There has recently been a dramatic renewal of interest in hadron spectroscopy and charm physics. This renaissance has been driven in part by the discovery of a plethora of charmonium-like XYZ states at BESⅢ and B fac...There has recently been a dramatic renewal of interest in hadron spectroscopy and charm physics. This renaissance has been driven in part by the discovery of a plethora of charmonium-like XYZ states at BESⅢ and B factories, and the observation of an intriguing proton-antiproton threshold enhancement and the possibly related X(1835) meson state at BESⅢ, as well as the threshold measurements of charm mesons and charm baryons. We present a detailed survey of the important topics in tau-charm physics and hadron physics that can be further explored at BESⅢ during the remaining operation period of BEPCⅡ. This survey will help in the optimization of the data-taking plan over the coming years, and provides physics motivation for the possible upgrade of BEPCⅡ to higher luminosity.展开更多
The liver is a common location of both primary and secondary malignancies. For unresectable liver cancer, many local ablative therapies have been developed. These include e.g., percutaneous ethanol injection (PEI), pe...The liver is a common location of both primary and secondary malignancies. For unresectable liver cancer, many local ablative therapies have been developed. These include e.g., percutaneous ethanol injection (PEI), percutaneous acetic acid injection, radiofrequency ablation (RFA), cryoablation, microwave ablation, laserinduced thermotherapy, and high-intensity focused ultrasound. RFA has recently gained interest and is the most widely applied thermoablative technique. RFA allows more effective tumor control in fewer treatment sessions compared with PEI, but with a higher rate of complications. However, there are certain circumstances where PEI therapy represents a better strategy to control liver tumors than RFA, especially in situations where RFA is difficult, for example when large vessels surround the tumor. In the context of hepatocellular carcinoma (HCC), both RFA and PEI are feasible and of benefit in non-operable patients. RFA seems superior to PEI in HCC > 2 cm, and the combination of interventions may be of benefit in selected patients. Liver resection is superior to RFA for patients with HCC meeting the Milan criteria, but RFA can be employed in tumors ≤ 3 cm and where there is an increased expected operative mortality. In addition, some lines of evidence indicate that RFA and PEI can be employed as a bridge to liver transplantation. The use of RFA in colorectal liver metastases is currently limited to unresectable disease and for patients unfit for surgery. The aim of this article is to summarize the current status of RFA in the management of liver tumors and compare it to the cheap and readily available technique of PEI.展开更多
Using a dedicated data sample taken in 2018 on the J/ψpeak,we perform a detailed study of the trigger efficiencies of the BESIII detector.The efficiencies are determined from three representative physics processes,na...Using a dedicated data sample taken in 2018 on the J/ψpeak,we perform a detailed study of the trigger efficiencies of the BESIII detector.The efficiencies are determined from three representative physics processes,namely Bhabha scattering,dimuon production and generic hadronic events with charged particles.The combined efficiency of all active triggers approaches 100%in most cases,with uncertainties small enough not to affect most physics analyses.展开更多
High mobility group box 1(HMGB1)is an evolutionarily conserved non-histone chromatin-binding protein.During infection or injury,activated immune cells and damaged cells release HMGB1 into the extracellular space,where...High mobility group box 1(HMGB1)is an evolutionarily conserved non-histone chromatin-binding protein.During infection or injury,activated immune cells and damaged cells release HMGB1 into the extracellular space,where HMGB1 functions as a proinflammatory mediator and contributes importantly to the pathogenesis of inflammatory diseases.Recent studies reveal that infl ammasomes,intracellular protein complexes,critically regulate HMGB1 release from activated immune cells in response to a variety of exogenous and endogenous danger signals.Double stranded RNA dependent kinase(PKR),an intracellular danger-sensing molecule,physically interacts with inflammasome components and is important for infl ammasome activation and HMGB1 release.Together,these studies not only unravel novel mechanisms of HMGB1 release during infl ammation,but also provide potential therapeutic targets to treat HMGB1-related infl ammatory diseases.展开更多
Pancreatic ductal adenocarcinoma(PDAC) represents the fourth cause of death in cancer and has a 5-year survival of < 5%.Only about 15% of the patients present with a resectable PDAC with potential to undergo "...Pancreatic ductal adenocarcinoma(PDAC) represents the fourth cause of death in cancer and has a 5-year survival of < 5%.Only about 15% of the patients present with a resectable PDAC with potential to undergo "curative" surgery.After surgery,local and systemic recurrence,is though very common.The median survival of resected patients with adjuvant chemotherapy after surgery is only 20-23 mo.This underscores the significant need to improve PDAC management strategies.Increased survival rate is dependent on new breakthroughs in our understanding of not at least tumor biology.The aim of this review is to update and comment on recent knowledge concerning PDAC biology and new diagnostics and treatment modalities.One fundamental approach to improve survival rates is by earlier and improved diagnosis of the disease.In recent years,novel blood-based biomarkers have emerged based on genetic,epigenetic and protein changes in PDAC with very promising results.For biomarkers to enter clinical practice they need to have been developed using adequate control groups and provide high sensitivity and specificity and by this identify patients at risk already in a pre-symptomatic stage.Another way to improve outcomes,is by employing neoadjuvant treatments thereby increasing the number of resectable cases.Novel systemic treatment regimes like FOLFIRINOX and nab-paclitaxel have demonstrated improvements in prolonging survival in advanced cases,but long-term survival is still scarce.The future improved understanding of PDAC biology will inevitably render new treatment options directed against both the cancer cells and the surrounding microenvironment.展开更多
Acute pancreatitis(AP)is a common clinical condition with an incidence of about 300 or more patients per million annually.About 10%-15%of patients will develop severe acute pancreatitis(SAP)and of those, 10%-30%may di...Acute pancreatitis(AP)is a common clinical condition with an incidence of about 300 or more patients per million annually.About 10%-15%of patients will develop severe acute pancreatitis(SAP)and of those, 10%-30%may die due to SAP-associated complications.Despite the improvements done in the diagnosis and management of AP,the mortality rate has not significantly declined during the last decades.Toll-like receptors(TLRs)are pattern-recognition receptors that seem to play a major role in the development of numerous diseases,which make these molecules attractive as potential therapeutic targets.TLRs are involved in the development of the systemic inflammatory response syndrome,a potentially lethal complication in SAP.In the present review,we explore the current knowledge about the role of different TLRs that have been described associated with AP.The main candidate for targeting seems to be TLR4,which recognizes numerous damage-associated molecular patterns related to AP.TLR2 has also been linked with AP,but there are only limited studies that exclusively studied its role in AP.There is also data suggesting that TLR9 may play a role in AP.展开更多
AIM:To assess whether gemcitabine-based combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone.METHODS:A quantitative up-to-date meta-analysis was undert...AIM:To assess whether gemcitabine-based combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone.METHODS:A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy in locally advanced or metastatic pancreatic cancer.Inclusion was limited to highquality randomized clinical trials.RESULTS:Twenty-six studies were included in the present analysis,with a total of 8808 patients recruited.The studies were divided into four subgroups based on the different kinds of cytotoxic agents,including platinum,fluoropyrimidine,camptothecin and targeted agents.Patients treated with gemcitabine monotherapy had significantly lower objective response rate [risk ratio(RR),0.72;95% confidence interval(CI):0.63-0.83;P < 0.001],and lower 1-year overall survival(RR,0.90;95%CI:0.82-0.99;P = 0.04).Gemcitabine monotherapy caused fewer complications,including fewer grade 3-4 toxicities:including vomiting(RR,0.75;95%CI:0.62-0.89;P = 0.001),diarrhea(RR,0.66;95%CI:0.49-0.89;P = 0.006),neutropenia(RR,0.88;95%CI:0.72-1.06;P = 0.18),anemia(RR,0.96;95%CI:0.82-1.12;P = 0.60),and thrombocytopenia(RR,0.76;95%CI:0.60-0.97;P = 0.03) compared with gemcitabine combination therapies.CONCLUSION:Gemcitabine combination therapy provides a modest improvement of survival,but is associated with more toxicity compared with gemcitabine monotherapy.展开更多
In recent years,the penetration of renewable resources into AC power systems has increased tremendously,creating a significantly impact on the latter’s operations and stability.In this respect,it is also important to...In recent years,the penetration of renewable resources into AC power systems has increased tremendously,creating a significantly impact on the latter’s operations and stability.In this respect,it is also important to gain a basic analytical understanding of such impact on the steady-state stability of power systems with electrically weak AC/DC interconnections,but such works are not very evident in the literature.Therefore,a classical analytic model of the single and multi-infeed HVDC system which now incorporates renewable resources is proposed.Then the well-established concept of voltage sensitivity of the AC/DC interconnection is applied to analyze the impact of the renewable resources on the steady-state stability of these composite system models,as well as on the influence of system conditions and parameters.This impact is also compared with that arising from other types of shunt devices alternatively connected at the same AC/DC interconnection,therefore their relative beneficial or negative impacts will also be benchmarked.展开更多
The mechanical failure of solid oxide fuel cell(SOFC) components may cause cracks with consequences such as gas leakage,structure instability and reduction of cell lifetime.A comprehensive 3D model of the thermal stre...The mechanical failure of solid oxide fuel cell(SOFC) components may cause cracks with consequences such as gas leakage,structure instability and reduction of cell lifetime.A comprehensive 3D model of the thermal stresses of an anode-supported planar SOFC is presented in this work.The main objective of this paper is to get an interconnect optimized design by evaluating the thermal stresses of an anode-supported SOFC for different designs,which would be a new criterion for interconnect design.The model incorporates the momentum,mass,heat,ion and electron transport,as well as steady-state mechanics.Heat from methane steam reforming and water-gas shift reaction were considered in our model.The results examine the relationship between the interconnect structures and thermal stresses in SOFC at certain mechanical properties.A wider interconnect of the anode side lowers the stress obviously.The simulation results also indicate that thermal stress of coflow design is smaller than that of counterflow,corresponding to the temperature distribution.This study shows that it is possible to design interconnects for an optimum thermal stress performance of the cell.展开更多
High human equilibrative nucleoside transporter 1(hENT1)-expression has shown a survival benefit in pancreatic cancer patients treated with gemcitabine in several studies.The aim of this systematic review was to summa...High human equilibrative nucleoside transporter 1(hENT1)-expression has shown a survival benefit in pancreatic cancer patients treated with gemcitabine in several studies.The aim of this systematic review was to summarize the results and try to assess the predictive value of hENT1 for determining gemcitabine outcome in pancreatic cancer.Relevant articles were obtained from PubMed,Embase and Cochrane databases.Studies evaluating hENT1-expression in pancreatic tumor cells from patients treated with gemcitabine were selected.Outcome measures were overall survival,disease-free survival(DFS),toxicity and response rate.The database searches identified 10 studies that met the eligibility criteria,and a total of 855 patients were included.Nine of 10 studies showed a statistically significant longer overall survival in univariate analyses in patients with high hENT1-expression compared to those with low expression.In the 7 studies that reported DFS as an outcome measure,6 had statistically longer DFS in the high hENT1 groups.Both toxicity and response rate were reported in only 2 articles and it was therefore hard to draw any major conclusions.This review provides evidence that hENT1 is a predictive marker for pancreatic cancer patients treated with gemcitabine.Some limitations of the review have to be taken into consideration,the majority of the included studies had a retrospective design,and there was no standardized scoring protocol for hENT1-expression.展开更多
Gram-negative sepsis is a severe clinical syndrome associated with significant morbidity and mortality.Lipopolysaccharide(LPS),expressed on Gram-negative bacteria,is a potent pro-inflammatory toxin that induces inflam...Gram-negative sepsis is a severe clinical syndrome associated with significant morbidity and mortality.Lipopolysaccharide(LPS),expressed on Gram-negative bacteria,is a potent pro-inflammatory toxin that induces inflammation and coagulation via two separate receptor systems.One is Toll-like receptor 4(TLR4),expressed on cell surfaces and in endosomes,and the other is the cytosolic receptor caspase-11(caspases-4 and-5 in hu-mans).Extracellular LPS binds to high mobility group box 1(HMGB1)protein,a cytokine-like molecule.The HMGB1-LPS complex is transported via receptor for advanced glycated end products(RAGE)-endocytosis to the endolysosomal system to reach the cytosolic LPS receptor caspase-11 to induce HMGB1 release,inflammation,and coagulation that may cause multi-organ failure.The insight that LPS needs HMGB1 assistance to generate severe inflammation has led to successful therapeutic results in preclinical Gram-negative sepsis studies target-ing HMGB1.However,to date,no clinical studies have been performed based on this strategy.HMGB1 is also actively released by peripheral sensory nerves and this mechanism is fundamental for the initiation and prop-agation of inflammation during tissue injury.Homeostasis is achieved when other neurons actively restrict the inflammatory response via monitoring by the central nervous system and the vagus nerve through the cholinergic anti-inflammatory pathway.The neuronal control in Gram-negative sepsis needs further studies since a deeper understanding of the interplay between HMGB1 and acetylcholine may have beneficial therapeutic implications.Herein,we review the synergistic overlapping mechanisms of LPS and HMGB1 and discuss future treatment opportunities in Gram-negative sepsis.展开更多
Pancreatic ductal adenocarcinoma carries a poor prognosis with annual deaths almost matching the reported incidence rates. Surgical resection offers the only potential cure. Yet, even among patients that undergo tumor...Pancreatic ductal adenocarcinoma carries a poor prognosis with annual deaths almost matching the reported incidence rates. Surgical resection offers the only potential cure. Yet, even among patients that undergo tumor resection, recurrence rates are high and long-term survival is scarce. Various tumorrelated factors have been identified as predictors of survival after potentially curative resection. These factors include tumor size, lymph node disease, tumor grade, vascular invasion, perineural invasion and surgical resection margin. This article will re-evaluate the importance of these factors based on recent publications on the topic, with potential implications for treatment and outcome in patients with pancreatic cancer.展开更多
Hydropower gains increasing importance as a steerable and controllable power source in a renewable energy mix and deregulated markets. Although hydropower produces fossil-free energy, it has a significant impact on th...Hydropower gains increasing importance as a steerable and controllable power source in a renewable energy mix and deregulated markets. Although hydropower produces fossil-free energy, it has a significant impact on the local environment. This review investigates the effects of flow alterations by hydropower on the downstream river system and the possibilities to integrate these effects into hydraulic modeling. The results show that various effects of flow regulation on the ecosystem, but also social and economic effects on related communities were observed in the last decades. The application of hydraulic models for investigations of ecological effects is common. Especially hydraulic effects and effects on fish were extensively modeled with the help of hydraulic 1D- and 2D-simulations. Current applications to investigate social and economic effects integrated into hydraulic modeling are meanwhile limited. Approaches to realizing this integration are presented. Further research on the economic valuation of ecosystems and integration of social and economic effects to hydraulic models is necessary to develop holistic tools to support decision-making on sustainable hydropower.展开更多
Background Brain natriuretic peptide （BNP） is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects （CHF）. BNP has natriuretic ef...Background Brain natriuretic peptide （BNP） is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects （CHF）. BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients （BNP 〉 3000 ng/L） with 10 matched, healthy controls. Methods Cutaneous microvascular blood flow in the forearm was measured by laser Doppler Flowmetry. Local heating （＋44°C, 10 min） was used to evoke a maximum local dilator response. Results Non-invasive iontophoretic administration of either BNP or acetylcholine （ACh）, a known endothelium-dependent dilator, elicited an increase in local flow. The nitric oxide synthase inhibitor, l-N-Arginine- methyl-ester （L-NAME）, blocked the BNP response （in controls）. Interestingly, responses to BNP in CHF patients were reduced to about one third of those seen in healthy controls （increase in flow： 251% in CHF vs. 908% in controls; P 〈 0.001）. In contrast, the vasodilator responses to ACh and to local heating were only somewhat attenuated in CHF patients. Thus, dilator capacity and nitric oxide signalling were not af- fected to the same extent as BNP-mediated dilation, indicating a specific downregulation of the latter response. Conclusions The findings show for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulated in CHF.展开更多
Novel treatment modalities are necessary for pancreatic cancer. Immunotherapy with immune checkpoint inhibition has shown effect in other solid tumors, and could have a place in pancreatic cancer treatment. Most avail...Novel treatment modalities are necessary for pancreatic cancer. Immunotherapy with immune checkpoint inhibition has shown effect in other solid tumors, and could have a place in pancreatic cancer treatment. Most available clinical studies on immune checkpoint inhibitors for pancreatic cancer are not yet completed and are still recruiting patients. Among the completed trials, there have been findings of a preliminary nature such as delayed disease progression and enhanced overall survival after treatment with immune checkpoint inhibitors in mono- or combination therapy. However, due to small sample sizes, major results are not yet identifiable. The present article provides a clinical overview of immune checkpoint inhibition in pancreatic cancer. Pub Med, Clinical Trials.gov and American Society of Clinical Oncology's meeting abstracts were systematically searched for relevant clinical studies. Four articles, five abstracts and 25 clinical trials were identified and analyzed in detail.展开更多
Coupling between subwavelength-diameter silica wires and silicon-based waveguides is studied using the parallel three-dimensional （3D） finite-different time-domain method. Conventional butt-coupling to a silica-subs...Coupling between subwavelength-diameter silica wires and silicon-based waveguides is studied using the parallel three-dimensional （3D） finite-different time-domain method. Conventional butt-coupling to a silica-substrated silicon wire waveguide gives above 40% transmission at the wavelength range from 1300 to 1750 nm with good robustness against axial misalignments. Slow light can be generated by counterdirectional coupling between a silica wire and a two-dimensional （2D） silicon photonic crystal slab waveguide. Through dispersion-band engineering, 82% transmission is achieved over a coupling distance of 50 lattice constants, The group velocity is estimated as 1/35 of the light speed in vacuum.展开更多
基金Supported in part by National Key Basic Research Program of China (2015CB856700)National Natural Science Foundation of China (NSFC) (11335008,11425524, 11625523, 11635010, 11735014, 11822506, 11935018)+18 种基金the Chinese Academy of Sciences (CAS) Large-Scale Scientific Facility Programthe CAS Center for Excellence in Particle Physics (CCEPP)Joint Large-Scale Scientific Facility Funds of the NSFC and CAS (U1532257, U1532258, U1732263)CAS Key Research Program of Frontier Science (QYZDJ-SSW-SLH003, QYZDJ-SSW-SLH040)100 Talents Program of CASCAS PIFIthe Thousand Talents Program of ChinaIN-PAC and Shanghai Key Laboratory for Particle Physics and CosmologyGerman Research Foundation DFG under Contracts NosCollaborative Research Center CRC 1044, FOR 2359Istituto Nazionale di Fisica Nucleare, ItalyKoninklijke Nederlandse Akademie van Wetenschappen (KNAW) (530-4CDP03)Ministry of Development of Turkey (DPT2006K-120470)National Science and Technology fundThe Knut and Alice Wallenberg Foundation (Sweden) (2016.0157)The Swedish Research CouncilU. S. Department of Energy (DE-FG02-05ER41374, DESC-0010118, DE-SC-0012069)University of Groningen (Ru G) and the Helmholtzzentrum fuer Schwerionenforschung Gmb H (GSI), Darmstadtthe Russian Ministry of Science and Higher Education (14.W03.31.0026).
文摘There has recently been a dramatic renewal of interest in hadron spectroscopy and charm physics. This renaissance has been driven in part by the discovery of a plethora of charmonium-like XYZ states at BESⅢ and B factories, and the observation of an intriguing proton-antiproton threshold enhancement and the possibly related X(1835) meson state at BESⅢ, as well as the threshold measurements of charm mesons and charm baryons. We present a detailed survey of the important topics in tau-charm physics and hadron physics that can be further explored at BESⅢ during the remaining operation period of BEPCⅡ. This survey will help in the optimization of the data-taking plan over the coming years, and provides physics motivation for the possible upgrade of BEPCⅡ to higher luminosity.
文摘The liver is a common location of both primary and secondary malignancies. For unresectable liver cancer, many local ablative therapies have been developed. These include e.g., percutaneous ethanol injection (PEI), percutaneous acetic acid injection, radiofrequency ablation (RFA), cryoablation, microwave ablation, laserinduced thermotherapy, and high-intensity focused ultrasound. RFA has recently gained interest and is the most widely applied thermoablative technique. RFA allows more effective tumor control in fewer treatment sessions compared with PEI, but with a higher rate of complications. However, there are certain circumstances where PEI therapy represents a better strategy to control liver tumors than RFA, especially in situations where RFA is difficult, for example when large vessels surround the tumor. In the context of hepatocellular carcinoma (HCC), both RFA and PEI are feasible and of benefit in non-operable patients. RFA seems superior to PEI in HCC > 2 cm, and the combination of interventions may be of benefit in selected patients. Liver resection is superior to RFA for patients with HCC meeting the Milan criteria, but RFA can be employed in tumors ≤ 3 cm and where there is an increased expected operative mortality. In addition, some lines of evidence indicate that RFA and PEI can be employed as a bridge to liver transplantation. The use of RFA in colorectal liver metastases is currently limited to unresectable disease and for patients unfit for surgery. The aim of this article is to summarize the current status of RFA in the management of liver tumors and compare it to the cheap and readily available technique of PEI.
基金Supported in part by National Key Basic Research Program of China(2015CB856700)National Natural Science Foundation of China(NSFC)(11625523,11635010,11735014,11822506,11835012,11935015,11935016,11935018,11961141012)+15 种基金the Chinese Academy of Sciences(CAS)Large-Scale Scientific Facility ProgramJoint Large-Scale Scientific Facility Funds of the NSFC and CAS(U 1732263,U 1832207)CAS Key Research Program of Frontier Sciences(QYZDJ-SSWSLH003,QYZDJ-SSW-SLH040)100 Talents Program of CASINPAC and Shanghai Key Laboratory for Particle Physics and CosmologyERC(758462)German Research Foundation DFG under Contracts Nos.Collaborative Research Center CRC 1044,FOR 2359Istituto Nazionale di Fisica Nucleare,ItalyMinistry of Development o f Turkey(DPT2006K-120470)National Science and Technology fundOlle Engkvist Foundation(200-0605)STFC(United Kingdom)The Knut and Alice Wallenberg Foundation(Sweden)(2016.0157)The Royal Society,UK(DH140054,DH160214)The Swedish Research CouncilU.S.Department of Energy(DEFG02-05ER41374,DE-SC-0012069)。
文摘Using a dedicated data sample taken in 2018 on the J/ψpeak,we perform a detailed study of the trigger efficiencies of the BESIII detector.The efficiencies are determined from three representative physics processes,namely Bhabha scattering,dimuon production and generic hadronic events with charged particles.The combined efficiency of all active triggers approaches 100%in most cases,with uncertainties small enough not to affect most physics analyses.
文摘High mobility group box 1(HMGB1)is an evolutionarily conserved non-histone chromatin-binding protein.During infection or injury,activated immune cells and damaged cells release HMGB1 into the extracellular space,where HMGB1 functions as a proinflammatory mediator and contributes importantly to the pathogenesis of inflammatory diseases.Recent studies reveal that infl ammasomes,intracellular protein complexes,critically regulate HMGB1 release from activated immune cells in response to a variety of exogenous and endogenous danger signals.Double stranded RNA dependent kinase(PKR),an intracellular danger-sensing molecule,physically interacts with inflammasome components and is important for infl ammasome activation and HMGB1 release.Together,these studies not only unravel novel mechanisms of HMGB1 release during infl ammation,but also provide potential therapeutic targets to treat HMGB1-related infl ammatory diseases.
文摘Pancreatic ductal adenocarcinoma(PDAC) represents the fourth cause of death in cancer and has a 5-year survival of < 5%.Only about 15% of the patients present with a resectable PDAC with potential to undergo "curative" surgery.After surgery,local and systemic recurrence,is though very common.The median survival of resected patients with adjuvant chemotherapy after surgery is only 20-23 mo.This underscores the significant need to improve PDAC management strategies.Increased survival rate is dependent on new breakthroughs in our understanding of not at least tumor biology.The aim of this review is to update and comment on recent knowledge concerning PDAC biology and new diagnostics and treatment modalities.One fundamental approach to improve survival rates is by earlier and improved diagnosis of the disease.In recent years,novel blood-based biomarkers have emerged based on genetic,epigenetic and protein changes in PDAC with very promising results.For biomarkers to enter clinical practice they need to have been developed using adequate control groups and provide high sensitivity and specificity and by this identify patients at risk already in a pre-symptomatic stage.Another way to improve outcomes,is by employing neoadjuvant treatments thereby increasing the number of resectable cases.Novel systemic treatment regimes like FOLFIRINOX and nab-paclitaxel have demonstrated improvements in prolonging survival in advanced cases,but long-term survival is still scarce.The future improved understanding of PDAC biology will inevitably render new treatment options directed against both the cancer cells and the surrounding microenvironment.
文摘Acute pancreatitis(AP)is a common clinical condition with an incidence of about 300 or more patients per million annually.About 10%-15%of patients will develop severe acute pancreatitis(SAP)and of those, 10%-30%may die due to SAP-associated complications.Despite the improvements done in the diagnosis and management of AP,the mortality rate has not significantly declined during the last decades.Toll-like receptors(TLRs)are pattern-recognition receptors that seem to play a major role in the development of numerous diseases,which make these molecules attractive as potential therapeutic targets.TLRs are involved in the development of the systemic inflammatory response syndrome,a potentially lethal complication in SAP.In the present review,we explore the current knowledge about the role of different TLRs that have been described associated with AP.The main candidate for targeting seems to be TLR4,which recognizes numerous damage-associated molecular patterns related to AP.TLR2 has also been linked with AP,but there are only limited studies that exclusively studied its role in AP.There is also data suggesting that TLR9 may play a role in AP.
文摘AIM:To assess whether gemcitabine-based combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone.METHODS:A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy in locally advanced or metastatic pancreatic cancer.Inclusion was limited to highquality randomized clinical trials.RESULTS:Twenty-six studies were included in the present analysis,with a total of 8808 patients recruited.The studies were divided into four subgroups based on the different kinds of cytotoxic agents,including platinum,fluoropyrimidine,camptothecin and targeted agents.Patients treated with gemcitabine monotherapy had significantly lower objective response rate [risk ratio(RR),0.72;95% confidence interval(CI):0.63-0.83;P < 0.001],and lower 1-year overall survival(RR,0.90;95%CI:0.82-0.99;P = 0.04).Gemcitabine monotherapy caused fewer complications,including fewer grade 3-4 toxicities:including vomiting(RR,0.75;95%CI:0.62-0.89;P = 0.001),diarrhea(RR,0.66;95%CI:0.49-0.89;P = 0.006),neutropenia(RR,0.88;95%CI:0.72-1.06;P = 0.18),anemia(RR,0.96;95%CI:0.82-1.12;P = 0.60),and thrombocytopenia(RR,0.76;95%CI:0.60-0.97;P = 0.03) compared with gemcitabine combination therapies.CONCLUSION:Gemcitabine combination therapy provides a modest improvement of survival,but is associated with more toxicity compared with gemcitabine monotherapy.
文摘In recent years,the penetration of renewable resources into AC power systems has increased tremendously,creating a significantly impact on the latter’s operations and stability.In this respect,it is also important to gain a basic analytical understanding of such impact on the steady-state stability of power systems with electrically weak AC/DC interconnections,but such works are not very evident in the literature.Therefore,a classical analytic model of the single and multi-infeed HVDC system which now incorporates renewable resources is proposed.Then the well-established concept of voltage sensitivity of the AC/DC interconnection is applied to analyze the impact of the renewable resources on the steady-state stability of these composite system models,as well as on the influence of system conditions and parameters.This impact is also compared with that arising from other types of shunt devices alternatively connected at the same AC/DC interconnection,therefore their relative beneficial or negative impacts will also be benchmarked.
基金financially supported by the Research Fund for International Young Scientists(51550110238)the Fundamental Research Funds for the Central Universities (ZYGX2015J108)
文摘The mechanical failure of solid oxide fuel cell(SOFC) components may cause cracks with consequences such as gas leakage,structure instability and reduction of cell lifetime.A comprehensive 3D model of the thermal stresses of an anode-supported planar SOFC is presented in this work.The main objective of this paper is to get an interconnect optimized design by evaluating the thermal stresses of an anode-supported SOFC for different designs,which would be a new criterion for interconnect design.The model incorporates the momentum,mass,heat,ion and electron transport,as well as steady-state mechanics.Heat from methane steam reforming and water-gas shift reaction were considered in our model.The results examine the relationship between the interconnect structures and thermal stresses in SOFC at certain mechanical properties.A wider interconnect of the anode side lowers the stress obviously.The simulation results also indicate that thermal stress of coflow design is smaller than that of counterflow,corresponding to the temperature distribution.This study shows that it is possible to design interconnects for an optimum thermal stress performance of the cell.
文摘High human equilibrative nucleoside transporter 1(hENT1)-expression has shown a survival benefit in pancreatic cancer patients treated with gemcitabine in several studies.The aim of this systematic review was to summarize the results and try to assess the predictive value of hENT1 for determining gemcitabine outcome in pancreatic cancer.Relevant articles were obtained from PubMed,Embase and Cochrane databases.Studies evaluating hENT1-expression in pancreatic tumor cells from patients treated with gemcitabine were selected.Outcome measures were overall survival,disease-free survival(DFS),toxicity and response rate.The database searches identified 10 studies that met the eligibility criteria,and a total of 855 patients were included.Nine of 10 studies showed a statistically significant longer overall survival in univariate analyses in patients with high hENT1-expression compared to those with low expression.In the 7 studies that reported DFS as an outcome measure,6 had statistically longer DFS in the high hENT1 groups.Both toxicity and response rate were reported in only 2 articles and it was therefore hard to draw any major conclusions.This review provides evidence that hENT1 is a predictive marker for pancreatic cancer patients treated with gemcitabine.Some limitations of the review have to be taken into consideration,the majority of the included studies had a retrospective design,and there was no standardized scoring protocol for hENT1-expression.
文摘Gram-negative sepsis is a severe clinical syndrome associated with significant morbidity and mortality.Lipopolysaccharide(LPS),expressed on Gram-negative bacteria,is a potent pro-inflammatory toxin that induces inflammation and coagulation via two separate receptor systems.One is Toll-like receptor 4(TLR4),expressed on cell surfaces and in endosomes,and the other is the cytosolic receptor caspase-11(caspases-4 and-5 in hu-mans).Extracellular LPS binds to high mobility group box 1(HMGB1)protein,a cytokine-like molecule.The HMGB1-LPS complex is transported via receptor for advanced glycated end products(RAGE)-endocytosis to the endolysosomal system to reach the cytosolic LPS receptor caspase-11 to induce HMGB1 release,inflammation,and coagulation that may cause multi-organ failure.The insight that LPS needs HMGB1 assistance to generate severe inflammation has led to successful therapeutic results in preclinical Gram-negative sepsis studies target-ing HMGB1.However,to date,no clinical studies have been performed based on this strategy.HMGB1 is also actively released by peripheral sensory nerves and this mechanism is fundamental for the initiation and prop-agation of inflammation during tissue injury.Homeostasis is achieved when other neurons actively restrict the inflammatory response via monitoring by the central nervous system and the vagus nerve through the cholinergic anti-inflammatory pathway.The neuronal control in Gram-negative sepsis needs further studies since a deeper understanding of the interplay between HMGB1 and acetylcholine may have beneficial therapeutic implications.Herein,we review the synergistic overlapping mechanisms of LPS and HMGB1 and discuss future treatment opportunities in Gram-negative sepsis.
文摘Pancreatic ductal adenocarcinoma carries a poor prognosis with annual deaths almost matching the reported incidence rates. Surgical resection offers the only potential cure. Yet, even among patients that undergo tumor resection, recurrence rates are high and long-term survival is scarce. Various tumorrelated factors have been identified as predictors of survival after potentially curative resection. These factors include tumor size, lymph node disease, tumor grade, vascular invasion, perineural invasion and surgical resection margin. This article will re-evaluate the importance of these factors based on recent publications on the topic, with potential implications for treatment and outcome in patients with pancreatic cancer.
文摘Hydropower gains increasing importance as a steerable and controllable power source in a renewable energy mix and deregulated markets. Although hydropower produces fossil-free energy, it has a significant impact on the local environment. This review investigates the effects of flow alterations by hydropower on the downstream river system and the possibilities to integrate these effects into hydraulic modeling. The results show that various effects of flow regulation on the ecosystem, but also social and economic effects on related communities were observed in the last decades. The application of hydraulic models for investigations of ecological effects is common. Especially hydraulic effects and effects on fish were extensively modeled with the help of hydraulic 1D- and 2D-simulations. Current applications to investigate social and economic effects integrated into hydraulic modeling are meanwhile limited. Approaches to realizing this integration are presented. Further research on the economic valuation of ecosystems and integration of social and economic effects to hydraulic models is necessary to develop holistic tools to support decision-making on sustainable hydropower.
文摘Background Brain natriuretic peptide （BNP） is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects （CHF）. BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients （BNP 〉 3000 ng/L） with 10 matched, healthy controls. Methods Cutaneous microvascular blood flow in the forearm was measured by laser Doppler Flowmetry. Local heating （＋44°C, 10 min） was used to evoke a maximum local dilator response. Results Non-invasive iontophoretic administration of either BNP or acetylcholine （ACh）, a known endothelium-dependent dilator, elicited an increase in local flow. The nitric oxide synthase inhibitor, l-N-Arginine- methyl-ester （L-NAME）, blocked the BNP response （in controls）. Interestingly, responses to BNP in CHF patients were reduced to about one third of those seen in healthy controls （increase in flow： 251% in CHF vs. 908% in controls; P 〈 0.001）. In contrast, the vasodilator responses to ACh and to local heating were only somewhat attenuated in CHF patients. Thus, dilator capacity and nitric oxide signalling were not af- fected to the same extent as BNP-mediated dilation, indicating a specific downregulation of the latter response. Conclusions The findings show for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulated in CHF.
文摘Novel treatment modalities are necessary for pancreatic cancer. Immunotherapy with immune checkpoint inhibition has shown effect in other solid tumors, and could have a place in pancreatic cancer treatment. Most available clinical studies on immune checkpoint inhibitors for pancreatic cancer are not yet completed and are still recruiting patients. Among the completed trials, there have been findings of a preliminary nature such as delayed disease progression and enhanced overall survival after treatment with immune checkpoint inhibitors in mono- or combination therapy. However, due to small sample sizes, major results are not yet identifiable. The present article provides a clinical overview of immune checkpoint inhibition in pancreatic cancer. Pub Med, Clinical Trials.gov and American Society of Clinical Oncology's meeting abstracts were systematically searched for relevant clinical studies. Four articles, five abstracts and 25 clinical trials were identified and analyzed in detail.
基金This work was supported by the Swedish Foundation for Strategic Research (SSF) through the INGVAR Program,the SSF Strategic Research Center in Photonics,and the Swedish Research Council (VR).
文摘Coupling between subwavelength-diameter silica wires and silicon-based waveguides is studied using the parallel three-dimensional （3D） finite-different time-domain method. Conventional butt-coupling to a silica-substrated silicon wire waveguide gives above 40% transmission at the wavelength range from 1300 to 1750 nm with good robustness against axial misalignments. Slow light can be generated by counterdirectional coupling between a silica wire and a two-dimensional （2D） silicon photonic crystal slab waveguide. Through dispersion-band engineering, 82% transmission is achieved over a coupling distance of 50 lattice constants, The group velocity is estimated as 1/35 of the light speed in vacuum.
