Inflammatory myofibroblastic tumor(IMT) is rare in clinical practice.As its treatment mainly involves surgery,radiotherapy alone is seldom reported in literature.Here we report a case of lowly malignant cranial IMT wi...Inflammatory myofibroblastic tumor(IMT) is rare in clinical practice.As its treatment mainly involves surgery,radiotherapy alone is seldom reported in literature.Here we report a case of lowly malignant cranial IMT with intracranial invasion in a female patient. As surgery was not suitable,intensity modulated radiation therapy(IMRT) was administered.After radiotherapy,the cranial lesions tended to show efficacy.展开更多
Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the devel...Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.展开更多
BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and tre...BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,and overall publication count,while Zucman-Rossi J ranked first in citation count.The five most popular journals were the World Journal of Gastroenterology,Hepatology,Journal of Hepatology,Oncotarget,and Oncogene,while Nature Genetics,Hepatology,and Nature Reviews Disease Primers had the most citations.We extracted 2293 keywords from the publications,120 of which appeared more than ten times.The most frequent were HCC,telomerase and human telomerase reverse transcriptase(hTERT).Keywords such as mutational landscape,TERT promoter mutations,landscape,risk,and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years.CONCLUSION Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.展开更多
Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation,which may be a potential strategy for cancer therapy.Here we demonstrated for the first time that Resveratrol(RSV),a t...Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation,which may be a potential strategy for cancer therapy.Here we demonstrated for the first time that Resveratrol(RSV),a traditional Chinese medicine(TCM)chemical monomer,could effectually inhibit the growth of colon cancer cells through the ROS-dependent ferroptosis pathway.Mechanistically,RSV evoked the increase of reactive oxygen species and lipid peroxidation in colorectal cancer cells,and eventually lead to ferroptosis.Furthermore,RSV could promote ferroptosis by downregulating the expression of the channel protein solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).To improve the delivery efficiency of RSV,a biomimetic nanocarrier was developed by coating RSV-loaded poly(ε-caprolactone)-poly(ethylene glycol)(PCL-PEG)nanoparticles with erythrocyte membrane(RSV-NPs@RBCm).The RSV-NPs@RBCm provide the possibility to escape macrophage phagocytosis and have a long circulation effect.In addition,when coupled with a tumor-penetrating peptide iRGD,which could trigger enhanced tissue penetration tumor-specifically,the delivery of RSV-NPs@RBCm into tumors would be significantly improved results from the in vivo study demonstrated an excellent treatment efficacy for CRC.Altogether,our study highlighted the therapeutic potential of RSV as a ferroptosis-inducing anticancer agent and when loaded into a biomimetic nanoplatform,it might pave the way for the application of RSV loaded nanosystems for colorectal cancer treatment.展开更多
Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited pa...Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020.Healthy adults from a community were recruited as healthy controls.Muscle strength was assessed using the Medical Research Council(MRC)scale.At the first visit to the hospital,patients were assessed for maximal grade of fasciculations,total fasciculation score,and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography.The sensitivity and specificity of maximal grade of fasciculations,total fasciculation score,and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses.Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9%and 9.8%,respectively(χ^(2)=172.436,P<0.01).Of the 16 limb muscles detected,the total fasciculation score[median(interquartile range)]was 29(15,41)in ALS patients and 3(0,8)in neuropathy-radiculopathy patients(Z=9.642,P<0.001).Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4,followed by patients with MRC score 5,and then in those with MRC score 0 and 1.The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6%and 93.4%,respectively(cut-off value 14).In patients with ALS,for muscles with MRC score 4 and 5,the percentage of muscles with fasciculation grades≥3 was 42.3%and 24.1%respectively,while in neuropathy-radiculopathy patients,the percentage for muscles with MRC score 4 and 5 was only 1.7%and 0,respectively.Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.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
Numerous small-molecule amines(SMAs)play critical roles in maintaining bone homeostasis and promoting bone regeneration regardless of whether they are applied as drugs or biomaterials.On the one hand,SMAs promote bone...Numerous small-molecule amines(SMAs)play critical roles in maintaining bone homeostasis and promoting bone regeneration regardless of whether they are applied as drugs or biomaterials.On the one hand,SMAs promote bone formation or inhibit bone resorption through the regulation of key molecular signaling pathways in osteoblasts/osteoclasts;on the other hand,owing to their alkaline properties as well as their antioxidant and anti-inflammatory features,most SMAs create a favorable microenvironment for bone homeostasis.However,due to a lack of information on their structure/bioactivity and underlying mechanisms of action,certain SMAs cannot be developed into drugs or biomaterials for bone disease treatment.In this review,we thoroughly summarize the current understanding of SMA effects on bone homeostasis,including descriptions of their classifications,biochemical features,recent research advances in bone biology and related regulatory mechanisms in bone regeneration.In addition,we discuss the challenges and prospects of SMA translational research.展开更多
The complexity of software system has been increasing with software evolution, which affects the stability of software structure. Most of the existing measurement methods focus on the analysis of the macro-characteris...The complexity of software system has been increasing with software evolution, which affects the stability of software structure. Most of the existing measurement methods focus on the analysis of the macro-characteristics of the network topology, but lacked a certain depth and expansion to explore the nature of the complexity of the software structure, for this purpose, the complex network control theory was applied to the study of software network controllability. Firstly, the Source-Driver (SD) model was established based on the system control theory, the driver node sets were obtained by the minimum input theorem in the control process of software network topology;Then the relationship between the degree and center degree, the relationship between the in-degree and the out-degree of the software network topology were further analyzed owing to the non-uniqueness of the driver node sets;Finally, the values of the four indicators in the software system were compared. Experimental results show that the driver node sets in the software networks are mainly composed of nodes with low degree values, but it does not mean that the nodes whose in-degree values and out-degree values are also low;The action on control nodes and driver nodes are not random, the controllability of the driver nodes is closely related to the in-degree, when selecting the driver node sets, the network topology characteristics should be considered comprehensively, and the nodes with high degree and center degree are the first choice. The results have important guiding significance for the control, maintenance and redesign of software architecture.展开更多
Multidrug resistance(MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence.Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, univ...Multidrug resistance(MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence.Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.展开更多
The problem of mobile localization for wireless sensor network has attracted considerable attention in recent years. The localization accuracy will drastically grade in non-line of sight(NLOS) conditions. In this pape...The problem of mobile localization for wireless sensor network has attracted considerable attention in recent years. The localization accuracy will drastically grade in non-line of sight(NLOS) conditions. In this paper, we propose a mobile localization strategy based on Kalman filter. The key technologies for the proposed method are the NLOS identification and mitigation. The proposed method does not need the prior knowledge of the NLOS error and it is independent of the physical measurement ways. Simulation results show that the proposed method owns the higher localization accuracy when compared with other methods.展开更多
AIM: To investigate the activation of autophagy in rat retina after optic nerve crush(ONC) and evaluate its relationship with apoptosis of retinal ganglion cells(RGCs).METHODS: The ONC model was established. Western b...AIM: To investigate the activation of autophagy in rat retina after optic nerve crush(ONC) and evaluate its relationship with apoptosis of retinal ganglion cells(RGCs).METHODS: The ONC model was established. Western blots were performed to investigate expression of p62, LC3 and Beclin-1. Transmission electron microscopy was performed to discover the autophagosomes in the retina after ONC. Immunohistochemistry was used to confirm the distribution of LC3. TUNEL was performed to confirm the relationship between autophagy and RGC apoptosis. RESULTS: p62/Beclin-1 ratio was declined shortly after ONC until to day 7 after ONC and then restored to a normal level at day 21. There was an opposite change in the LC3-II/LC3 I ratio in the retina compared to the p62/Beclin-1 ratio. Increased autophagosomes were found after ONC using transmission electron microscopy, and most of the LC3-stained cells were colocalized with RGCs and Müller cells. More LC3-immunoreactive cells and apoptotic RGCs were found on day 7 following ONC. CONCLUSION: Possible activation of autophagy in RGCs after ONC;autophagy mainly occurred in RGCs and Müller cells, and the apoptosis of RGCs after ONC may be partly associated with autophagic activation.展开更多
The relationship between the levels of renalase and changes in proteinuria, hypertension, renal function, renal tubular epithelial cell apoptosis and B-cell lymphoma-2 （Bcl-2） expression was investigated in patients...The relationship between the levels of renalase and changes in proteinuria, hypertension, renal function, renal tubular epithelial cell apoptosis and B-cell lymphoma-2 （Bcl-2） expression was investigated in patients （chronic nephritis, primary nephrotic syndrome or other kidney disease） that underwent renal biopsy. The study group comprised 72 patients undergoing renal biopsy. Patient profiles and renal function were collected. Concentrations of renalase and Bcl-2 were measured by immunohistochemistry. Tubular injury was detected by periodic acid Schiff staining （PAS） and renal tubular epithelial cell apoptosis was assessed by TUNEL assay. The expression of renalase was significantly lower in renal biopsy specimens than in normal kidney tissues. There was a positive linear relationship between renalase and some serum and cardiac indices; a negative correlation was found between age, eGFR, Ccr and 24-h urinary protein. Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with renalase. The results showed that renalase probably increased the expression of Bel-2. By two independent samples t-test, renalase levels were significantly increased in the non-hypertension group than in the hypertension group. One-way ANOVA showed that renalase expression was higher in samples with Lee＇s grade Ⅲ than in those with Lee＇s grade V. The expression of renalase was significantly decreased in patients who underwent renal biopsy, and was also associated with blood and renal function. The research proved that renalase may reduce renal tubular injury and apoptosis of renal tubular epithelial cells through the mitochondrial apoptosis pathway, finally achieving the purpose of delaying the progress of renal failure.展开更多
AIM:To investigate the role of tumor microenvironment(TME)-related long non-coding RNA(lncRNA)in uveal melanoma(UM),probable prognostic signature and potential small molecule drugs using bioinformatics analysis.METHOD...AIM:To investigate the role of tumor microenvironment(TME)-related long non-coding RNA(lncRNA)in uveal melanoma(UM),probable prognostic signature and potential small molecule drugs using bioinformatics analysis.METHODS:UM expression profile data were downloaded from the Cancer Genome Atlas(TCGA)and bioinformatics methods were used to find prognostic lncRNAs related to UM immune cell infiltration.The gene expression profile data of 80 TCGA specimens were analyzed using the single sample Gene Set Enrichment Analysis(ss GSEA)method,and the immune cell infiltration of a single specimen was evaluated.Finally,the specimens were divided into high and low infiltration groups.The differential expression between the two groups was analyzed using the R package‘edge R’.Univariate,multivariate and Least Absolute Shrinkage and Selection Operator(LASSO)Cox regression analyses were performed to explore the prognostic value of TMErelated lncRNAs.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional analyses were also performed.The Connectivity Map(CMap)data set was used to screen molecular drugs that may treat UM.RESULTS:A total of 2393 differentially expressed genes were identified and met the criteria for the low and high immune cell infiltration groups.Univariate Cox analysis of lncRNA genes with differential expression identified 186 genes associated with prognosis.Eight prognostic markers of TME-included lncRNA genes were established as potentially independent prognostic elements.Among 269 differentially expressed lncRNAs,69 were up-regulated and 200 were down-regulated.Univariate Cox regression analysis of the risk indicators and clinical characteristics of the 8 lncRNA gene constructs showed that age,TNM stage,tumor base diameter,and low and high risk indices had significant prognostic value.We screened the potential small-molecule drugs for UM,including W-13,AH-6809 and Imatinib.CONCLUSION:The prognostic markers identified in this study are reliable biomarkers of UM.This study expands our current understanding of the role of TME-related lncRNAs in UM genesis,which may lay the foundations for future treatment of this disease.展开更多
AIM: To investigate the effect of amniotic membrane transplantation (AMT) on the expressions of inflammatory-related, angiogenic-related and growth-related cytokines in rat corneas after chemical injury. METHODS: Alka...AIM: To investigate the effect of amniotic membrane transplantation (AMT) on the expressions of inflammatory-related, angiogenic-related and growth-related cytokines in rat corneas after chemical injury. METHODS: Alkali wounds were inflicted on the central corneas of rats by applying a round filter paper soaked in 1mol/L NaOH for 40 seconds. One week after alkali burn, 12 rats were randomly divided into 2 groups: the AMT group and the control group, and AMT was performed on the rats in the AMT group. Corneal opacity and neovascularization were observed by slit-lamp microscopy. The protein levels of interleukin (IL)-2, interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta were determined by enzyme-linked immunosorbent assay 2 weeks after AMT. The mRNA levels of matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were evaluated by real-time quantitative PCR. RESULTS: In the AMT group, the corneal opacity was improved (P =0.011) and the area of corneal neovascularization was significantly decreased (P=0.005) compared with the control group. The amount of IL-2 and IFN-gamma secreted by Th1 cells were decreased after AMT, whereas the amount of IL-10 and TGF-beta secreted by Th2 cells were increased ( P <0.05). The level of MMP-2 was significantly down-regulated (P=0.013) at the nnRNA level in the AMT group, while the expression of EGF was significantly higher (P= 0.022) compared with the control. CONCLUSION: AMT may suppress corneal neovascularization after chemical injury by modulating the expressions of soluble factors.展开更多
AIM:To investigate the effect of side-stream smoking on gut microflora composition,intestinal inflammation and expression of tight junction proteins.METHODS:C57BL/6 mice were exposed to side-stream cigarette smoking f...AIM:To investigate the effect of side-stream smoking on gut microflora composition,intestinal inflammation and expression of tight junction proteins.METHODS:C57BL/6 mice were exposed to side-stream cigarette smoking for one hour daily over eight weeks.Cecal contents were collected for microbial composition analysis.Large intestine was collected for immunoblotting and quantitative reverse transcriptase polymerase chain reaction analyses of the inflammatory pathway and tight junction proteins.RESULTS:Side-stream smoking induced significant changes in the gut microbiota with increased mouse intestinal bacteria,Clostridium but decreased Fermicutes(Lactoccoci and Ruminococcus),Enterobacteriaceae family and Segmented filamentous baceteria compared to the control mice.Meanwhile,side-stream smoking inhibited the nuclear factor-κB pathway with reduced phosphorylation of p65 and IκBα,accompanied with unchanged mRNA expression of tumor necrosis factor-α or interleukin-6.The contents of tight junction proteins,claudin3 and ZO2 were up-regulated in the large intestine of mice exposed side-stream smoking.In addition,side-stream smoking increased c-Jun N-terminal kinase and p38 MAPK kinase signaling,while inhibiting AMPactivated protein kinase in the large intestine.CONCLUSION:Side-stream smoking altered gut microflora composition and reduced the inflammatory response,which was associated with increased expression of tight junction proteins.展开更多
文摘Inflammatory myofibroblastic tumor(IMT) is rare in clinical practice.As its treatment mainly involves surgery,radiotherapy alone is seldom reported in literature.Here we report a case of lowly malignant cranial IMT with intracranial invasion in a female patient. As surgery was not suitable,intensity modulated radiation therapy(IMRT) was administered.After radiotherapy,the cranial lesions tended to show efficacy.
基金supported by the National Natural Science Foundation of China (81921002,81900970,82130027)Innovative Research Team of High-Level Local Universities in Shanghai (SHSMUZLCX20212400)+1 种基金Young Physician Innovation Team Project (QC202003)of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghai“Rising Stars of Medical Talent”Youth Development Program is also acknowledged。
文摘Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.
基金the Beijing Hope Run Special Fund of Cancer Foundation of China,No.LC2020L05.
文摘BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,and overall publication count,while Zucman-Rossi J ranked first in citation count.The five most popular journals were the World Journal of Gastroenterology,Hepatology,Journal of Hepatology,Oncotarget,and Oncogene,while Nature Genetics,Hepatology,and Nature Reviews Disease Primers had the most citations.We extracted 2293 keywords from the publications,120 of which appeared more than ten times.The most frequent were HCC,telomerase and human telomerase reverse transcriptase(hTERT).Keywords such as mutational landscape,TERT promoter mutations,landscape,risk,and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years.CONCLUSION Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.
基金by the National Natural Science Foundation of China(81773211,81871942,82073308,81672411)the High-level startup fund of Nanjing Medical University(KY109RC2019010)the Natural Science Foundation of Jiangsu Province(BK20201086).
文摘Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation,which may be a potential strategy for cancer therapy.Here we demonstrated for the first time that Resveratrol(RSV),a traditional Chinese medicine(TCM)chemical monomer,could effectually inhibit the growth of colon cancer cells through the ROS-dependent ferroptosis pathway.Mechanistically,RSV evoked the increase of reactive oxygen species and lipid peroxidation in colorectal cancer cells,and eventually lead to ferroptosis.Furthermore,RSV could promote ferroptosis by downregulating the expression of the channel protein solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).To improve the delivery efficiency of RSV,a biomimetic nanocarrier was developed by coating RSV-loaded poly(ε-caprolactone)-poly(ethylene glycol)(PCL-PEG)nanoparticles with erythrocyte membrane(RSV-NPs@RBCm).The RSV-NPs@RBCm provide the possibility to escape macrophage phagocytosis and have a long circulation effect.In addition,when coupled with a tumor-penetrating peptide iRGD,which could trigger enhanced tissue penetration tumor-specifically,the delivery of RSV-NPs@RBCm into tumors would be significantly improved results from the in vivo study demonstrated an excellent treatment efficacy for CRC.Altogether,our study highlighted the therapeutic potential of RSV as a ferroptosis-inducing anticancer agent and when loaded into a biomimetic nanoplatform,it might pave the way for the application of RSV loaded nanosystems for colorectal cancer treatment.
基金funded by the CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-003)National High Level Hospital Clinical Research Funding(2022-PUMCH-B-017)The Strategic Priority Research Program(Pilot study)"Biological Basis of Aging and Therapeutic Strategies"of the Chinese Academy of Sciences(grant XDB39040000).
文摘Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020.Healthy adults from a community were recruited as healthy controls.Muscle strength was assessed using the Medical Research Council(MRC)scale.At the first visit to the hospital,patients were assessed for maximal grade of fasciculations,total fasciculation score,and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography.The sensitivity and specificity of maximal grade of fasciculations,total fasciculation score,and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses.Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9%and 9.8%,respectively(χ^(2)=172.436,P<0.01).Of the 16 limb muscles detected,the total fasciculation score[median(interquartile range)]was 29(15,41)in ALS patients and 3(0,8)in neuropathy-radiculopathy patients(Z=9.642,P<0.001).Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4,followed by patients with MRC score 5,and then in those with MRC score 0 and 1.The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6%and 93.4%,respectively(cut-off value 14).In patients with ALS,for muscles with MRC score 4 and 5,the percentage of muscles with fasciculation grades≥3 was 42.3%and 24.1%respectively,while in neuropathy-radiculopathy patients,the percentage for muscles with MRC score 4 and 5 was only 1.7%and 0,respectively.Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.
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.
基金the support for this work from the National Natural Science Foundation of China [Grant Nos.32122046,32000959,82030067,and 82161160342]the National Key R&D Program [Grant No.2018YFA0703100]+3 种基金the Youth Innovation Promotion Association of CAS [Grant No.2019350]the Guangdong Natural Science Foundation [Grant No.2020A1515111190]the Shenzhen Fundamental Research Foundation [Grant Nos.JCYJ20190812162809131,JCYJ20200109114006014,JCYJ20210324113001005,JCYJ20210324115814040,and JSGGKQTD20210831174330015]the Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties [Grant No.SZGSP001]。
文摘Numerous small-molecule amines(SMAs)play critical roles in maintaining bone homeostasis and promoting bone regeneration regardless of whether they are applied as drugs or biomaterials.On the one hand,SMAs promote bone formation or inhibit bone resorption through the regulation of key molecular signaling pathways in osteoblasts/osteoclasts;on the other hand,owing to their alkaline properties as well as their antioxidant and anti-inflammatory features,most SMAs create a favorable microenvironment for bone homeostasis.However,due to a lack of information on their structure/bioactivity and underlying mechanisms of action,certain SMAs cannot be developed into drugs or biomaterials for bone disease treatment.In this review,we thoroughly summarize the current understanding of SMA effects on bone homeostasis,including descriptions of their classifications,biochemical features,recent research advances in bone biology and related regulatory mechanisms in bone regeneration.In addition,we discuss the challenges and prospects of SMA translational research.
文摘The complexity of software system has been increasing with software evolution, which affects the stability of software structure. Most of the existing measurement methods focus on the analysis of the macro-characteristics of the network topology, but lacked a certain depth and expansion to explore the nature of the complexity of the software structure, for this purpose, the complex network control theory was applied to the study of software network controllability. Firstly, the Source-Driver (SD) model was established based on the system control theory, the driver node sets were obtained by the minimum input theorem in the control process of software network topology;Then the relationship between the degree and center degree, the relationship between the in-degree and the out-degree of the software network topology were further analyzed owing to the non-uniqueness of the driver node sets;Finally, the values of the four indicators in the software system were compared. Experimental results show that the driver node sets in the software networks are mainly composed of nodes with low degree values, but it does not mean that the nodes whose in-degree values and out-degree values are also low;The action on control nodes and driver nodes are not random, the controllability of the driver nodes is closely related to the in-degree, when selecting the driver node sets, the network topology characteristics should be considered comprehensively, and the nodes with high degree and center degree are the first choice. The results have important guiding significance for the control, maintenance and redesign of software architecture.
基金supported by the Science and Technology Program of China (2012ZX09103101-053)the Natural Science Foundation of Guangdong Province (52013050014183 and 2013CXZDA006)+1 种基金the Program for New Century Excellent Talents in University (D.M.Zhang)the project was supported by Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (D. M. Zhang)
文摘Multidrug resistance(MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence.Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.
基金supported by the National Natural Science Foundation of China under Grant No. 61403068, No. 61232016, No. U1405254 and No. 61501100Fundamental Research Funds for the Central Universities of China under Grant No. N130323002 and No. N130323004+3 种基金Natural Science Foundation of Hebei Province under Grant No. F2015501097 and No. F2016501080Scientific Research Fund of Hebei Provincial Education Department under Grant No. Z2014078the PAPD fundNEUQ internal funding under Grant No. XNB201509 and XNB201510
文摘The problem of mobile localization for wireless sensor network has attracted considerable attention in recent years. The localization accuracy will drastically grade in non-line of sight(NLOS) conditions. In this paper, we propose a mobile localization strategy based on Kalman filter. The key technologies for the proposed method are the NLOS identification and mitigation. The proposed method does not need the prior knowledge of the NLOS error and it is independent of the physical measurement ways. Simulation results show that the proposed method owns the higher localization accuracy when compared with other methods.
基金Supported by Science and Technology Project of Nantong,China(No.MS22015002)
文摘AIM: To investigate the activation of autophagy in rat retina after optic nerve crush(ONC) and evaluate its relationship with apoptosis of retinal ganglion cells(RGCs).METHODS: The ONC model was established. Western blots were performed to investigate expression of p62, LC3 and Beclin-1. Transmission electron microscopy was performed to discover the autophagosomes in the retina after ONC. Immunohistochemistry was used to confirm the distribution of LC3. TUNEL was performed to confirm the relationship between autophagy and RGC apoptosis. RESULTS: p62/Beclin-1 ratio was declined shortly after ONC until to day 7 after ONC and then restored to a normal level at day 21. There was an opposite change in the LC3-II/LC3 I ratio in the retina compared to the p62/Beclin-1 ratio. Increased autophagosomes were found after ONC using transmission electron microscopy, and most of the LC3-stained cells were colocalized with RGCs and Müller cells. More LC3-immunoreactive cells and apoptotic RGCs were found on day 7 following ONC. CONCLUSION: Possible activation of autophagy in RGCs after ONC;autophagy mainly occurred in RGCs and Müller cells, and the apoptosis of RGCs after ONC may be partly associated with autophagic activation.
文摘The relationship between the levels of renalase and changes in proteinuria, hypertension, renal function, renal tubular epithelial cell apoptosis and B-cell lymphoma-2 （Bcl-2） expression was investigated in patients （chronic nephritis, primary nephrotic syndrome or other kidney disease） that underwent renal biopsy. The study group comprised 72 patients undergoing renal biopsy. Patient profiles and renal function were collected. Concentrations of renalase and Bcl-2 were measured by immunohistochemistry. Tubular injury was detected by periodic acid Schiff staining （PAS） and renal tubular epithelial cell apoptosis was assessed by TUNEL assay. The expression of renalase was significantly lower in renal biopsy specimens than in normal kidney tissues. There was a positive linear relationship between renalase and some serum and cardiac indices; a negative correlation was found between age, eGFR, Ccr and 24-h urinary protein. Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with renalase. The results showed that renalase probably increased the expression of Bel-2. By two independent samples t-test, renalase levels were significantly increased in the non-hypertension group than in the hypertension group. One-way ANOVA showed that renalase expression was higher in samples with Lee＇s grade Ⅲ than in those with Lee＇s grade V. The expression of renalase was significantly decreased in patients who underwent renal biopsy, and was also associated with blood and renal function. The research proved that renalase may reduce renal tubular injury and apoptosis of renal tubular epithelial cells through the mitochondrial apoptosis pathway, finally achieving the purpose of delaying the progress of renal failure.
基金Supported by Shanghai Key Laboratory of Fundus Diseases,2017(No.01030)Luzhou Southwest Medical University,Municipal Department Level(No.2017LZXNYD-J01)。
文摘AIM:To investigate the role of tumor microenvironment(TME)-related long non-coding RNA(lncRNA)in uveal melanoma(UM),probable prognostic signature and potential small molecule drugs using bioinformatics analysis.METHODS:UM expression profile data were downloaded from the Cancer Genome Atlas(TCGA)and bioinformatics methods were used to find prognostic lncRNAs related to UM immune cell infiltration.The gene expression profile data of 80 TCGA specimens were analyzed using the single sample Gene Set Enrichment Analysis(ss GSEA)method,and the immune cell infiltration of a single specimen was evaluated.Finally,the specimens were divided into high and low infiltration groups.The differential expression between the two groups was analyzed using the R package‘edge R’.Univariate,multivariate and Least Absolute Shrinkage and Selection Operator(LASSO)Cox regression analyses were performed to explore the prognostic value of TMErelated lncRNAs.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional analyses were also performed.The Connectivity Map(CMap)data set was used to screen molecular drugs that may treat UM.RESULTS:A total of 2393 differentially expressed genes were identified and met the criteria for the low and high immune cell infiltration groups.Univariate Cox analysis of lncRNA genes with differential expression identified 186 genes associated with prognosis.Eight prognostic markers of TME-included lncRNA genes were established as potentially independent prognostic elements.Among 269 differentially expressed lncRNAs,69 were up-regulated and 200 were down-regulated.Univariate Cox regression analysis of the risk indicators and clinical characteristics of the 8 lncRNA gene constructs showed that age,TNM stage,tumor base diameter,and low and high risk indices had significant prognostic value.We screened the potential small-molecule drugs for UM,including W-13,AH-6809 and Imatinib.CONCLUSION:The prognostic markers identified in this study are reliable biomarkers of UM.This study expands our current understanding of the role of TME-related lncRNAs in UM genesis,which may lay the foundations for future treatment of this disease.
基金Science and Technology Project for Social Development of Nantong, China (No. S2009029)
文摘AIM: To investigate the effect of amniotic membrane transplantation (AMT) on the expressions of inflammatory-related, angiogenic-related and growth-related cytokines in rat corneas after chemical injury. METHODS: Alkali wounds were inflicted on the central corneas of rats by applying a round filter paper soaked in 1mol/L NaOH for 40 seconds. One week after alkali burn, 12 rats were randomly divided into 2 groups: the AMT group and the control group, and AMT was performed on the rats in the AMT group. Corneal opacity and neovascularization were observed by slit-lamp microscopy. The protein levels of interleukin (IL)-2, interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta were determined by enzyme-linked immunosorbent assay 2 weeks after AMT. The mRNA levels of matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were evaluated by real-time quantitative PCR. RESULTS: In the AMT group, the corneal opacity was improved (P =0.011) and the area of corneal neovascularization was significantly decreased (P=0.005) compared with the control group. The amount of IL-2 and IFN-gamma secreted by Th1 cells were decreased after AMT, whereas the amount of IL-10 and TGF-beta secreted by Th2 cells were increased ( P <0.05). The level of MMP-2 was significantly down-regulated (P=0.013) at the nnRNA level in the AMT group, while the expression of EGF was significantly higher (P= 0.022) compared with the control. CONCLUSION: AMT may suppress corneal neovascularization after chemical injury by modulating the expressions of soluble factors.
基金Supported by INBRE P20RR016474USDA-NRI 200835203-19084USDA-AFRI 2009-65203-05716
文摘AIM:To investigate the effect of side-stream smoking on gut microflora composition,intestinal inflammation and expression of tight junction proteins.METHODS:C57BL/6 mice were exposed to side-stream cigarette smoking for one hour daily over eight weeks.Cecal contents were collected for microbial composition analysis.Large intestine was collected for immunoblotting and quantitative reverse transcriptase polymerase chain reaction analyses of the inflammatory pathway and tight junction proteins.RESULTS:Side-stream smoking induced significant changes in the gut microbiota with increased mouse intestinal bacteria,Clostridium but decreased Fermicutes(Lactoccoci and Ruminococcus),Enterobacteriaceae family and Segmented filamentous baceteria compared to the control mice.Meanwhile,side-stream smoking inhibited the nuclear factor-κB pathway with reduced phosphorylation of p65 and IκBα,accompanied with unchanged mRNA expression of tumor necrosis factor-α or interleukin-6.The contents of tight junction proteins,claudin3 and ZO2 were up-regulated in the large intestine of mice exposed side-stream smoking.In addition,side-stream smoking increased c-Jun N-terminal kinase and p38 MAPK kinase signaling,while inhibiting AMPactivated protein kinase in the large intestine.CONCLUSION:Side-stream smoking altered gut microflora composition and reduced the inflammatory response,which was associated with increased expression of tight junction proteins.
