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| 1 | Bioinspired Adhesive and Antibacterial Microneedles for Versatile Transdermal Drug Delivery显示文摘Microneedles have attracted increasing interest among various medical fields due to their painless,noninvasive,and efficient way of drug delivery.However,practical applications of these microneedles in different epidermal locations and environments are still restricted by their low adhesion and poor antimicrobial activity.Here,inspired by the antibacterial strategy of Paenibacillus polymyxa and adhesion mechanisms of mussel byssi and octopus tentacles,we develop hierarchical microneedles with multifunctional adhesive and antibacterial abilities.With polydopamine hydrogel as the microneedle base and a loop of suctioncup-structured concave chambers encircling each microneedle,the generated microneedles can fit the skin well;keep strong adhesion in dry,moist,and wet environments;and realize self-repair after being split into two parts.Besides,as polymyxin is loaded into both the hydrogel tips and the polydopamine base,the microneedles are endowed with excellent ability to resist common bacteria during storage and usage.We have demonstrated that these microneedles not only showed excellent adhesion when applied to knuckles and ideal antibacterial activity but also performed well in drug-sustained release and treatment for the osteoarthritis rat model.These results indicate that bioinspired multifunctional microneedles will break through the limitation of traditional methods and be ideal candidates for versatile transdermal drug delivery systems. | Xiaoxuan Zhang Guopu Chen Yunru Yu Lingyu Sun Yuanjin Zhao | 2020 | Research2020，，1： | 14 |
| 2 | Microbiota or short-chain fatty acids: which regulates diabetes?显示文摘Diabetes mellitus,with sustained high-sugar levels in the blood,has been steadily rising in prevalence worldwide.Around 12–14%of the US population has been diagnosed with diabetes in recent years.1 One major reason for the rise of diabetes is dietary changes.Increased consumption of processed carbohydrates with inadequate consumption of dietary fiber(DF)has been recognized as a major risk factor for diabetes,as hypothesized several decades ago by Trowell. | Chang H Kim | 2018 | Cellular & Molecular Immunology2018，15，2： | 13 |
| 3 | Association between vitamin D and hepatitis C virus infection: A meta-analysis显示文摘AIM:To evaluate the association between 25-hydroxyvitamin D[25(OH)D]and sustained virological response(SVR)in hepatitis C virus(HCV)infected individuals.METHODS:Relevant studies were identified by systematically searching MEDLINE databases up to March2012 and abstracts of the European and American Congress of Hepatology conducted in 2011.Studies must provide information on SVR and the levels of 25(OH)D3and/or 25(OH)D2[henceforth referred to as 25(OH)D]in sera samples from HCV infected individuals.The inclusion criteria were:clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group;provided information on SVR rates;and were reported in the English languageas full papers.Due to the heterogeneity of studies in categorizing serum vitamin D levels,a cut-off value of30 ng/mL of serum 25(OH)D was used.Heterogeneity was assessed using I2statistics.The summary odds ratios with their corresponding 95%CI were calculated based on a random-effects model.RESULTS:Overall,11 studies(8 observational and 3interventional)involving 1575 individuals were included and 1117 HCV infected individuals(71%)showed low vitamin D levels.Most of the studies included monoinfected HCV individuals with the mean age ranging from 38 to 56 years.Four studies were conducted in human immunodeficiency virus/HCV infected individuals.Regarding vitamin D measurement,most of the studies employed radioimmunoassays(n=5)followed by chemiluminescence(n=4)and just one study employed high performance/pressure liquid chromatography(HPLC).Basal vitamin D levels varied from 17 to43 ng/mL in the studies selected,and most of the HCV infected individuals had genotype 1(1068/1575)with mean viral load varying from log 4.5-5.9 UI/mL.With regard to HCV treatment,most of the studies(n=8)included HCV individuals without previous treatment,where the pooled SVR rate was 46.4%.High rates of SVR were observed in HCV individuals with vitamin D levels above 30 ng/mL(OR=1.57;95%CI:1.12-2.2)and those supplemented with vitamin D(OR=4.59;95%CI:1.67-12.63)regardless of genotype.CONCLUSION:Our results demonstrated high prevalence of vitamin D deficiency and high SVR in individuals with higher serum vitamin D levels or receiving vitamin D supplementation. | Livia Melo Villar José Antonio Del Campo Isidora Ranchal Elisabeth Lampe Manuel Romero-Gomez | 2013 | World Journal of Gastroenterology2013，19，35： | 9 |
| 4 | Evidence-based consensus on the diagnosis, prevention and management of hepatitis C virus disease显示文摘Hepatitis C virus(HCV) is a potent human pathogen and is one of the main causes of chronic hepatitis round the world. The present review describes the evidencebased consensus on the diagnosis, prevention and management of HCV disease. Various techniques, for the detection of anti-HCV immunoglobulin G immunoassays, detection of HCV RNA by identifying virus-specific molecules nucleic acid testings, recognition of core antigen for diagnosis of HCV, quantitative antigenassay, have been used to detect HCV RNA and core antigen. Advanced technologies such as nanoparticlebased diagnostic assays, loop-mediated isothermal amplification and aptamers and Ortho trak-C assay have also come to the front that provides best detection results with greater ease and specificity for detection of HCV. It is of immense importance to prevent this infection especially among the sexual partners, injecting drug users, mother-to-infant transmission of HCV, household contact, healthcare workers and people who get tattoos and piercing on their skin. Management of this infection is intended to eradicate it out of the body of patients. Management includes examining the treatment(efficacy and protection), assessment of hepatic condition before commencing therapy, controlling the parameters upon which dual and triple therapies work, monitoring the body after treatment and adjusting the co-factors. Examining the treatment in some special groups of people(HIV/HCV co-infected, hemodialysis patients, renal transplanted patients). | Mahrukh Akbar Shaheen Muhammad Idrees | 2015 | World Journal of Hepatology2015，7，3： | 9 |
| 5 | Vitamin D deficiency and hepatitis viruses-associated liver diseases:a literature review显示文摘The secosteroid hormone vitamin D has, in addition to its effects in bone metabolism also functions in the modulation of immune responses against infectious agents and in inhibiting tumorigenesis. Thus, deficiency of vitamin D is associated with several malignancies, but also with a plethora of infectious diseases. Among other communicable diseases, vitamin D deficiency is involved in the pathogenesis of chronic liver diseases caused by hepatitis B and C viruses(HBV, HCV) and high prevalence of vitamin D deficiency with serum levels below 20 mg/mL in patients with HBV and HCV infection are found worldwide. Several studies have assessed the effects of vitamin D supplementation on the sustained virological response(SVR) to interferon(IFN) plus ribavirin(RBV) therapy in HBV and HCV infection. In these studies, inconsistent results were reported. This review addresses general aspects of vitamin D deficiency and, in particular, the significance of vitamin D hypovitaminosis in the outcome of HBVand HCV-related chronic liver diseases. Furthermore,current literature was reviewed in order to understand the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients. | Nghiem Xuan Hoan Hoang Van Tong Le Huu Song Christian G Meyer Thirumalaisamy P Velavan | 2018 | World Journal of Gastroenterology2018，24，4： | 9 |
| 6 | Gut microbiota drives macrophage-dependent self-renewal of intestinal stem cells via niche enteric serotonergic neurons显示文摘Lgr5+intestinal stem cells(ISCs)reside within specialized niches at the crypt base and harbor self-renewal and differentiation capacities.ISCs in the crypt base are sustained by their surrounding niche for precise modulation of self-renewal and differentiation.However,how intestinal cells in the crypt niche and microbiota in enteric cavity coordinately regulate ISC stemness remains unclear.Here,we show that ISCs are regulated by microbiota and niche enteric serotonergic neurons.The gut microbiota metabolite valeric acid promotes Tph2 expression in enteric serotonergic neurons via blocking the recruitment of the NuRD complex onto Tph2 promoter.5-hydroxytryptamine(5-HT)in turn activates PGE2 production in a PGE2+macrophage subset through its receptors HTR2A/3 A;and PGE2 via binding its receptors EP1/EP4,promotes Wnt/β-catenin signaling in ISCs to promote their self-renewal.Our findings illustrate a complex crosstalk among microbiota,intestinal nerve cells,intestinal immune cells and ISCs,revealing a new layer of ISC regulation by niche cells and microbiota. | Pingping Zhu Tiankun Lu Jiayi Wu Dongdong Fan Benyu Liu Xiaoxiao Zhu Hui Guo Ying Du Feng Liu Yong Tian Zusen Fan | 2022 | Cell Research2022，32，6： | 8 |
| 7 | Clinical deep remission and related factors in a large cohort of patients with rheumatoid arthritis显示文摘Background:Clinical remission is the treatment target in rheumatoid arthritis (RA).This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.Methods:This study composed of 342 patients with RA.Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016.The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site.Subsequently,patients fulfilled remission criteria were further analyzed.The practicability of different definitions of remission of RA was rated by a panel of rheumatologists.Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.Results:In this cohort of 342 patients with RA,the proportions of patients achieving remission were 38.0%,29.5%,24.9%,21.1%,19.0%,18.1%,and 17.0%,based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP),DAS28 using ESR (DAS28-ESR),routine assessment of patient index data 3 (RAPID-3),Boolean,simplified disease activity index (SDAI),clinical disease activity index,and the newly described clinical deep remission (CliDR),respectively.Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0,respectively).Compared with the non-sustained intensive group,sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%,23.8%,and 21.3% in patients with RA based on Boolean (χ^2=3.937,P=0.047),SDAI (χ^2=4.666,P=0.031),and CliDR criteria (χ^2=4.297,P=0.038).The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide,followed by methotrexate,and hydroxychloroquine.Compared with the non-remission group,patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months,Z=-2.295,P=0.022).Conclusions:The findings in this study indicated that clinical deep remission is achievable in patients with RA.Sustained intensive DMARD treatment is needed to achieve a better outcome in RA. | Jia-Jia Liu Ru Li Yu-Zhou Gan Rui-Jun Zhang Jing Li Yue-Ming Cai Jin-Xia Zhao Hua Liao Jing Xu Lian-Jie Shi Ji Li Sheng-Guang Li Xiao-Lin Sun Jing He Xu Liu Hua Ye Zhan-Guo Li | 2019 | Chinese Medical Journal2019，，9： | 7 |
| 8 | The USDA cucumber (Cucumis sativus L.) collection: genetic diversity, population structure, genome-wide association studies, and core collection development显示文摘Germplasm collections are a crucial resource to conserve natural genetic diversity and provide a source of novel traits essential for sustained crop improvement.Optimal collection,preservation and utilization of these materials depends upon knowledge of the genetic variation present within the collection.Here we use the high-throughput genotyping-by-sequencing(GBS)technology to characterize the United States National Plant Germplasm System(NPGS)collection of cucumber(Cucumis sativus L.).The GBS data,derived from 1234 cucumber accessions,provided more than 23 K high-quality single-nucleotide polymorphisms(SNPs)that are well distributed at high density in the genome(~1 SNP/10.6 kb).The SNP markers were used to characterize genetic diversity,population structure,phylogenetic relationships,linkage disequilibrium,and population differentiation of the NPGS cucumber collection.These results,providing detailed genetic analysis of the U.S.cucumber collection,complement NPGS descriptive information regarding geographic origin and phenotypic characterization.We also identified genome regions significantly associated with 13 horticulturally important traits through genome-wide association studies(GWAS).Finally,we developed a molecularly informed,publicly accessible core collection of 395 accessions that represents at least 96%of the genetic variation present in the NPGS.Collectively,the information obtained from the GBS data enabled deep insight into the diversity present and genetic relationships among accessions within the collection,and will provide a valuable resource for genetic analyses,gene discovery,crop improvement,and germplasm preservation. | Xin Wang Kan Bao Umesh K.Reddy Yang Bai Sue A.Hammar Chen Jiao Todd C.Wehner Axel O.Ramírez-Madera Yiqun Weng Rebecca Grumet Zhangjun Fei | 2018 | Horticulture Research2018，5，1： | 7 |
| 9 | Advances in hepatitis C therapy: What is the current state-what come's next?显示文摘Chronic hepatitis C virus(HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver disease.It is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ribavirin.However,treatment of HCV has undergone a revolutionary change in recent years.The admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents(DAA).Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal failure.High rates of sustained virological response(SVR) rates can be achieved with these novel drugs.Even in difficult to treat populations such as patients with liver cirrhosis,HCV-human immunodeficiency virus co-infections,after liver transplantion,or with chronic kidney disease comparable high rates of SVR can be achieved.The anticipated 2nd generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or posttransplant patients.These 2nd generations DAAs will have higher resistance barriers,higher antiviral effects and a pan-genotypic spectrum.This review highlights the current state of the art of antiviral treatment in hepatitis Cand gives an outlook for upcoming therapies. | Steffen Zopf Andreas E Kremer Markus F Neurath Juergen Siebler | 2016 | World Journal of Hepatology2016，8，3： | 7 |
| 10 | Direct anti-HCV agents显示文摘Unlike human immunodeficiency virus(HIV)and hepatitis B virus(HBV),hepatitis C virus(HCV)infection is a curable disease.Current direct antiviral agent(DAA)targets are focused on HCV NS3/4A protein(protease),NS5 B protein(polymerase)and NS5 A protein.The first generation of DAAs includes boceprevir and telaprevir,which are protease inhibitors and were approved for clinical use in2011.The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin.More effective and less toxic second generation DAAs supplanted these drugs by 2013.The second generation of DAAs includes sofosbuvir(Sovaldi),simeprevir(Olysio),and fixed combination medicines Harvoni and Viekira Pak.These drugs increase cure rates to over 90%without the need for interferon and effectively treat all HCV genotypes.With these drugs the 'cure HCV'goal has become a reality.Concerns remain about drug resistance mutations and the high cost of these drugs.The investigation of new HCV drugs is progressing rapidly;fixed dose combination medicines in phase III clinical trials include Viekirax,asunaprevirtdaclatasvirtbeclabuvir,grazoprevirtelbasvir and others. | Xingquan Zhang | 2016 | Acta Pharmaceutica Sinica B2016，6，1： | 6 |
| 11 | Carotid endarterectomy for treatment of carotid in-stent restenosis:longterm follow-up results and surgery experiences from one single centre显示文摘Objective Few studies have reported the surgical treatment of carotid in-stent restenosis(ISR),more data and longer follow-up are needed.We describe the surgical treatment of ISR by standard carotid endarterectomy(CEA)with stent removal,including long-term follow-up in 10 patients from our centre.Methods Ten patients from our centre who underwent CEA with stent removal for ISR were retrospectively analysed,including nine symptomatic and one asymptomatic ISR of at least 70%with mean age 67.3,the median time between carotid artery stenting and CEA was 17 months(range,2-54 months).results Standard CEA with stent removal was performed in all 10 patients without much technical difficulty(9 male and 1 female,mean age 67.3).Two cases were performed in hybrid operation room.There were a total of three complications that happened in three patients(30%)respectively.An asymptomatic dissecting aneurysm was formed on the petrous internal carotid artery in one patient who was followed up without intervention.In the second case,dissection occurred in the arterial wall distal to the site of the stent after stent removal revealed by intraoperative angiography,and another stent was implanted.The patient sustained temporary hypoglossal nerve dysfunction postoperatively.The third patient suffered cerebral hyperperfusion with complete recovery when discharged.No neurological complications occurred in other seven patients.After follow-up of 25 months(range,11-54 months),one patient died of rectal cancer without ischaemic attack and restenosis 4 years postoperation;in one patient occurred recurrent symptomatic restenosis(90%)1 year later;all other patients remained asymptomatic and without recurrent restenosis(>50%)by follow-up carotid ultrasound or CT angiography.conclusion It seems that CEA with stent removal is a reasonable choice,by experienced hand,for symptomatic ISR with higher but acceptable complications.The indication of stent removal for asymptomatic ISR needs further observation. | Le-Bao Yu Wei Yan Qian Zhang Ji-Zong Zhao Yan Zhang Rong Wang Jun-Shi Shao Dong Zhang | 2017 | Stroke & Vascular Neurology2017，2，3： | 6 |
| 12 | Stratigraphic thermohistory and its implications for regional geoevolution in the Tarim Basin,NW China显示文摘Fourteen vitrinite reflectance profiles from the Tarim Basin,NW China,show that the vitrinite reflectance profiles of individual wells follow a faulted and dislocated dual-stage pattern in the eastern section of the Tazhong Uplift and in the Tabei Uplift.Vitrinite reflectance values in these profiles change sharply at the unconformity beneath the Lower Carboniferous Bachu or Upper Devonian Donghetang Formations,where the overlying Triassic to Carboniferous strata are still in a mature phase within the 'liquid oil window'.However,the underlying Lower Paleozoic reached the overmature phase beyond the 'liquid oil window' towards the end of the Silurian,or in the Early Devonian at the latest.Whereas the vitrinite reflectance profiles are attributed to a continuous,single-stage pattern in the western section of the Tazhong Uplift,in which the Lower Paleozoic is also in an overmature phase,their overmaturity would have been achieved relatively late in geological time.The stratigraphic thermohistory has the following implications to regional geoevolution:(1) The overmature Lower Ordovician to Cambrian strata in the eastern section of the Tazhong Uplift and in the Tabei Uplift,as well as in the Manjiaer Depression,could not have acted as the source kitchen for normal oil(so-called black oil);(2) The dissimilarity in vitrinite reflectance profiles between the eastern and western sections of the Tazhong Uplift reveals Early Paleozoic paleotectonic features,i.e.,lower at the east and higher at the west,whereas recent tectonic features formed since the Late Paleozoic are in reverse,i.e.,higher in the east and lower at the west;(3) Reconstruction of the denuded thickness of sediments overlying the Lower Ordovician strata suggests reconsideration on the paleotectonic features in the Tarim Basin;(4) Based on the sustained duration of the 'liquid oil window' for overmature source beds,it is predicted that the Suntuoguole Lower Uplift between the Awati and Manjiaer Depressions is a favorable potential source kitchen for Lower Paleozoic black oil. | WANG TieGuan1,DAI ShiFeng2,LI MeiJun1,ZHANG WeiBiao1,3,Qiu NanSheng1 & WANG GuangLi1 1 State Key Laboratory of Petroleum Resources and Prospecting,China University of Petroleum,Beijing 102249,China 2 State Key Laboratory of Coal Resources & Safe Mining,China University of Mining & Technology,Beijing 100083,China 3 Exploration Research Center,Exploration & Development Institute,China Petrochemical Corporation,Beijing 100083,China | 2010 | Science China Earth Sciences2010，53，10： | 6 |
| 13 | Shugan-decoction relieves visceral hyperalgesia and reduces TRPV1 and SP colon expression显示文摘AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for assessment of SGD effects on psychological stress-induced changes using the classic water avoidance stress(WAS)test.Untreated model rats were exposed to chronic(1 h/d for 10 d consecutive)WAS conditions;experimental treatment model rats were administered with intragastric SGD at1 h before WAS on consecutive days 4-10(low-dose:0.1g/mL;mid-dose:0.2 g/mL;high-dose:0.4 g/mL);control treatment model rats were similarly administered with the irritable bowel syndrome drug,dicetel(0.0042g/mL);untreated normal control rats received no drug and were not subjected to the WAS test.At the end of the 10-d WAS testing period,a semi-quantitative measurement of visceral sensitivity was made by assessing the abdominal withdrawal reflex(AWR)to colorectal balloon-induced distension(at 5 mmHg increments)to determine the pain pressure threshold(PPT,evidenced by pain behavior).Subsequently,the animals were sacrificed and colonic tissues collected for assessment of changes in expressions of proteins related to visceral hypersensitivity(transient receptor potential vanilloid 1,TRPV1)and sustained visceral hyperalgesia(substance P,SP)by immunohistochemistry and real-time polymerase chain reaction.Inter-group differences were assessed by paired t test or repeated measures analysis of variance.RESULTS:The WAS test successfully induced visceral hypersensitivity,as evidenced by a significantly reduced AWR pressure in the untreated model group as compared to the untreated normal control group(190.4±3.48 mmHg vs 224.0±4.99 mmHg,P<0.001).SGD treatments at mid-dose and high-dose and the dicetel treatment significantly increased the WAS-reduced PPT(212.5±2.54,216.5±3.50 and 217.7±2.83 mmHg respectively,all P<0.001);however,the low-dose SGD treatment produced no significant effect on the WAS-reduced PPT(198.3±1.78 mmHg,P>0.05).These trends corresponded to the differential expressions observed for both TRPV1 protein(mid-dose:1.64±0.08 and high-dose:1.69±0.12 vs untreated model:3.65±0.32,P<0.001)and mRNA(0.44±0.16 and0.15±0.03 vs 1.39±0.15,P<0.001)and SP protein(0.99±0.20 and 1.03±0.23 vs 2.03±0.12,P<0.01)and mRNA(1.64±0.19 and 1.32±0.14 vs 2.60±0.33,P<0.05).These differential expressions of TRPV1 and SP related to mid-and high-dose SGD treatments were statistically similar to the changes induced by dicetel treatment.No signs of overt damage to the rat system were observed for any of the SGD dosages.CONCLUSION:Shugan-decoction can reduce chronic stress-induced visceral hypersensitivity in rats,and the regulatory mechanism may involve mediating the expressions of TRPV1 and SP in colon tissues. | Jing-Juan Shang Jian-Ye Yuan Hui Xu Rong-Zhu Tang Yue-Bin Dong Jian-Qun Xie | 2013 | World Journal of Gastroenterology2013，19，44： | 6 |
| 14 | Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: A systematic review显示文摘AIM: To identify severe adverse events (SAEs) leading to treatment discontinuation that occur during antiviral therapy in hepatitis C virus (HCV)-infected cirrhotic patients. METHODS: We identified all the articles published prior to December 2011 in the PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases that presented these data in cirrhotic patients. These studies evaluated the rate of SAEs leading to discontinuation of standard care treatment: Pegylated interferon (PegIFN) alpha 2a (135-180 μg/wk) or PegIFN alpha 2b (1 or 1.5 μg/kg per week) and ribavirin (800-1200 mg/d). Patients with genotype 1 + 4 underwent treatment for 48 wk, whereas those with genotypes 2 + 3 were treated for 24 wk.RESULTS: We included 17 papers in this review, comprising of 1133 patients. Treatment was discontinued due to SAEs in 14.5% of the patients. The most common SAEs were: severe thrombocytopenia and/or neutropenia (23.2%), psychiatric disorders (15.5%), decompensation of liver cirrhosis (12.1%) and severe anemia (11.2%). The proportion of patients who needed to discontinue their therapy due to SAEs was significantly higher in patients with Child-Pugh class B and Cvs those with Child-Pugh class A: 22%vs 11.4% (P = 0.003). A similar discontinuation rate was found in cirrhotic patients treated with PegIFN alpha 2a and those treated with PegIFN alpha 2b, in combination with ribavirin: 14.2%vs 13.7% (P = 0.96). The overall sustained virological response rate in cirrhotic patients was 37% (95%CI: 33.5-43.1) but was significantly lower in patients with genotype 1 + 4 than in those with genotype 2 + 3: 20.5% (95%CI: 17.9-24.8) vs 56.5% (95%CI: 51.5-63.2), (P < 0.0001). CONCLUSION: Fourteen point five percent of HCV cirrhotic patients treated with PegIFN and ribavirin needed early discontinuation of therapy due to SAEs, the most common cause being hematological disorders. | Simona Bota Ioan Sporea Roxana Sirli Alina Popescu Adriana Maria Neghinǎ Mirela Dǎnilǎ Mihnea Strǎin | 2013 | World Journal of Hepatology2013，5，3： | 6 |
| 15 | Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals显示文摘AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation parameter(CAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study initiation.Liver stiffness/fibrosis was measured before and 47 wk after treatment completion.Patients with genotype 3 and patients with cirrhosis were excluded.RESULTS One hundred and one patients were included in the study.Post-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P < 0.05).Post-SVR,48 patients(47.5%) had steatosis on CAP;of these,6.25% had advanced fibrosis.Patients with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),CAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P < 0.05.Interestingly,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness(≥ 7 k Pa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV) patients post-SVR.These patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced fibrosis.Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR. | Mazen Noureddin Micaela M Wong Tsuyoshi Todo Shelly C Lu Arun J Sanyal Edward A Mena | 2018 | World Journal of Gastroenterology2018，24，11： | 6 |
| 16 | Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade显示文摘PD-1 blockade represents a major therapeutic avenue in anticancer immunotherapy.Delineating mechanisms of secondary resistance to this strategy is increasingly important.Here,we identified the deleterious role of signaling via the type I interferon(IFN)receptor in tumor and antigen presenting cells,that induced the expression of nitric oxide synthase 2(N0S2),associated with intratumor accumulation of regulatory T cells(Treg)and myeloid cells and acquired resistance to anti-PD-1 monoclonal antibody(mAb).Sustained IFNP transcription was observed in resistant tumors,in turn inducing PD-L1 and N0S2 expression in both tumor and dendritic cells(DC).Whereas PD-L1 was not involved in secondary resistance to anti-PD-1 mAb,pharmacological or genetic inhibition of N0S2 maintained long-term control of tumors by PD-1 blockade,through reduction of Treg and DC activation.Resistance to immunotherapies,including anti-PD-1 mAb in melanoma patients,was also correlated with the induction of a type I IFN signature.Hence,the role of type I IFN in response to PD-1 blockade should be revisited as sustained type I IFN signaling may contribute to resistance to therapy. | Nicolas Jacquelot Takahiro Yamazaki Maria PRoberti Connie PMDuong Miles CAndrews Loic Verlingue Gladys Ferrere Sonia Becharef Marie Vetizou Romain Daillere Meriem Messaoudene David PEnot Gautier Stoll Stefano Ugel Maria Marigo Shin Foong Ngiow Aurelien Marabelle Armelle Prevost-Blondel Pierre-Olivier Gaudreau Vancheswaran Gopalakrishnan Alexander MEggermont Paule Opolon Christophe Klein Gabriele Madonna Paolo AAscierto Antje Sucker Dirk Schadendorf Mark JSm yth Jean-Charles Soria Guido Kroemer Vincenzo Bronte Jennifer Wargo and Laurence Zitvogel | 2019 | Cell Research2019，29，10： | 6 |
| 17 | Application of sustained delivery microsphere of cyclosporine A for preventing posterior capsular opacification in rabbits显示文摘AIM:To explore the inhibitory effect of a sustained cyclosporin A (CsA) delivery microsphere (CsA-MS) on posterior capsular opacification (PCO) in rabbit eyes after cataract extraction. ·METHODS:Twenty New Zealand white rabbits accepted cataract extraction plus intraocular lens implantation and their left eyes were intraoperatively injected CsA-MS prepared using polymer polylactioglycolic acid (PLGA) as a carrier and their right eyes were injected with empty MS. The changes in cornea, anterior chamber reaction, intraocular pressure, PCO and CsA concentration in aqueous humor were examined postoperatively and all the eyes were enucleated 3 months after surgery for histopathological and morphological examination with light microscopy and electron microscopy. · RESULTS:Conjunctival hyperemia, corneal edema, intraocular pressure and anterior chamber response of experimental and control eyes were similar, while PCO in CsA MS injected eyes was greatly improved compared with that in control eyes. Posterior capsules in CsA-MS injected eyes were smooth and lens epithelial cells (LEC) did not proliferate significantly (P >0.05), while LEC in posterior capsule of control eyes had different degrees of proliferation and cortical regeneration. LEC in CsA-MS injected eyes were not functionally active and underwent apoptosis, whereas LEC in control eyes were functionally active (F-test, P =0.025). In addition, the cornealultrastructure showed no differences between CsA-MS and MS injected eyes. CONCLUSION:CsA-MS has high bioavailability in rabbit eyes and could inhibit postoperative PCO occurrence and development during the study period, suggesting that CsA-MS may be a promising, effective and safe administration route to prevent PCO in clinic. | Cheng Pei Yi Xu Jean Xin.Jiang Li-Jun Cui Li Li Li Qin | 2013 | International Journal of Ophthalmology(English edition)2013，6，1： | 6 |
| 18 | Hepatitis C virus related cirrhosis decreased as indication to liver transplantation since the introduction of direct-acting antivirals: A single-center study显示文摘AIM To evaluate waiting list(WL) registration and liver transplantation(LT) rates in patients with hepatitis C virus(HCV)-related cirrhosis since the introduction of direct-acting antivirals(DAAs).METHODS All adult patients with cirrhosis listed for LT at Padua University Hospital between 2006-2017 were retrospectively collected using a prospectivelyupdated database; patients with HCV-related cirrhosis were divided by indication for LT [dec-HCV vs HCV/hepatocellular carcinoma(HCC)] and into two interval times(2006-2013 and 2014-2017) according to the introduction of DAAs. For each patient, indications to LT, severity of liver dysfunction and the outcome in the WL were assessed and compared between the two different time periods. For patients receiving DAA-based regimens, the achievement of viral eradication and the outcome were also evaluated. RESULTS One thousand one hundred and ninty-four [male(M)/female(F): 925/269] patients were included. Considering the whole cohort, HCV-related cirrhosis was the main etiology at the time of WL registration(490/1194 patients, 41%). HCV-related cirrhosis significantly decreased as indication to WL registration after DAA introduction(from 43.3% in 2006-2013 to 37.2% in 2014-2017, P = 0.05), especially amongst decHCV(from 24.2% in 2006-2013 to 15.9% in 2014-2017, P = 0.007). Even HCV remained the most common indication to LT over time(289/666, 43.4%), there was a trend towards a decrease after DAAs introduction(from 46.3% in 2006-2013 to 39% in 2014-2017, P = 0.06). HCV patients(M/F: 43/11, mean age: 57.7 ± 8 years) who achieved viral eradication in the WL had better transplant-free survival(log-rank test P = 0.02) and delisting rate(P = 0.002) than untreated HCV patients. CONCLUSION Introduction of DAAs significantly reduced WL registrations for HCV related cirrhosis, especially in the setting of decompensated cirrhosis. | Alberto Ferrarese Giacomo Germani Martina Gambato Francesco Paolo Russo Marco Senzolo Alberto Zanetto Sarah Shalaby Umberto Cillo Giacomo Zanus Paolo Angeli Patrizia Burra | 2018 | World Journal of Gastroenterology2018，24，38： | 5 |
| 19 | Risks of rapid decline renal function in patients with type 2 diabetes显示文摘Progressive rising population of diabetes and related nephropathy, namely, diabetic kidney disease and associated end stage renal disease has become a major global public health issue. Results of observational studies indicate that most diabetic kidney disease progresses over decades; however, certain diabetes patients display a rapid decline in renal function, which may lead to renal failure within months. Although the definition of rapid renal function decline remained speculative, in general,it is defined by the decrease of estimated glomerular filtration rate(e GFR) in absolute rate of loss or percent change. Based on the Kidney Disease: Improving Global Outcomes 2012 clinical practice guidelines, a rapid decline in renal function is defined as a sustained declinein e GFR of > 5 m L/min per 1.73 m2 per year. It has been reported that potential factors contributing to a rapid decline in renal function include ethnic/genetic and demographic causes, smoking habits, increased glycated hemoglobin levels, obesity, albuminuria, anemia, low serum magnesium levels, high serum phosphate levels, vitamin D deficiency, elevated systolic blood pressure, pulse pressure, brachial-ankle pulse wave velocity values, retinopathy, and cardiac autonomic neuropathy. This article reviews current literatures in this area and provides insight on the early detection of diabetic subjects who are at risk of a rapid decline in renal function in order to develop a more aggressive approach to renal and cardiovascular protection. | Yi-Jing Sheen Wayne HH Sheu | 2014 | World Journal of Diabetes2014，5，6： | 5 |
| 20 | Preparation and in vitro-in vivo evaluation of intestinal retention pellets of Berberine chloride to enhance hypoglycemic and lipid-lowing efficacy显示文摘Berberine chloride(BBR) is a pharmacokinetic profile of drug with poor bioavailability but good therapeutic efficacy,which is closely related to the discovery of BBR intestinal target.The major aim of this paper is to develop BBR intestinal retention type sustained-release pellets and evaluate their in vivo and in vitro behaviors base on the aspect of local action on intestinal tract. Here,wet milling technology is used to improve dissolution and dissolution rate of BBR by decreasing the particle size and increasing the wettability. The pellets are prepared by liquid layer deposition technology,and then the core pellets are coated with Eudragit~?L30 D-55 and Eudragit~?NE30 D aqueous dispersion. The prepared pellets show high drug loading capacity,and the drug loading up to 93%. Meanwhile,it possesses significant sustained drug release effect in purified water which is expected to improve the pharmacokinetic behavior of BBR. The pharmacokinetics results demonstrate that the halflife of BBR was increased significantly from 24 h to 36 h and the inter-and intra-subject variability are decreased compared to commercial BBR tablets. The retention test results indicate that the pellet size and Eudragit~?NE30 D plays an important role in retention time of the pellet,and it is found that the pellets with small particle size and high Eudragit~?NE30 D coating content can stay longer in the intestine than the pellets with large particle size. All in all,BBR intestinal retention type pellets are prepared successfully in this study,and the pellets show satisfactory in vivo and in vitro behaviors. | Guofei Li Mingming Zhao Xianying Su Lin Song Limei Zhao | 2019 | Asian Journal of Pharmaceutical Sciences2019，14，5： | 5 |
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