Electrochemical CO2 reduction to chemicals or fuels presents one of the most promising strategies for managing the global carbon balance, which yet poses a significant challenge due to lack of efficient and durable el...Electrochemical CO2 reduction to chemicals or fuels presents one of the most promising strategies for managing the global carbon balance, which yet poses a significant challenge due to lack of efficient and durable electrocatalyst as well as the understanding of the CO2 reduction reaction(CO2RR) mechanism.Benefiting from the large surface area, high electrical conductivity, and tunable structure, carbon-based metal-free materials(CMs) have been extensively studied as cost-effective electrocatalysts for CO2RR.The development of CMs with low cost, high activity and durability for CO2RR has been considered as one of the most active and competitive directions in electrochemistry and material science.In this review article,some up-to-date strategies in improving the CO2RR performance on CMs are summarized.Specifically, the approaches to optimize the adsorption of CO2RR intermediates, such as tuning the physical and electronic structure are introduced, which can enhance the electrocatalytic activity of CMs effectively.Finally, some design strategies are proposed to prepare CMs with high activity and selectivity for CO2RR.展开更多
AIM:To assess the rigorous relationship between human leukocyte antigens(HLA)-DR alleles and outcomes of hepatitis B virus(HBV) infections by means of metaanalysis.METHODS:Medline/PubMed,EMBASE,CNKI and VIP were searc...AIM:To assess the rigorous relationship between human leukocyte antigens(HLA)-DR alleles and outcomes of hepatitis B virus(HBV) infections by means of metaanalysis.METHODS:Medline/PubMed,EMBASE,CNKI and VIP were searched to identify relevant studies.Study quality was evaluated using the Newcastle-Ottawa Scale.Odds ratios(OR) and 95% confidence interval(95% CI) were pooled using Stata 11.0.Subgroup analyses were performed by ethnicity.Heterogeneity and publication bias analyses were performed to validate the credibility.RESULTS:A total of 2609 patients with chronic hepatitis B and 2606 controls spontaneously recovering from prior HBV infection were included.Meta-analysis showed that HLA-DR*04(OR = 0.72,95% CI:0.60-0.85) and DR*13(OR = 0.27,95% CI:0.19-0.37) alleles were significantly associated with HBV clearance while patients carrying HLA-DR*03(OR = 1.47,95% CI:1.16-1.87) or DR*07(OR = 1.59,95% CI:1.24-2.03) alleles had a significantly increased risk of chronic HBV persistence.For the HLA-DR*01 polymorphism,a significantly association with HBV clearance was found in Chinese Han group(OR = 0.48,95% CI:0.26-0.86),but not found in other ethnic groups(P = 0.191).For other polymorphisms,no association with the HBV infection outcome was found.CONCLUSION:HLA-DR*04 and DR*13 alleles may be the protective factors for HBV clearance and HLADR*03,and DR*07 alleles may be the risk factors for HBV persistence.展开更多
AIM: To describe a population of outpatients in China infected by hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and assess their current management status. METHODS: A multicenter, cross-sectional study of HB...AIM: To describe a population of outpatients in China infected by hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and assess their current management status. METHODS: A multicenter, cross-sectional study of HBV- and/or HCV-infected patients was conducted from August to November, 2011 in western China. Patients >= 18 years of age with HBV and/or HCV infections who visited outpatient departments at 10 hospitals were evaluated, whether treated or not. Data were collected on the day of visit from medical records and patient interviews. RESULTS: A total 4010 outpatients were analyzed, including 2562 HBV- infected and 1406 HCV-infected and 42 HBV/HCV co-infected patients. The median duration of documented infection was 7.5 years in HBV- infected and 1.8 years in HCV-infected patients. Cirrhosis was the most frequent hepatic complication (12.2%), appearing in one-third of patients within 3 years prior to or at diagnosis. The HCV genotype was determined in only 10% of HCV-infected patients. Biopsy data were only available for 54 patients (1.3%). Antiviral medications had been received by 58.2% of patients with HBV infection and 66.6% with HCV infection. Nucleos(t) ide analogs were the major antiviral medications prescribed for HBV- infected patients (most commonly adefovir dipivoxil and lamivudine). Ribavirin + pegylated interferon was prescribed for two-thirds of HCV-infected patients. In the previous 12 mo, around one-fifth patients had been hospitalized due to HBV or HCV infection. CONCLUSION: This observational, real-life study has identified some gaps between clinical practice and guideline recommendations in China. To achieve better health outcomes, several improvements, such as disease monitoring and optimizing antiviral regimens, should be made to improve disease management. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.展开更多
AIM To investigate the association between interferoninduced protein with tetratricopeptide repeats 1(IFIT1) polymorphisms and interferon-α(IFNα) treatment efficiency among Chinese hepatitis B virus(HBV) infection p...AIM To investigate the association between interferoninduced protein with tetratricopeptide repeats 1(IFIT1) polymorphisms and interferon-α(IFNα) treatment efficiency among Chinese hepatitis B virus(HBV) infection patients.METHODS Two hundred and twenty five newly diagnosed chronichepatitis B(CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen(HBe Ag) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms(SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.RESULTS At the end of the treatment, HBe Ag seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218(A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64(95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response(response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype(response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBe Ag seroconversion, combined response or sustained response was observed.CONCLUSION IFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.展开更多
AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic...AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.展开更多
AIM To investigate the mechanism by which hepatitis C virus(HCV) core protein-induced mi R-93-5 p up-regulation regulates the interferon(IFN) signaling pathway.METHODS HCV-1 b core protein was exogenously expressed in...AIM To investigate the mechanism by which hepatitis C virus(HCV) core protein-induced mi R-93-5 p up-regulation regulates the interferon(IFN) signaling pathway.METHODS HCV-1 b core protein was exogenously expressed in Huh7 cells using pc DNA3.1(+) vector. The expression of mi R-93-5 p and interferon receptor 1(IFNAR1) was measured using quantitative reverse transcriptionpolymerase chain reaction and Western blot. The protein expression and phosphorylation level of STAT1 were evaluated by Western blot. The overexpression and silencing of mi R-93-5 p and IFNAR1 were performed using mi R-93-5 p agomir and antagomir, and pc DNA3.1-IFNAR1 and IFNAR1 si RNA, respectively. Luciferase assay was used to identify whether IFNAR1 is a target of mi R-93-5 p. Cellular experiments were also conducted.RESULTS Serum mi R-93-5 p level was increased in patients with HCV-1 b infection and decreased to normal level after HCV-1 b clearance, but persistently increased in those with pegylated interferon-α resistance, compared with healthy subjects. Serum mi R-93-5 p expression had an AUC value of 0.8359 in distinguishing patients with pegylated interferon-α resistance from those with pegylated interferon-α sensitivity. HCV-1 b core protein increased mi R-93-5 p expression and induced inactivation of the IFN signaling pathway in Huh7 cells. Furthermore, IFNAR1 was identified as a direct target of mi R-93-5 p, and IFNAR1 restore could rescue mi R-93-5 p-reduced STAT1 phosphorylation, suggesting that the mi R-93-5 p-IFNAR1 axis regulates the IFN signaling pathway.CONCLUSION HCV-1 b core protein-induced mi R-93-5 p up-regulation inhibits the IFN signaling pathway by directly targeting IFNAR1, and the mi R-93-5 p-IFNAR1 axis regulates STAT1 phosphorylation. This axis may be a potential therapeutic target for HCV-1 b infection.展开更多
BACKGROUND Porphyria is a rare disease with complex classification. Erythropoietic protoporphyria(EPP) is an autosomal recessively inherited disease, and most are caused by mutations in the FECH gene. EPP combined wit...BACKGROUND Porphyria is a rare disease with complex classification. Erythropoietic protoporphyria(EPP) is an autosomal recessively inherited disease, and most are caused by mutations in the FECH gene. EPP combined with liver injury is even rarer.CASE SUMMARY This paper reports a case of EPP which was admitted to the hospital with abnormal liver function and diagnosed by repeated questioning of medical history, screening of common causes of severe liver injury, and second generation sequencing of the whole exon genome. We also summarize the clinical characteristics of EPP with liver injury, and put forward some suggestions on EPP to provide a reference for the diagnosis of such rare disease.CONCLUSION A new mutation locus(c.32_35 dupCCCT) which may be related to the disease was found by detecting the FECH gene in the pedigree of this case.展开更多
One of the major challenges associated with fuel cells is the design of highly efficient electrocatalysts to reduce the high overpotential of the oxygen reduction reaction (ORR). Here we report Polyaniline (PANI) base...One of the major challenges associated with fuel cells is the design of highly efficient electrocatalysts to reduce the high overpotential of the oxygen reduction reaction (ORR). Here we report Polyaniline (PANI) based micro/nanomaterials with or without transition metals, prepared by the emulsion polymerization and subsequent heat treatment. PANI microspheres with the diameter of about 0.7 mu m have been prepared in basic (NH3 solution) condition, using two different types of surfactant (CTAB, SDS) as the stabilizer, ammonium persulphate (APS) as oxidant with aniline/surfactants molar ratio at 1/1 under the hydrothermal treatment. PANI nanorods, Fe-PANI, and Fe-Co-PANI have been synthesized in acidic (HCI) medium with aniline/surfactants molar ratio at 1/2 and polymerization carried out without stirring for 24 h. Products mainly Fe-Co-PANI have shown high current density with increasing sweep rate and excellent specific capacitance 1753 F/g at the scan rate of 1 mV/s. Additionally, it has shown high thermal stability by thermogravimetric analysis (TGA). Fe-PANI has been investigated for excellent performance toward ORR with four electron selectivity in the basic electrolyte. The PANI-based catalysts from emulsion polymerization demonstrate that the method is valuable for making non-precious metal heterogeneous electrocatalysts for ORR or energy storage and conversion technology. (C) 2016 Science Press and Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. and Science Press. All rights reserved.展开更多
A binder-free Ir-dispersed ordered mesoporous carbon（Ir-OMC） catalytic electrode has been prepared through a designed in-situ carbonization method, which involves coating resorcinol and formaldehyde mixtures with ir...A binder-free Ir-dispersed ordered mesoporous carbon（Ir-OMC） catalytic electrode has been prepared through a designed in-situ carbonization method, which involves coating resorcinol and formaldehyde mixtures with iridium precursors onto the three-dimensional nickel foam framework, followed by insitu calcination in Natmosphere at 800 ℃ for 3 h. This electrode shows a large surface area, ordered mesoporous structure and homogeneous distribution of metal nanoparticles. It presents good activity and stability towards hydrogen evolution reaction, which is attributed to the efficient mass and electron transport from the intimate contact among Ir nanoparticles, ordered mesoporous carbon matrix and 3 D conductive substrate. We hope that this in-situ carbonization synthetic route can also be applied to design more high-performance catalysts for water splitting, fuel cells and other clean energy devices.展开更多
BACKGROUND Tenofovir disoproxil fumarate(TDF)is a prodrug of a nucleotide analogue.As an antiviral drug,TDF has been proposed in the first-line treatment of chronic hepatitis B(CHB).Qingzhong,a brand name of TDF,comme...BACKGROUND Tenofovir disoproxil fumarate(TDF)is a prodrug of a nucleotide analogue.As an antiviral drug,TDF has been proposed in the first-line treatment of chronic hepatitis B(CHB).Qingzhong,a brand name of TDF,commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd.,and Viread,another brand name of TDF,commercialized by GlaxoSmithKline,have both been approved by the State Food and Drug Administration,China.AIM To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients.METHODS This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857.A total of 330 Chinese CHB patients,among which 232 were hepatitis B e antigen(HBeAg)-positive,were included in this 5-year-long,multicenter,double-blinded,double-dummy,randomized-controlled,noninferiority phase III trial.The participants were initially randomized into two groups:Group A(n=161),in which the participants received 300 mg Qingzhong once a day for 48 wk;and Group B,in which the participants received 300 mg Viread once a day for 48 wk.Starting from week 49,all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th week.In this study,the primary endpoint was the decrease in plasma level of hepatitis B virus(HBV)DNA at the 96th week,while the secondary endpoints were suppression of HBV replication,alanine aminotransferase(ALT)normalization,HBeAg loss,and HBeAg seroconversion rates.RESULTS For the participants with HBeAg-positive CHB,the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B(5.77 vs 5.73 log10 IU/mL,P>0.05)at the 96th week.In addition,similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA,HBeAg loss,and HBeAg seroconversion(71.05%vs 77.97%,31.00%vs 27.27%,and 20.22%vs 15.79%,respectively,in Group A vs Group B;P>0.05).For the participants with HBeAg-negative CHB,the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B(4.46 vs 4.70 log10 IU/mL,P>0.05)at the 96th week.In addition,similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA(87.23%vs 94.12%in Group A vs Group B,respectively;P>0.05).Finally,similar percentages of CHB patients(HBeAg-positive or HBeAg-negative)in the two groups exhibited normalization of ALT(80.14%vs 84.57%in Group A vs Group B,respectively;P>0.05),and similar incidences of adverse events were observed(106 vs 104 in Group A vs Group B,respectively;P>0.05).CONCLUSION Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.展开更多
The hydrogen evolution reaction(HER) – as an essential half reaction in water electrolysis and chlor-alkali process has been well studied in acidic electrolyte, but much less has been known in basic medium. In this s...The hydrogen evolution reaction(HER) – as an essential half reaction in water electrolysis and chlor-alkali process has been well studied in acidic electrolyte, but much less has been known in basic medium. In this study, by combining kinetic modeling and electrochemical measurements, we show that hydrated alkali cation clusters can adsorb on the surface of HER catalyst in basic electrolyte. The bound H2 O molecules in the "clusters" can thus be in-situ activated through the hydration effect, which dissociate on the catalyst surface as the reactant of HER. The effective concentration and hydration energy of alkali cation can influence the H2 O dissociation rate, and hence the kinetics of HER. Our work demonstrates a new understanding of the HER mechanism in basic reaction electrolyte.展开更多
BACKGROUND Entecavir(ETV)is a potent and selective nucleotide analog with significant activity against hepatitis B virus(HBV).ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety...BACKGROUND Entecavir(ETV)is a potent and selective nucleotide analog with significant activity against hepatitis B virus(HBV).ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV(Baraclude)when used in Chinese patients with chronic hepatitis B(CHB)in phase III clinical trials(Clinical Trials.gov number,NCT-01926288)at weeks 48,96,and 144.AIM To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C.METHODS In this double-blind study,we randomly assigned patients to receive 0.5 mg/d ETV(Group A)or ETV maleate(Group B)(ratio,1:1),each with a placebo tablet for 48 wk.Then,all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49.The primary efficacy endpoint was the reduction in HBV DNA levels from baseline.Secondary endpoints included the proportion of patients with undetectable HBV DNA(<20 IU/m L),serologic response,serum alanine aminotransferase(ALT)normalization and development of resistance mutations.RESULTS Two hundred eighteen patients who were hepatitis B e antigen(HBe Ag)positive and 57 who were HBe Ag negative were analyzed and predominantly presented with genotype B(49.82%)or C(48.73%).For the HBe Ag-positive CHB patients,the mean HBV DNA level decrease(6.61 Log10 IU/m L vs 6.69 Log10 IU/m L,P>0.05),viral suppression with HBV DNA<20 IU/m L(83.33%vs 79.17%,P>0.05)and HBe Ag seroconversion(28.77%vs 20.00%,P>0.05)occurred similarly between Groups A and B at week 192.However,there was a significant difference in the proportion of patients with normal ALT levels(91.14%vs 78.38%,P<0.05).For the HBe Ag-negative CHB patients,no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline(6.05 Log10 IU/m L vs 6.03 Log10 IU/m L,P>0.05),percentages of patients who achieved undetectable HBV DNA(100%vs 100%,P>0.05)and rates of ALT normalization(95.65%vs 100.00%,P>0.05).Safety and adverse event profiles were similar between Groups A and B.Two HBe Ag-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV.CONCLUSION Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.展开更多
Objective:To study the effect of p53-targeted small molecular reactivator of p53 and induction of tumor apoptosis (RITA) combined with temozolomide (TMZ) on the glioma cell growth in vitro.Methods:Human glioma cell li...Objective:To study the effect of p53-targeted small molecular reactivator of p53 and induction of tumor apoptosis (RITA) combined with temozolomide (TMZ) on the glioma cell growth in vitro.Methods:Human glioma cell lines U87 were cultured and randomly divided into RITA+TMZ group (treated with 5 μmol/L RITA and 10 μmol/L TMZ), TMZ group (treated with 10 μmol/L TMZ) and control group (treated with drug-free DMEM). After 24 h of treatment, the expression of p53 downstream cell cycle molecules, apoptosis molecules and invasion molecules in cells were measured.Results:p21cip1, Per2, ATM and E-cadherin protein expression in RITA+TMZ group and TMZ group were significantly higher than those in control group while CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail and Slug protein expression were significantly lower than those in control group;p21cip1, Per2, ATM and E-cadherin protein expression in RITA+TMZ group were significantly higher than those in TMZ group while CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail and Slug protein expression were significantly lower than those in TMZ group.Conclusion:p53-targeted small molecular RITA combined with temozolomide treatment of glioma cells can induce p53-mediated cell cycle arrest, cell apoptosis activation and cell invasion inhibition.展开更多
Background and Aims:Tenofovir amibufenamide(TMF)is a novel phosphoramidated prodrug of tenofovir with nonin-ferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate(TDF)in 48 weeks of treatmen...Background and Aims:Tenofovir amibufenamide(TMF)is a novel phosphoramidated prodrug of tenofovir with nonin-ferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate(TDF)in 48 weeks of treatment.Here,we update 96-week comparison results.Methods:Patients with chronic hepatitis B were assigned(2:1)to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks.The virological suppression was defined as HBV DNA levels<20 IU/mL at week 96.Safety was evaluated thoroughly with focusing on bone,renal,and metabolic pa-rameters.Results:Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations.Noninferior efficacy was maintained in the pooled population,while it was first achieved in patients with HBV DNA≥7 or 8 log10 IU/mL at baseline.Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted,while a smaller decline of which was seen in the TMF group than in the TDF group(p=0.01).For bone mineral density,patients receiv-ing TMF displayed significantly lower reduction levels in the densities of spine,hip,and femur neck at week 96 than those receiving TDF.In addition,the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend.Conclusions:TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles(NCT03903796).展开更多
Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patien...Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 data.In this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung damage.They were randomly assigned at a 2:1 ratio to receive either UC-MSCs(4×10^(7)cells per infusion)or placebo on day 0,3,and 6.The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28.Other imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and analyzed.In all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo(the mediandifference was-13.31%,95%Cl-29.14%,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.45%;95%CI-30.82%,-0.39%;P=0.043).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:27.00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two groups.These results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.展开更多
Prognostication of coma patients after brain injury is important, yet challenging. In this study, we evaluated the predictive value of amplitude-integrated electroencephalography （aEEG） for neurological outcomes in ...Prognostication of coma patients after brain injury is important, yet challenging. In this study, we evaluated the predictive value of amplitude-integrated electroencephalography （aEEG） for neurological outcomes in coma patients. From January 2013 to January 2016, 128 coma patients after acute brain injury were prospectively enrolled and monitored with aEEG. The 6-month neurological outcome was evaluated using the Cerebral Performance Category Scale. aEEG monitoring commenced at a median of 7.5 days after coma onset. Continuous normal voltage predicted a good 6-month neurological outcome with a sensitivity of 93.6% and specificity of 85.2%. In contrast, continuous extremely low voltage, burst-suppression, or a flat tracing was correlated with poor 6-month neurological outcome with a sensitivity of 76.5% and specificity of 100%. In conclusion, aEEG is a promising predictor of 6-month neurological outcome for coma patients after acute brain injury.展开更多
In this paper,we present a novel ocean visualization framework,which focuses on analyzing multidimensional and spatiotemporal ocean data.GPU-based visualization methods are explored to effectively visualize ocean data...In this paper,we present a novel ocean visualization framework,which focuses on analyzing multidimensional and spatiotemporal ocean data.GPU-based visualization methods are explored to effectively visualize ocean data.An improved ray casting algorithm for heterogeneous multisection ocean volume data is presented.A two-layer spherical shell is taken as the ocean data proxy geometry,which enables oceanographers to obtain a real geographic background based on global terrain.An efficient ray sampling technique including an adaptive sampling technique and a preintegrated transfer function is proposed to achieve high-effectiveness and high-efficiency rendering.Moreover,an interactive transfer function is also designed to analyze the 3D structure of ocean temperature and salinity anomaly phenomena.Based on the framework,an integrated visualization system called i4Ocean is created.The visualization of ocean temperature and salinity anomalies extracted interactively by the transfer function is demonstrated.展开更多
The vegetative state is a complex condition with unclear mechanisms and limited diagnostic, prognostic, and therapeutic methods. In this study, we aimed to explore the proteomic profile of tears from patients in a tra...The vegetative state is a complex condition with unclear mechanisms and limited diagnostic, prognostic, and therapeutic methods. In this study, we aimed to explore the proteomic profile of tears from patients in a traumatic vegetative state and identify potential diagnostic markers using tears-a body fluid that can be collected noninvasively. Using iTRAQ quantitative proteomic technology, in the discovery phase, tear samples collected from 16 patients in a traumatic vegetative state and 16 normal individuals were analyzed. Among 1080 identified tear proteins, 57 were upregulated and 15 were downregulated in the patients compared to the controls. Bioinformatics analysis revealed that the differentially-expressed proteins were mainly involved in the wound response and immune response signaling pathways. Furthermore, we verified the levels of 7 differentially-expressed proteins in tears from 50 traumatic vegetative state patients and 50 normal controls （including the samples used in the discovery phase） using ELISA. The results showed that this 7-protein panel had a high discrimination ability for traumatic vegetative state （area under the curve = 0.999）. In sum- mary, the altered tear proteomic profile identified in this study provides a basis for potential tear protein markers for diagnosis and prognosis of the traumatic vegetative state and also provides novel insights into the mechanisms of traumatic vegetative state.展开更多
Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses,but the underlying mechanism remains unclear.In this study,the N proteins of highly pathogenic hum...Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses,but the underlying mechanism remains unclear.In this study,the N proteins of highly pathogenic human coronaviruses,including severe acute respiratory syndrome coronavirus(SARS-CoV),middle east respiratory syndrome coronavirus(MERS-CoV)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),were found to bind MASP-2,a key serine protease in the lectin pathway of complement activation,resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation,and the deposition of MASP-2,C4b,activated C3 and C5b-9.Aggravated inflammatory lung injury was observed in mice infected with adenovirus expressing the N protein.Complement hyperactivation was also observed in SARS-CoV-2-infected patients.Either blocking the N protein:MASP-2 interaction,MASP-2 depletion or suppressing complement activation can significantly alleviate N protein-induced complement hyperactivation and lung injury in vitro and in vivo.Altogether,these data suggested that complement suppression may represent a novel therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.展开更多
基金supported by the National Key R&D Program of China (2016YFB0600902)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB17000000)+2 种基金Dalian National Laboratory for Clean Energy (DNL180401)the Youth Innovation Promotion Association CASthe Singapore Ministry of Education Academic Research Fund (AcRF) Tier 1: RG9/17, RG115/17, RG115/18 and Tier 2: MOE2016-T2-2-004
文摘Electrochemical CO2 reduction to chemicals or fuels presents one of the most promising strategies for managing the global carbon balance, which yet poses a significant challenge due to lack of efficient and durable electrocatalyst as well as the understanding of the CO2 reduction reaction(CO2RR) mechanism.Benefiting from the large surface area, high electrical conductivity, and tunable structure, carbon-based metal-free materials(CMs) have been extensively studied as cost-effective electrocatalysts for CO2RR.The development of CMs with low cost, high activity and durability for CO2RR has been considered as one of the most active and competitive directions in electrochemistry and material science.In this review article,some up-to-date strategies in improving the CO2RR performance on CMs are summarized.Specifically, the approaches to optimize the adsorption of CO2RR intermediates, such as tuning the physical and electronic structure are introduced, which can enhance the electrocatalytic activity of CMs effectively.Finally, some design strategies are proposed to prepare CMs with high activity and selectivity for CO2RR.
基金Supported by The National Natural Science Foundation of China,No.30972598National Basic Research Program of China (973 Program),No.2007CB512903the State Key Project Specialized for Infectious Diseases,No.2008ZX10002-007
文摘AIM:To assess the rigorous relationship between human leukocyte antigens(HLA)-DR alleles and outcomes of hepatitis B virus(HBV) infections by means of metaanalysis.METHODS:Medline/PubMed,EMBASE,CNKI and VIP were searched to identify relevant studies.Study quality was evaluated using the Newcastle-Ottawa Scale.Odds ratios(OR) and 95% confidence interval(95% CI) were pooled using Stata 11.0.Subgroup analyses were performed by ethnicity.Heterogeneity and publication bias analyses were performed to validate the credibility.RESULTS:A total of 2609 patients with chronic hepatitis B and 2606 controls spontaneously recovering from prior HBV infection were included.Meta-analysis showed that HLA-DR*04(OR = 0.72,95% CI:0.60-0.85) and DR*13(OR = 0.27,95% CI:0.19-0.37) alleles were significantly associated with HBV clearance while patients carrying HLA-DR*03(OR = 1.47,95% CI:1.16-1.87) or DR*07(OR = 1.59,95% CI:1.24-2.03) alleles had a significantly increased risk of chronic HBV persistence.For the HLA-DR*01 polymorphism,a significantly association with HBV clearance was found in Chinese Han group(OR = 0.48,95% CI:0.26-0.86),but not found in other ethnic groups(P = 0.191).For other polymorphisms,no association with the HBV infection outcome was found.CONCLUSION:HLA-DR*04 and DR*13 alleles may be the protective factors for HBV clearance and HLADR*03,and DR*07 alleles may be the risk factors for HBV persistence.
基金Supported by Financial support for this study was provided by Merck Sharp and Dohme(China)Ltd
文摘AIM: To describe a population of outpatients in China infected by hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and assess their current management status. METHODS: A multicenter, cross-sectional study of HBV- and/or HCV-infected patients was conducted from August to November, 2011 in western China. Patients >= 18 years of age with HBV and/or HCV infections who visited outpatient departments at 10 hospitals were evaluated, whether treated or not. Data were collected on the day of visit from medical records and patient interviews. RESULTS: A total 4010 outpatients were analyzed, including 2562 HBV- infected and 1406 HCV-infected and 42 HBV/HCV co-infected patients. The median duration of documented infection was 7.5 years in HBV- infected and 1.8 years in HCV-infected patients. Cirrhosis was the most frequent hepatic complication (12.2%), appearing in one-third of patients within 3 years prior to or at diagnosis. The HCV genotype was determined in only 10% of HCV-infected patients. Biopsy data were only available for 54 patients (1.3%). Antiviral medications had been received by 58.2% of patients with HBV infection and 66.6% with HCV infection. Nucleos(t) ide analogs were the major antiviral medications prescribed for HBV- infected patients (most commonly adefovir dipivoxil and lamivudine). Ribavirin + pegylated interferon was prescribed for two-thirds of HCV-infected patients. In the previous 12 mo, around one-fifth patients had been hospitalized due to HBV or HCV infection. CONCLUSION: This observational, real-life study has identified some gaps between clinical practice and guideline recommendations in China. To achieve better health outcomes, several improvements, such as disease monitoring and optimizing antiviral regimens, should be made to improve disease management. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
文摘AIM To investigate the association between interferoninduced protein with tetratricopeptide repeats 1(IFIT1) polymorphisms and interferon-α(IFNα) treatment efficiency among Chinese hepatitis B virus(HBV) infection patients.METHODS Two hundred and twenty five newly diagnosed chronichepatitis B(CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen(HBe Ag) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms(SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.RESULTS At the end of the treatment, HBe Ag seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218(A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64(95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response(response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype(response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBe Ag seroconversion, combined response or sustained response was observed.CONCLUSION IFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.
基金Supported by Yigan Biological Products Co.,Ltd.of Guangzhou Pharmaceutical Holdings Ltd.(GPC,Guangzhou,China)Guangdong Provincial Sci.&Tech.Project,No.2012A080204009+2 种基金Guangdong Provincial Natural Science Fund,No.2014A030313 770Guangdong Provincial Public Benefit Foundation,No.2015A010107011National Key Program for Management of AIDS and Viral Hepatitis during the China "11~(th) 5-Year Plan" Period,No.2008ZX10002-003
文摘AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.
基金Supported by National Natural Science Foundation of China,No.81371849the TMMU Key Project for Clinical Research,No.2012XLC05
文摘AIM To investigate the mechanism by which hepatitis C virus(HCV) core protein-induced mi R-93-5 p up-regulation regulates the interferon(IFN) signaling pathway.METHODS HCV-1 b core protein was exogenously expressed in Huh7 cells using pc DNA3.1(+) vector. The expression of mi R-93-5 p and interferon receptor 1(IFNAR1) was measured using quantitative reverse transcriptionpolymerase chain reaction and Western blot. The protein expression and phosphorylation level of STAT1 were evaluated by Western blot. The overexpression and silencing of mi R-93-5 p and IFNAR1 were performed using mi R-93-5 p agomir and antagomir, and pc DNA3.1-IFNAR1 and IFNAR1 si RNA, respectively. Luciferase assay was used to identify whether IFNAR1 is a target of mi R-93-5 p. Cellular experiments were also conducted.RESULTS Serum mi R-93-5 p level was increased in patients with HCV-1 b infection and decreased to normal level after HCV-1 b clearance, but persistently increased in those with pegylated interferon-α resistance, compared with healthy subjects. Serum mi R-93-5 p expression had an AUC value of 0.8359 in distinguishing patients with pegylated interferon-α resistance from those with pegylated interferon-α sensitivity. HCV-1 b core protein increased mi R-93-5 p expression and induced inactivation of the IFN signaling pathway in Huh7 cells. Furthermore, IFNAR1 was identified as a direct target of mi R-93-5 p, and IFNAR1 restore could rescue mi R-93-5 p-reduced STAT1 phosphorylation, suggesting that the mi R-93-5 p-IFNAR1 axis regulates the IFN signaling pathway.CONCLUSION HCV-1 b core protein-induced mi R-93-5 p up-regulation inhibits the IFN signaling pathway by directly targeting IFNAR1, and the mi R-93-5 p-IFNAR1 axis regulates STAT1 phosphorylation. This axis may be a potential therapeutic target for HCV-1 b infection.
基金Supported by the Clinical Innovation Project from the Southwest Hospital,No.SWH2016ZDCX1007
文摘BACKGROUND Porphyria is a rare disease with complex classification. Erythropoietic protoporphyria(EPP) is an autosomal recessively inherited disease, and most are caused by mutations in the FECH gene. EPP combined with liver injury is even rarer.CASE SUMMARY This paper reports a case of EPP which was admitted to the hospital with abnormal liver function and diagnosed by repeated questioning of medical history, screening of common causes of severe liver injury, and second generation sequencing of the whole exon genome. We also summarize the clinical characteristics of EPP with liver injury, and put forward some suggestions on EPP to provide a reference for the diagnosis of such rare disease.CONCLUSION A new mutation locus(c.32_35 dupCCCT) which may be related to the disease was found by detecting the FECH gene in the pedigree of this case.
基金support by the National Natural Science Foundation of China(Grant no.21373042)
文摘One of the major challenges associated with fuel cells is the design of highly efficient electrocatalysts to reduce the high overpotential of the oxygen reduction reaction (ORR). Here we report Polyaniline (PANI) based micro/nanomaterials with or without transition metals, prepared by the emulsion polymerization and subsequent heat treatment. PANI microspheres with the diameter of about 0.7 mu m have been prepared in basic (NH3 solution) condition, using two different types of surfactant (CTAB, SDS) as the stabilizer, ammonium persulphate (APS) as oxidant with aniline/surfactants molar ratio at 1/1 under the hydrothermal treatment. PANI nanorods, Fe-PANI, and Fe-Co-PANI have been synthesized in acidic (HCI) medium with aniline/surfactants molar ratio at 1/2 and polymerization carried out without stirring for 24 h. Products mainly Fe-Co-PANI have shown high current density with increasing sweep rate and excellent specific capacitance 1753 F/g at the scan rate of 1 mV/s. Additionally, it has shown high thermal stability by thermogravimetric analysis (TGA). Fe-PANI has been investigated for excellent performance toward ORR with four electron selectivity in the basic electrolyte. The PANI-based catalysts from emulsion polymerization demonstrate that the method is valuable for making non-precious metal heterogeneous electrocatalysts for ORR or energy storage and conversion technology. (C) 2016 Science Press and Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. and Science Press. All rights reserved.
基金support of the National Natural Science Foundation of China (21403218, 21476226, 21403029)Ministry of Science and Technology of the People’s Republic of China under contact of 2016YFA0202800+2 种基金the Youth Innovation Promotion Association of the CASthe Scientific Research Project of the Education Department of Liaoning Province (L2014022)the Fundamental Research Funds for the Central Universities (DUT15ZD225)
文摘A binder-free Ir-dispersed ordered mesoporous carbon（Ir-OMC） catalytic electrode has been prepared through a designed in-situ carbonization method, which involves coating resorcinol and formaldehyde mixtures with iridium precursors onto the three-dimensional nickel foam framework, followed by insitu calcination in Natmosphere at 800 ℃ for 3 h. This electrode shows a large surface area, ordered mesoporous structure and homogeneous distribution of metal nanoparticles. It presents good activity and stability towards hydrogen evolution reaction, which is attributed to the efficient mass and electron transport from the intimate contact among Ir nanoparticles, ordered mesoporous carbon matrix and 3 D conductive substrate. We hope that this in-situ carbonization synthetic route can also be applied to design more high-performance catalysts for water splitting, fuel cells and other clean energy devices.
基金Supported by The 13th Five-year Science and Technology Major Project of China,on the Prevention and Treatment of Major Infectious Diseases,No.2017ZX10202202.
文摘BACKGROUND Tenofovir disoproxil fumarate(TDF)is a prodrug of a nucleotide analogue.As an antiviral drug,TDF has been proposed in the first-line treatment of chronic hepatitis B(CHB).Qingzhong,a brand name of TDF,commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd.,and Viread,another brand name of TDF,commercialized by GlaxoSmithKline,have both been approved by the State Food and Drug Administration,China.AIM To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients.METHODS This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857.A total of 330 Chinese CHB patients,among which 232 were hepatitis B e antigen(HBeAg)-positive,were included in this 5-year-long,multicenter,double-blinded,double-dummy,randomized-controlled,noninferiority phase III trial.The participants were initially randomized into two groups:Group A(n=161),in which the participants received 300 mg Qingzhong once a day for 48 wk;and Group B,in which the participants received 300 mg Viread once a day for 48 wk.Starting from week 49,all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th week.In this study,the primary endpoint was the decrease in plasma level of hepatitis B virus(HBV)DNA at the 96th week,while the secondary endpoints were suppression of HBV replication,alanine aminotransferase(ALT)normalization,HBeAg loss,and HBeAg seroconversion rates.RESULTS For the participants with HBeAg-positive CHB,the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B(5.77 vs 5.73 log10 IU/mL,P>0.05)at the 96th week.In addition,similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA,HBeAg loss,and HBeAg seroconversion(71.05%vs 77.97%,31.00%vs 27.27%,and 20.22%vs 15.79%,respectively,in Group A vs Group B;P>0.05).For the participants with HBeAg-negative CHB,the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B(4.46 vs 4.70 log10 IU/mL,P>0.05)at the 96th week.In addition,similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA(87.23%vs 94.12%in Group A vs Group B,respectively;P>0.05).Finally,similar percentages of CHB patients(HBeAg-positive or HBeAg-negative)in the two groups exhibited normalization of ALT(80.14%vs 84.57%in Group A vs Group B,respectively;P>0.05),and similar incidences of adverse events were observed(106 vs 104 in Group A vs Group B,respectively;P>0.05).CONCLUSION Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.
基金support from the National Natural Science Foundation of China (21808035)the Scientific Research Project of the Education Department of Fujian Province (JT180343, JT180089)+5 种基金the Fundamental Research Funds of FJUT (GY-Z18041, GY-Z160120)the Youth Innovation Project in the Natural Science Foundation of Fujian Province (2019J05058)the University Program for Outstanding Youth Scientific Research Talent Training in Fujian Province (GY-Z18162)the Quangang Petrochemical Research Institute of Fujian Normal University (2017YJY10)the Scientific Research Project of the Education Department of Liaoning Province (L2014022)the Fundamental Research Funds for the Central Universities (DUT15ZD225)。
文摘The hydrogen evolution reaction(HER) – as an essential half reaction in water electrolysis and chlor-alkali process has been well studied in acidic electrolyte, but much less has been known in basic medium. In this study, by combining kinetic modeling and electrochemical measurements, we show that hydrated alkali cation clusters can adsorb on the surface of HER catalyst in basic electrolyte. The bound H2 O molecules in the "clusters" can thus be in-situ activated through the hydration effect, which dissociate on the catalyst surface as the reactant of HER. The effective concentration and hydration energy of alkali cation can influence the H2 O dissociation rate, and hence the kinetics of HER. Our work demonstrates a new understanding of the HER mechanism in basic reaction electrolyte.
文摘BACKGROUND Entecavir(ETV)is a potent and selective nucleotide analog with significant activity against hepatitis B virus(HBV).ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV(Baraclude)when used in Chinese patients with chronic hepatitis B(CHB)in phase III clinical trials(Clinical Trials.gov number,NCT-01926288)at weeks 48,96,and 144.AIM To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C.METHODS In this double-blind study,we randomly assigned patients to receive 0.5 mg/d ETV(Group A)or ETV maleate(Group B)(ratio,1:1),each with a placebo tablet for 48 wk.Then,all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49.The primary efficacy endpoint was the reduction in HBV DNA levels from baseline.Secondary endpoints included the proportion of patients with undetectable HBV DNA(<20 IU/m L),serologic response,serum alanine aminotransferase(ALT)normalization and development of resistance mutations.RESULTS Two hundred eighteen patients who were hepatitis B e antigen(HBe Ag)positive and 57 who were HBe Ag negative were analyzed and predominantly presented with genotype B(49.82%)or C(48.73%).For the HBe Ag-positive CHB patients,the mean HBV DNA level decrease(6.61 Log10 IU/m L vs 6.69 Log10 IU/m L,P>0.05),viral suppression with HBV DNA<20 IU/m L(83.33%vs 79.17%,P>0.05)and HBe Ag seroconversion(28.77%vs 20.00%,P>0.05)occurred similarly between Groups A and B at week 192.However,there was a significant difference in the proportion of patients with normal ALT levels(91.14%vs 78.38%,P<0.05).For the HBe Ag-negative CHB patients,no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline(6.05 Log10 IU/m L vs 6.03 Log10 IU/m L,P>0.05),percentages of patients who achieved undetectable HBV DNA(100%vs 100%,P>0.05)and rates of ALT normalization(95.65%vs 100.00%,P>0.05).Safety and adverse event profiles were similar between Groups A and B.Two HBe Ag-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV.CONCLUSION Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.
文摘Objective:To study the effect of p53-targeted small molecular reactivator of p53 and induction of tumor apoptosis (RITA) combined with temozolomide (TMZ) on the glioma cell growth in vitro.Methods:Human glioma cell lines U87 were cultured and randomly divided into RITA+TMZ group (treated with 5 μmol/L RITA and 10 μmol/L TMZ), TMZ group (treated with 10 μmol/L TMZ) and control group (treated with drug-free DMEM). After 24 h of treatment, the expression of p53 downstream cell cycle molecules, apoptosis molecules and invasion molecules in cells were measured.Results:p21cip1, Per2, ATM and E-cadherin protein expression in RITA+TMZ group and TMZ group were significantly higher than those in control group while CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail and Slug protein expression were significantly lower than those in control group;p21cip1, Per2, ATM and E-cadherin protein expression in RITA+TMZ group were significantly higher than those in TMZ group while CDK4, CDK6, p-Rb, E2F, MDM2, c-myc, ILK, Snail and Slug protein expression were significantly lower than those in TMZ group.Conclusion:p53-targeted small molecular RITA combined with temozolomide treatment of glioma cells can induce p53-mediated cell cycle arrest, cell apoptosis activation and cell invasion inhibition.
文摘Background and Aims:Tenofovir amibufenamide(TMF)is a novel phosphoramidated prodrug of tenofovir with nonin-ferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate(TDF)in 48 weeks of treatment.Here,we update 96-week comparison results.Methods:Patients with chronic hepatitis B were assigned(2:1)to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks.The virological suppression was defined as HBV DNA levels<20 IU/mL at week 96.Safety was evaluated thoroughly with focusing on bone,renal,and metabolic pa-rameters.Results:Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations.Noninferior efficacy was maintained in the pooled population,while it was first achieved in patients with HBV DNA≥7 or 8 log10 IU/mL at baseline.Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted,while a smaller decline of which was seen in the TMF group than in the TDF group(p=0.01).For bone mineral density,patients receiv-ing TMF displayed significantly lower reduction levels in the densities of spine,hip,and femur neck at week 96 than those receiving TDF.In addition,the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend.Conclusions:TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles(NCT03903796).
基金Funded by The National Key R&D Program of China and others.ClinicalTrials.gov number,NCT04288102supported by The National Key R&D Program of China(2020YFC0841900,2020YFC0844000,2020YFC08860900)+1 种基金The Innovation Groups of the National Natural Science Foundation of China(81721002)The National Science and Technology Major Project(2017YFA0105703).
文摘Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 data.In this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung damage.They were randomly assigned at a 2:1 ratio to receive either UC-MSCs(4×10^(7)cells per infusion)or placebo on day 0,3,and 6.The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28.Other imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and analyzed.In all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo(the mediandifference was-13.31%,95%Cl-29.14%,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.45%;95%CI-30.82%,-0.39%;P=0.043).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:27.00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two groups.These results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.
基金supported by the National Natural Science Foundation of China(81671198)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant(20152212)the Shanghai Shenkang Clinical Research Plan of the Shenkang Hospital Development Center(16CR3011A)
文摘Prognostication of coma patients after brain injury is important, yet challenging. In this study, we evaluated the predictive value of amplitude-integrated electroencephalography （aEEG） for neurological outcomes in coma patients. From January 2013 to January 2016, 128 coma patients after acute brain injury were prospectively enrolled and monitored with aEEG. The 6-month neurological outcome was evaluated using the Cerebral Performance Category Scale. aEEG monitoring commenced at a median of 7.5 days after coma onset. Continuous normal voltage predicted a good 6-month neurological outcome with a sensitivity of 93.6% and specificity of 85.2%. In contrast, continuous extremely low voltage, burst-suppression, or a flat tracing was correlated with poor 6-month neurological outcome with a sensitivity of 76.5% and specificity of 100%. In conclusion, aEEG is a promising predictor of 6-month neurological outcome for coma patients after acute brain injury.
基金supported by the National Natural Science Foundation of China[grant number 42030406]the Marine Science&Technology Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)[grant number 2018SDKJ0102]+2 种基金the National Key R&D Program of China[grant number 2016YFC1401008]the ESA-NRSCC Scientific Cooperation Project on Earth Observation Science and Applications:Dragon 5[grant number 58393]the Open Fund of Key Laboratory of Urban Land Resources Monitoring and Simulation,Ministry of Natural Resources[grant number KF-2020-05-085].
文摘In this paper,we present a novel ocean visualization framework,which focuses on analyzing multidimensional and spatiotemporal ocean data.GPU-based visualization methods are explored to effectively visualize ocean data.An improved ray casting algorithm for heterogeneous multisection ocean volume data is presented.A two-layer spherical shell is taken as the ocean data proxy geometry,which enables oceanographers to obtain a real geographic background based on global terrain.An efficient ray sampling technique including an adaptive sampling technique and a preintegrated transfer function is proposed to achieve high-effectiveness and high-efficiency rendering.Moreover,an interactive transfer function is also designed to analyze the 3D structure of ocean temperature and salinity anomaly phenomena.Based on the framework,an integrated visualization system called i4Ocean is created.The visualization of ocean temperature and salinity anomalies extracted interactively by the transfer function is demonstrated.
基金supported by the National Natural Science Foundation of China(81671198)the Grant of Shanghai Municipal Education Commission-Gaofeng Clinical Medicine(20152212)the Shanghai Shenkang Clinical Research Plan of the Shanghai Hospital Development Center(16CR3011A)
文摘The vegetative state is a complex condition with unclear mechanisms and limited diagnostic, prognostic, and therapeutic methods. In this study, we aimed to explore the proteomic profile of tears from patients in a traumatic vegetative state and identify potential diagnostic markers using tears-a body fluid that can be collected noninvasively. Using iTRAQ quantitative proteomic technology, in the discovery phase, tear samples collected from 16 patients in a traumatic vegetative state and 16 normal individuals were analyzed. Among 1080 identified tear proteins, 57 were upregulated and 15 were downregulated in the patients compared to the controls. Bioinformatics analysis revealed that the differentially-expressed proteins were mainly involved in the wound response and immune response signaling pathways. Furthermore, we verified the levels of 7 differentially-expressed proteins in tears from 50 traumatic vegetative state patients and 50 normal controls （including the samples used in the discovery phase） using ELISA. The results showed that this 7-protein panel had a high discrimination ability for traumatic vegetative state （area under the curve = 0.999）. In sum- mary, the altered tear proteomic profile identified in this study provides a basis for potential tear protein markers for diagnosis and prognosis of the traumatic vegetative state and also provides novel insights into the mechanisms of traumatic vegetative state.
基金funded by the National Science and Technology Major Projects(2018ZX09711003-005-005 and 2018ZX09201017-007)the National Basic Research Program of China(2012CB518902).
文摘Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses,but the underlying mechanism remains unclear.In this study,the N proteins of highly pathogenic human coronaviruses,including severe acute respiratory syndrome coronavirus(SARS-CoV),middle east respiratory syndrome coronavirus(MERS-CoV)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),were found to bind MASP-2,a key serine protease in the lectin pathway of complement activation,resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation,and the deposition of MASP-2,C4b,activated C3 and C5b-9.Aggravated inflammatory lung injury was observed in mice infected with adenovirus expressing the N protein.Complement hyperactivation was also observed in SARS-CoV-2-infected patients.Either blocking the N protein:MASP-2 interaction,MASP-2 depletion or suppressing complement activation can significantly alleviate N protein-induced complement hyperactivation and lung injury in vitro and in vivo.Altogether,these data suggested that complement suppression may represent a novel therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.
