BACKGROUND Liver cirrhosis patients admitted to intensive care unit(ICU)have a high mortality rate.AIM To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis.MET...BACKGROUND Liver cirrhosis patients admitted to intensive care unit(ICU)have a high mortality rate.AIM To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis.METHODS We extracted demographic,etiological,vital sign,laboratory test,comorbidity,complication,treatment,and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV(MIMIC-IV)and electronic ICU(eICU)collaborative research database(eICU-CRD).Predictor selection and model building were based on the MIMIC-IV dataset.The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors.The final predictors were included in the multivariate logistic regression model,which was used to construct a nomogram.Finally,we conducted external validation using the eICU-CRD.The area under the receiver operating characteristic curve(AUC),decision curve,and calibration curve were used to assess the efficacy of the models.RESULTS Risk factors,including the mean respiratory rate,mean systolic blood pressure,mean heart rate,white blood cells,international normalized ratio,total bilirubin,age,invasive ventilation,vasopressor use,maximum stage of acute kidney injury,and sequential organ failure assessment score,were included in the multivariate logistic regression.The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases,respectively.The calibration curve also confirmed the predictive ability of the model,while the decision curve confirmed its clinical value.CONCLUSION The nomogram has high accuracy in predicting in-hospital mortality.Improving the included predictors may help improve the prognosis of patients.展开更多
Background:In vivo experiments were conducted to examine the effects of the targeted drug anlotinib on the stemness of hepatocellular carcinoma(HCC)cells and lenvatinib-resistant liver cancer cells and to explore the ...Background:In vivo experiments were conducted to examine the effects of the targeted drug anlotinib on the stemness of hepatocellular carcinoma(HCC)cells and lenvatinib-resistant liver cancer cells and to explore the underlying molecular mechanisms.Methods:A subcutaneous xenograft model of Hep3B-derived HCC was established in nude mice,which were randomly divided into 2 groups(n=5 males per group):(1)intragastric administration of anlotinib(0.4 mg/kg)and(2)intragastric administration of normal saline.We constructed lenvatinib-resistant cell lines and randomly divided the mice into 3 groups(n=5 males per group):(1)intragastric administration of anlotinib,(2)intragastric administration of lenvatinib,and(3)intragastric administration of normal saline.After 2 weeks of treatment,tumor tissues were harvested,and mRNA and proteins were isolated from the tissues.Changes in the expression of cancer stemness markers(epithelial cell adhesion molecule[EpCAM],CD13,CD90,aldehyde dehydrogenase 1[ALDH1],CD44,and CD45),totipotency factors(sex-determining region Y-box 2[Sox2],Nanog,octamer-binding transcription factor 4[Oct4]),and genes related to the Notch signaling pathway were examined.Results:Compared with that in the control group,tumor size and weight were reduced in nude mice treated with anlotinib.These differences were statistically significant in both the types of nude mice.Anlotinib affected stemness markers and totipotency factors by downregulating the expression of CD133,CD90,and G-protein–coupled receptor 5(LGR5)and upregulating the expression of intercellular adhesion molecule 1(ICAM-1)and Sox2.In addition,lenvatinib-resistant cell lines increased Notch signaling pathway,whereas anlotinib inhibited Notch signaling pathway.Conclusions:The antitumor effect of anlotinib on HCC and lenvatinib-resistant HCC cellsmay occur through inhibition of the Notch signaling pathway.Anlotinib may be the drug of choice for sequential therapy in lenvatinib-resistant liver cancer.展开更多
BACKGROUND Mucinous adenocarcinoma(MC)has attracted much attention as a distinct histologic subtype of colorectal cancer in recent years.However,data about its epidemiologic and prognostic characteristics are limited....BACKGROUND Mucinous adenocarcinoma(MC)has attracted much attention as a distinct histologic subtype of colorectal cancer in recent years.However,data about its epidemiologic and prognostic characteristics are limited.Therefore,patient data extracted from the National Cancer Institute’s Surveillance,Epidemiology,and End Results Program were collected to analyze the epidemiologic and clinicopathological characteristics of MC.AIM To determine the epidemiologic and clinicopathological characteristics of MC.METHODS The incidence trend of MC was calculated through the Joinpoint Regression Program.Cox regression analyses were performed to identify prognostic factors associated with overall survival(OS).A nomogram was established to predict the survival probability of individual patients with MC.RESULTS We found that rates of MC decreased from 4.50/100000 in 2000 to 1.54/100000 in 2018.Rates of MCs in patients aged≤50 years decreased 2.27%/year during 2000-2018.The incidence of appendiceal MCs increased from 0.14/100000 in 2000 to 0.24/100000 in 2018,while the incidence in other anatomic subsites continued to decrease.On multivariable Cox analyses,age,race,tumor site,T stage,N stage,M stage,surgery,and chemotherapy were associated with OS.A nomogram was developed based on these factors,and the area under the curve for 1-year,3-year,and 5-year OS in the training cohort was 0.778,0.778,and 0.768,respectively.CONCLUSION Our results demonstrated that MC incidence decreased in almost all anatomic subgroups except for the appendix.A nomogram predicting the survival probability of patients with MCs showed good performance.展开更多
Objective Xiaoaiping (XAP) is a traditional Chinese medicine that is a commonly used as an anticancerdrug in clinical practice owing to its high efficiency and low toxicity. Specifically, XAP can effectively inhibitth...Objective Xiaoaiping (XAP) is a traditional Chinese medicine that is a commonly used as an anticancerdrug in clinical practice owing to its high efficiency and low toxicity. Specifically, XAP can effectively inhibitthe growth of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is a key HCC diagnostic marker andis closely related to certain malignant cytological behaviors of HCC. However, whether AFP expression andXAP treatment are related to the invasion and metastasis of HCC remains unclear. In the present study, weaimed to evaluate the effects and underlying mechanism of XAP on the invasion and metastasis of HCC..Methods Using a cell scratch assay, Transwell technology, and western blotting we detected the differentinvasion and metastatic abilities of Hep3B cells in XAP treatment and blank control groups. This allowedcomparison of the invasion and metastatic abilities of Hep3B cells with differing levels of AFP expression.AFP mRNA sequencing technology was used to analyze the mechanism of tumor invasion and metastasisassociated with AFP and XAP treatment.Results Cell invasion and metastasis abilities in the XAP group were significantly lower than those in thecontrol group (P < 0.05). Additionally, compared to the control group, the expression of AFP significantlydecreased after XAP treatment (P < 0.05). The ability of Hep3B cells to invade and metastasize waspromoted when AFP expression was up-regulated, whereas it was inhibited when AFP was silenced. XAPinjection and AFP regulate the invasion and metastatic ability of HCC by affecting matrix metalloproteinases(MMPs).Conclusion XAP injection inhibits the invasion and metastatic ability of HCC by influencing the expressionof AFP;additionally, this inhibition of AFP is achieved by affecting MMPs.展开更多
BACKGROUND Liver cirrhosis is the leading cause of liver-related mortality worldwide. It is currently a global health challenge.AIM This research intended to explore and analyse research trends and frontiers in this f...BACKGROUND Liver cirrhosis is the leading cause of liver-related mortality worldwide. It is currently a global health challenge.AIM This research intended to explore and analyse research trends and frontiers in this field during the last 10 years, providing new inspiration for clinical decisionmaking and scientific research.METHODS Publications on hepatic cirrhosis research were retrieved from the Web of Science Core Collection on April 4, 2021. Bibliometric visualisation was conducted through VOSviewer and CiteSpace.RESULTS The analytic research was based on original articles and reviews. A total of 7775records of hepatic cirrhosis published from 2011 to 2020 were retrieved. In the past ten years, the number of related annual publications has increased significantly, especially in the United States and China. All publications were distributed among 109 countries. The United States contributed the most(21.95%)and was consistently the leading driving force, with a solid academic reputation in this area. The University of Barcelona distributed the most related articles(177articles) and was cited the most frequently. The Journal of Hepatology ranked third in the top 10journals, which has the highest impact factor(impact factor 2019 = 20.582). Jasmohan S. Bajaj was the most productive author(72 articles). Burst keywords(e.g., sofosbuvir, burden, care, sarcopenia,chronic liver failure, human gut microbiome, and nonalcoholic fatty liver disease) and a succession of reference citation bursts have provided clues about research frontiers in recent years.CONCLUSION This study identified developing trends in the evolution of liver cirrhosis to provide new inspiration for researchers.展开更多
A large-span steel–concrete composite beam with precast hollow core slabs(CBHCSs)is a relatively new floor structure that can be applied to various long-span structures.However,human-induced vibrations may present se...A large-span steel–concrete composite beam with precast hollow core slabs(CBHCSs)is a relatively new floor structure that can be applied to various long-span structures.However,human-induced vibrations may present serviceability issues in such structures.To alleviate vibrations,both the walking forces excited by humans and the associated floor responses must be elucidated.In this study,150 load–time histories of walking,excited by 25 test participants,are obtained using a force measuring plate.The dynamic loading factors and phase angles in the Fourier series functions for one-step walking are determined.Subsequently,walking tests are performed on seven CBHCS specimens to capture the essential dynamic properties of mode shapes,natural frequencies,damping ratios,and acceleration time histories.The CBHCS floor system generally exhibits a high frequency(>10 Hz)and low damping(damping ratio<2%).Sensitivity studies using the finite element method are conducted to investigate the vibration performance of the CBHCS floor system,where the floor thickness,steel beam type,contact time,and human weight are considered.Finally,analytical expressions derived for the fundamental frequency and peak acceleration agree well with the experimental results and are hence proposed for practical use.展开更多
Objective The objective of this study was to investigate the inhibitory effects of sorafenib and regorafenib on the growth of hepatocellular carcinoma(HCC)using a subcutaneous transplantation tumor model in nude mice ...Objective The objective of this study was to investigate the inhibitory effects of sorafenib and regorafenib on the growth of hepatocellular carcinoma(HCC)using a subcutaneous transplantation tumor model in nude mice and exploring the effects of sorafenib and regorafenib on the expression of hypoxia-inducible factor(HIF)-1α,HIF-2α,and HIF-1βin HCC tissues collected from HCC-transplanted nude mice.Methods HepG2 cells were inoculated intradermally into nude mice.The mice were randomly assigned to either sorafenib treatment(100 mg/kg),regorafenib treatment(20 mg/kg),or solvent control group(dimethylsulfoxide)(n=8 per group)and received once-daily treatment for 14 days.The tumor volumes were recorded every 3 days after the initiation of treatment.The expression levels of HIF-1α,HIF-1β,HIF-2α,and SART1 in the HCC tissues were examined via quantitative real-time PCR(qRT-PCR)analysis and Western blotting.Results The tumors in the sorafenib and regorafenib treatment groups grew slower and smaller than did the tumors in the solvent control group.qPCR analysis and western blotting demonstrated that the mRNA and protein expressions of HIF-1αand HIF-1βwere down-regulated.The expression of HIF-2αand SART1 was up-regulated in the sorafenib treatment group(P<0.05);meanwhile,the expression of HIF-1αand HIF-1βwas up-regulated,and that of HIF-2αand SART1 was down-regulated in the regorafenib treatment group(P<0.05).Conclusion The expression of hypoxia-associated factor is up-regulated by sorafenib and down-regulated by regorafenib,which may induce the different effects of sorafenib on the expression of HIFs.展开更多
Sepsis is the leading cause of death in intensive care unit(ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive care, whi...Sepsis is the leading cause of death in intensive care unit(ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive care, while there still lacks of specific molecular therapy. As a type of immune dysfunction disease,macrophages have been recognized as the key immune cells precipitating in the whole process of sepsis,which is activated into M1-like to trigger various inflammatory responses at early stage whereas polarized into M2-like to cause immunosuppression in later stage. Therefore, great attention has been paid on the design of nanomedicines to regulate the functions of macrophages for etiological treatment of sepsis, by virtue of the unique advantages of nano-drug delivery systems, such as enhanced drug bioavailability, targetability, reduced side-effects. This critical review aims to summarize the recent progress of macrophages-regulating nanoparticles for sepsis therapy. First, the essential roles of macrophages in the development and progression of sepsis have been introduced, including the positive roles of macrophages to combat infections and dysfunction of macrophages to cause body damages. We then focus our main attention to discuss the nanomedicines with different therapeutic mechanisms corresponding to each stage of sepsis, such as infection blockage, inflammation inhibition, immune functions recovery, as well as multifunctional nanomedicines. Finally, a few limitations of current nanomedicines are highlighted,and future perspective are speculated for potential clinical translation, which might pave the way for the development of macrophages-centered nanomedicines for more effective sepsis therapy.展开更多
Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse form...Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse formation and function.The evolutionarily conserved retromer complex and its associated GTPase-activating protein TBC1D5 are critical regulators of membrane trafficking and cellular signaling.However,their functions in regulating the formation of NMJ are less understood.Here,we report that TBC1D5 is required for inhibition of synaptic growth,and loss of TBC1D5 leads to abnormal presynaptic terminal development,including excessive satellite boutons and branch formation.Ultrastructure analysis reveals that the size of synaptic vesicles and the density of subsynaptic reticulum are increased in TBC1D5mutant boutons.Disruption of interactions of TBC1D5 with Rab7 and retromer phenocopies the loss of TBC1D5.Unexpectedly,we find that TBC1D5 is functionally linked to Rab6,in addition to Rab7,to regulate synaptic growth.Mechanistically,we show that loss of TBC1D5 leads to upregulated BMP signaling by increasing the protein level of BMP type Ⅱ receptor Wishful Thinking(Wit)at NMJ.Overall,our data establish that TBC1D5 in coordination with retromer constrains synaptic growth by regulating Rab7 activity,which negatively regulates BMP signaling through inhibiting Wit level.展开更多
Chinese mitten crab(Eriocheir sinensis) is an important aquaculture species in Crustacea.Functional analysis, although essential, has been hindered due to the lack of sufficient genomic or transcriptomic resources. In...Chinese mitten crab(Eriocheir sinensis) is an important aquaculture species in Crustacea.Functional analysis, although essential, has been hindered due to the lack of sufficient genomic or transcriptomic resources. In this study, transcriptome sequencing was conducted on 59 samples representing diverse developmental stages(fertilized eggs, zoea, megalopa, three sub-stages of larvae,juvenile crabs, and adult crabs) and different tissues(eyestalk, hepatopancreas, and muscle from juvenile crabs, and eyestalk, hepatopancreas, muscle, heart, stomach, gill, thoracic ganglia, intestine, ovary, and testis from adult crabs) of E. sinensis. A comprehensive reference transcriptome was assembled, including 19,023 protein-coding genes. Hierarchical clustering based on 128 differentially expressed cuticle-related genes revealed two distinct expression patterns during the early larval developmental stages, demonstrating the distinct roles of these genes in "crab-like" cuticle formation during metamorphosis and cuticle calcification after molting. Phylogenetic analysis of1406 one-to-one orthologous gene families identified from seven arthropod species and Caenorhabditis elegans strongly supported the hypothesis that Malacostraca and Branchiopoda do not form a monophyletic group. Furthermore, Branchiopoda is more phylogenetically closely related to Hexapoda, and the clade of Hexapoda and Branchiopoda and the clade of Malacostraca belong to the Pancrustacea. This study offers a high-quality transcriptome resource for E. sinensis and demonstrates the evolutionary relationships of major arthropod groups. The differentially expressed genes identified in this study facilitate further investigation of the cuticle-related gene expression networks which are likely associated with "crab-like" cuticle formation during metamorphosis and cuticle calcification after molting.展开更多
The assembly of neurons into complex circuits relies upon appropriate axonal navigation to distant targets.Although considerable progress has been made toward understanding the regulation of the guidance and branching...The assembly of neurons into complex circuits relies upon appropriate axonal navigation to distant targets.Although considerable progress has been made toward understanding the regulation of the guidance and branching of axon extension,the molecular and cellular mechanisms underlying the coordination of the motility of the axon tip,axon growth,and branching remain largely unknown(Sudhof,2017).The Drosophila mushroom body(MB),the major site for associative learning and memory,is a powerful model system to investigate complex axon behaviors.The MB is a bilaterally symmetric central brain structure,mainly composed of Kenyon cells,MB output neurons,and dopaminergic neurons(Li et al.,2020).Among the seven neuronal subtypes of~2000 Kenyon cells,Y,a/β,and a/β'subtypes extend axons in a fascicle and bifurcate to produce two sister branches,one projecting into the dorsal lobe and the other into the medial lobe.展开更多
基金Supported by Natural Science Foundation of Sichuan Province,No.2022NSFSC1378.
文摘BACKGROUND Liver cirrhosis patients admitted to intensive care unit(ICU)have a high mortality rate.AIM To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis.METHODS We extracted demographic,etiological,vital sign,laboratory test,comorbidity,complication,treatment,and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV(MIMIC-IV)and electronic ICU(eICU)collaborative research database(eICU-CRD).Predictor selection and model building were based on the MIMIC-IV dataset.The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors.The final predictors were included in the multivariate logistic regression model,which was used to construct a nomogram.Finally,we conducted external validation using the eICU-CRD.The area under the receiver operating characteristic curve(AUC),decision curve,and calibration curve were used to assess the efficacy of the models.RESULTS Risk factors,including the mean respiratory rate,mean systolic blood pressure,mean heart rate,white blood cells,international normalized ratio,total bilirubin,age,invasive ventilation,vasopressor use,maximum stage of acute kidney injury,and sequential organ failure assessment score,were included in the multivariate logistic regression.The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases,respectively.The calibration curve also confirmed the predictive ability of the model,while the decision curve confirmed its clinical value.CONCLUSION The nomogram has high accuracy in predicting in-hospital mortality.Improving the included predictors may help improve the prognosis of patients.
基金supported by the Natural Science Foundation of the Hubei Province(no.2023 AFB894)Open for the Key Laboratory of Biological Targeted Therapy in 2021(no.2021swbx019).
文摘Background:In vivo experiments were conducted to examine the effects of the targeted drug anlotinib on the stemness of hepatocellular carcinoma(HCC)cells and lenvatinib-resistant liver cancer cells and to explore the underlying molecular mechanisms.Methods:A subcutaneous xenograft model of Hep3B-derived HCC was established in nude mice,which were randomly divided into 2 groups(n=5 males per group):(1)intragastric administration of anlotinib(0.4 mg/kg)and(2)intragastric administration of normal saline.We constructed lenvatinib-resistant cell lines and randomly divided the mice into 3 groups(n=5 males per group):(1)intragastric administration of anlotinib,(2)intragastric administration of lenvatinib,and(3)intragastric administration of normal saline.After 2 weeks of treatment,tumor tissues were harvested,and mRNA and proteins were isolated from the tissues.Changes in the expression of cancer stemness markers(epithelial cell adhesion molecule[EpCAM],CD13,CD90,aldehyde dehydrogenase 1[ALDH1],CD44,and CD45),totipotency factors(sex-determining region Y-box 2[Sox2],Nanog,octamer-binding transcription factor 4[Oct4]),and genes related to the Notch signaling pathway were examined.Results:Compared with that in the control group,tumor size and weight were reduced in nude mice treated with anlotinib.These differences were statistically significant in both the types of nude mice.Anlotinib affected stemness markers and totipotency factors by downregulating the expression of CD133,CD90,and G-protein–coupled receptor 5(LGR5)and upregulating the expression of intercellular adhesion molecule 1(ICAM-1)and Sox2.In addition,lenvatinib-resistant cell lines increased Notch signaling pathway,whereas anlotinib inhibited Notch signaling pathway.Conclusions:The antitumor effect of anlotinib on HCC and lenvatinib-resistant HCC cellsmay occur through inhibition of the Notch signaling pathway.Anlotinib may be the drug of choice for sequential therapy in lenvatinib-resistant liver cancer.
基金Supported by Science&Technology Department of Sichuan Province,No.2021JDTD0003Scientific Research Cooperation Project of Suining First People’s Hospital and the Affiliated Hospital of Southwest Medical University,No.2021SNXNYD05.
文摘BACKGROUND Mucinous adenocarcinoma(MC)has attracted much attention as a distinct histologic subtype of colorectal cancer in recent years.However,data about its epidemiologic and prognostic characteristics are limited.Therefore,patient data extracted from the National Cancer Institute’s Surveillance,Epidemiology,and End Results Program were collected to analyze the epidemiologic and clinicopathological characteristics of MC.AIM To determine the epidemiologic and clinicopathological characteristics of MC.METHODS The incidence trend of MC was calculated through the Joinpoint Regression Program.Cox regression analyses were performed to identify prognostic factors associated with overall survival(OS).A nomogram was established to predict the survival probability of individual patients with MC.RESULTS We found that rates of MC decreased from 4.50/100000 in 2000 to 1.54/100000 in 2018.Rates of MCs in patients aged≤50 years decreased 2.27%/year during 2000-2018.The incidence of appendiceal MCs increased from 0.14/100000 in 2000 to 0.24/100000 in 2018,while the incidence in other anatomic subsites continued to decrease.On multivariable Cox analyses,age,race,tumor site,T stage,N stage,M stage,surgery,and chemotherapy were associated with OS.A nomogram was developed based on these factors,and the area under the curve for 1-year,3-year,and 5-year OS in the training cohort was 0.778,0.778,and 0.768,respectively.CONCLUSION Our results demonstrated that MC incidence decreased in almost all anatomic subgroups except for the appendix.A nomogram predicting the survival probability of patients with MCs showed good performance.
文摘Objective Xiaoaiping (XAP) is a traditional Chinese medicine that is a commonly used as an anticancerdrug in clinical practice owing to its high efficiency and low toxicity. Specifically, XAP can effectively inhibitthe growth of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is a key HCC diagnostic marker andis closely related to certain malignant cytological behaviors of HCC. However, whether AFP expression andXAP treatment are related to the invasion and metastasis of HCC remains unclear. In the present study, weaimed to evaluate the effects and underlying mechanism of XAP on the invasion and metastasis of HCC..Methods Using a cell scratch assay, Transwell technology, and western blotting we detected the differentinvasion and metastatic abilities of Hep3B cells in XAP treatment and blank control groups. This allowedcomparison of the invasion and metastatic abilities of Hep3B cells with differing levels of AFP expression.AFP mRNA sequencing technology was used to analyze the mechanism of tumor invasion and metastasisassociated with AFP and XAP treatment.Results Cell invasion and metastasis abilities in the XAP group were significantly lower than those in thecontrol group (P < 0.05). Additionally, compared to the control group, the expression of AFP significantlydecreased after XAP treatment (P < 0.05). The ability of Hep3B cells to invade and metastasize waspromoted when AFP expression was up-regulated, whereas it was inhibited when AFP was silenced. XAPinjection and AFP regulate the invasion and metastatic ability of HCC by affecting matrix metalloproteinases(MMPs).Conclusion XAP injection inhibits the invasion and metastatic ability of HCC by influencing the expressionof AFP;additionally, this inhibition of AFP is achieved by affecting MMPs.
文摘BACKGROUND Liver cirrhosis is the leading cause of liver-related mortality worldwide. It is currently a global health challenge.AIM This research intended to explore and analyse research trends and frontiers in this field during the last 10 years, providing new inspiration for clinical decisionmaking and scientific research.METHODS Publications on hepatic cirrhosis research were retrieved from the Web of Science Core Collection on April 4, 2021. Bibliometric visualisation was conducted through VOSviewer and CiteSpace.RESULTS The analytic research was based on original articles and reviews. A total of 7775records of hepatic cirrhosis published from 2011 to 2020 were retrieved. In the past ten years, the number of related annual publications has increased significantly, especially in the United States and China. All publications were distributed among 109 countries. The United States contributed the most(21.95%)and was consistently the leading driving force, with a solid academic reputation in this area. The University of Barcelona distributed the most related articles(177articles) and was cited the most frequently. The Journal of Hepatology ranked third in the top 10journals, which has the highest impact factor(impact factor 2019 = 20.582). Jasmohan S. Bajaj was the most productive author(72 articles). Burst keywords(e.g., sofosbuvir, burden, care, sarcopenia,chronic liver failure, human gut microbiome, and nonalcoholic fatty liver disease) and a succession of reference citation bursts have provided clues about research frontiers in recent years.CONCLUSION This study identified developing trends in the evolution of liver cirrhosis to provide new inspiration for researchers.
基金The authors acknowledge the financial support provided by the National Natural Science Foundation of China(51890902 and 51708058).
文摘A large-span steel–concrete composite beam with precast hollow core slabs(CBHCSs)is a relatively new floor structure that can be applied to various long-span structures.However,human-induced vibrations may present serviceability issues in such structures.To alleviate vibrations,both the walking forces excited by humans and the associated floor responses must be elucidated.In this study,150 load–time histories of walking,excited by 25 test participants,are obtained using a force measuring plate.The dynamic loading factors and phase angles in the Fourier series functions for one-step walking are determined.Subsequently,walking tests are performed on seven CBHCS specimens to capture the essential dynamic properties of mode shapes,natural frequencies,damping ratios,and acceleration time histories.The CBHCS floor system generally exhibits a high frequency(>10 Hz)and low damping(damping ratio<2%).Sensitivity studies using the finite element method are conducted to investigate the vibration performance of the CBHCS floor system,where the floor thickness,steel beam type,contact time,and human weight are considered.Finally,analytical expressions derived for the fundamental frequency and peak acceleration agree well with the experimental results and are hence proposed for practical use.
文摘Objective The objective of this study was to investigate the inhibitory effects of sorafenib and regorafenib on the growth of hepatocellular carcinoma(HCC)using a subcutaneous transplantation tumor model in nude mice and exploring the effects of sorafenib and regorafenib on the expression of hypoxia-inducible factor(HIF)-1α,HIF-2α,and HIF-1βin HCC tissues collected from HCC-transplanted nude mice.Methods HepG2 cells were inoculated intradermally into nude mice.The mice were randomly assigned to either sorafenib treatment(100 mg/kg),regorafenib treatment(20 mg/kg),or solvent control group(dimethylsulfoxide)(n=8 per group)and received once-daily treatment for 14 days.The tumor volumes were recorded every 3 days after the initiation of treatment.The expression levels of HIF-1α,HIF-1β,HIF-2α,and SART1 in the HCC tissues were examined via quantitative real-time PCR(qRT-PCR)analysis and Western blotting.Results The tumors in the sorafenib and regorafenib treatment groups grew slower and smaller than did the tumors in the solvent control group.qPCR analysis and western blotting demonstrated that the mRNA and protein expressions of HIF-1αand HIF-1βwere down-regulated.The expression of HIF-2αand SART1 was up-regulated in the sorafenib treatment group(P<0.05);meanwhile,the expression of HIF-1αand HIF-1βwas up-regulated,and that of HIF-2αand SART1 was down-regulated in the regorafenib treatment group(P<0.05).Conclusion The expression of hypoxia-associated factor is up-regulated by sorafenib and down-regulated by regorafenib,which may induce the different effects of sorafenib on the expression of HIFs.
基金supported by National Natural Science Foundation of China(Nos.U1903125,82073799)Natural Science Foundation of Hunan Province in China(Nos.2021JJ20084,2021JJ70016)the Science and Technology Innovation Program of Hunan Province(No.2021RC3020)。
文摘Sepsis is the leading cause of death in intensive care unit(ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive care, while there still lacks of specific molecular therapy. As a type of immune dysfunction disease,macrophages have been recognized as the key immune cells precipitating in the whole process of sepsis,which is activated into M1-like to trigger various inflammatory responses at early stage whereas polarized into M2-like to cause immunosuppression in later stage. Therefore, great attention has been paid on the design of nanomedicines to regulate the functions of macrophages for etiological treatment of sepsis, by virtue of the unique advantages of nano-drug delivery systems, such as enhanced drug bioavailability, targetability, reduced side-effects. This critical review aims to summarize the recent progress of macrophages-regulating nanoparticles for sepsis therapy. First, the essential roles of macrophages in the development and progression of sepsis have been introduced, including the positive roles of macrophages to combat infections and dysfunction of macrophages to cause body damages. We then focus our main attention to discuss the nanomedicines with different therapeutic mechanisms corresponding to each stage of sepsis, such as infection blockage, inflammation inhibition, immune functions recovery, as well as multifunctional nanomedicines. Finally, a few limitations of current nanomedicines are highlighted,and future perspective are speculated for potential clinical translation, which might pave the way for the development of macrophages-centered nanomedicines for more effective sepsis therapy.
基金supported by research grants from the National Natural Science Foundation of China(31671510 and 31871461 to H.H.31771592 to W.X.)。
文摘Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse formation and function.The evolutionarily conserved retromer complex and its associated GTPase-activating protein TBC1D5 are critical regulators of membrane trafficking and cellular signaling.However,their functions in regulating the formation of NMJ are less understood.Here,we report that TBC1D5 is required for inhibition of synaptic growth,and loss of TBC1D5 leads to abnormal presynaptic terminal development,including excessive satellite boutons and branch formation.Ultrastructure analysis reveals that the size of synaptic vesicles and the density of subsynaptic reticulum are increased in TBC1D5mutant boutons.Disruption of interactions of TBC1D5 with Rab7 and retromer phenocopies the loss of TBC1D5.Unexpectedly,we find that TBC1D5 is functionally linked to Rab6,in addition to Rab7,to regulate synaptic growth.Mechanistically,we show that loss of TBC1D5 leads to upregulated BMP signaling by increasing the protein level of BMP type Ⅱ receptor Wishful Thinking(Wit)at NMJ.Overall,our data establish that TBC1D5 in coordination with retromer constrains synaptic growth by regulating Rab7 activity,which negatively regulates BMP signaling through inhibiting Wit level.
基金This work was supported by the National Program on Key Basic Research Project of China （973 Program 2015CB964902）, the National Natural Science Foundation of China （NSFC H81170466 and H81370597）, and the CAMS Initiatives for Innovative Medicine （2016-12M-1-018） awarded to F.M.
基金supported by the Shanghai Agriculture Applied Technology Development Program,China(Grant No.G2017-02-08-00-10-F00076)the Agriculture Research System of Shanghai,China(Grant No.201704)+3 种基金the Leading Agricultural Talents in Shanghai Project,China(Grant No.D-8004-16-0217)the Shanghai Science and Technology Committee Programs,China(Grant Nos.16391905300 and 13DZ2251800)the Young teachers training Project of Shanghai Municipal Education Commission,China(Grant No.A1-2039-17-0011)the Doctoral Program of Shanghai Ocean University,China(Grant No.A2-0203-00-100315)
文摘Chinese mitten crab(Eriocheir sinensis) is an important aquaculture species in Crustacea.Functional analysis, although essential, has been hindered due to the lack of sufficient genomic or transcriptomic resources. In this study, transcriptome sequencing was conducted on 59 samples representing diverse developmental stages(fertilized eggs, zoea, megalopa, three sub-stages of larvae,juvenile crabs, and adult crabs) and different tissues(eyestalk, hepatopancreas, and muscle from juvenile crabs, and eyestalk, hepatopancreas, muscle, heart, stomach, gill, thoracic ganglia, intestine, ovary, and testis from adult crabs) of E. sinensis. A comprehensive reference transcriptome was assembled, including 19,023 protein-coding genes. Hierarchical clustering based on 128 differentially expressed cuticle-related genes revealed two distinct expression patterns during the early larval developmental stages, demonstrating the distinct roles of these genes in "crab-like" cuticle formation during metamorphosis and cuticle calcification after molting. Phylogenetic analysis of1406 one-to-one orthologous gene families identified from seven arthropod species and Caenorhabditis elegans strongly supported the hypothesis that Malacostraca and Branchiopoda do not form a monophyletic group. Furthermore, Branchiopoda is more phylogenetically closely related to Hexapoda, and the clade of Hexapoda and Branchiopoda and the clade of Malacostraca belong to the Pancrustacea. This study offers a high-quality transcriptome resource for E. sinensis and demonstrates the evolutionary relationships of major arthropod groups. The differentially expressed genes identified in this study facilitate further investigation of the cuticle-related gene expression networks which are likely associated with "crab-like" cuticle formation during metamorphosis and cuticle calcification after molting.
基金supported by research grants from the National Natural Science Foundation of China(31871461 and 31671510 to H.H.).
文摘The assembly of neurons into complex circuits relies upon appropriate axonal navigation to distant targets.Although considerable progress has been made toward understanding the regulation of the guidance and branching of axon extension,the molecular and cellular mechanisms underlying the coordination of the motility of the axon tip,axon growth,and branching remain largely unknown(Sudhof,2017).The Drosophila mushroom body(MB),the major site for associative learning and memory,is a powerful model system to investigate complex axon behaviors.The MB is a bilaterally symmetric central brain structure,mainly composed of Kenyon cells,MB output neurons,and dopaminergic neurons(Li et al.,2020).Among the seven neuronal subtypes of~2000 Kenyon cells,Y,a/β,and a/β'subtypes extend axons in a fascicle and bifurcate to produce two sister branches,one projecting into the dorsal lobe and the other into the medial lobe.
