-Nan Hospital China Medical UniversityTainan 709204Taiwan School of Chinese Medicine China Medical UniversityTaichung 40447Taiwan

bACKgROUND Liver cancer is among the top five most common cancers globally. Lipid-lowering drugs such as statins can lower the risk of liver cancer, but may also cause liver damage. LipoCol Forte capsules(LFC), a red yeast rice product, have demonstrated significant antihypercholesterolemic effects and a good safety profile in clinical *** To evaluate whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort *** We used data from Taiwan’s National Health Insurance Research Database, which includes electronic medical records for up to 99.99% of Taiwan’s population. LFC users and LFC non-users were matched 1:1 by propensity scores between January 2010 and December 2017. All had followup data for at least 1 year. Statistical analyses compared demographic distributions including sex, age, comorbidities, and prescribed medications. Cox regression analyses estimated adjusted hazard ratios(aHRs) after adjusting for potential *** We enrolled 33231 LFC users and 33231 non-LFC users(controls). No significant differences between the study cohorts were identified regarding comorbidities and medications [standardized mean difference(SMD) gnificantly lower in the LFC cohort compared with controls [aHR 0.91;95% confidence interval(CI): 0.86-0.95;P gnificantly reduced in both females(aHR 0.87;95%CI: 0.8-0.94;P bidities(including hypertension, ischemic stroke, diabetes mellitus, hyperlipidemia, hepatitis b infection and hepatitis C infection). Those using LFC for more than 84 drug days had a 0.64-fold lower risk of liver cancer compared with controls(P < 0.001). Compared with controls, the

关键词： LipoCol Forte capsules Hyperlipidemia Liver cancer Hepatocellular carcinoma Retrospective cohort study Taiwan National Health Insurance Research Database

Subgrouping time-dependent prescribing patterns of first-onset major depressive episodes by psychotropics dissection

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World Journal of Psychiatry 2021年第11期11卷 1116-1128页

作者： Hsi-Chung Chen Hui-Hsuan Hsu Mong-Liang Lu Ming-Chyi Huang Chun-Hsin Chen Tzu-Hua Wu Wei-Chung Mao Chuhsing K Hsiao Po-hsiu Kuo Department of Psychiatry&Center of Sleep Disorders National Taiwan University HospitalTaipei 100Taiwan Center of Statistical Consultation and Research National Taiwan University HospitalTaipei 100Taiwan Department of Psychiatry Wan-Fang Hospital&School of MedicineCollege of MedicineTaipei Medical UniversityTaipei 100Taiwan Department of Psychiatry Taipei City HospitalSongde BranchTaipei 100Taiwan Department of Clinical Pharmacy School of PharmacyCollege of PharmacyTaipei Medical UniversityTaipei 110Taiwan Department of Psychiatry Cheng-Hsin General HospitalTaipei 100Taiwan graduate Institute of Epidemiology and Preventive Medicine College of Public HealthNational Taiwan UniversityTaipei 100Taiwan

bACKgROUND Subgrouping patients with major depressive disorder is a promising solution for the issue of ***,the link between available subtypes and distinct pathological mechanisms is weak and yields disappointing results in clinical *** To develop a novel approach for classification of patients with time-dependent prescription patterns at first onset in real-world *** Drug-naive patients experiencing their first major depressive episode(n=105)participated in this *** agents prescribed in the first 24 mo following disease onset were recorded monthly and categorized as antidepressants,augmentation agents,and *** cumulative doses of agents in each category were converted into relevant *** parameters were used to summarize the time-dependent prescription patterns for each psychotropic load:Stability,amount,frequency,and the time trend of monthly prescriptions.A K-means cluster analysis was used to derive subgroups of participants based on these input parameters of psychotropic agents across 24 *** validity of the resulting data-driven clusters was compared using relevant severity *** Four distinct clusters were derived from K-means analysis,which matches experts’consent:"Short-term antidepressants use","long-term antidepressants use","long-term antidepressants and sedatives use",and"long-term antidepressants,sedatives,and augmentation use".At the first 2 years of disease course,the four clusters differed on the number of antidepressants used at adequate dosage and duration,frequency of outpatient service use,and number of psychiatric *** the first 2 years following disease onset,depression severity was differed in the four *** Our findings suggested a new approach to optimize the subgrouping of patients with major depressive disorder,which may assist future etiological and treatment response studies.

关键词： First episode Depression Classification Psychopharmacology Depression treatment

Detection of urine DNA markers for monitoring recurrent hepatocellular carcinoma

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Hepatoma Research 2017年第6期3卷 105-111页

作者： Hie-Won Hann Surbhi Jain grace Park Jamin DSteffen Wei Song ying-hsiu Su Liver Disease Prevention Center Division of Gastroenterology and HepatologyThomas Jefferson University HospitalPhiladelphiaPA19107USA JbS Science Inc.DoylestownPA18902USA The baruch S.blumberg Institute DoylestownPA18902USA.

Aim: This study aimed to explore the potential of detecting hepatocellular carcinoma (HCC)-associated DNA markers, TP53249T mutations and aberrant methylation of RASSF1A and gSTP1 genes, for monitoring HCC recurrence. HCC remains a leading cause of death worldwide, with one of the fastest growing incidence rates in the US. While treatment options are available and new ones emerging, there remains a poor prognosis of this disease mostly due to its late diagnosis and high recurrence rate. Although there are no specific guidelines addressing how HCC recurrence should be monitored, recurrence is usually monitored by serum-alpha fetal protein and imaging methods such as magnetic resonance imaging (MRI). However, early detection of recurrent HCC remains limited, particularly at the site of treated lesion. Methods: Here, the authors followed 10 patients that were treated for a primary HCC, and monitored for months or years later. At these follow-up visits, urine was collected and tested retrospectively for 3 DNA biomarkers that associate with HCC development. Results:This 10-patient study compared detection of urine DNA markers with MRI for monitoring HCC recurrence. Five patients were confirmed by MRI for recurrence, and all 5 had detectable DNA biomarkers up to 9 months before recurrence confirmation by MRI. Conclusion:Overall, this suggests that detection of HCC-associated DNA markers in urine could provide a promising tool to complement detection of recurrent HCC by imaging.

关键词： Hepatocellular carcinoma recurrence circulating-tumor DNA liver cancer biomarker urine tumor marker hepatitis b virus

Aryl hydrocarbon receptor signaling promotes ORMDL3- dependent generation of sphingosine-1-phosphate by inhibiting sphingosine-1-phosphate lyase

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Cellular & Molecular Immunology 2019年第10期16卷 783-790页

作者： Hsueh-Chun Wang Tzu-Hsuan Wong Li-Ting Wang Hsiang-Han Su hsiu-yueh yu Ai-Hsuan Wu yu-Chun Lin Hua-Ling Chen Jau-Ling Suen Shih-Hsien Hsu Li-Chen Chen yufeng Zhou Shau-Ku Huang Department of Medical Research China Medical University HospitalChina Medical University40402 TaichungTaiwanChina graduate Institute of Medicine College of MedicineKaohsiung Medical UniversityKaohsiungTaiwanChina Division of Allergy Asthma and RheumatologyDepartment of PediatricsChang Gung Memorial HospitalTaoyuanTaiwanChina National Institute of Environmental Health Sciences National Health Research InstitutesMiaoliTaiwanChina Research Center of Environmental Medicine Kaohsiung Medical UniversityKaohsiungTaiwanChina Center for Research Resources and Development Kaohsiung Medical UniversityKaohsiungTaiwanChina Community Medicine Research Center Chang Gung Memorial Hospital at KeelungKeelungTaiwanChina Department of Pediatrics Xiamen Chang Gung HospitalXiamenChina Johns Hopkins University School of Medicine BaltimoreMDUSA Key Laboratory of Neonatal Disease Children’s Hospital and Institute of Biomedical SciencesMinistry of HealthFudan University201102 ShanghaiChina Lou-Hu Hospital Shen-Zhen UniversityShen-ZhenChina

Aryl hydrocarbon receptor(AhR),a cellular chemical sensor,controls cellular homeostasis,and sphingosine-1-phosphate(S1P),a bioactive intermediate of sphingolipid metabolism,is believed to have a role in immunity and inflammation,but their potential crosstalk is currently *** aimed to determine whether there is a functional linkage between AhR signaling and sphingolipid *** showed that AhR ligands,including an environmental polycyclic aromatic hydrocarbon(PAH),induced S1P generation,and inhibited S1P lyase(S1PL)activity in resting cells,antigen/IgE-activated mast cells,and mouse lungs exposed to the AhR ligand alone or in combination with antigen *** reduction of S1PL activity was due to AhR-mediated oxidation of S1PL at residue 317,which was reversible by the addition of an antioxidant or in cells with knockdown of the ORMDL3 gene encoding an ER transmembrane protein,whereas C317A S1PL mutant-transfected cells were resistant to the AhR-mediated ***,analysis of AhR ligand-treated cells showed a time-dependent increase of the ORMDL3–S1PL complex,which was confirmed by FRET *** change increased the S1P levels,which in turn,induced mast cell degranulation via S1PR2 *** addition,elevated levels of plasma S1P were found in children with asthma compared to non-asthmatic *** results suggest a new regulatory pathway whereby the AhR–ligand axis induces ORMDL3-dependent S1P generation by inhibiting S1PL,which may contribute to the expression of allergic diseases.

关键词： Aryl hydrocarbon receptor ORMDL sphingolipid biosynthesis regulator 3 Sphingosine-1-phosphate Sphingosine-1-phosphate lyase

Link between colorectal cancer and polymorphisms in the uridine-diphosphoglucuronosyltransferase 1A7and 1A1 genes

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World Journal of gastroenterology 2005年第21期11卷 3250-3254页

作者： Kung-Sheng Tang Hui-Fen Chiu Hong-Hwa Chen Hock-Liew Eng Chia-Jung Tsai hsiu-Chen Teng Ching-Shan Huang Department of Medical Technology Fooyin University KaohsiungTaiwan graduate Institute of Medicine Kaohsiung Medical University Kaohsiung TaiwanChina graduate Institute of Medicine and Department of Pharmacology Kaohsiung Medical University Kaohsiung Taiwan China Department of Colorectal Surgery Chang gung Memorial Hospital KaohsiungTaiwanChina Department of Pathology Chang gung Memorial Hospital Kaohsiung Taiwan China Department of Medical Management Fooyin University KaohsiungTaiwan China Department of Medical Technology Fooyin University Kaohsiung Taiwan Department of Laboratory Medicine Cathay General Hospital Taipei Taiwan China

AIM: To investigate the relationship between single nucleotide polymorphisms in the uridine-diphosphoglucurono-syltransferase (UgT) UgT1A7 and UgT1A1 genes and patients suffering from colorectal cancer (CRC). METHODS: A case-control study was designed in order to investigate the genotypes of the UgT1A7 and UgT1A1 genes, which were identified by the polymerase chain reaction-restriction fragment length polymorphism (RFLP) method, for 268 CRC patients and 441 healthy controls. RESULTS: The results of simple logistical regressions revealed odds ratios (ORs) of 1.97 (PgT1A7*1/*3 genotype,UgT1A7*3 allele,and variant-211 UgT1A1 *** interaction of UgT1A7*3 allele and variant-211 UgT1A1 allele produced an additive effect on the risk for the development of CRC [observed OR (2.34) greater than expected OR (1.59)]. For the 268 patients, the results of simple logistical regressions indicated that the OR of developing metastases was 4.90 (Pg UgT1A7*3 allele and variant-211 UgT1A1 allele, respectively. The results of multivariate logistical regressions confirmed these findings (OR = 2.51, P= 0.01; and OR=2.71,P=0.01,respectively).The interaction of these two variants resulted in an additive effect on the risk for metastases amongst patients [observed OR (6.83) greater than expected OR (4.56)]. CONCLUSION: In conclusion, carriage of the UgT1A7*3 allele, as well as variant-211 UgT1A1 allele represents a risk factor for the development of, and a determinant for, metastases associated with CRC patients.

关键词： Colorectal cancer UgT1A7*3 allele Variant211 UgT1A1 allele Metastases

Predictors of the outcomes of acute-on-chronic hepatitis b liver failure

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World Journal of gastroenterology 2012年第36期18卷 5078-5083页

作者： hsiu-Lung Fan Po-Sheng yang Hui-Wei Chen Teng-Wei Chen De-Chuan Chan Chi-Hong Chu Jyh-Cherng yu Shih-Ming Kuo Chung-bao Hsieh Division of general Surgery Department of SurgeryTri-Service General HospitalNational Defense Medical Center Division of general Surgery Department of SurgeryMackay Memorial Hospital School of Medicine University of PittsburghPittsburghPA 15261United States Division of Pediatric Surgery Department of SurgeryTri-Service General HospitalNational Defense Medical Center

AIM： To identify the risk factors in predicting the out- come of acute-on-chronic hepatitis b liver failure pa- tients. METHODS： We retrospectively divided 113 patients with acute-on-chronic liver failure-hepatitis b virus （ACLF-HbV） and without concurrent hepatitis C or D virus infection and hepatocellular carcinoma into two groups according to their outcomes after anti-HbV therapy. Their demographic, clinical, and biochemical data on the day of diagnosis and after the first week of treatment were analyzed using the Mann-Whitney U test, Fisher＇s exact test, and a multiple logistic regres- sion analysis. RESULTS： The study included 113 patients （87 men and 26 women） with a mean age of 49.84 years. Fifty- two patients survived, and 61 patients died. Liver failure （85.2%）, sepsis （34.4%）, and multiple organ failure （39.3%） were the main causes of death. Mul- tivariate analyses showed that Acute Physiology and Chronic Health Evaluation （APACHE） Ⅱ scores ≥ 12 [odds ratio （OR） = 7.160, 95% CI： 2.834-18.092, P 〈 0.001] and positive blood culture （OR = 13.520, 95% CI： 2.740-66.721, P = 0.001） on the day of diagnosis and model for end-stage liver disease （MELD） scores 28 （OR = 8.182, 95% CI： 1.884-35.527, P = 0.005） after the first week of treatment were independent predictors of mortality. CONCLUSION： APACHE II scores on the day of diag- nosis and MELD scores after the first week of anti-HbV therapy are feasible predictors of outcome in ACLF- HbV patients.

关键词： Lamivudine Liver failure Hepatitis b virus Acute Physiology and Chronic Health Evaluation ]]score Model for end-stage liver disease scores

Expression of CD86 and increased infiltration of NK cells are associated with Helicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

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World Journal of gastroenterology 2005年第28期11卷 4357-4362页

作者： Sung-Hsin Kuo Li-Tzong Chen Chi-Long Chen Shin-Lian Doong Kun-Huei yeh Hui-Chen Hsu Ming-Shiang Wu Jaw-Town Lin hsiu-Po Wang Ann-Lii Cheng Departments of Oncology National Taiwan University Hospital Taipei Cancer Research Center and Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan China Division of Cancer Research National Health Research Institutes Taipei Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taipei Taiwan China Department of Pathologyl Taipei MedicalUniversity Taipei Taiwan China graduate Institute of Microbiology National Taiwan University College of Medicine Taipei Taiwan China Departments of Oncology National Taiwan University Hospital Taipei Cancer Research Center National Taiwan University College of Medicine Taipei Taiwan China Department of Internal Mcclicine National Taiwan University Hospital Taipei Taiwan China Department of Emergency Medicine National Taiwan University Hospital Taipei Taiwan China Department of internal Medicine and Department of Oncology National Taiwan University Hospital Taipei Cancer Research Center National Taiwan University College of MedicineTaipei Division of Cancer Research National Health Research Institutes Taipei Taiwan China

AIM： A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue （MALT） lymphomas remain Helicobacter pylori （ H pylori）-dependent. However,unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori- spedfic intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 （b7.2） and the infiltration of CD56 （＋） natural killer （NK） cells can be useful markers to predict Hpylori-dependent status of high-grade gastric MALT iymphoma.METHODS： Lymphoma biopsies from 26 patients who had participated in a prospective study of Hpylori-eradication for stage IE high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade Ⅱ or less alter H pylori eradication were dassified as H pylori-dependent; others were dassified as H *** infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry. RESULTS： There were 16 H pylori-dependent and 10 H pylori-independent cases. CD86 expression was detected in 11 （68.8%） of 16 H pylori-dependent cases but in none of 10 H pylori-independent cases （P = 0.001）.H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 （＋） NK cells than H pylori-independent cases （2.8±1.4% vs 1.1±0.8%, P = 0.003）. CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 （＋） NK cells compared to CD86-negative cases （2.9±1.1% vs 1.4±1.3%; P= 0.005）.CONCLUSION： These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with Hpylori-dependent state of early-stage high-grade gastric M

关键词： MALT lymphoma Hpylori CD86 CD56