Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Prediction models of hepatocellular carcinoma development in chronic hepatitis B patients

Chronic hepatitis B virus(HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma(HCC). Applying the same strategies for antiviral therapy and HCC surveillance to all chronic hepatitis B(CHB) patients would be a burden worldwide. To properly manage CHB patients, it is necessary to identify and classify the risk for HCC development in such patients. Several HCC risk scores based on risk factors such as cirrhosis, age, male gender, and high viral load have been used, and have negative predictive values of ≥ 95%. Most of these have been derived from, and internally validated in, treatment-na?ve Asian CHB patients. Herein, we summarized various HCC prediction models, including IPM(Individual Prediction Model), CU-HCC(Chinese University-HCC), GAG-HCC(Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-HCC), NGM-HCC(NomogramHCC), REACH-B(Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B), and Page-B score. To develop a noninvasive test of liver fibrosis, we also introduced a new scoring system that uses liver stiffness values from transient elastography, including an LSM(Liver Stiffness Measurement)-based model, LSM-HCC, and mR EACH-B(modified REACH-B).

Complete remission of advanced hepatocellular carcinoma by radiofrequency ablation after sorafenib therapy

Sorafenib,a potent multikinase inhibitor,lead to a significant improvement in progression free survival and overall survival in patients with advanced hepatocellular carcinoma(HCC).Though sorafenib has proven its efficacy in advanced stage HCC,there are limitedreports on the role of sorafenib allowing for curative treatment by down-staging.We herein report a case of advanced HCC with vascular invasion,which showed treatment response by sorafenib therapy as to allow for radiofrequency ablation as curative treatment.The patient was followed-up for 6 mo without recurrence with continued sorafenib therapy.

A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation

Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia.Clostridium difficile infection(CDI)is a common nosocomial diarrheal disease.Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI.The use of broadspectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome.Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI.Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.

Suppressed estrogen supply via extra-ovarian progesterone receptor membrane component 1 in menopause

In post-menopausal women,intra-mammary estrogen,which is converted from extra-ovarian estrone(E1),promotes the growth of breast cancer.Since the aromatase inhibitor letrozole does not suppress 17β-estradiol(E2)production from E1,high intra-mammary E1 concentrations impair letrozole's therapeutic efficacy.Progesterone receptor membrane component 1(Pgrmc1)is a non-classical progesterone receptor associated with breast cancer progression.In the present study,we introduced a Pgrmc1 heterozygous knockout(hetero KO)murine model exhibiting low Pgrmc1 expression,and observed estrogen levels and steroidogenic gene expression.Naïve Pgrmc1 hetero KO mice exhibited low estrogen(E2 and E1)levels and low progesterone receptor(PR)expression,compared to wild-type mice.In contrast,Pgrmc1 hetero KO mice that have been ovariectomized(OVX),including letrozole-treated OVX mice(OVX-letrozole),exhibited high estrogen levels and PR expression.Increased extra-ovarian estrogen production in Pgrmc1 hetero KO mice was observed with the induction of steroid sulfatase(STS).In MCF-7 cell,letrozole suppressed PR expression,but PGRMC1 knockdown increased PR and STS expression.Our presented results highlight the important role of Pgrmc1 in modulating estrogen production when ovary-derived estrogen is limited,thereby suggesting a potential therapeutic approach for letrozole resistance.

Cardiac rehabilitation in a heart failure patient after left ventricular assist device insertion and subsequent heart transplantation:A case report

BACKGROUND Insertion of a left ventricular assist device(LVAD)and heart transplantation(HT)improve the survival of patients with heart failure.In addition,cardiac rehabilitation(CR)further increases the functional capacity.This case report describes a successful case of CR after LVAD insertion and subsequent HT.CASE SUMMARY In the present case,during the LVAD insertion period,peak oxygen consumption(VO2)increased by 12.16%after CR.HT was performed 7 mo after the LVAD insertion,and the patient participated in phases I and II CR.The peak VO2 increased from 17.24 to 22.29 m L/kg/min.This improvement was more significant than that reported in previous studies on CR after LVAD insertion or HT.The patient’s quality of life also improved.The total average score of the short form-36 questionnaire increased from 29.5 points at admission to 53.3 points 9 mo after HT.CONCLUSION A tailored CR program after LVAD insertion or HT may improve the patients’quality of life and increase survival.

Effect of the semen extract of Cuscuta chinensis on inflammatory responses in LPS-stimulated BV-2 microglia

AIM: To investigate the anti-inflammatory activities of the semen extract of Cuscuta chinensis Lam.(Cuscutae Semen; CS) on the production of inflammatory mediators, nitric oxide(NO), prostaglandin 2(PGE2), and proinflammatory cytokines in lipopolysaccharide(LPS)-stimulated BV-2 microglia. METHOD: BV-2 cells were treated with CS extract for 30 min, and then stimulated with LPS or without for 24 h. The levels of NO, PGE2 and proinflammatory cytokines were measured by Griess assay and ELISA. The expression of inducible nitric oxide synthase(iNOS), and cyclooxygenase(COX)-2 mRNA and protein was determined by RT-PCR and Western blot, respectively. The phosphorylation of extracellular signal-regulated kinase 1/2(ERK1/2), Jun N-terminal kinase(JNK), and p38 mitogen-activated protein kinase(MAPK), and the nuclear expression of nuclear factor(NF)-κB p65 were investigated by Western blot analysis. RESULTS: CS extract significantly decreased the production of NO and PGE2 by suppressing the expression of iNOS and COX-2 in activated microglia. CS extract decreased the production of TNF-α, IL-1β, and IL-6 by down-regulating their transcription levels. In addition, CS extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of NF-κB p65 in activated microglia. CONCLUSION: These results indicate that CS extract is capable of suppressing the inflammatory response by microglia activation, suggesting that CS extract has potential in the treatment of brain inflammation.

Fungal diversity notes 111-252-taxonomic and phylogenetic contributions to fungal taxa

This paper is a compilation of notes on 142 fungal taxa,including five new families,20 new genera,and 100 new species,representing a wide taxonomic and geographic range.The new families,Ascocylindricaceae,Caryosporaceae and Wicklowiaceae(Ascomycota)are introduced based on their distinct lineages and unique morphology.The new Dothideomycete genera Pseudomassariosphaeria(Amniculicolaceae),Heracleicola,Neodidymella and Pseudomicrosphaeriopsis(Didymellaceae),Pseudopithomyces(Didymosphaeriaceae),Brunneoclavispora,Neolophiostoma and Sulcosporium(Halotthiaceae),Lophiohelichrysum(Lophiostomataceae),Galliicola,Populocrescentia and Vagicola(Phaeosphaeriaceae),Ascocylindrica(Ascocylindricaceae),Elongatopedicellata(Roussoellaceae),Pseudoasteromassaria(Latoruaceae)and Pseudomonodictys(Macrodiplodiopsidaceae)are introduced.The newly described species of Dothideomycetes(Ascomycota)are Pseudomassariosphaeria bromicola(Amniculicolaceae),Flammeascoma lignicola(Anteagloniaceae),Ascocylindrica marina(Ascocylindricaceae),Lembosia xyliae(Asterinaceae),Diplodia crataegicola and Diplodia galiicola(Botryosphaeriaceae),Caryospora aquatica(Caryosporaceae),Heracleicola premilcurensis and Neodidymella thailandicum(Didymellaceae),Pseudopithomyces palmicola(Didymosphaeriaceae),Floricola viticola(Floricolaceae),Brunneoclavispora bambusae,Neolophiostoma pigmentatum and Sulcosporium thailandica(Halotthiaceae),Pseudoasteromassaria fagi(Latoruaceae),Keissleriella dactylidicola(Lentitheciaceae),Lophiohelichrysum helichrysi(Lophiostomataceae),Aquasubmersa japonica(Lophiotremataceae),Pseudomonodictys tectonae(Macrodiplodiopsidaceae),Microthyrium buxicola and Tumidispora shoreae(Microthyriaceae),Alloleptosphaeria clematidis,Allophaeosphaeria cytisi,Allophaeosphaeria subcylindrospora,Dematiopleospora luzulae,Entodesmium artemisiae,Galiicola pseudophaeosphaeria,Loratospora luzulae,Nodulosphaeria senecionis,Ophiosphaerella aquaticus,Populocrescentia forlicesenensis and Vagicola vagans(Phaeosphaeriaceae),Elongatopedicellata lignicola,Roussoella magnatum and Roussoella angustior(Roussoellaceae)and Shrungabeeja longiappendiculata(Tetraploasphaeriaceae).The new combinations Pseudomassariosphaeria grandispora,Austropleospora archidendri,Pseudopithomyces chartarum,Pseudopithomyces maydicus,Pseudopithomyces sacchari,Vagicola vagans,Punctulariopsis cremeoalbida and Punctulariopsis efibulata Dothideomycetes.The new genera Dictyosporella(Annulatascaceae),and Tinhaudeus(Halosphaeriaceae)are introduced in Sordariomycetes(Ascomycota)while Dictyosporella aquatica(Annulatascaceae),Chaetosphaeria rivularia(Chaetosphaeriaceae),Beauveria gryllotalpidicola and Beauveria loeiensis(Cordycipitaceae),Seimatosporium sorbi and Seimatosporium pseudorosarum(Discosiaceae),Colletotrichum aciculare,Colletotrichum fusiforme and Colletotrichum hymenocallidicola(Glomerellaceae),Tinhaudeus formosanus(Halosphaeriaceae),Pestalotiopsis subshorea and Pestalotiopsis dracaenea(Pestalotiopsiceae),Phaeoacremonium tectonae(Togniniaceae),Cytospora parasitica and Cytospora tanaitica(Valsaceae),Annulohypoxylon palmicola,Biscogniauxia effusae and Nemania fusoideis(Xylariaceae)are introduced as novel species to order Sordariomycetes.The newly described species of Eurotiomycetes are Mycocalicium hyaloparvicellulum(Mycocaliciaceae).Acarospora septentrionalis and Acarospora castaneocarpa(Acarosporaceae),Chapsa multicarpa and Fissurina carassensis(Graphidaceae),Sticta fuscotomentosa and Sticta subfilicinella(Lobariaceae)are newly introduced in class Lecanoromycetes.In class Pezizomycetes,Helvella pseudolacunosa and Helvella rugosa(Helvellaceae)are introduced as new species.The new families,Dendrominiaceae and Neoantrodiellaceae(Basidiomycota)are introduced together with a new genus Neoantrodiella(Neoantrodiellaceae),here based on both morphology coupled with molecular data.In the class Agaricomycetes,Agaricus pseudolangei,Agaricus haematinus,Agaricus atrodiscus and Agaricus exilissimus(Agaricaceae),Amanita melleialba,Amanita pseudosychnopyramis and Amanita subparvipantherina(Amanitaceae),Entoloma calabrum,Cora barbulata,Dictyonema gomezianum and Inocybe granulosa(Inocybaceae),Xerocomellus sarnarii(Boletaceae),Cantharellus eucalyptorum,Cantharellus nigrescens,Cantharellus tricolor and Cantharellus variabilicolor(Cantharellaceae),Cortinarius alboamarescens,Cortinarius brunneoalbus,Cortinarius ochroamarus,Cortinarius putorius and Cortinarius seidlii(Cortinariaceae),Hymenochaete micropora and Hymenochaete subporioides(Hymenochaetaceae),Xylodon ramicida(Schizoporaceae),Colospora andalasii(Polyporaceae),Russula guangxiensis and Russula hakkae(Russulaceae),Tremella dirinariae,Tremella graphidis and Tremella pyrenulae(Tremellaceae)are introduced.Four new combinations Neoantrodiella gypsea,Neoantrodiella thujae(Neoantrodiellaceae),Punctulariopsis cremeoalbida,Punctulariopsis efibulata(Punctulariaceae)are also introduced here for the division Basidiomycota.Furthermore Absidia caatinguensis,Absidia koreana and Gongronella koreana(Cunninghamellaceae),Mortierella pisiformis and Mortierella formosana(Mortierellaceae)are newly introduced in the Zygomycota,while Neocallimastix cameroonii and Piromyces irregularis(Neocallimastigaceae)are introduced in the Neocallimastigomycota.Reference specimens or changes in classification and notes are provided for Alternaria ethzedia,Cucurbitaria ephedricola,Austropleospora,Austropleospora archidendri,Byssosphaeria rhodomphala,Lophiostoma caulium,Pseudopithomyces maydicus,Massariosphaeria,Neomassariosphaeria and Pestalotiopsis montellica.

Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model

Background Ursodeoxycholic acid(UDCA),statins,and ezetimibe(EZE)have demonstrated beneficial effects against nonalcoholic fatty liver disease(NAFLD).We investigated the efficacy of the combination of UDCA and the mix of rosuvastatin(RSV)/EZE in the treatment of NAFLD.Methods NAFLD mouse models were developed by injecting thioacetamide,fasting,and high-carbohydrate refeeding,highfat diet,and choline-deficient L-amino acid-defined high-fat diet(CDAHFD).Low-dose UDCA(L-UDCA;15 mg/kg)or highdose UDCA(H-UDCA;30 mg/kg)was administered with RSV/EZE.We also employed an in vitro model of NAFLD developed using palmitic acid-treated Hepa1c1c7 cells.Results Co-administration of RSV/EZE with UDCA significantly decreased the collagen accumulation,serum alanine aminotransferase(ALT)levels,and mRNA levels of fibrosis-related markers than those observed in the vehicle group in thioacetamide-treated mice(all P<0.01).In addition,in the group fasted and refed with a high-carbohydrate diet,UDCA/RSV/EZE treatment decreased the number of apoptotic cells and serum ALT levels compared with those observed in the vehicle group(all P<0.05).Subsequently,H-UDCA/RSV/EZE treatment decreased the number of ballooned hepatocytes and stearoyl-CoA desaturase 1(SCD-1)mRNA levels(P=0.027)in the liver of high-fat diet-fed mice compared with those observed in the vehicle group.In the CDAHFD-fed mouse model,UDCA/RSV/EZE significantly attenuated collagen accumulation and fibrosis-related markers compared to those observed in the vehicle group(all P<0.05).In addition,UDCA/RSV/EZE treatment significantly restored cell survival and decreased the protein levels of apoptosis-related markers compared to RSV/EZE treatment in palmitic acid-treated Hepa1c1c7 cells(all P<0.05).Conclusion Combination therapy involving UDCA and RSV/EZE may be a novel strategy for potent inhibition of NAFLD progression.

Tenofovir disoproxil fumarate is not associated with a lower risk of hepatocellular carcinoma compared to entecavir in patients with chronic hepatitis B

A paper published several years ago suggested that tenofovir disoproxil fumarate(TDF)was superior to entecavir(ETV)for reducing the risk of hepatocellular carcinoma(HCC).Since then,many observational studies have been conducted comparing TDF and ETV.Many studies in Asia demonstrated similar HCC risks between ETV and TDF groups.Similarly,recent studies involving Caucasian and European did not observe any differences in HCC risk between these groups.In this article,we briefly review studies that compared the incidence rates of HCC between ETV and TDF and discuss potential reasons for the discrepant results.