To understand the aerosol characteristics in a regional background environment,fine-particle(PM_(2.5),n=228)samples were collected over a one-year period at the Shangdianzi(SDZ)station,which is a Global Atmospheric Wa...To understand the aerosol characteristics in a regional background environment,fine-particle(PM_(2.5),n=228)samples were collected over a one-year period at the Shangdianzi(SDZ)station,which is a Global Atmospheric Watch regional background station in North China.The chemical and optical characteristics of PM_(2.5)were analyzed,including organic carbon,elemental carbon,water-soluble organic carbon,water-soluble inorganic ions,and fluorescent components of watersoluble organic matter.The source factors of major aerosol components are apportioned,and the sources of the fluorescent chromophores are further analyzed.The major chemical components of PM_(2.5)at SDZ were NO_(3)^(-),organic matter,SO_(4)^(2-),and NH_(4)^(+).Annually,water-soluble organic carbon contributed 48%±15%to the total organic carbon.Secondary formation(52%)and fossil fuel combustion(63%)are the largest sources of water-soluble organic matter and water-insoluble organic matter,respectively.In addition,three humic-like and one protein-like matter were identified via parallel factor analysis for excitation–emission matrices.The fluorescence intensities of the components were highest in winter and lowest in summer,indicating the main impact of burning sources.This study contributes to understanding the chemical and optical characteristics of ambient aerosols in the background atmosphere.展开更多
Tropomyosin(TM)in shrimp is one of the predominant causes of food allergy around the world.In the present study,the effect of seabuckthorn juice against TM-induced shrimp allergy was investigated in BALB/c mice.Allerg...Tropomyosin(TM)in shrimp is one of the predominant causes of food allergy around the world.In the present study,the effect of seabuckthorn juice against TM-induced shrimp allergy was investigated in BALB/c mice.Allergic symptoms,spleen index,intestinal section and diarrhea were measured in shrimp allergy mice.As the results,seabuckthorn juice suppressed the lesions in jejunum tissue,diarrhea and allergic symptoms in shrimp allergy mice.Seabuckthorn juice also reduced serum concentrations of tumor necrosis factor-a(TNF-α)as well as immunoglobulin E(IgE)and stimulated the secretion of interleukin-10(IL-10)in mice with shrimp allergy.Taken together,our findings suggest that increased IL-10 by seabuckthorn juice inhibits Th2 cytokine production to suppress shrimp allergic symptoms.Furthermore,seabuckthorn juice also regulates shrimp allergy by reducing jejunum lesions,inhibiting levels of TNF-αand IgE.展开更多
AIM: To explore the expression and replication of hepatitis B virus (HBV) DNA in primary duck hepatocytes (PDHs).METHODS: Complete HBV genome was transfected into PDHs by electroporation (transfected group, 1.19×...AIM: To explore the expression and replication of hepatitis B virus (HBV) DNA in primary duck hepatocytes (PDHs).METHODS: Complete HBV genome was transfected into PDHs by electroporation (transfected group, 1.19×1012copies of linear HBV DNA/1×107 PDHs). After 1-5 d of transfection, HBsAg and HBeAg in the supernatant and lysate of PDHs were measured with the IMX System.Meanwhile, replicative intermediates of HBV DNA were analyzed by Southern blotting and Dot blotting. PDHs electroporated were used as control group.RESULTS: HBsAg in the hepatocyte lysates of transfected group was 15.24 (1 d), 14.55 (3 d) and 5.13 (5 d; P/N values, positive≥2.1) respectively. HBeAg was negative (<2.1). Both HBsAg and HBeAg were negative in the supernatant of transfected group. Dot blotting revealed that HBV DNA was strongly positive in the transfected group and negative in the control group. Southern blot analysis of intracellular total DNA indicated that there were relaxed circular (rc DNA), covalently closed circular (ccc DNA), and single-stranded (ss DNA) HBV DNA replicative intermediates in the transfected group, there was no integrated HBV DNA in the cellular genome. These parameters were negative in control group.CONCLUSION: Expression and replication of HBV genes can occur in hepatocytes from non-mammalian species.HBV replication has no critical species-specificity, and yet hepatic-specific regulating factors in hepatocytes may be essential for viral replication.展开更多
OBJECTIVE: To clarify the natural history, of chronic hepatitis B so as to evaluate its long-term therapeutic outcome of the patients and the efficacy of antiviral drugs. METHODS: A cohort of 183 biopsy-proven chronic...OBJECTIVE: To clarify the natural history, of chronic hepatitis B so as to evaluate its long-term therapeutic outcome of the patients and the efficacy of antiviral drugs. METHODS: A cohort of 183 biopsy-proven chronic hepatitis B patients (mean age of 31.75±8.03 years, male/female ratio: 152:31) and 247 controls were followed up retrospectively for 11.81±4.08 years. This study was focused on long-term clinical outcome including the rates of liver cirrhosis, hepatocellular carcinoma and death, apart from the long-term effect of antiviral drugs and prognostic factors. RESULTS: In the 183 chronic hepatitis B patients, 22 (12.02%) developed liver cirrhosis, 12 (6.56%) developed hepatocellular carcinoma, and 20 (10.93%) died. The 5-, 10- and 15-year survival rates were 97. 27%, 91.62%, and 84.47%, respectively. The 5-, 10- and 15-year incidence rates of HCC were O, 3.19%, and 11.56%, respectively. In the 247 controls, 6 (2.43%) died; none of them developed cirrhosis or HCC. The rates of death, liver cirrhosis, and HCC in the hepatitis B patients were markedly different (P<0. 005) compared with the controls. The overall mortality of hepatitis B patients was 4.5-fold higher than the general population. Cox multiple regression analysis showed that old age, severe histological injury, and positive HBeAg were closely related to liver cirrhosis; old age, severe histological injury, and male were major factors leading to death. The independent variable of predicted HCC was not found. CONCLUSION: The long-term outcome of hepatitis B patients is poor and the efficacy of antiviral drugs needs further study.展开更多
The design of the catalyst layer(CL)offers a feasible way to realize the commercialization of proton exchange membrane fuel cells(PEMFCs).An in-depth understanding of catalyst inks is critical to achieving the optimal...The design of the catalyst layer(CL)offers a feasible way to realize the commercialization of proton exchange membrane fuel cells(PEMFCs).An in-depth understanding of catalyst inks is critical to achieving the optimal CL structure and cell performance.In this work,the effects of the solvent evaporation process during ink drying on the formation of the CL microstructure are particularly considered to reveal the structure-property correlations among the catalyst ink,drying process,CL microstructure and fuel cell performance.An increase in the alcohol content of the catalyst ink increases the amount of free ionomers while allowing the ionomer backbone to be more stretched in the dispersion medium.The higher alcohol content contributes to rapid solvent evaporation and thus inhibits the formation of coffee rings;as a result,a more developed ionomer network with a denser pore structure is obtained.Therefore,the alcohol-rich electrode exhibits better proton conduction capability,but higher oxygen transport resistance.For complex fuel cell operating conditions,a catalyst ink formulation with 50 wt%alcohol content is preferred due to its proper ionomer and pore size distribution,providing satisfactory fuel cell performance.展开更多
Objective:As a traditional herbal formula,Mahuang Xixin Fuzi decoction(MXFD)has been used to treat allergic rhinitis(AR).It regulates the transcription factor GATA3 in T cells,blocks Th2 skewing and rebalances the Th1...Objective:As a traditional herbal formula,Mahuang Xixin Fuzi decoction(MXFD)has been used to treat allergic rhinitis(AR).It regulates the transcription factor GATA3 in T cells,blocks Th2 skewing and rebalances the Th1/Th2 immunity.Type 2 innate lymphoid cells(ILC2s)are closely associated with GATA3.However,it remains unknown whether ILC2s could be one mechanism through which MXFD acts.We sought to elucidate the efficacy and mechanism of action of this decoction in AR treatment.Methods:Forty C57BL/6J female mice were equally divided into control,model,loratadine-and MXFDtreated groups in random.AR was induced by ovalbumin(OVA),and then treatment with loratadine or MXFD was administered.AR scores were evaluated and compared before and after treatment.Pathological changes in the nasal mucosa and lung were observed using hematoxylin-eosin staining of tissue samples.Activation of ILC2 in nasal mucosa was assessed by immunofluorescence and quantitative polymerase chain reaction analysis.ILC2 cell count in lungs was measured by flow cytometry and levels of interleukin-(IL)4,IL-5 and IL-13 in serum were detected by ELISA.Results:The decoction alleviated the symptoms of AR in mice,improved vascular congestion and expansion,glandular hyperplasia and inflammatory cell infiltration in mouse nasal mucosa and slowly improved the interstitial pneumonia and lesions.Meanwhile,MXFD reduced the number and percentage of ILC2s in the nasal mucosa and lungs,downregulated the expression of GATA3 mRNA and RORa mRNA,and reduced the related inflammatory cytokine levels,including IL-4,IL-5 and IL-13.Conclusion:These data suggest that inhibition of ILC2s by MXFD may be an important means by which to treat AR.展开更多
Background:The mechanism of Huajiao(Zanthoxylum bungeanum Maxim.),as a commonly used herbal medicine,has been suggested as a potential agent for colon cancer.This study aims to use network pharmacology and molecular d...Background:The mechanism of Huajiao(Zanthoxylum bungeanum Maxim.),as a commonly used herbal medicine,has been suggested as a potential agent for colon cancer.This study aims to use network pharmacology and molecular docking to identify the bioactive constituents of Huajiao and the underlying mechanisms of cancer prevention.Methods:Putative components of Huajiao and their relevant targets were identified from the Traditional Chinese Medicine Systematic Pharmacology and Swiss target prediction database.Subsequently,targets interacting with colon cancer were collected using the databases of GeneCards,OMIM and Drugbank.Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analyses were performed to explore the therapeutic signalling pathways related to Huajiao for carcinoma.P rotein-protein interaction and compound-target networks were constructed using Cytoscape 3.8.2.Finally,Discovery studio software was accustomed to identifying key genes and active components of Huajiao.Results:Seventeen potentially active compounds,197 interacting targets and 1,636 disease-related targets were collected,of which 111 cross-targets were obtained.A complete of twenty-two key targets were identified by PPI network analysis,including AKT1,TP53,TNF,JUN,IL6 and HSP90AA1.These key targets are significantly involved in biological processes and pathways,such as those involved in phosphatidylinositol 3-kinase signalling,promoting maturation,structural maintenance and proper regulation of specific target proteins,and regulating tumor cell growth arrest and apoptosis.KEGG enrichment showed that three signalling pathways were closely related to the cancer prevention,endocrine resistance and viral hepatitis pathways in carcinoma.AKT1,TP53,TNF,JUN,IL6 and HSP90AA1 were identified as the most vital genes and were validated by molecular docking simulations.Conclusion:The present study demonstrates that Huajiao produces preventive effects against colon cancer by modulating multiple components of multiple targets and pathways.Moreover,these data provide new insights into developing Huajiao compounds as new anti-colon cancer drugs.展开更多
Aerosol ammonium(NH_(4)^(+)),mainly produced from the reactions of ammonia(NH_(3))with acids in the atmosphere,has significant impacts on air pollution,radiative forcing,and human health.Understanding the source and f...Aerosol ammonium(NH_(4)^(+)),mainly produced from the reactions of ammonia(NH_(3))with acids in the atmosphere,has significant impacts on air pollution,radiative forcing,and human health.Understanding the source and formation mechanism of NH_(4)^(+)can provide scientific insights into air quality improvements.However,the sources of NH_(3)in urban areas are not well understood,and few studies focus on NH_(3)/NH_(4)^(+)at different heights within the atmospheric boundary layer,which hinders a comprehensive understanding of aerosol NH_(4)^(+).In this study,we perform both field observation and modeling studies(the Community Multiscale Air Quality,CMAQ)to investigate regional NH_(3)emission sources and vertically resolved NH_(4)^(+)formation mechanisms during the winter in Beijing.Both stable nitrogen isotope analyses and CMAQ model suggest that combustion-related NH_(3)emissions,including fossil fuel sources,NH_(3)slip,and biomass burning,are important sources of aerosol NH_(4)^(+)with more than 60%contribution occurring on heavily polluted days.In contrast,volatilization-related NH_(3)sources(livestock breeding,N-fertilizer application,and human waste)are dominant on clean days.Combustion-related NH_(3)is mostly local from Beijing,and biomass burning is likely an important NH_(3)source(~15%–20%)that was previously overlooked.More effective control strategies such as the two-product(e.g.,reducing both SO_(2)and NH_(3))control policy should be considered to improve air quality.展开更多
Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population.However,limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines....Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population.However,limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines.In this study,132 high BMI(Body mass index)(obesity and overweight,BMI≥24 kg/m^(2))and 82 normal BMI(BMI<24 kg/m^(2))participants were enrolled.Adverse events(AEs),Spike receptor-binding domain IgG antibody(anti-RBD-IgG),neutralizing antibodies(NAbs),and specific B-cell and T-cell responses were evaluated 21–105 days after full-course inactivated COVID-19 vaccination.The overall incidence of AEs was similar in individuals with and without obesity/overweight.No serious vaccine-related AEs occurred.Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI.Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group.The frequencies of RBD-specific memory B cells(MBCs)and the numbers of spike-specific TNF-α+spot-forming cells(SFCs)in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight.A similar trend of weakened humoral responses was also observed in individuals with central obesity.Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.展开更多
Dear Editor Coronavirus disease 19(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),remains a pandemic.Cancer patients have a higher risk of poor outcomes for SARS-CoV-2 infection than t...Dear Editor Coronavirus disease 19(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),remains a pandemic.Cancer patients have a higher risk of poor outcomes for SARS-CoV-2 infection than the general population[1].Vaccines were shown to effectively prevent SARS-CoV-2 infection,severe disease progression,and mortality.Inactivated SARS-CoV-2 vaccines(BBIBPCorV and CoronaVac)have been approved and widely used in China,with the former shown to be more effective than the latter[2].Hence,there is an urgent need to investigate the safety and humoral immune responses of inactivated vaccines in cancer patients.展开更多
Tenofovir disoproxil fumarate(TDF),is a product of tenofovir and has been recommended for long-term use by guidelines1 because of its favorable efficacy in the treatment of human immunodeficiency virus(HIV)and hepatit...Tenofovir disoproxil fumarate(TDF),is a product of tenofovir and has been recommended for long-term use by guidelines1 because of its favorable efficacy in the treatment of human immunodeficiency virus(HIV)and hepatitis B virus(HBV)infection.Hence,a better understanding of the safety profiles of long-term TDF use is extremely important.Lactic acidosis,as a rare but fatal adverse event of TDF,were reported both in HIV-infected patients,2-4 and in CHB patients.5-7 Hyperlactatemia occurred in 15.6%HIV-infected patients using TDF in a Cameroon cohort study8 and was 3%in another South Africa cohort study.9 Therefore,TDF increases the risk of abnormal serum lactate,but the mechanism is unclear.展开更多
Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IF...Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.展开更多
Background and Aims:Currently,insufficient clinical data are available to address whether low-level viremia(LLV)observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strat...Background and Aims:Currently,insufficient clinical data are available to address whether low-level viremia(LLV)observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strategies should be altered if LLV occurs.This study compared the clinical out-comes of patients with a maintained virological response(MVR)and patients who experienced LLV and their treatment strategies.Methods:A retrospective cohort of 674 patients with chronic hepatitis B virus(HBV)infection who received antiviral treatment for more than 12 months was analyzed for the development of end-stage liver disease and treatment strategies during the follow-up period.End-stage liver disease included decompensated liver cirrhosis and hepatocellular carcinoma(HCC).Results:During a median 42-month follow-up,end-stage liver disease developed more frequently in patients who experienced LLV than in those who experienced MVR(7.73%and 15.85%vs.0.77%and 5.52%at 5 and 10 years,respectively;p=0.000).The trend was consistent after propensity score matching.In the high-risk group of four HCC risk models,LLV patients had a higher risk of HCC development(p<0.05).By Cox proportional hazard model analysis,LLV was an independent risk factor for end-stage liver disease and HCC(hazard ratio[HR]=6.280,confidence interval[CI]=2.081-18.951,p=0.001;HR=5.108,CI=1.392-18.737,respectively;p=0.014).Patients achieved a lower rate of end-stage liver disease by adjusting treatment compared to continuing the original treatment once LLV occurred(p<0.05).Conclusions:LLV is an independent risk factor for end-stage liver disease and HCC,and treatment adjustments can be considered.展开更多
Natural killer(NK)cells have a vital role in killing hepatocellular carcinoma(HCC)cells;however,the mechanism underlying tumor-infiltrating NK(TINK)-cell dysfunction remains poorly understood.Using flow cytometry stai...Natural killer(NK)cells have a vital role in killing hepatocellular carcinoma(HCC)cells;however,the mechanism underlying tumor-infiltrating NK(TINK)-cell dysfunction remains poorly understood.Using flow cytometry staining,we precisely characterized the frequency,phenotype and function of NK subsets distinguished by CD27 and CD11b in 30 patients with HCC in comparison to 30 healthy controls.Interestingly,we found a substantial proportion of liver-infiltrating CD11b?CD27?(DN)NK subsets in tumor tissue from HCC patients.Remarkably,these relatively expanded DN NK subsets exhibited an inactive and immature phenotype.By detecting the expression of CD107a and interferon-gamma(IFN-γ)on NK subsets and NK cells,we demonstrated that DN NK subsets exhibited a poor cytotoxic capacity and deficient potential to produce IFN-γin comparison to the other three subsets,which contributed to the dysfunction of TINK cells in HCC patients.In addition,we found that the presence of DN NK cells was closely associated with the clinical outcomes of HCC patients,as the frequency of DN NK cells among TINK cells was positively correlated with tumor stage and size.A large percentage of DN NK cells among TINK cells was an independent prognostic factor for lower survival in the 60-month follow-up period.In conclusion,a substantial proportion of CD11b?CD27?NK subsets among TINK cells accounts for NK-cell dysfunction in patients with HCC and is associated with tumor progression.Our study may provide a novel therapeutic target for the treatment of patients with HCC.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.42130513 and 41625014)the National Key Research and Development Program of China(Grant No.2019YFA0606801)。
文摘To understand the aerosol characteristics in a regional background environment,fine-particle(PM_(2.5),n=228)samples were collected over a one-year period at the Shangdianzi(SDZ)station,which is a Global Atmospheric Watch regional background station in North China.The chemical and optical characteristics of PM_(2.5)were analyzed,including organic carbon,elemental carbon,water-soluble organic carbon,water-soluble inorganic ions,and fluorescent components of watersoluble organic matter.The source factors of major aerosol components are apportioned,and the sources of the fluorescent chromophores are further analyzed.The major chemical components of PM_(2.5)at SDZ were NO_(3)^(-),organic matter,SO_(4)^(2-),and NH_(4)^(+).Annually,water-soluble organic carbon contributed 48%±15%to the total organic carbon.Secondary formation(52%)and fossil fuel combustion(63%)are the largest sources of water-soluble organic matter and water-insoluble organic matter,respectively.In addition,three humic-like and one protein-like matter were identified via parallel factor analysis for excitation–emission matrices.The fluorescence intensities of the components were highest in winter and lowest in summer,indicating the main impact of burning sources.This study contributes to understanding the chemical and optical characteristics of ambient aerosols in the background atmosphere.
基金supported by the National Natural Science Fund(31601395)the Open Research Fund Program of Beijing Key Laboratory of Plant Resource Research and Development,Beijing Technology and Business University(PRRD-2021-YB8)+1 种基金the Key Program for Shaanxi Science and Technology(2020NY-146)Lueyang Black-Bone Chicken Industry Development Research Institute(WJYJY-2021-9)。
文摘Tropomyosin(TM)in shrimp is one of the predominant causes of food allergy around the world.In the present study,the effect of seabuckthorn juice against TM-induced shrimp allergy was investigated in BALB/c mice.Allergic symptoms,spleen index,intestinal section and diarrhea were measured in shrimp allergy mice.As the results,seabuckthorn juice suppressed the lesions in jejunum tissue,diarrhea and allergic symptoms in shrimp allergy mice.Seabuckthorn juice also reduced serum concentrations of tumor necrosis factor-a(TNF-α)as well as immunoglobulin E(IgE)and stimulated the secretion of interleukin-10(IL-10)in mice with shrimp allergy.Taken together,our findings suggest that increased IL-10 by seabuckthorn juice inhibits Th2 cytokine production to suppress shrimp allergic symptoms.Furthermore,seabuckthorn juice also regulates shrimp allergy by reducing jejunum lesions,inhibiting levels of TNF-αand IgE.
基金Professor Hong Yu at Intelligent Fishery Innovative Team(No.C202109)in School of Information Engineering of Dalian Ocean University for her support of this workfunded by the National Natural Science Foundation of China(No.31800615 and No.21933010)。
基金Supported by the National Natural Science Foundation of China,No. 39670340the Applied Basic Research Programs of ScienceTechnology Commission Foundation of Chongqing, No.20021889
文摘AIM: To explore the expression and replication of hepatitis B virus (HBV) DNA in primary duck hepatocytes (PDHs).METHODS: Complete HBV genome was transfected into PDHs by electroporation (transfected group, 1.19×1012copies of linear HBV DNA/1×107 PDHs). After 1-5 d of transfection, HBsAg and HBeAg in the supernatant and lysate of PDHs were measured with the IMX System.Meanwhile, replicative intermediates of HBV DNA were analyzed by Southern blotting and Dot blotting. PDHs electroporated were used as control group.RESULTS: HBsAg in the hepatocyte lysates of transfected group was 15.24 (1 d), 14.55 (3 d) and 5.13 (5 d; P/N values, positive≥2.1) respectively. HBeAg was negative (<2.1). Both HBsAg and HBeAg were negative in the supernatant of transfected group. Dot blotting revealed that HBV DNA was strongly positive in the transfected group and negative in the control group. Southern blot analysis of intracellular total DNA indicated that there were relaxed circular (rc DNA), covalently closed circular (ccc DNA), and single-stranded (ss DNA) HBV DNA replicative intermediates in the transfected group, there was no integrated HBV DNA in the cellular genome. These parameters were negative in control group.CONCLUSION: Expression and replication of HBV genes can occur in hepatocytes from non-mammalian species.HBV replication has no critical species-specificity, and yet hepatic-specific regulating factors in hepatocytes may be essential for viral replication.
基金The project was supported by the fund for young hepatologists,Chongqing,China(Chinese Medical Association 1998).
文摘OBJECTIVE: To clarify the natural history, of chronic hepatitis B so as to evaluate its long-term therapeutic outcome of the patients and the efficacy of antiviral drugs. METHODS: A cohort of 183 biopsy-proven chronic hepatitis B patients (mean age of 31.75±8.03 years, male/female ratio: 152:31) and 247 controls were followed up retrospectively for 11.81±4.08 years. This study was focused on long-term clinical outcome including the rates of liver cirrhosis, hepatocellular carcinoma and death, apart from the long-term effect of antiviral drugs and prognostic factors. RESULTS: In the 183 chronic hepatitis B patients, 22 (12.02%) developed liver cirrhosis, 12 (6.56%) developed hepatocellular carcinoma, and 20 (10.93%) died. The 5-, 10- and 15-year survival rates were 97. 27%, 91.62%, and 84.47%, respectively. The 5-, 10- and 15-year incidence rates of HCC were O, 3.19%, and 11.56%, respectively. In the 247 controls, 6 (2.43%) died; none of them developed cirrhosis or HCC. The rates of death, liver cirrhosis, and HCC in the hepatitis B patients were markedly different (P<0. 005) compared with the controls. The overall mortality of hepatitis B patients was 4.5-fold higher than the general population. Cox multiple regression analysis showed that old age, severe histological injury, and positive HBeAg were closely related to liver cirrhosis; old age, severe histological injury, and male were major factors leading to death. The independent variable of predicted HCC was not found. CONCLUSION: The long-term outcome of hepatitis B patients is poor and the efficacy of antiviral drugs needs further study.
基金financially supported by the National Key Research and Development Program of China(2018YFB1502503)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA21090101)。
文摘The design of the catalyst layer(CL)offers a feasible way to realize the commercialization of proton exchange membrane fuel cells(PEMFCs).An in-depth understanding of catalyst inks is critical to achieving the optimal CL structure and cell performance.In this work,the effects of the solvent evaporation process during ink drying on the formation of the CL microstructure are particularly considered to reveal the structure-property correlations among the catalyst ink,drying process,CL microstructure and fuel cell performance.An increase in the alcohol content of the catalyst ink increases the amount of free ionomers while allowing the ionomer backbone to be more stretched in the dispersion medium.The higher alcohol content contributes to rapid solvent evaporation and thus inhibits the formation of coffee rings;as a result,a more developed ionomer network with a denser pore structure is obtained.Therefore,the alcohol-rich electrode exhibits better proton conduction capability,but higher oxygen transport resistance.For complex fuel cell operating conditions,a catalyst ink formulation with 50 wt%alcohol content is preferred due to its proper ionomer and pore size distribution,providing satisfactory fuel cell performance.
基金the National Natural Science Foundation of China(81774375)the Fundamental Research Funds for the Central Universities(2018-JYB-ZDSYS002).
文摘Objective:As a traditional herbal formula,Mahuang Xixin Fuzi decoction(MXFD)has been used to treat allergic rhinitis(AR).It regulates the transcription factor GATA3 in T cells,blocks Th2 skewing and rebalances the Th1/Th2 immunity.Type 2 innate lymphoid cells(ILC2s)are closely associated with GATA3.However,it remains unknown whether ILC2s could be one mechanism through which MXFD acts.We sought to elucidate the efficacy and mechanism of action of this decoction in AR treatment.Methods:Forty C57BL/6J female mice were equally divided into control,model,loratadine-and MXFDtreated groups in random.AR was induced by ovalbumin(OVA),and then treatment with loratadine or MXFD was administered.AR scores were evaluated and compared before and after treatment.Pathological changes in the nasal mucosa and lung were observed using hematoxylin-eosin staining of tissue samples.Activation of ILC2 in nasal mucosa was assessed by immunofluorescence and quantitative polymerase chain reaction analysis.ILC2 cell count in lungs was measured by flow cytometry and levels of interleukin-(IL)4,IL-5 and IL-13 in serum were detected by ELISA.Results:The decoction alleviated the symptoms of AR in mice,improved vascular congestion and expansion,glandular hyperplasia and inflammatory cell infiltration in mouse nasal mucosa and slowly improved the interstitial pneumonia and lesions.Meanwhile,MXFD reduced the number and percentage of ILC2s in the nasal mucosa and lungs,downregulated the expression of GATA3 mRNA and RORa mRNA,and reduced the related inflammatory cytokine levels,including IL-4,IL-5 and IL-13.Conclusion:These data suggest that inhibition of ILC2s by MXFD may be an important means by which to treat AR.
文摘Background:The mechanism of Huajiao(Zanthoxylum bungeanum Maxim.),as a commonly used herbal medicine,has been suggested as a potential agent for colon cancer.This study aims to use network pharmacology and molecular docking to identify the bioactive constituents of Huajiao and the underlying mechanisms of cancer prevention.Methods:Putative components of Huajiao and their relevant targets were identified from the Traditional Chinese Medicine Systematic Pharmacology and Swiss target prediction database.Subsequently,targets interacting with colon cancer were collected using the databases of GeneCards,OMIM and Drugbank.Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analyses were performed to explore the therapeutic signalling pathways related to Huajiao for carcinoma.P rotein-protein interaction and compound-target networks were constructed using Cytoscape 3.8.2.Finally,Discovery studio software was accustomed to identifying key genes and active components of Huajiao.Results:Seventeen potentially active compounds,197 interacting targets and 1,636 disease-related targets were collected,of which 111 cross-targets were obtained.A complete of twenty-two key targets were identified by PPI network analysis,including AKT1,TP53,TNF,JUN,IL6 and HSP90AA1.These key targets are significantly involved in biological processes and pathways,such as those involved in phosphatidylinositol 3-kinase signalling,promoting maturation,structural maintenance and proper regulation of specific target proteins,and regulating tumor cell growth arrest and apoptosis.KEGG enrichment showed that three signalling pathways were closely related to the cancer prevention,endocrine resistance and viral hepatitis pathways in carcinoma.AKT1,TP53,TNF,JUN,IL6 and HSP90AA1 were identified as the most vital genes and were validated by molecular docking simulations.Conclusion:The present study demonstrates that Huajiao produces preventive effects against colon cancer by modulating multiple components of multiple targets and pathways.Moreover,these data provide new insights into developing Huajiao compounds as new anti-colon cancer drugs.
基金supported by the National Natural Science Foundation of China(42130513,41905110,and 41961130384)the Royal Society Newton Advanced Fellowship,United Kingdom(NAFR1191220)the Research Grants Council of the Hong Kong Special Administrative Region,China(T24/504/17 and A-Poly U502/16)。
文摘Aerosol ammonium(NH_(4)^(+)),mainly produced from the reactions of ammonia(NH_(3))with acids in the atmosphere,has significant impacts on air pollution,radiative forcing,and human health.Understanding the source and formation mechanism of NH_(4)^(+)can provide scientific insights into air quality improvements.However,the sources of NH_(3)in urban areas are not well understood,and few studies focus on NH_(3)/NH_(4)^(+)at different heights within the atmospheric boundary layer,which hinders a comprehensive understanding of aerosol NH_(4)^(+).In this study,we perform both field observation and modeling studies(the Community Multiscale Air Quality,CMAQ)to investigate regional NH_(3)emission sources and vertically resolved NH_(4)^(+)formation mechanisms during the winter in Beijing.Both stable nitrogen isotope analyses and CMAQ model suggest that combustion-related NH_(3)emissions,including fossil fuel sources,NH_(3)slip,and biomass burning,are important sources of aerosol NH_(4)^(+)with more than 60%contribution occurring on heavily polluted days.In contrast,volatilization-related NH_(3)sources(livestock breeding,N-fertilizer application,and human waste)are dominant on clean days.Combustion-related NH_(3)is mostly local from Beijing,and biomass burning is likely an important NH_(3)source(~15%–20%)that was previously overlooked.More effective control strategies such as the two-product(e.g.,reducing both SO_(2)and NH_(3))control policy should be considered to improve air quality.
基金supported by the National Science and Technology Major Project of China(No.2017ZX10202203-007,No.2017ZX10202203-008,and No.2018ZX10302206-003)a pilot project of clinical cooperation between traditional Chinese and western medicine for significant and complicated diseases of National Administration of Traditional Chinese Medicine:hepatic fibrosis.We also acknowledge the support of the National Natural Science Foundation of China(No.81772198)+1 种基金the Natural Science Foundation of Chongqing,China(No.cstc2020jcyj-msxmX0389)General Project of Chongqing Natural Science Foundation(No.cstc2020jcyj-msxmX0015).
文摘Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population.However,limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines.In this study,132 high BMI(Body mass index)(obesity and overweight,BMI≥24 kg/m^(2))and 82 normal BMI(BMI<24 kg/m^(2))participants were enrolled.Adverse events(AEs),Spike receptor-binding domain IgG antibody(anti-RBD-IgG),neutralizing antibodies(NAbs),and specific B-cell and T-cell responses were evaluated 21–105 days after full-course inactivated COVID-19 vaccination.The overall incidence of AEs was similar in individuals with and without obesity/overweight.No serious vaccine-related AEs occurred.Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI.Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group.The frequencies of RBD-specific memory B cells(MBCs)and the numbers of spike-specific TNF-α+spot-forming cells(SFCs)in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight.A similar trend of weakened humoral responses was also observed in individuals with central obesity.Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.
基金the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University and conformed with the ethical guidelines of the Declaration of Helsinki(Ratification No.133/2022)Written informed consentwas obtained fromall the participants.This study has been registered at ClinicalTrials.gov(NCT05043246).
文摘Dear Editor Coronavirus disease 19(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),remains a pandemic.Cancer patients have a higher risk of poor outcomes for SARS-CoV-2 infection than the general population[1].Vaccines were shown to effectively prevent SARS-CoV-2 infection,severe disease progression,and mortality.Inactivated SARS-CoV-2 vaccines(BBIBPCorV and CoronaVac)have been approved and widely used in China,with the former shown to be more effective than the latter[2].Hence,there is an urgent need to investigate the safety and humoral immune responses of inactivated vaccines in cancer patients.
基金This work was supported in part by grants from the National Science and Technology Major Project of China(2017ZX10202203008,2017ZX10202203007)the National Natural Science Foundation of China(81772171)+1 种基金the Chongqing Talents Project(cstc2021ycjh-bgzxm0150)Remarkable Innovation–Clinical Research Project,the Second Affiliated Hospital of Chongqing Medical University。
文摘Tenofovir disoproxil fumarate(TDF),is a product of tenofovir and has been recommended for long-term use by guidelines1 because of its favorable efficacy in the treatment of human immunodeficiency virus(HIV)and hepatitis B virus(HBV)infection.Hence,a better understanding of the safety profiles of long-term TDF use is extremely important.Lactic acidosis,as a rare but fatal adverse event of TDF,were reported both in HIV-infected patients,2-4 and in CHB patients.5-7 Hyperlactatemia occurred in 15.6%HIV-infected patients using TDF in a Cameroon cohort study8 and was 3%in another South Africa cohort study.9 Therefore,TDF increases the risk of abnormal serum lactate,but the mechanism is unclear.
基金The authors would like to thank the patients and their families for their contribution to this studyThis study was supported by the National Science and Technology Major Project of China(2008ZX10002-006,2012ZX10002007001,2017ZX10202203-007,2017ZX10202203-008)+2 种基金the National Natural Science Foundation of China(81171561,30972584)This study was also supported in part by Shanghai Roche Pharmaceuticals LtdWriting assistance was provided by Stefanie Chuah,from Mudskipper Business Ltd,funded by F Hoffmann-La Roche
文摘Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.
基金This workwas supported by grants from the National Basic Research Program of China 973, grant no. 2012CB517600 (no. 2012CB517604), the National Natural Science Foundation of China (no. 81030015, 81070568, 81370015, and 81000295), the International Cooperation and Exchange Projects of Shanghai Science and Technology Committee (no. 14430721000), and the Chinese Medical Association Clinical Research Special Fund (no. 13030280413).
基金the National Science and Technology Major Project of China(2017ZX10202203-007,2017ZX10202203-008 and 2018ZX10302-206-003)the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University N/A and Guizhou Science and Technology Project QiankeheJC(2016)1086.
文摘Background and Aims:Currently,insufficient clinical data are available to address whether low-level viremia(LLV)observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strategies should be altered if LLV occurs.This study compared the clinical out-comes of patients with a maintained virological response(MVR)and patients who experienced LLV and their treatment strategies.Methods:A retrospective cohort of 674 patients with chronic hepatitis B virus(HBV)infection who received antiviral treatment for more than 12 months was analyzed for the development of end-stage liver disease and treatment strategies during the follow-up period.End-stage liver disease included decompensated liver cirrhosis and hepatocellular carcinoma(HCC).Results:During a median 42-month follow-up,end-stage liver disease developed more frequently in patients who experienced LLV than in those who experienced MVR(7.73%and 15.85%vs.0.77%and 5.52%at 5 and 10 years,respectively;p=0.000).The trend was consistent after propensity score matching.In the high-risk group of four HCC risk models,LLV patients had a higher risk of HCC development(p<0.05).By Cox proportional hazard model analysis,LLV was an independent risk factor for end-stage liver disease and HCC(hazard ratio[HR]=6.280,confidence interval[CI]=2.081-18.951,p=0.001;HR=5.108,CI=1.392-18.737,respectively;p=0.014).Patients achieved a lower rate of end-stage liver disease by adjusting treatment compared to continuing the original treatment once LLV occurred(p<0.05).Conclusions:LLV is an independent risk factor for end-stage liver disease and HCC,and treatment adjustments can be considered.
基金the National Natural Science Foundation of China(81171560,30930082,81171561 and 30972584)the National Science and Technology Major Project of China(2008ZX10002-006,2012ZX1002007001,2011ZX09302005,2012ZX09303001-001 and 2012ZX10002003)+3 种基金the National High Technology Research and Development Program of China(2011AA020111)the Key Project of the Chongqing Science and Technology Commission(cstc2012ggyyjsB10007)the Chongqing Natural Science Foundation(cstc2011jjA10025)the Medical Research Fund of the Chongqing Municipal Health Bureau(2009-1-71).
文摘Natural killer(NK)cells have a vital role in killing hepatocellular carcinoma(HCC)cells;however,the mechanism underlying tumor-infiltrating NK(TINK)-cell dysfunction remains poorly understood.Using flow cytometry staining,we precisely characterized the frequency,phenotype and function of NK subsets distinguished by CD27 and CD11b in 30 patients with HCC in comparison to 30 healthy controls.Interestingly,we found a substantial proportion of liver-infiltrating CD11b?CD27?(DN)NK subsets in tumor tissue from HCC patients.Remarkably,these relatively expanded DN NK subsets exhibited an inactive and immature phenotype.By detecting the expression of CD107a and interferon-gamma(IFN-γ)on NK subsets and NK cells,we demonstrated that DN NK subsets exhibited a poor cytotoxic capacity and deficient potential to produce IFN-γin comparison to the other three subsets,which contributed to the dysfunction of TINK cells in HCC patients.In addition,we found that the presence of DN NK cells was closely associated with the clinical outcomes of HCC patients,as the frequency of DN NK cells among TINK cells was positively correlated with tumor stage and size.A large percentage of DN NK cells among TINK cells was an independent prognostic factor for lower survival in the 60-month follow-up period.In conclusion,a substantial proportion of CD11b?CD27?NK subsets among TINK cells accounts for NK-cell dysfunction in patients with HCC and is associated with tumor progression.Our study may provide a novel therapeutic target for the treatment of patients with HCC.