We present here an investigation of the self-pulsing phenomenon of negative corona and parallel-plate discharge in argon within one frame of a one-dimensional fluid model in cylinder–cylinder electrode geometry.The t...We present here an investigation of the self-pulsing phenomenon of negative corona and parallel-plate discharge in argon within one frame of a one-dimensional fluid model in cylinder–cylinder electrode geometry.The transition from corona to parallel-plate discharge is obtained by changing the inner and outer radii of the electrodes.The model reproduces the self-pulsing waveform well and provides the spatiotemporal behaviors of the charged particles and electric field during the pulse.The self-pulsing shows a common feature that occurs in various configurations and that does not depend on a specific electrode structure.The self-pulsing is the transformation between a weak-current Townsend mode and a large-current normal glow mode.The behavior of the positive ions is the dominant factor in the formation of the pulse.展开更多
<strong>Objective:</strong> To explore the application of intelligent equipment in non-negative pressure isolation ward for COVID-2019 patients. <strong>Method:</strong> From February 1 to Marc...<strong>Objective:</strong> To explore the application of intelligent equipment in non-negative pressure isolation ward for COVID-2019 patients. <strong>Method:</strong> From February 1 to March 17, 2020, intelligent equipment, such as communication interaction system, intelligent disinfection robot, delivering robot, were used in non- negative pressure isolation ward of COVID-2019. With the help of communication interaction system to supervise the implementation of infection prevention and control, and observe the incorrect situation of pee use and personal behavior before and after the implementation. The disinfection robot and meal delivery robot were used in ward disinfection and life nursing combined with nursing practice. <strong>Result:</strong> Through the supervision of communication interaction system, the frequency of pee use and personal behavior was reduced. The frequency of bad articles before and after improvement was wearing protective clothing (2.80%/0.84%), taking off protective clothing (5.87%/0.84%), personal behavior observation (8.38%/1.90%), P < 0.01. The robot disinfected and delivered medicine for 912.5 h, saving 225 shifts of nursing staff. <strong>Conclusion:</strong> Intelligent equipment is a good option for infection control in isolation ward of COVID-2019. It can not only reduce the workload of health workers, but also the cross-infection.展开更多
Background and Aims:Hepatitis B virus(HBV)infection is a major risk factor for cirrhosis and liver cancer,and its treatment continues to be difficult.We previously demonstrated that a dopamine analog inhibited the pac...Background and Aims:Hepatitis B virus(HBV)infection is a major risk factor for cirrhosis and liver cancer,and its treatment continues to be difficult.We previously demonstrated that a dopamine analog inhibited the packaging of pregenomic RNA into capsids.The present study aimed to determine the effect of dopamine on the expressions of hepatitis B virus surface and e antigens(HBsAg and HBeAg,respectively)and to elucidate the underlying mechanism.Methods:We used dopamine-treated HBVinfected HepG2.2.15 and NTCP-G2 cells to monitor HBsAg and HBeAg expression levels.We analyzed interferon-stimulated gene 15(ISG15)expression in dopamine-treated cells.We knocked down ISG15 and then monitored HBsAg and HBeAg expression levels.We analyzed the expression of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway factors in dopamine-treated cells.We used dopamine hydrochloride-treated adeno-associated virus/HBV-infected mouse model to evaluate HBV DNA,HBsAg,and HBeAg expression.HBV virus was collected from HepAD38.7 cell culture medium.Results:Dopamine inhibited HBsAg and HBeAg expression and upregulated ISG15 expression in HepG2.2.15 and HepG2-NTCP cell lines.ISG15 knockdown increased HBsAg and HBeAg expression in HepG2.2.15 cells.Dopamine-treated cells activated the JAK/STAT pathway,which upregulated ISG15 expression.In the adeno-associated virus-HBV murine infection model,dopamine downregulated HBsAg and HBeAg expression and activated the JAK-STAT/ISG15 axis.Conclusions:Dopamine inhibits the expression of HBsAg and HBeAg by activating the JAK/STAT pathway and upregulating ISG15 expression.展开更多
Background and aim Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically inves...Background and aim Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation.Methods Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation.Results Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained undetectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9%)patients with an estimated annual incidence of HBsAg seroclearance of 3.6%.Patients with EOT HBsAg levels of≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of>1000 IU/mL(33.3%vs.5.4%).The proportion of patients with HBsAg≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL.Conclusions Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg seroclearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.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
Background and Aims:Functional cure(FC)is characterized by the clearance of the hepatitis B surface antigen from the serum of patients with chronic hepatitis B(CHB).However,the level of intrahepatic covalently closed ...Background and Aims:Functional cure(FC)is characterized by the clearance of the hepatitis B surface antigen from the serum of patients with chronic hepatitis B(CHB).However,the level of intrahepatic covalently closed circular DNA(cccDNA)and hepatitis B virus(HBV)integration remains unclear.We conducted this study to determine them and reveal their value in the treatment of CHB.Methods:There were two sessions to elucidate the changes in intrahepatic cccDNA and HBV integration after antiviral therapy.In the first session,116 patients were enrolled and divided into FC,non-functional cure(NFC),and CHB groups,including 48 patients with functionally cured CHB,27 with CHB without functional cure after antiviral treatment,and 41 with treatment-naïve CHB.Patients were tested for both intrahepatic cccDNA and other viral markers.All patients in the FC group were followed up for at least 24 weeks to observe relapse.In the second session,another ten patients were included for in-depth whole-genome sequencing to analyze HBV integration.Results:Thirteen patients in the FC group were negative for intrahepatic cccDNA.Intrahepatic cccDNA was much higher in the CHB group compared with the FC group.Seven patients had HBsAg seroreversion,including two with virological relapse.Integration of HBV was detected in one(33.3%)functionally cured patients and in seven(100%)with CHB.28.0%of the HBV breakpoints were assigned in the 1,500 nt to 1,900 nt range of the HBV genome.Conclusions:After achieving an FC,the rate of intrahepatic cccDNA and HBV integration was significantly reduced in patients with CHB.For those patients who cleared intrahepatic cccDNA,the chances of developing virological relapse were even lower.展开更多
Background and Aims:To investigate the safety and efficacy of double plasma molecular adsorption system(DPMAS)with sequential low-dose plasma exchange(LPE)in treating early hepatitis B virus-related acute-on-chronic l...Background and Aims:To investigate the safety and efficacy of double plasma molecular adsorption system(DPMAS)with sequential low-dose plasma exchange(LPE)in treating early hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).Methods:Clinical data of patients with HBVACLF were prospectively collected,including patients in a DPMAS with sequential LPE(DPMAS+LPE)group and those in a standard medical treatment(SMT)group.The primary endpoint was death or liver transplantation(LT)at 12 weeks of follow-up.Propensity-score matching was performed to control the effects of confounding factors on prognosis between the two groups.Results:After 2 weeks,total bilirubin,alanine aminotransferase,blood urea nitrogen levels,and Chinese Group on the Study of Severe Hepatitis B score,were significantly lower in the DPMAS+LPE group than those in the SMT group(p<0.05).After 4 weeks,laboratory parameters of the two groups were similar.The cumulative survival rate of the DPMAS+LPE group was significantly higher than that of the SMT group at 4 weeks(97.9%vs.85.4%,p=0.027),but not at 12 weeks(85.4%vs.83.3%,p=0.687).Cytokine levels were significantly lower in 12-week survival group than in the death-or-LT group(p<0.05).Functional enrichment analysis showed that downregulated cytokines were mainly involved in positive regulation of proliferation and activation of lymphocytes and monocytes,regulation of immune effect response,regulation of endotoxin response,and glial cell proliferation.Conclusion:DPMAS+LPE significantly improved the 4-week cumulative survival rate,and ameliorated the inflammatory response in patients.DPMAS+LPE may be a promising modality for patients with early HBV-ACLF.展开更多
As a class of nanomaterials with natural enzyme-like characteristics, nanozymes have shown their great potential in various applications. Reducible metal oxides featured with defect structures, and single-atom catalys...As a class of nanomaterials with natural enzyme-like characteristics, nanozymes have shown their great potential in various applications. Reducible metal oxides featured with defect structures, and single-atom catalysts with isolated metal sites are regarded as two of the most promising nanozymes. However, the strategies to construct highly performed nanozymes by combining these advantages are rarely reported. Herein, we report the coordination-unsaturated single-atomic Cu species supported on sintered CeO_(2), which combines the advantages of defect engineering and single-atom catalysis, exhibiting a largely enhanced peroxidase(POD)-like activity. The high-temperature calcination induces the transformation of inert Cu_(1)O_(4) species into coordination-unsaturated Cu_(1)O_(3) sites. This novel Cu_(1)O_(3) active sites with an unsaturated coordination work as a new type of defect sites to greatly activate the isolated Cu atoms and accelerate the dissociation of H_(2)O_(2) to form hydroxyl radicals(·OH). The obtained nanozyme with a high POD-like activity possesses low cytotoxicity, showing potential applications for the tumor inhibition in vitro and in vivo.展开更多
Water/solid interfaces play crucial roles in a wide range of physicochemical and technological processes.However,our microscopic understanding of the interfacial water under ambient temperature is relatively primitive...Water/solid interfaces play crucial roles in a wide range of physicochemical and technological processes.However,our microscopic understanding of the interfacial water under ambient temperature is relatively primitive.Herein,we report the direct experimental construction of two-dimensional(2D)ice-like water layer on hydrophilic surface at room temperature by using environment-controlled atomic force microscopy.In contrast to the prevailing view that nanoscale confinement is needed for the formation of 2D ice-like water,we find that 2D ice-like water can form on mica surface at temperatures above the freezing point without confinement.The 2D ice-like water layer shows epitaxial relation with the underlying mica lattice and good thermostability.In addition,the growth of ice-like water layer can be well controlled by the mechanical force from the scanning tip.Furthermore,the friction properties of 2D ice-like water layer are also probed by friction force microscopy.It is found that the icelike water layer can dramatically reduce the friction.These results provide deep understanding of 2D ice-like water formation on solid surfaces without nanoscale confinement and suggest means of growing 2D ices on surfaces at room temperature.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:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable ...Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients,and was safe and well tolerated.展开更多
Background and Aims: Non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical practice.The diagnostic accuracy of transient elastography-based liver stif...Background and Aims: Non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical practice.The diagnostic accuracy of transient elastography-based liver stiffness measurement(LSM)for liver fibrosis could be affected by liver necroinflam-mation,the latter of which could intensify stiffness of the liver.Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation.Methods: Three cross-sectional cohorts of liver biopsy-proven chronic liver dis-ease patients were enrolled,including 1417 chronic hepatitis B(CHB)patients from 10 different medical centers,106 non-al-coholic steatohepatitis patients,and 143 patients with auto-immune-related liver diseases.Another longitudinal cohort of 14 entecavir treatment patients was also included.The re-ceiver operating characteristic(ROC)curve was employed to explore the diagnostic value of LSM.Results: In CHB patients,LSM value ascended with the increased severity of liver nec-roinflammation in patients with the same fibrosis stage.Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoim-mune-related liver diseases populations.Furthermore,the ROC curve exhibited that LSM could identify moderate and se-vere inflammation in CHB patients(area under the ROC curve as 0.779 and 0.838)and in non-alcoholic steatohepatitis pa-tients(area under the ROC curve as 0.826 and 0.871),respec-tively.Such moderate diagnostic value was also found in autoimmune-related liver diseases patients.In addition,in the longitudinal entecavir treated CHB cohort,a decline of LSM values was observed in parallel with the control of inflam-matory activity in liver.Conclusions: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.展开更多
Background and Aims:The safety and efficacy of mesenchymal stem cells(MSCs)in the treatment of acute-onchronic liver failure(ACLF)have been validated.However,the impact of the pathological ACLF microenvironment on MSC...Background and Aims:The safety and efficacy of mesenchymal stem cells(MSCs)in the treatment of acute-onchronic liver failure(ACLF)have been validated.However,the impact of the pathological ACLF microenvironment on MSCs is less well understood.This study was designed to explore the changes in the functional properties of MSCs exposed to ACLF serum.Methods:MSCs were cultured in the presence of 10%,30%and 50%serum concentrations from ACLF patients and healthy volunteers.Then,the cell morphology,phenotype,apoptosis and proliferation of MSCs were evaluated,including the immunosuppressive effects.Subsequently,mRNA sequencing analysis was used to identify the molecules and pathways involved in MSC functional changes in the context of ACLF.Results:In the presence of ACLF serum,MSC morphology significantly changed but phenotype did not.Besides,MSC proliferation activity was weakened,while the apoptosis rate was lightly increased.Most importantly,the immunosuppressive function of MSCs was enhanced in a lowconcentration serum environment but transformed into a proinflammatory response in a high-concentration serum environment.RNA sequencing indicated that 10%serum concentration from ACLF patients mediated the PI3K-Akt pathway to enhance the anti-inflammatory effect of MSCs,while the 50%serum concentration from ACLF patients promoted the conversion of MSCs into a proinflammatory function by affecting the cell cycle.Conclusions:The 50%ACLF serum concentration is more similar to the environment in the human body,which means that direct peripheral blood intravenous infusion of MSCs may reduce the effect of transplantation.Combining treatments of plasma exchange to reduce harmful substances in serum may promote MSCs to exert a stronger anti-inflammatory effect.展开更多
Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin...Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice.Methods:In this prospective,multicenter,observational,non-interventional cohort study,patients were assessed for up to 1 year after peg-IFNαtreatment cessation.Treating physicians established the dosing and treatment duration according to Chinese clinical practice.Effectiveness of peg-IFNαtreatment was measured by the percentage of:patients with HBV DNA<2000 IU/mL and loss of hepatitis B surface antigen(commonly known as HBsAg);HBV DNA level at end of treatment(EOT),and 6 months and 1 year posttreatment;and time course change in quantitative HBV DNA and HBsAg.Results:At EOT,6 months posttreatment,and 1 year posttreatment,the percentage of patients with HBV DNA<2000 IU/mL was 90.0%,81.8%,and 82.2%,and that of patients with HBsAg loss was 6.5%,9.4%,and 9.5%,respectively.The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment.The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment.The incidence of adverse events was 52.0%.Conclusions:Peg-IFNαhas the potential to provide functional cure(HBsAg loss)for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China.展开更多
SARS-CoV-2,the causative agent for COVID-19,infect human mainly via respiratory tract,which is heavily inhabited by local microbiota.However,the interaction between SARS-CoV-2 and nasopharyngeal microbiota,and the ass...SARS-CoV-2,the causative agent for COVID-19,infect human mainly via respiratory tract,which is heavily inhabited by local microbiota.However,the interaction between SARS-CoV-2 and nasopharyngeal microbiota,and the association with metabolome has not been well characterized.Here,metabolomic analysis of blood,urine,and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients,and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19.Results showed lactic acid,L-proline,and chlorogenic acid methyl ester(CME)were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones.Nasopharyngeal commensal bacteria including Gemella morbillorum,Gemella haemolysans and Leptotrichia hofstadii were notably depleted in the pharynges of COVID-19 patients,while Prevotella histicola,Streptococcus sanguinis,and Veillonella dispar were relatively increased.The abundance of G.haemolysans and L.hofstadii were significantly positively associated with serum CME,which might be an anti-SARS-CoV-2 bacterial metabolite.This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility.The findings were based on a very limited number of patients enrolled in this study;a larger size of cohort will be appreciated for further investigation.展开更多
Worldwide,more than 240 million people are chronically infected with hepatitis B virus(HBV),1 and more than 887,000 deaths in 2015 are due to HBV-related end-stage liver disease or hepatocellular carcinoma.China has t...Worldwide,more than 240 million people are chronically infected with hepatitis B virus(HBV),1 and more than 887,000 deaths in 2015 are due to HBV-related end-stage liver disease or hepatocellular carcinoma.China has the largest burden of HBV in the world,with approximately 70 million HBV carriers,of which 20e30 million are chronic hepatitis B(CHB)patients.2,3 As the development of medicine,the treatment goal of CHB is getting higher and higher.展开更多
Hemorrhagic fever with renal syndrome(HFRS)is an acute zoonosis with a global distribution.China is one of the countries with a high incidence of HFRS,which has long endangered the lives and health of the Chinese peop...Hemorrhagic fever with renal syndrome(HFRS)is an acute zoonosis with a global distribution.China is one of the countries with a high incidence of HFRS,which has long endangered the lives and health of the Chinese people.The Infectious Disease Branch of the Chinese Preventive Medicine Association and the Infectious Diseases Branch of the Chinese Medical Association organized national multidisciplinary experts,based on domestic and international research results combined with experts’practical experiences,to reach this consensus after thorough discussion.This consensus contains 17 recommendations aimed at prevention and identification of important clinical issues to further standardize the prevention,diagnosis,and treatment of HFRS.展开更多
Over the past two decades,layer-by-layer(LbL) assembly of micro/nanocapsules has been of interest for the investigation of bio-nano interactions to explore bio-applications,such as drug delivery.The choice of an appro...Over the past two decades,layer-by-layer(LbL) assembly of micro/nanocapsules has been of interest for the investigation of bio-nano interactions to explore bio-applications,such as drug delivery.The choice of an appropriate template that can be easily dissolved under mild conditions is one of the challenges for the assembly of LbL capsules.Herein,we report the engineering of LbL capsules with tunable morphologies using cuprous oxide(Cu_2O) particles as templates.Cu_2O particles with cubic,tetradecahedral or spherical morphologies were synthesized via hydrothermal processes,which can be dissolved under mild condition(e.g.,sodium thiosulfate solution).The influence of capsule morphologies on cell association was investigated,which indicates that LbL capsules with cubic geometry promoted cell association up to 4 and 9-fold than tetradecahedral and spherical capsules,respectively.The reported method provides a new avenue for the assembly of LbL capsules with different morphologies,which has the potential for better understanding of biological interactions of LbL capsules.展开更多
The intrinsic hypoxic tumor microenvironment and limited accumulation of photosensitizers(PSs) result in unsatisfied efficiency of photodynamic therapy(PDT).To enhance the PDT efficiency against solid tumors,a functio...The intrinsic hypoxic tumor microenvironment and limited accumulation of photosensitizers(PSs) result in unsatisfied efficiency of photodynamic therapy(PDT).To enhance the PDT efficiency against solid tumors,a functional oxygen self-supplying and PS-delivering nanosystem is fabricated via the combination of catalase(CAT),chlorin e6(Ce6) and metal-phenolic network(MPN) capsule.It is demonstrated that the CAT encapsulated in the capsules(named CCM capsules) could catalyze the degradation of hydrogen peroxide(H;O;) to produce molecular oxygen(O;),which could be converted into cytotoxicity reactive oxygen species(ROS) by surface-loaded Ce6 under 660 nm laser irradiation,leading to synergistic anticancer effects in vitro and in vivo.Therefore,the application of CCM capsule could be a promising strategy to improve PDT effectiveness.展开更多
基金supported in part by the Electrostatic Research Foundation of Liu Shanghe Academicians and Experts Workstation,Beijing Orient Institute of Measurement and Test(No.BOIMTLSHJD20221002)。
文摘We present here an investigation of the self-pulsing phenomenon of negative corona and parallel-plate discharge in argon within one frame of a one-dimensional fluid model in cylinder–cylinder electrode geometry.The transition from corona to parallel-plate discharge is obtained by changing the inner and outer radii of the electrodes.The model reproduces the self-pulsing waveform well and provides the spatiotemporal behaviors of the charged particles and electric field during the pulse.The self-pulsing shows a common feature that occurs in various configurations and that does not depend on a specific electrode structure.The self-pulsing is the transformation between a weak-current Townsend mode and a large-current normal glow mode.The behavior of the positive ions is the dominant factor in the formation of the pulse.
文摘<strong>Objective:</strong> To explore the application of intelligent equipment in non-negative pressure isolation ward for COVID-2019 patients. <strong>Method:</strong> From February 1 to March 17, 2020, intelligent equipment, such as communication interaction system, intelligent disinfection robot, delivering robot, were used in non- negative pressure isolation ward of COVID-2019. With the help of communication interaction system to supervise the implementation of infection prevention and control, and observe the incorrect situation of pee use and personal behavior before and after the implementation. The disinfection robot and meal delivery robot were used in ward disinfection and life nursing combined with nursing practice. <strong>Result:</strong> Through the supervision of communication interaction system, the frequency of pee use and personal behavior was reduced. The frequency of bad articles before and after improvement was wearing protective clothing (2.80%/0.84%), taking off protective clothing (5.87%/0.84%), personal behavior observation (8.38%/1.90%), P < 0.01. The robot disinfected and delivered medicine for 912.5 h, saving 225 shifts of nursing staff. <strong>Conclusion:</strong> Intelligent equipment is a good option for infection control in isolation ward of COVID-2019. It can not only reduce the workload of health workers, but also the cross-infection.
基金supported by a grant from the National Natural Science Foundation of China(82170612)Guangzhou Science and Technology Program Key Projects(2023B01J1007)National Natural Science Foundation of China(No.81870597).
文摘Background and Aims:Hepatitis B virus(HBV)infection is a major risk factor for cirrhosis and liver cancer,and its treatment continues to be difficult.We previously demonstrated that a dopamine analog inhibited the packaging of pregenomic RNA into capsids.The present study aimed to determine the effect of dopamine on the expressions of hepatitis B virus surface and e antigens(HBsAg and HBeAg,respectively)and to elucidate the underlying mechanism.Methods:We used dopamine-treated HBVinfected HepG2.2.15 and NTCP-G2 cells to monitor HBsAg and HBeAg expression levels.We analyzed interferon-stimulated gene 15(ISG15)expression in dopamine-treated cells.We knocked down ISG15 and then monitored HBsAg and HBeAg expression levels.We analyzed the expression of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway factors in dopamine-treated cells.We used dopamine hydrochloride-treated adeno-associated virus/HBV-infected mouse model to evaluate HBV DNA,HBsAg,and HBeAg expression.HBV virus was collected from HepAD38.7 cell culture medium.Results:Dopamine inhibited HBsAg and HBeAg expression and upregulated ISG15 expression in HepG2.2.15 and HepG2-NTCP cell lines.ISG15 knockdown increased HBsAg and HBeAg expression in HepG2.2.15 cells.Dopamine-treated cells activated the JAK/STAT pathway,which upregulated ISG15 expression.In the adeno-associated virus-HBV murine infection model,dopamine downregulated HBsAg and HBeAg expression and activated the JAK-STAT/ISG15 axis.Conclusions:Dopamine inhibits the expression of HBsAg and HBeAg by activating the JAK/STAT pathway and upregulating ISG15 expression.
基金Natural Science Foundation of China(No.82070611 to Liang Peng)Natural Science Foundation of Guangdong Province(No.2020A1515010317 to Liang Peng)+4 种基金GuangDong Basic and Applied Basic Research Foundation(No.21202104030000608 and 2021A1515220029 to Liang Peng)Guangzhou Science and Technology Plan Projects(No.202102010204 and 2023B03J1287 to Liang Peng,No.202102080064 to Wenxiong Xu)Sun Yat-Sen University Clinical Research 5010 Program(No.2020007 and 2018009 to Liang Peng)Transformation of Scientific and Technological Achievements Project of Sun Yat-sen University(No.82000-18843236 to Liang Peng)Five-Year Plan of Third Affiliated Hospital of Sun Yat-sen University(No.K00006 and P02421 to Liang Peng).
文摘Background and aim Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation.Methods Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation.Results Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained undetectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9%)patients with an estimated annual incidence of HBsAg seroclearance of 3.6%.Patients with EOT HBsAg levels of≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of>1000 IU/mL(33.3%vs.5.4%).The proportion of patients with HBsAg≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL.Conclusions Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg seroclearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.
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The National Science and Technology Major Project (2018ZX10302204-002)the National Natural Science Foundation of China (81672701).
文摘Background and Aims:Functional cure(FC)is characterized by the clearance of the hepatitis B surface antigen from the serum of patients with chronic hepatitis B(CHB).However,the level of intrahepatic covalently closed circular DNA(cccDNA)and hepatitis B virus(HBV)integration remains unclear.We conducted this study to determine them and reveal their value in the treatment of CHB.Methods:There were two sessions to elucidate the changes in intrahepatic cccDNA and HBV integration after antiviral therapy.In the first session,116 patients were enrolled and divided into FC,non-functional cure(NFC),and CHB groups,including 48 patients with functionally cured CHB,27 with CHB without functional cure after antiviral treatment,and 41 with treatment-naïve CHB.Patients were tested for both intrahepatic cccDNA and other viral markers.All patients in the FC group were followed up for at least 24 weeks to observe relapse.In the second session,another ten patients were included for in-depth whole-genome sequencing to analyze HBV integration.Results:Thirteen patients in the FC group were negative for intrahepatic cccDNA.Intrahepatic cccDNA was much higher in the CHB group compared with the FC group.Seven patients had HBsAg seroreversion,including two with virological relapse.Integration of HBV was detected in one(33.3%)functionally cured patients and in seven(100%)with CHB.28.0%of the HBV breakpoints were assigned in the 1,500 nt to 1,900 nt range of the HBV genome.Conclusions:After achieving an FC,the rate of intrahepatic cccDNA and HBV integration was significantly reduced in patients with CHB.For those patients who cleared intrahepatic cccDNA,the chances of developing virological relapse were even lower.
基金This study was supported by grants from the National major science and technology project for the prevention and treatment of AIDS and viral hepatitis(2018ZX10302204-002-002 to LP,2018ZX10302205-002 to CX)Natural Science Foundation of China(No.81873572 to LP,82070611 to LP)+3 种基金Guangzhou Science and Technology Plan Projects(201904010442 to CX,202102010204 to LP)Guangdong Science and Technology Plan Projects(2020A1515010317 to CX)Sun Yat-Sen University Clinical Research 5010 Program(2018009 to CX,2020007 to LP)the Five-Year Plan of Third Affiliated Hospital of Sun Yat-Sen University(K00006 to LP).
文摘Background and Aims:To investigate the safety and efficacy of double plasma molecular adsorption system(DPMAS)with sequential low-dose plasma exchange(LPE)in treating early hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).Methods:Clinical data of patients with HBVACLF were prospectively collected,including patients in a DPMAS with sequential LPE(DPMAS+LPE)group and those in a standard medical treatment(SMT)group.The primary endpoint was death or liver transplantation(LT)at 12 weeks of follow-up.Propensity-score matching was performed to control the effects of confounding factors on prognosis between the two groups.Results:After 2 weeks,total bilirubin,alanine aminotransferase,blood urea nitrogen levels,and Chinese Group on the Study of Severe Hepatitis B score,were significantly lower in the DPMAS+LPE group than those in the SMT group(p<0.05).After 4 weeks,laboratory parameters of the two groups were similar.The cumulative survival rate of the DPMAS+LPE group was significantly higher than that of the SMT group at 4 weeks(97.9%vs.85.4%,p=0.027),but not at 12 weeks(85.4%vs.83.3%,p=0.687).Cytokine levels were significantly lower in 12-week survival group than in the death-or-LT group(p<0.05).Functional enrichment analysis showed that downregulated cytokines were mainly involved in positive regulation of proliferation and activation of lymphocytes and monocytes,regulation of immune effect response,regulation of endotoxin response,and glial cell proliferation.Conclusion:DPMAS+LPE significantly improved the 4-week cumulative survival rate,and ameliorated the inflammatory response in patients.DPMAS+LPE may be a promising modality for patients with early HBV-ACLF.
基金supported by the National Key Research and Development Program of China (2021YFA1501103)the National Science Fund for Distinguished Young Scholars of China (22225110)+3 种基金the National Natural Science Foundation of China (22102088)the foundation of Key Laboratory of Colloid and Interface Chemistry (Shandong University), Ministry of Education (202202)the Taishan Scholar Project of Shandong Province of Chinathe Young Scholars Program of Shandong University。
文摘As a class of nanomaterials with natural enzyme-like characteristics, nanozymes have shown their great potential in various applications. Reducible metal oxides featured with defect structures, and single-atom catalysts with isolated metal sites are regarded as two of the most promising nanozymes. However, the strategies to construct highly performed nanozymes by combining these advantages are rarely reported. Herein, we report the coordination-unsaturated single-atomic Cu species supported on sintered CeO_(2), which combines the advantages of defect engineering and single-atom catalysis, exhibiting a largely enhanced peroxidase(POD)-like activity. The high-temperature calcination induces the transformation of inert Cu_(1)O_(4) species into coordination-unsaturated Cu_(1)O_(3) sites. This novel Cu_(1)O_(3) active sites with an unsaturated coordination work as a new type of defect sites to greatly activate the isolated Cu atoms and accelerate the dissociation of H_(2)O_(2) to form hydroxyl radicals(·OH). The obtained nanozyme with a high POD-like activity possesses low cytotoxicity, showing potential applications for the tumor inhibition in vitro and in vivo.
基金This research was financially supported by the Grant for Taishan Scholar Advantage Characteristic Discipline of Shandong Province,the Start-up Grant for QiLu Young Scholars of Shandong University,the Grant from Danish Council for Independent Research(No.9040-00219B)EU H2020RISE 2016‐MNR4S Cell project.
文摘Water/solid interfaces play crucial roles in a wide range of physicochemical and technological processes.However,our microscopic understanding of the interfacial water under ambient temperature is relatively primitive.Herein,we report the direct experimental construction of two-dimensional(2D)ice-like water layer on hydrophilic surface at room temperature by using environment-controlled atomic force microscopy.In contrast to the prevailing view that nanoscale confinement is needed for the formation of 2D ice-like water,we find that 2D ice-like water can form on mica surface at temperatures above the freezing point without confinement.The 2D ice-like water layer shows epitaxial relation with the underlying mica lattice and good thermostability.In addition,the growth of ice-like water layer can be well controlled by the mechanical force from the scanning tip.Furthermore,the friction properties of 2D ice-like water layer are also probed by friction force microscopy.It is found that the icelike water layer can dramatically reduce the friction.These results provide deep understanding of 2D ice-like water formation on solid surfaces without nanoscale confinement and suggest means of growing 2D ices on surfaces at room temperature.
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Ascletis Pharmaceuticals Co.,Ltd.provided financial support for this study(MANASA)
文摘Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients,and was safe and well tolerated.
基金the National S&T Major Project for Infectious Diseases(2017ZX10201201,2017ZX10202202,2017ZX10302201 and 2017ZX10202203)the project from Beijing Municipal Science & Technology Commission(Z161100000116047)+1 种基金Project funded by China Postdoc-toral Science Foundation(2017M620544,2018T110014)Project funded by Shenzhen Municipal Health Commission(SZSM201612071)
文摘Background and Aims: Non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical practice.The diagnostic accuracy of transient elastography-based liver stiffness measurement(LSM)for liver fibrosis could be affected by liver necroinflam-mation,the latter of which could intensify stiffness of the liver.Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation.Methods: Three cross-sectional cohorts of liver biopsy-proven chronic liver dis-ease patients were enrolled,including 1417 chronic hepatitis B(CHB)patients from 10 different medical centers,106 non-al-coholic steatohepatitis patients,and 143 patients with auto-immune-related liver diseases.Another longitudinal cohort of 14 entecavir treatment patients was also included.The re-ceiver operating characteristic(ROC)curve was employed to explore the diagnostic value of LSM.Results: In CHB patients,LSM value ascended with the increased severity of liver nec-roinflammation in patients with the same fibrosis stage.Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoim-mune-related liver diseases populations.Furthermore,the ROC curve exhibited that LSM could identify moderate and se-vere inflammation in CHB patients(area under the ROC curve as 0.779 and 0.838)and in non-alcoholic steatohepatitis pa-tients(area under the ROC curve as 0.826 and 0.871),respec-tively.Such moderate diagnostic value was also found in autoimmune-related liver diseases patients.In addition,in the longitudinal entecavir treated CHB cohort,a decline of LSM values was observed in parallel with the control of inflam-matory activity in liver.Conclusions: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.
基金This study was supported by grants from the Natural Science Foundation of China(No.82070611 and 81873572)National Major Science and Technology Project for the Prevention and Treatment of AIDS and Viral Hepatitis(No.2018ZX10302204002 and 2018ZX10302205-002)+3 种基金Guangzhou Science and Technology Plan Projects(No.201904010442)Sun Yatsen University Clinical Research 5010 Program(No.2018009)Research Project on Degree and Postgraduate Education Reform in Guangdong Province(No.2018JGXM04)Young Teacher Training Program of Sun Yat-sen University(No.16ykpy40).
文摘Background and Aims:The safety and efficacy of mesenchymal stem cells(MSCs)in the treatment of acute-onchronic liver failure(ACLF)have been validated.However,the impact of the pathological ACLF microenvironment on MSCs is less well understood.This study was designed to explore the changes in the functional properties of MSCs exposed to ACLF serum.Methods:MSCs were cultured in the presence of 10%,30%and 50%serum concentrations from ACLF patients and healthy volunteers.Then,the cell morphology,phenotype,apoptosis and proliferation of MSCs were evaluated,including the immunosuppressive effects.Subsequently,mRNA sequencing analysis was used to identify the molecules and pathways involved in MSC functional changes in the context of ACLF.Results:In the presence of ACLF serum,MSC morphology significantly changed but phenotype did not.Besides,MSC proliferation activity was weakened,while the apoptosis rate was lightly increased.Most importantly,the immunosuppressive function of MSCs was enhanced in a lowconcentration serum environment but transformed into a proinflammatory response in a high-concentration serum environment.RNA sequencing indicated that 10%serum concentration from ACLF patients mediated the PI3K-Akt pathway to enhance the anti-inflammatory effect of MSCs,while the 50%serum concentration from ACLF patients promoted the conversion of MSCs into a proinflammatory function by affecting the cell cycle.Conclusions:The 50%ACLF serum concentration is more similar to the environment in the human body,which means that direct peripheral blood intravenous infusion of MSCs may reduce the effect of transplantation.Combining treatments of plasma exchange to reduce harmful substances in serum may promote MSCs to exert a stronger anti-inflammatory effect.
基金The authors wish to thank all of the investigators and participating study sites,which are listed in Supplemental Table 1,as well as all the patients who participated in this studyThe authors also wish to thank Michelle Belanger,MD,of Edanz Medical Writing for providing medical writing assistance,which was funded by Shanghai Roche Pharmaceuticals Ltd.The study was funded by Shanghai Roche Pharmaceuticals Ltd
文摘Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice.Methods:In this prospective,multicenter,observational,non-interventional cohort study,patients were assessed for up to 1 year after peg-IFNαtreatment cessation.Treating physicians established the dosing and treatment duration according to Chinese clinical practice.Effectiveness of peg-IFNαtreatment was measured by the percentage of:patients with HBV DNA<2000 IU/mL and loss of hepatitis B surface antigen(commonly known as HBsAg);HBV DNA level at end of treatment(EOT),and 6 months and 1 year posttreatment;and time course change in quantitative HBV DNA and HBsAg.Results:At EOT,6 months posttreatment,and 1 year posttreatment,the percentage of patients with HBV DNA<2000 IU/mL was 90.0%,81.8%,and 82.2%,and that of patients with HBsAg loss was 6.5%,9.4%,and 9.5%,respectively.The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment.The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment.The incidence of adverse events was 52.0%.Conclusions:Peg-IFNαhas the potential to provide functional cure(HBsAg loss)for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China.
基金supported by National Science and Technology Major Project(2018ZX10302204)Shenzhen Science and Technology Program(Grant No.KQTD20200820145822023)+3 种基金Emergency special program for 2019-nCov of Guangdong province science and technology project(2020B111105001)Guangzhou science and technology project(202008040003)Clinical Research Foundation of the third Affiliated Hospital of Sun Yat-sen University(YHJH201904)National Natural Science Foundation of China(Grant No.31900056).
文摘SARS-CoV-2,the causative agent for COVID-19,infect human mainly via respiratory tract,which is heavily inhabited by local microbiota.However,the interaction between SARS-CoV-2 and nasopharyngeal microbiota,and the association with metabolome has not been well characterized.Here,metabolomic analysis of blood,urine,and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients,and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19.Results showed lactic acid,L-proline,and chlorogenic acid methyl ester(CME)were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones.Nasopharyngeal commensal bacteria including Gemella morbillorum,Gemella haemolysans and Leptotrichia hofstadii were notably depleted in the pharynges of COVID-19 patients,while Prevotella histicola,Streptococcus sanguinis,and Veillonella dispar were relatively increased.The abundance of G.haemolysans and L.hofstadii were significantly positively associated with serum CME,which might be an anti-SARS-CoV-2 bacterial metabolite.This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility.The findings were based on a very limited number of patients enrolled in this study;a larger size of cohort will be appreciated for further investigation.
基金This work was supported by grants from the National Science and Technology Major Project of China(2018ZX10302204-002,2012ZX10002004 and 2012ZX10002007)the Natural Science Foundation of China(81672701).
文摘Worldwide,more than 240 million people are chronically infected with hepatitis B virus(HBV),1 and more than 887,000 deaths in 2015 are due to HBV-related end-stage liver disease or hepatocellular carcinoma.China has the largest burden of HBV in the world,with approximately 70 million HBV carriers,of which 20e30 million are chronic hepatitis B(CHB)patients.2,3 As the development of medicine,the treatment goal of CHB is getting higher and higher.
文摘Hemorrhagic fever with renal syndrome(HFRS)is an acute zoonosis with a global distribution.China is one of the countries with a high incidence of HFRS,which has long endangered the lives and health of the Chinese people.The Infectious Disease Branch of the Chinese Preventive Medicine Association and the Infectious Diseases Branch of the Chinese Medical Association organized national multidisciplinary experts,based on domestic and international research results combined with experts’practical experiences,to reach this consensus after thorough discussion.This consensus contains 17 recommendations aimed at prevention and identification of important clinical issues to further standardize the prevention,diagnosis,and treatment of HFRS.
基金financially supported by research general programs from the National Natural Science Foundation of China(Nos.21603120,21872085)Fundamental Research Funding of Shandong University(No.2017JC003)。
文摘Over the past two decades,layer-by-layer(LbL) assembly of micro/nanocapsules has been of interest for the investigation of bio-nano interactions to explore bio-applications,such as drug delivery.The choice of an appropriate template that can be easily dissolved under mild conditions is one of the challenges for the assembly of LbL capsules.Herein,we report the engineering of LbL capsules with tunable morphologies using cuprous oxide(Cu_2O) particles as templates.Cu_2O particles with cubic,tetradecahedral or spherical morphologies were synthesized via hydrothermal processes,which can be dissolved under mild condition(e.g.,sodium thiosulfate solution).The influence of capsule morphologies on cell association was investigated,which indicates that LbL capsules with cubic geometry promoted cell association up to 4 and 9-fold than tetradecahedral and spherical capsules,respectively.The reported method provides a new avenue for the assembly of LbL capsules with different morphologies,which has the potential for better understanding of biological interactions of LbL capsules.
基金supported by the Innovation Project of Jinan Science and Technology Bureau (No. 2020GXRC022)the Project for Scientific Research Innovation Team of Young Scholar in Colleges and Universities of Shandong Province (No. 2020KJC001)the National Natural Science Foundation of China (No. 21677090)。
文摘The intrinsic hypoxic tumor microenvironment and limited accumulation of photosensitizers(PSs) result in unsatisfied efficiency of photodynamic therapy(PDT).To enhance the PDT efficiency against solid tumors,a functional oxygen self-supplying and PS-delivering nanosystem is fabricated via the combination of catalase(CAT),chlorin e6(Ce6) and metal-phenolic network(MPN) capsule.It is demonstrated that the CAT encapsulated in the capsules(named CCM capsules) could catalyze the degradation of hydrogen peroxide(H;O;) to produce molecular oxygen(O;),which could be converted into cytotoxicity reactive oxygen species(ROS) by surface-loaded Ce6 under 660 nm laser irradiation,leading to synergistic anticancer effects in vitro and in vivo.Therefore,the application of CCM capsule could be a promising strategy to improve PDT effectiveness.