Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residin...Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residing in tumor tissues are commonly known as tumor-associated macrophages(TAMs)and promote or inhibit tumor growth depending on the activation state2.展开更多
For various sexually mature insects,including the brown planthopper(BPH,Nilaparvata lugens),the abdominal vibration(AV)signal is the initiation of the mating process,and itiscritical to the successofmating.Currently,t...For various sexually mature insects,including the brown planthopper(BPH,Nilaparvata lugens),the abdominal vibration(AV)signal is the initiation of the mating process,and itiscritical to the successofmating.Currently,there are few studies on the genetic and molecular mechanisms of AV regulation.Ourprevious AV-related transcriptomic study in female BPH identified myoinhibitory peptide(NlMIP)as a gene that potentially affects AV statusinfemales,buthow NlMIP affects AV status remains unknown.In this study,we confirmed that NlMIP regulates AV production and mating behavior in female BPH.When the RNAi knockdown efficiency of NlMIP was 59.00%,the probability of females producing AV and the mating rate in 1 h decreased by 38.89 and 61.11%,respectively.In addition,six mature peptides of NlMIP were synthesized and they were able to regulate AV production and mating behavior in females,with NlMIP2having the strongest effect.The A-family neuropeptide GPCR 10(NlA10)was found to be a potential receptor for NlMIP based on a phylogenetic tree analysis and the fact that NlMIP mature peptides effectively activated NlA10.After NlA10was knocked down,the probability of females producing AV and the mating rate in 1 h had reductions of 28.89 and 43.33%,respectively.When activated by NlMIP2,NlA10 coupled the Gαi/q signalling pathways,thereby inhibiting the downstream AC/cAMP/PKA,activating the PLC/Ca^(2+)/PKC signalling pathways and then activating MEK1/2 in a cascade to mediate the phosphorylation of ERK1/2,and finally regulating the AV of females.These results provide a basis for the prevention and control of the brown planthopper pest by disrupting female AV.展开更多
AIM:To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy(DR)or retinal vein occlusion(RVO).METHODS:Th...AIM:To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy(DR)or retinal vein occlusion(RVO).METHODS:This is a retrospective case control study.The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor(VEGF)for patients diagnosed with macular edema secondary to DR(DME)or RVO(RVO-ME)at Xijing Hospital from August 2021 to July 2022.Meanwhile,aqueous humor samples during vitrectomy from patients with idiopathic macular hole(IMH)were also collected and served as controls.The aqueous humor concentrations of VEGF,platelet-derived factor(PDGF),interleukin(IL)-6,IL-8,IL-18,tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP-1)were measured with Human Premixed Multi-Analyte Kit(Luminex).The difference of the aqueous cytokines and the correlation between the two diseases were analyzed.RESULTS:A total of 40 eyes of 38 patients were enrolled in the study,including 13 eyes of 11 DME patients(DME group),16 eyes of 16 RVO-ME patients(RVO-ME group)and 11 eyes of 11 IMH patients(control group).The VEGF,PDGF,IL-6,IL-8,and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group(all P<0.05),the levels of TNF-αwas higher in the DME group than in the control group(P<0.05).The VEGF,IL-6,MCP-1,and TNF-αlevels in the aqueous humor were significantly higher in the DR group than those in the RVO group(all P<0.05).Correlation analyses revealed that there were complex positive correlations between IL-6,IL-8,IL-18,MCP-1,and TNF-αlevels in the aqueous humor of eyes with two diseases.CONCLUSION:Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME,the roles of these factors are more significant or more likely to be activated in DR patients,suggesting different treatment strategies should be considered for the two diseases.展开更多
BACKGROUND The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma(HCC)is a common clinical concern.AIM To analyse the prognostic factors of overall survival(OS)in patients with unre...BACKGROUND The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma(HCC)is a common clinical concern.AIM To analyse the prognostic factors of overall survival(OS)in patients with unresectable HCC who received conversion therapy.METHODS One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort(n=120)and a validation cohort(n=30).Using the independent risk factors in the training cohort,a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection.The nomogram was internally validated with the bootstrapping method.The predictive performance of nomogram was assessed by Harrell’s concordance index(C-index),calibration plot and timedependent receiver operating characteristic curves and compared with six other conventional HCC staging systems.RESULTS Multivariate Cox analysis identified that albumin,blood urea nitrogen,gamma-glutamyl transpeptidase to platelet ratio,platelet to lymphocyte ratio,macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model.The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS,which were higher than those of the six conventional HCC staging systems(0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort).The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS.Decision curve analyses indicated satisfactory clinical utility.With a total nomogram score of 196,patients were accurately classified into low-risk and high-risk groups.Furthermore,we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/.CONCLUSION The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy,which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.展开更多
Introduction:The difficulty in treating lung adenocarcinoma(LUAD)is caused by a shortage of knowledge about the biological mechanisms and a lack of treatment choices.Objectives:The aim of this study was to identify a ...Introduction:The difficulty in treating lung adenocarcinoma(LUAD)is caused by a shortage of knowledge about the biological mechanisms and a lack of treatment choices.Objectives:The aim of this study was to identify a valuable molecular target for the treatment of LUAD.Methods:Using multiple databases,we screened for hub genes in LUAD using Cytoscape and explored the expression and prognosis of DLG associated protein 5(DLGAP5)in LUAD.We investigated the genetic variation,functional enrichment,and epigenetic activity of DLGAP5.Furthermore,we evaluated the relationship between the tumor microenvironment(TME)and DLGAP5.Results:Our study identified 10 hub genes in LUAD:CDC45,KIAA0101,DLGAP5,CDT1,NCAPG,CCNB1,CDCA5,CDC20,KIF11,and AURKA.We discovered that DLGAP5 was overexpressed and associated with poor prognosis in LUAD.DLGAP5 exhibited an overall genetic variation frequency of 2%,and its DNA promoter was hypomethylated in LUAD(p<0.05).The expression of DLGAP5 in LUAD showed a positive correlation with the majority of N6-methyladenosine(m6A)-methylation genes.Additionally,DLGAP5 was primarily associated with the cell cycle in LUAD.Notably,there was a significant favorable association between DLGAP5 and CD274,CTLA4,HAVCR2,and LAG3 in LUAD.Conclusion:DLGAP5 may be a therapeutic target for LUAD,as it affects cancer cells proliferation and development through the regulation of cell-cycle checkpoints and modulation of immune cell infiltration and immune checkpoints in the TME.展开更多
AIM:To assess the efficacy versus the adverse effects of various concentrations of atropine in the prevention of myopia in Asian children.METHODS:Databases(PubMed,EMBASE,the Cochrane Library and Web of science)were co...AIM:To assess the efficacy versus the adverse effects of various concentrations of atropine in the prevention of myopia in Asian children.METHODS:Databases(PubMed,EMBASE,the Cochrane Library and Web of science)were comprehensively searched from inception to April 2022.Types of studies included were randomized clinical trials(RCTs).The published languages were limited to English.Two researchers assessed the quality of included studies independently using Cochrane risk of bias tool based on the Cochrane Handbook for Systematic Reviews of Interventions.Funnel plots and Egger’s test were used for detection of publication bias.Meta-analyses were conducted using STATA(version 15.0;StataCorp).RESULTS:A total of 15 RCTs involving 2268 patients were included in the study.In the atropine group,spherical equivalent progressed at a significantly lower rate[weighted mean difference(WMD)=0.39,95%confidence interval(CI):0.23,0.54]than in the control group.A WMD of 0.15 mm was associated with less axial elongation(95%CI-0.19,-0.10).Different doses showed statistically significant differences(P<0.05)and an improved effect could result from a higher concentration.Changes in photopic pupil size and mesopic pupil size in atropine group is 0.70 mm(95%CI:0.33,1.06)and 0.38 mm(95%CI:0.22,0.54)more than the control group.In the present Meta-analysis,no changes in accommodative amplitude(AA)were associated with atropine administration.Atropine administration increased the risk of adverse effects by 1.37 times.CONCLUSION:Concentrations of less than 1%atropine are able to effectively retard diopter and axis growth of myopia in Asian children in a dose-dependent manner.Meanwhile,it caused pupil enlargement,but induced no change in the AA within this range.Further study is required to determine the dosage needed to achieve maximum efficacy and minimal side effects.展开更多
Peripheral nerve injury not only affects the site of the injury, but can also induce neuronal apoptosis at the spinal cord. However, many acupuncture clinicians still focus only on the injury site, selecting acupoints...Peripheral nerve injury not only affects the site of the injury, but can also induce neuronal apoptosis at the spinal cord. However, many acupuncture clinicians still focus only on the injury site, selecting acupoints entirely along the injured nerve trunk and neglecting other regions; this may delay onset of treatment efficacy and rehabilitation. Therefore, in the present study, we compared the clinical efficacy of acupuncture at Governor vessel and local meridian acupoints combined(GV/LM group) with acupuncture at local meridian acupoints alone(LM group) in the treatment of patients with peripheral nerve injury. In the GV/LM group(n = 15), in addition to meridian acupoints at the injury site, the following acupoints on the Governor vessel were stimulated: Baihui(GV20), Fengfu(GV16), Dazhui(GV14), and Shenzhu(GV12), selected to treat nerve injury of the upper limb, and Jizhong(GV6), Mingmen(GV4), Yaoyangguan(GV3), and Yaoshu(GV2) to treat nerve injury of the lower limb. In the LM group(n = 15), only meridian acupoints along the injured nerve were selected. Both groups had electroacupuncture treatment for 30 minutes, once a day, 5 times per week, for 6 weeks. Two cases dropped out of the LM group. A good or excellent clinical response was obtained in 80% of the patients in the GV/LM group and 38.5% of the LM group. In a second study, an additional 20 patients underwent acupuncture with the same prescription as the GV/LM group. Electomyographic nerve conduction tests were performed before and after acupuncture to explore the mechanism of action of the treatment. An effective response was observed in 80.0% of the patients, with greater motor nerve conduction velocity and amplitude after treatment, indicating that electroacupuncture on specific Governor vessel acupoints promotes functional motor nerve repair after peripheral nerve injury. In addition, electromyography was performed before, during and after electroacupuncture in one patient with radial nerve injury. After a single session, the patient's motor nerve conduction velocity increased by 23.2%, indicating that electroacupuncture at Governor vessel acupoints has an immediate therapeutic effect on peripheral nerve injury. Our results indicate that Governor vessel and local meridian acupoints used simultaneously promote functional repair after peripheral nerve injury. The mechanism of action may arise from an improvement of the local microenvironment in injured nervous tissue, as well as immediate effects of Governor vessel and local meridian acupoint stimulation to ensure the continuity between the peripheral and central nervous systems.展开更多
Objective To investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer’s disease (AD...Objective To investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer’s disease (AD). Methods Male Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin (1.5 mg/kg) on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde (MDA), glutathione reductase (GR) and reduced glutathione (GSH) levels in hippocampus and histopathology of hippocampal neurons. Results The MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract (3.0 g/kg). Conclusion R. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.展开更多
Impaired amyloid-β clearance from the brain is a core pathological event in Alzheimer's disease.The therapeutic effect of current pharmacotherapies is unsatisfactory,and some treatments cause severe side effects....Impaired amyloid-β clearance from the brain is a core pathological event in Alzheimer's disease.The therapeutic effect of current pharmacotherapies is unsatisfactory,and some treatments cause severe side effects.The meningeal lymphatic vessels might be a new route for amyloid-β clearance.This study investigated whether promoting dural lymphangiogenesis facilitated the clearance of amyloid-β from the brain.First,human lymphatic endothelial cells were treated with 100 ng/m L recombinant human vascular endothelial growth factor-C(rh VEGF-C) protein.Light microscopy verified that rh VEGF-C,a specific ligand for vascular endothelial growth factor receptor-3(VEGFR-3),significantly promoted tube formation of human lymphatic endothelial cells in vitro.In an in vivo study,200 μg/m L rh VEGF-C was injected into the cisterna magna of APP/PS1 transgenic mice,once every 2 days,four times in total.Immunofluorescence staining demonstrated high levels of dural lymphangiogenesis in Alzheimer's disease mice.One week after rh VEGF-C administration,enzyme-linked immunosorbent assay results showed that levels of soluble amyloid-β were decreased in cerebrospinal fluid and brain.The Morris water maze test demonstrated that spatial cognition was restored.These results indicate that the upregulation of dural lymphangiogenesis facilities amyloid-β clearance from the brain of APP/PS1 mice,suggesting the potential of the VEGF-C/VEGFR-3 signaling pathway as a therapeutic target for Alzheimer's disease.展开更多
Niclosamide,an oral antihelminthic drug,has been used to treat tapeworm infection for about 50 years.Niclosamide is also used as a molluscicide for water treatment in schistosomiasis control programs.Recently,several ...Niclosamide,an oral antihelminthic drug,has been used to treat tapeworm infection for about 50 years.Niclosamide is also used as a molluscicide for water treatment in schistosomiasis control programs.Recently,several groups have independently discovered that niclosamide is also active against cancer cells,but its precise mechanism of antitumor action is not fully understood.Evidence supports that niclosamide targets multiple signaling pathways (NF-κB,Wnt/β-catenin,Notch,ROS,mTORC1,and Stat3),most of which are closely involved with cancer stem cells.The exciting advances in elucidating the antitumor activity and the molecular targets of this drug will be discussed.A method for synthesizing a phosphate pro-drug of niclosamide is provided.Given its potential antitumor activity,clinical trials for niclosamide and its derivatives are warranted for cancer treatment.展开更多
Non-invasive tracing in vivo can be used to observe the migration and distribution of grafted stem cells,and can provide experimental evidence for treatment.This study utilized adenovirus-carrying enhanced green fluor...Non-invasive tracing in vivo can be used to observe the migration and distribution of grafted stem cells,and can provide experimental evidence for treatment.This study utilized adenovirus-carrying enhanced green fluorescent protein(AD5/F35-eGFP) and superparamagnetic iron oxide(SPIO)-labeled bone marrow mesenchymal stem cells(BMSCs).BMSCs,double-labeled by AD5/F35-eGFP and SPIO,were transplanted into rats with spinal cord injury via the subarachnoid space.MRI tracing results demonstrated that BMSCs migrated to the injured spinal cord over time(T2 hypointensity signals).This result was verified by immunofluorescence.These results indicate that MRI can be utilized to trace in vivo the SPIO-labeled BMSCs after grafting.展开更多
Introduction:Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer.This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the T...Introduction:Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer.This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma(NPC).Methods:A total of 2,626 patients with NPC were retrospectively analyzed.Platelet count >300 × 10~9/L was defined as thrombocytosis.Matched-pair analysis was performed between patients receiving chemoradiotherapy and radiotherapy.Results:Multivariate analysis showed that platelet count was an independent unfavorable prognostic factor for overall survival(OS)[hazard ratio(HR) = 1.810,95%confidence interval(CI) = 1.531-2.140,P < 0.001]and distant metastasis-free survival(DMFS)(HR = 1.873,95%CI = 1.475-2.379,P < 0.001) in the entire patient cohort.Further subgroup analysis revealed that increased platelet count was an independent unfavorable prognostic factor for OS and DMFS in patients with NPC stratified by early and advanced T category,N category,or TNM classification(all P < 0.001).Receiver operating characteristic(ROC) curves verified that the predictive value of TNM classification for OS was improved when combined with pretreatment platelet count(P = 0.030).Matched-pair analysis showed that chemoradiotherapy significantly improved OS only in advanced-stage NPC with thrombocytosis(HR = 0.416,95%CI = 0.226-0.765,P = 0.005).Conclusions:Pretreatment platelet count,when combined with TNM classification,is a useful indicator for metastasis and survival in patients with NPC.It may improve the predictive value of the TNM classification and help to identify patients likely to benefit from more aggressive therapeutic regimens.展开更多
AIM:To explore the association between AT-rich interactive domain 1A(ARID1A)protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer.METHODS:We r...AIM:To explore the association between AT-rich interactive domain 1A(ARID1A)protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer.METHODS:We retrospectively collected clinicopathologic data and archived paraffin-embedded primary colorectal cancer samples from 209 patients,including 111patients with colon cancer and 98 patients with rectal cancer.The tumor stage ranged from stageⅠto stageⅣaccording to the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis(TNM)staging system.All patients underwent resection of primary colorectal tumors.The expression of ARID1A protein in primary colorectal cancer tissues was examined by immunohistochemical staining.The clinicopathologic association and survival relevance of ARID1A protein loss in colorectal cancer were analyzed.RESULTS:ARID1A loss by immunohistochemistry was not rare in primary colorectal cancer tumors(25.8%).There were 7.4%,24.1%,22.2%and 46.3%of patients with ARID1A loss staged at TNM stageⅠ,Ⅱ,ⅢandⅣ,respectively,compared with 20.0%,22.6%,27.7%and 29.7%of patients without ARID1A loss staged at TNM stageⅠ,Ⅱ,ⅢandⅣ,respectively.In patients with ARID1A loss,the distant metastasis rate was 46.3%.However,only 29.7%of patients without ARID1A loss were found to have distant metastasis.In terms of pathologic differentiation,there were 25.9%,66.7%and 7.4%with poorly,moderately and well differentiated tumors in patients with ARID1A loss,and 14.2%,72.3%and 13.5%with poorly,moderately and well differentiated tumors in patients without ARID1A loss,respectively.ARID1A loss was associated with late TNM stage(P=0.020),distant metastasis(P=0.026),and poor pathological classification(P=0.035).However,patients with positive ARID1A had worse overall survival compared to those with negative ARID1A in stageⅣcolorectal cancer(HR=2.49,95%CI:1.13-5.51).CONCLUSION:ARID1A protein loss is associated with clinicopathologic characteristics in colorectal cancer patients and with survival in stageⅣpatients.展开更多
In our previous study, we found that the edible alcohol extract of the root of the medicinal plant Rhodiola crenulata(RCE) improved spatial cognition in a rat model of Alzheimer's disease. Another study from our l...In our previous study, we found that the edible alcohol extract of the root of the medicinal plant Rhodiola crenulata(RCE) improved spatial cognition in a rat model of Alzheimer's disease. Another study from our laboratory showed that RCE enhanced neural cell proliferation in the dentate gyrus of the hippocampus and prevented damage to hippocampal neurons in a rat model of chronic stress-induced depression. However, the mechanisms underlying the neuroprotective effects of RCE are unclear. In the present study, we investigated the anti-apoptotic effect of RCE and its neuroprotective mechanism of action in a rat model of Alzheimer's disease established by intracerebroventricular injection of streptozotocin. The rats were pre-administered RCE at doses of 1.5, 3.0 or 6.0 g/kg for 21 days before model establishment. ATP and cytochrome c oxidase levels were significantly decreased in rats with Alzheimer's disease. Furthermore, neuronal injury was obvious in the hippocampus, with the presence of a large number of apoptotic neurons. In comparison, in rats given RCE pretreatment, ATP and cytochrome c oxidase levels were markedly increased, the number of apoptotic neurons was reduced, and mitochondrial injury was mitigated. The 3.0 g/kg dose of RCE had the optimal effect. These findings suggest that pretreatment with RCE prevents mitochondrial dysfunction and protects hippocampal neurons from apoptosis in rats with Alzheimer's disease.展开更多
Nestin+ neurons have been shown to express choline acetyltransferase(ChAT) in the medial septum-diagonal band of Broca in adult rats. This study explored the projection of nestin+ neurons to the olfactory bulb and the...Nestin+ neurons have been shown to express choline acetyltransferase(ChAT) in the medial septum-diagonal band of Broca in adult rats. This study explored the projection of nestin+ neurons to the olfactory bulb and the time course of nestin+ neurons in the medial septum-diagonal band of Broca in adult rats during injury recovery after olfactory nerve transection. This study observed that all nestin+ neurons were double-labeled with ChAT in the medial septum-diagonal band of Broca. Approximately 53.6% of nestin+ neurons were projected to the olfactory bulb and co-labeled with fast blue. A large number of nestin+ neurons were not present in each region of the medial septum-diagonal band of Broca. Nestin+ neurons in the medial septum and vertical limb of the diagonal band of Broca showed obvious compensatory function. The number of nestin+ neurons decreased to a minimum later than nestin–/ChAT+ neurons in the medial septum-diagonal band of Broca. The results suggest that nestin+ cholinergic neurons may have a closer connection to olfactory bulb neurons. Nestin+ cholinergic neurons may have a stronger tolerance to injury than Nestin–/ChAT+ neurons. The difference between nestin+ and nestin–/ ChAT+ neurons during the recovery process requires further investigations.展开更多
Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularize...Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites.However,it has not been reported whether this material promotes axonal regeneration in vivo.In the present study,a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells.This functional scaffold promoted the directional growth and remyelination of regenerating axons.In vitro,the porcine decellularized optic nerve contained many straight,longitudinal channels with a uniform distribution,and microscopic pores were present in the channel wall.The spatial micro topological structure and extracellular matrix were conducive to the adhesion,survival and migration of neural stem cells.The scaffold promoted the directional growth of dorsal root ganglion neurites,and showed strong potential for myelin regeneration.Furthermore,we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo.Four weeks later,the regenerating axons grew straight,the myelin sheath in the injured/transplanted area recovered its structure,and simultaneously,the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced.Together,these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration.All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University(approval No.SYSU-IACUC-2019-B034)on February 28,2019.展开更多
In the present study we injected colchicine into the lateral ventricle of Sprague-Dawley rats to investigate the effects of colchicine on the number of different-type neurons in the basal forebrain and to search for n...In the present study we injected colchicine into the lateral ventricle of Sprague-Dawley rats to investigate the effects of colchicine on the number of different-type neurons in the basal forebrain and to search for neurons resistant to injury.After colchicine injection,the number of nestin+ cholinergic neurons was decreased at 1 day,but increased at 3 days and peaked at 14-28 days.The quantity of nestin-cholinergic neurons,parvalbumin-positive neurons and choline acetyl transferase-positive neurons decreased gradually.Our results indicate that nestin+ cholinergic neurons possess better tolerance to colchicine-induced neurotoxicity.展开更多
Electroencephalogram signals are time-varying complex electrophysiological signals. Existing studies show that approximate entropy, which is a nonlinear dynamics index, is not an ideal method for electroencephalogram ...Electroencephalogram signals are time-varying complex electrophysiological signals. Existing studies show that approximate entropy, which is a nonlinear dynamics index, is not an ideal method for electroencephalogram analysis. Clinical electroencephalogram measurements usually contain electrical interference signals, creating additional challenges in terms of maintaining robustness of the analytic methods. There is an urgent need for a novel method of nonlinear dynamical analysis of the electroencephalogram that can characterize seizure-related changes in cerebral dynamics. The aim of this paper was to study the fluctuations of approximate entropy in preictal, ictal, and postictal electroencephalogram signals from a patient with absence seizures, and to improve the algorithm used to calculate the approximate entropy. The approximate entropy algorithm, especially our modified version, could accurately describe the dynamical changes of the brain during absence seizures. We could also demonstrate that the complexity of the brain was greater in the normal state than in the ictal state. The fluctuations of the approximate entropy before epileptic seizures observed in this study can form a good basis for further study on the prediction of seizures with nonlinear dynamics.展开更多
BACKGROUND Acute pancreatitis(AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome(SIRS) with high morbidity and mortality, but no approved therapies are currently a...BACKGROUND Acute pancreatitis(AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome(SIRS) with high morbidity and mortality, but no approved therapies are currently available. P-selectin glycoprotein ligand 1(PSGL-1) is a transmembrane glycoprotein to initiate inflammatory responses. We hypothesized that PSGL-1 may be involved in the development of AP and would be a new target for the treatment of AP.AIM To investigate the role and mechanism of PSGL-1 in the development of AP.METHODS The PSGL-1 expression on leukocytes was detected in peripheral blood of AP patients and volunteers. Pancreatic injury, inflammatory cytokines expression, and inflammatory cell infiltration was measured in AP mouse models induced with PSGL-1 knockout(PSGL-1-/-) and wild-type(PSGL-1+/+) mice. Leukocyteendothelial cell adhesion was measured in a peripheral blood mononuclear cell(PBMC)-endothelial cell coculture system.RESULTS The expression of PSGL-1 on monocytes and neutrophils was significantly increased in AP patients. Compared with PSGL-1+/+ mice, PSGL-1-/-AP mice induced by caerulein exhibited lower serum amylase, less Interleukin-1 beta(IL-1 beta) and Interleukin-6(IL-6) expression, less neutrophil and macrophage infiltration, and reduced peripheral neutrophil and monocyte accounts. PSGL-1 deficiency alleviated leukocyte-endothelial cell adhesion via IL-6 but not IL-1 beta.CONCLUSION PSGL-1 deficiency effectively inhibits the development of AP by preventing leukocyte-endothelial cell adhesion via IL-6 stimulation and may become a potential therapeutic target for treating AP.展开更多
AIM: To investigate the anti-apoptotic capability of the hepatitis B virus(HBV) in the HepG2 hepatoma cell line and the underlying mechanisms.METHODS: Cell viability and apoptosis were measured by MTT assay and flow c...AIM: To investigate the anti-apoptotic capability of the hepatitis B virus(HBV) in the HepG2 hepatoma cell line and the underlying mechanisms.METHODS: Cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. Targeted knockdown of manganese superoxide dismutase(Mn SOD), AMP-activated protein kinase(AMPK) and hepatitis B virus X protein(HBx) genes as well as AMPK agonist AICAR and antagonist compound C were employed to determine the correlations of expression of these genes.RESULTS: HBV markedly protected the hepatoma cells from growth suppression and cell death in the condition of serum deprivation. A decrease of superoxide anion production accompanied with an increase of Mn SOD expression and activity was found in Hep G2.215 cells. Moreover, AMPK activation contributed to the up-regulation of Mn SOD. HBx protein was identified to induce the expression of AMPK and Mn SOD. CONCLUSION: Our results suggest that HBV suppresses mitochondrial superoxide level and exerts an antiapoptotic effect by activating AMPK/Mn SOD signaling pathway, which may provide a novel pharmacological strategy to prevent HCC.展开更多
基金the National Key R&D Program of China(Grant Nos.2020YFA0509400 and 2019YFA0110300 to JC)the National Natural Science Foundation of China(Grant Nos.82150117 and 82071745 to JC and 31900570 to GJ)+2 种基金the Nanshan Scholarship of Guangzhou Medical University start-up fund(to GJ)the Science and Technology Program of Guangzhou(Grant No.202002030069 to JC)the Guangdong Project(Grant No.2019QN01Y212 to JC)。
文摘Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residing in tumor tissues are commonly known as tumor-associated macrophages(TAMs)and promote or inhibit tumor growth depending on the activation state2.
基金funded by the National Natural Science Foundation of China(31730073)。
文摘For various sexually mature insects,including the brown planthopper(BPH,Nilaparvata lugens),the abdominal vibration(AV)signal is the initiation of the mating process,and itiscritical to the successofmating.Currently,there are few studies on the genetic and molecular mechanisms of AV regulation.Ourprevious AV-related transcriptomic study in female BPH identified myoinhibitory peptide(NlMIP)as a gene that potentially affects AV statusinfemales,buthow NlMIP affects AV status remains unknown.In this study,we confirmed that NlMIP regulates AV production and mating behavior in female BPH.When the RNAi knockdown efficiency of NlMIP was 59.00%,the probability of females producing AV and the mating rate in 1 h decreased by 38.89 and 61.11%,respectively.In addition,six mature peptides of NlMIP were synthesized and they were able to regulate AV production and mating behavior in females,with NlMIP2having the strongest effect.The A-family neuropeptide GPCR 10(NlA10)was found to be a potential receptor for NlMIP based on a phylogenetic tree analysis and the fact that NlMIP mature peptides effectively activated NlA10.After NlA10was knocked down,the probability of females producing AV and the mating rate in 1 h had reductions of 28.89 and 43.33%,respectively.When activated by NlMIP2,NlA10 coupled the Gαi/q signalling pathways,thereby inhibiting the downstream AC/cAMP/PKA,activating the PLC/Ca^(2+)/PKC signalling pathways and then activating MEK1/2 in a cascade to mediate the phosphorylation of ERK1/2,and finally regulating the AV of females.These results provide a basis for the prevention and control of the brown planthopper pest by disrupting female AV.
基金Supported by National Natural Science Foundation of China(No.81470654)Natural Science Foundation of Shaanxi Province(No.2019SF-047)。
文摘AIM:To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy(DR)or retinal vein occlusion(RVO).METHODS:This is a retrospective case control study.The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor(VEGF)for patients diagnosed with macular edema secondary to DR(DME)or RVO(RVO-ME)at Xijing Hospital from August 2021 to July 2022.Meanwhile,aqueous humor samples during vitrectomy from patients with idiopathic macular hole(IMH)were also collected and served as controls.The aqueous humor concentrations of VEGF,platelet-derived factor(PDGF),interleukin(IL)-6,IL-8,IL-18,tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP-1)were measured with Human Premixed Multi-Analyte Kit(Luminex).The difference of the aqueous cytokines and the correlation between the two diseases were analyzed.RESULTS:A total of 40 eyes of 38 patients were enrolled in the study,including 13 eyes of 11 DME patients(DME group),16 eyes of 16 RVO-ME patients(RVO-ME group)and 11 eyes of 11 IMH patients(control group).The VEGF,PDGF,IL-6,IL-8,and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group(all P<0.05),the levels of TNF-αwas higher in the DME group than in the control group(P<0.05).The VEGF,IL-6,MCP-1,and TNF-αlevels in the aqueous humor were significantly higher in the DR group than those in the RVO group(all P<0.05).Correlation analyses revealed that there were complex positive correlations between IL-6,IL-8,IL-18,MCP-1,and TNF-αlevels in the aqueous humor of eyes with two diseases.CONCLUSION:Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME,the roles of these factors are more significant or more likely to be activated in DR patients,suggesting different treatment strategies should be considered for the two diseases.
基金Supported by the National Natural Science Foundation of China,No.82072035Science and Guangzhou Planned Project of Science and Technology,No.202102010028.
文摘BACKGROUND The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma(HCC)is a common clinical concern.AIM To analyse the prognostic factors of overall survival(OS)in patients with unresectable HCC who received conversion therapy.METHODS One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort(n=120)and a validation cohort(n=30).Using the independent risk factors in the training cohort,a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection.The nomogram was internally validated with the bootstrapping method.The predictive performance of nomogram was assessed by Harrell’s concordance index(C-index),calibration plot and timedependent receiver operating characteristic curves and compared with six other conventional HCC staging systems.RESULTS Multivariate Cox analysis identified that albumin,blood urea nitrogen,gamma-glutamyl transpeptidase to platelet ratio,platelet to lymphocyte ratio,macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model.The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS,which were higher than those of the six conventional HCC staging systems(0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort).The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS.Decision curve analyses indicated satisfactory clinical utility.With a total nomogram score of 196,patients were accurately classified into low-risk and high-risk groups.Furthermore,we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/.CONCLUSION The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy,which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.
基金funded by the supporting funds for scientific research of the Sixth Affiliated Hospital,Sun Yat-sen University(P20200217202404781).
文摘Introduction:The difficulty in treating lung adenocarcinoma(LUAD)is caused by a shortage of knowledge about the biological mechanisms and a lack of treatment choices.Objectives:The aim of this study was to identify a valuable molecular target for the treatment of LUAD.Methods:Using multiple databases,we screened for hub genes in LUAD using Cytoscape and explored the expression and prognosis of DLG associated protein 5(DLGAP5)in LUAD.We investigated the genetic variation,functional enrichment,and epigenetic activity of DLGAP5.Furthermore,we evaluated the relationship between the tumor microenvironment(TME)and DLGAP5.Results:Our study identified 10 hub genes in LUAD:CDC45,KIAA0101,DLGAP5,CDT1,NCAPG,CCNB1,CDCA5,CDC20,KIF11,and AURKA.We discovered that DLGAP5 was overexpressed and associated with poor prognosis in LUAD.DLGAP5 exhibited an overall genetic variation frequency of 2%,and its DNA promoter was hypomethylated in LUAD(p<0.05).The expression of DLGAP5 in LUAD showed a positive correlation with the majority of N6-methyladenosine(m6A)-methylation genes.Additionally,DLGAP5 was primarily associated with the cell cycle in LUAD.Notably,there was a significant favorable association between DLGAP5 and CD274,CTLA4,HAVCR2,and LAG3 in LUAD.Conclusion:DLGAP5 may be a therapeutic target for LUAD,as it affects cancer cells proliferation and development through the regulation of cell-cycle checkpoints and modulation of immune cell infiltration and immune checkpoints in the TME.
文摘AIM:To assess the efficacy versus the adverse effects of various concentrations of atropine in the prevention of myopia in Asian children.METHODS:Databases(PubMed,EMBASE,the Cochrane Library and Web of science)were comprehensively searched from inception to April 2022.Types of studies included were randomized clinical trials(RCTs).The published languages were limited to English.Two researchers assessed the quality of included studies independently using Cochrane risk of bias tool based on the Cochrane Handbook for Systematic Reviews of Interventions.Funnel plots and Egger’s test were used for detection of publication bias.Meta-analyses were conducted using STATA(version 15.0;StataCorp).RESULTS:A total of 15 RCTs involving 2268 patients were included in the study.In the atropine group,spherical equivalent progressed at a significantly lower rate[weighted mean difference(WMD)=0.39,95%confidence interval(CI):0.23,0.54]than in the control group.A WMD of 0.15 mm was associated with less axial elongation(95%CI-0.19,-0.10).Different doses showed statistically significant differences(P<0.05)and an improved effect could result from a higher concentration.Changes in photopic pupil size and mesopic pupil size in atropine group is 0.70 mm(95%CI:0.33,1.06)and 0.38 mm(95%CI:0.22,0.54)more than the control group.In the present Meta-analysis,no changes in accommodative amplitude(AA)were associated with atropine administration.Atropine administration increased the risk of adverse effects by 1.37 times.CONCLUSION:Concentrations of less than 1%atropine are able to effectively retard diopter and axis growth of myopia in Asian children in a dose-dependent manner.Meanwhile,it caused pupil enlargement,but induced no change in the AA within this range.Further study is required to determine the dosage needed to achieve maximum efficacy and minimal side effects.
基金supported by the Guangdong Province Science and Technology Plan,No.2010B030700008the Guangzhou Science and Technology Plan Application Foundation,No.2012J4300062the Major Project of Science and Technology Plan of Dongguan City in 2012,No.2012105102022
文摘Peripheral nerve injury not only affects the site of the injury, but can also induce neuronal apoptosis at the spinal cord. However, many acupuncture clinicians still focus only on the injury site, selecting acupoints entirely along the injured nerve trunk and neglecting other regions; this may delay onset of treatment efficacy and rehabilitation. Therefore, in the present study, we compared the clinical efficacy of acupuncture at Governor vessel and local meridian acupoints combined(GV/LM group) with acupuncture at local meridian acupoints alone(LM group) in the treatment of patients with peripheral nerve injury. In the GV/LM group(n = 15), in addition to meridian acupoints at the injury site, the following acupoints on the Governor vessel were stimulated: Baihui(GV20), Fengfu(GV16), Dazhui(GV14), and Shenzhu(GV12), selected to treat nerve injury of the upper limb, and Jizhong(GV6), Mingmen(GV4), Yaoyangguan(GV3), and Yaoshu(GV2) to treat nerve injury of the lower limb. In the LM group(n = 15), only meridian acupoints along the injured nerve were selected. Both groups had electroacupuncture treatment for 30 minutes, once a day, 5 times per week, for 6 weeks. Two cases dropped out of the LM group. A good or excellent clinical response was obtained in 80% of the patients in the GV/LM group and 38.5% of the LM group. In a second study, an additional 20 patients underwent acupuncture with the same prescription as the GV/LM group. Electomyographic nerve conduction tests were performed before and after acupuncture to explore the mechanism of action of the treatment. An effective response was observed in 80.0% of the patients, with greater motor nerve conduction velocity and amplitude after treatment, indicating that electroacupuncture on specific Governor vessel acupoints promotes functional motor nerve repair after peripheral nerve injury. In addition, electromyography was performed before, during and after electroacupuncture in one patient with radial nerve injury. After a single session, the patient's motor nerve conduction velocity increased by 23.2%, indicating that electroacupuncture at Governor vessel acupoints has an immediate therapeutic effect on peripheral nerve injury. Our results indicate that Governor vessel and local meridian acupoints used simultaneously promote functional repair after peripheral nerve injury. The mechanism of action may arise from an improvement of the local microenvironment in injured nervous tissue, as well as immediate effects of Governor vessel and local meridian acupoint stimulation to ensure the continuity between the peripheral and central nervous systems.
文摘Objective To investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer’s disease (AD). Methods Male Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin (1.5 mg/kg) on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde (MDA), glutathione reductase (GR) and reduced glutathione (GSH) levels in hippocampus and histopathology of hippocampal neurons. Results The MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract (3.0 g/kg). Conclusion R. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.
基金supported by the National Natural Science Foundation of China,No.31371130 and 31600836the Special Foundation of Education Department of Guangdong Province of China+1 种基金the Medical Scientific Research Foundation of Guangdong Province of China,No.2013-159the Foundation of Medical Science and Technology Research of Guangdong Province of China,No.A2016273
文摘Impaired amyloid-β clearance from the brain is a core pathological event in Alzheimer's disease.The therapeutic effect of current pharmacotherapies is unsatisfactory,and some treatments cause severe side effects.The meningeal lymphatic vessels might be a new route for amyloid-β clearance.This study investigated whether promoting dural lymphangiogenesis facilitated the clearance of amyloid-β from the brain.First,human lymphatic endothelial cells were treated with 100 ng/m L recombinant human vascular endothelial growth factor-C(rh VEGF-C) protein.Light microscopy verified that rh VEGF-C,a specific ligand for vascular endothelial growth factor receptor-3(VEGFR-3),significantly promoted tube formation of human lymphatic endothelial cells in vitro.In an in vivo study,200 μg/m L rh VEGF-C was injected into the cisterna magna of APP/PS1 transgenic mice,once every 2 days,four times in total.Immunofluorescence staining demonstrated high levels of dural lymphangiogenesis in Alzheimer's disease mice.One week after rh VEGF-C administration,enzyme-linked immunosorbent assay results showed that levels of soluble amyloid-β were decreased in cerebrospinal fluid and brain.The Morris water maze test demonstrated that spatial cognition was restored.These results indicate that the upregulation of dural lymphangiogenesis facilities amyloid-β clearance from the brain of APP/PS1 mice,suggesting the potential of the VEGF-C/VEGFR-3 signaling pathway as a therapeutic target for Alzheimer's disease.
基金supported in part by grants from National Natural Science Foundation of China for Distinguished Young Scholars(81025021)the National Basic Research Program of China(973Program grant2009CB825506)+2 种基金the Major Research Plan of the National Natural Science Foundation of China(90713036)the National High Technology Research and Development Program of China(863Program grant2008AA02Z420)the Fundamental Research Foundation for the Central Universities to Jing-Xuan Pan
文摘Niclosamide,an oral antihelminthic drug,has been used to treat tapeworm infection for about 50 years.Niclosamide is also used as a molluscicide for water treatment in schistosomiasis control programs.Recently,several groups have independently discovered that niclosamide is also active against cancer cells,but its precise mechanism of antitumor action is not fully understood.Evidence supports that niclosamide targets multiple signaling pathways (NF-κB,Wnt/β-catenin,Notch,ROS,mTORC1,and Stat3),most of which are closely involved with cancer stem cells.The exciting advances in elucidating the antitumor activity and the molecular targets of this drug will be discussed.A method for synthesizing a phosphate pro-drug of niclosamide is provided.Given its potential antitumor activity,clinical trials for niclosamide and its derivatives are warranted for cancer treatment.
基金the National Natural Science Foundation of China,No.81000530, 30973093the Creative Talent Project of Henan Province Health Department, No.2010-4106
文摘Non-invasive tracing in vivo can be used to observe the migration and distribution of grafted stem cells,and can provide experimental evidence for treatment.This study utilized adenovirus-carrying enhanced green fluorescent protein(AD5/F35-eGFP) and superparamagnetic iron oxide(SPIO)-labeled bone marrow mesenchymal stem cells(BMSCs).BMSCs,double-labeled by AD5/F35-eGFP and SPIO,were transplanted into rats with spinal cord injury via the subarachnoid space.MRI tracing results demonstrated that BMSCs migrated to the injured spinal cord over time(T2 hypointensity signals).This result was verified by immunofluorescence.These results indicate that MRI can be utilized to trace in vivo the SPIO-labeled BMSCs after grafting.
基金supported by grants from the Hi-Tech Research and Development Program of China(No.2006AA02Z4B4)the National Natural Science Foundation of China(No.30770641No.31170805)
文摘Introduction:Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer.This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma(NPC).Methods:A total of 2,626 patients with NPC were retrospectively analyzed.Platelet count >300 × 10~9/L was defined as thrombocytosis.Matched-pair analysis was performed between patients receiving chemoradiotherapy and radiotherapy.Results:Multivariate analysis showed that platelet count was an independent unfavorable prognostic factor for overall survival(OS)[hazard ratio(HR) = 1.810,95%confidence interval(CI) = 1.531-2.140,P < 0.001]and distant metastasis-free survival(DMFS)(HR = 1.873,95%CI = 1.475-2.379,P < 0.001) in the entire patient cohort.Further subgroup analysis revealed that increased platelet count was an independent unfavorable prognostic factor for OS and DMFS in patients with NPC stratified by early and advanced T category,N category,or TNM classification(all P < 0.001).Receiver operating characteristic(ROC) curves verified that the predictive value of TNM classification for OS was improved when combined with pretreatment platelet count(P = 0.030).Matched-pair analysis showed that chemoradiotherapy significantly improved OS only in advanced-stage NPC with thrombocytosis(HR = 0.416,95%CI = 0.226-0.765,P = 0.005).Conclusions:Pretreatment platelet count,when combined with TNM classification,is a useful indicator for metastasis and survival in patients with NPC.It may improve the predictive value of the TNM classification and help to identify patients likely to benefit from more aggressive therapeutic regimens.
基金Supported by National High Technology Research and Development Program of China(863 Program),No.2012AA02A506National Natural Science Foundation of China,No.81372570+1 种基金the Science and Technology Foundation of Guangdong Province,China,No.2012B031800088the Science and Technology Foundation of Guangdong Province,China,No.C2011019
文摘AIM:To explore the association between AT-rich interactive domain 1A(ARID1A)protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer.METHODS:We retrospectively collected clinicopathologic data and archived paraffin-embedded primary colorectal cancer samples from 209 patients,including 111patients with colon cancer and 98 patients with rectal cancer.The tumor stage ranged from stageⅠto stageⅣaccording to the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis(TNM)staging system.All patients underwent resection of primary colorectal tumors.The expression of ARID1A protein in primary colorectal cancer tissues was examined by immunohistochemical staining.The clinicopathologic association and survival relevance of ARID1A protein loss in colorectal cancer were analyzed.RESULTS:ARID1A loss by immunohistochemistry was not rare in primary colorectal cancer tumors(25.8%).There were 7.4%,24.1%,22.2%and 46.3%of patients with ARID1A loss staged at TNM stageⅠ,Ⅱ,ⅢandⅣ,respectively,compared with 20.0%,22.6%,27.7%and 29.7%of patients without ARID1A loss staged at TNM stageⅠ,Ⅱ,ⅢandⅣ,respectively.In patients with ARID1A loss,the distant metastasis rate was 46.3%.However,only 29.7%of patients without ARID1A loss were found to have distant metastasis.In terms of pathologic differentiation,there were 25.9%,66.7%and 7.4%with poorly,moderately and well differentiated tumors in patients with ARID1A loss,and 14.2%,72.3%and 13.5%with poorly,moderately and well differentiated tumors in patients without ARID1A loss,respectively.ARID1A loss was associated with late TNM stage(P=0.020),distant metastasis(P=0.026),and poor pathological classification(P=0.035).However,patients with positive ARID1A had worse overall survival compared to those with negative ARID1A in stageⅣcolorectal cancer(HR=2.49,95%CI:1.13-5.51).CONCLUSION:ARID1A protein loss is associated with clinicopathologic characteristics in colorectal cancer patients and with survival in stageⅣpatients.
基金supported by grants of the Administrative Bureau of Chinese Traditional Medicine of Guangdong Province of China,No.2007109the Medical Research Foundation of Guangdong Province of China,No.A20111154
文摘In our previous study, we found that the edible alcohol extract of the root of the medicinal plant Rhodiola crenulata(RCE) improved spatial cognition in a rat model of Alzheimer's disease. Another study from our laboratory showed that RCE enhanced neural cell proliferation in the dentate gyrus of the hippocampus and prevented damage to hippocampal neurons in a rat model of chronic stress-induced depression. However, the mechanisms underlying the neuroprotective effects of RCE are unclear. In the present study, we investigated the anti-apoptotic effect of RCE and its neuroprotective mechanism of action in a rat model of Alzheimer's disease established by intracerebroventricular injection of streptozotocin. The rats were pre-administered RCE at doses of 1.5, 3.0 or 6.0 g/kg for 21 days before model establishment. ATP and cytochrome c oxidase levels were significantly decreased in rats with Alzheimer's disease. Furthermore, neuronal injury was obvious in the hippocampus, with the presence of a large number of apoptotic neurons. In comparison, in rats given RCE pretreatment, ATP and cytochrome c oxidase levels were markedly increased, the number of apoptotic neurons was reduced, and mitochondrial injury was mitigated. The 3.0 g/kg dose of RCE had the optimal effect. These findings suggest that pretreatment with RCE prevents mitochondrial dysfunction and protects hippocampal neurons from apoptosis in rats with Alzheimer's disease.
基金the Guangdong Natural Science Foundation of China,No.S2011040004372the Fundamental Research Funds for the Central Universities,No.11ykpy05
文摘Nestin+ neurons have been shown to express choline acetyltransferase(ChAT) in the medial septum-diagonal band of Broca in adult rats. This study explored the projection of nestin+ neurons to the olfactory bulb and the time course of nestin+ neurons in the medial septum-diagonal band of Broca in adult rats during injury recovery after olfactory nerve transection. This study observed that all nestin+ neurons were double-labeled with ChAT in the medial septum-diagonal band of Broca. Approximately 53.6% of nestin+ neurons were projected to the olfactory bulb and co-labeled with fast blue. A large number of nestin+ neurons were not present in each region of the medial septum-diagonal band of Broca. Nestin+ neurons in the medial septum and vertical limb of the diagonal band of Broca showed obvious compensatory function. The number of nestin+ neurons decreased to a minimum later than nestin–/ChAT+ neurons in the medial septum-diagonal band of Broca. The results suggest that nestin+ cholinergic neurons may have a closer connection to olfactory bulb neurons. Nestin+ cholinergic neurons may have a stronger tolerance to injury than Nestin–/ChAT+ neurons. The difference between nestin+ and nestin–/ ChAT+ neurons during the recovery process requires further investigations.
基金supported by grants from the National Key R&D Program of China,No.2017YFA0104704(to BQL)the Young Elite Scientist Sponsorship Program(YESS)by China Association for Science and Technology(CAST),No.2018QNRC001(to BQL)+1 种基金the Fundamental Research Funds for the Central Universities,China,No.18ykpy38(to BQL)the National Natural Science Foundation of China,Nos.81971157(to BQL),81891003(to YSZ).
文摘Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury.However,achieving good outcome remains difficult.Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites.However,it has not been reported whether this material promotes axonal regeneration in vivo.In the present study,a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells.This functional scaffold promoted the directional growth and remyelination of regenerating axons.In vitro,the porcine decellularized optic nerve contained many straight,longitudinal channels with a uniform distribution,and microscopic pores were present in the channel wall.The spatial micro topological structure and extracellular matrix were conducive to the adhesion,survival and migration of neural stem cells.The scaffold promoted the directional growth of dorsal root ganglion neurites,and showed strong potential for myelin regeneration.Furthermore,we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo.Four weeks later,the regenerating axons grew straight,the myelin sheath in the injured/transplanted area recovered its structure,and simultaneously,the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced.Together,these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration.All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University(approval No.SYSU-IACUC-2019-B034)on February 28,2019.
基金the National Natural Science Foundation of China,No. 30700436
文摘In the present study we injected colchicine into the lateral ventricle of Sprague-Dawley rats to investigate the effects of colchicine on the number of different-type neurons in the basal forebrain and to search for neurons resistant to injury.After colchicine injection,the number of nestin+ cholinergic neurons was decreased at 1 day,but increased at 3 days and peaked at 14-28 days.The quantity of nestin-cholinergic neurons,parvalbumin-positive neurons and choline acetyl transferase-positive neurons decreased gradually.Our results indicate that nestin+ cholinergic neurons possess better tolerance to colchicine-induced neurotoxicity.
基金supported by the National Natural Science Foundation of China, No.10671213 and 11101440the Natural Science Foundation of Guangdong ProvinceFundamental Research Funds for the Central Universities
文摘Electroencephalogram signals are time-varying complex electrophysiological signals. Existing studies show that approximate entropy, which is a nonlinear dynamics index, is not an ideal method for electroencephalogram analysis. Clinical electroencephalogram measurements usually contain electrical interference signals, creating additional challenges in terms of maintaining robustness of the analytic methods. There is an urgent need for a novel method of nonlinear dynamical analysis of the electroencephalogram that can characterize seizure-related changes in cerebral dynamics. The aim of this paper was to study the fluctuations of approximate entropy in preictal, ictal, and postictal electroencephalogram signals from a patient with absence seizures, and to improve the algorithm used to calculate the approximate entropy. The approximate entropy algorithm, especially our modified version, could accurately describe the dynamical changes of the brain during absence seizures. We could also demonstrate that the complexity of the brain was greater in the normal state than in the ictal state. The fluctuations of the approximate entropy before epileptic seizures observed in this study can form a good basis for further study on the prediction of seizures with nonlinear dynamics.
基金Supported by National Natural Science Foundation of China,No. 81670387,No. 31671440,and No. 81800402。
文摘BACKGROUND Acute pancreatitis(AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome(SIRS) with high morbidity and mortality, but no approved therapies are currently available. P-selectin glycoprotein ligand 1(PSGL-1) is a transmembrane glycoprotein to initiate inflammatory responses. We hypothesized that PSGL-1 may be involved in the development of AP and would be a new target for the treatment of AP.AIM To investigate the role and mechanism of PSGL-1 in the development of AP.METHODS The PSGL-1 expression on leukocytes was detected in peripheral blood of AP patients and volunteers. Pancreatic injury, inflammatory cytokines expression, and inflammatory cell infiltration was measured in AP mouse models induced with PSGL-1 knockout(PSGL-1-/-) and wild-type(PSGL-1+/+) mice. Leukocyteendothelial cell adhesion was measured in a peripheral blood mononuclear cell(PBMC)-endothelial cell coculture system.RESULTS The expression of PSGL-1 on monocytes and neutrophils was significantly increased in AP patients. Compared with PSGL-1+/+ mice, PSGL-1-/-AP mice induced by caerulein exhibited lower serum amylase, less Interleukin-1 beta(IL-1 beta) and Interleukin-6(IL-6) expression, less neutrophil and macrophage infiltration, and reduced peripheral neutrophil and monocyte accounts. PSGL-1 deficiency alleviated leukocyte-endothelial cell adhesion via IL-6 but not IL-1 beta.CONCLUSION PSGL-1 deficiency effectively inhibits the development of AP by preventing leukocyte-endothelial cell adhesion via IL-6 stimulation and may become a potential therapeutic target for treating AP.
基金Supported by National Nature Science Foundation of China, No. 81400639 and No. 81502507The Doctoral Start-up Foundation of Guangzhou Medical University of China, No. 2014C39The Science Foundation for Youth Scientists of the Second People’s Hospital of Guangdong Province of China, No. YQ2015-002
文摘AIM: To investigate the anti-apoptotic capability of the hepatitis B virus(HBV) in the HepG2 hepatoma cell line and the underlying mechanisms.METHODS: Cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. Targeted knockdown of manganese superoxide dismutase(Mn SOD), AMP-activated protein kinase(AMPK) and hepatitis B virus X protein(HBx) genes as well as AMPK agonist AICAR and antagonist compound C were employed to determine the correlations of expression of these genes.RESULTS: HBV markedly protected the hepatoma cells from growth suppression and cell death in the condition of serum deprivation. A decrease of superoxide anion production accompanied with an increase of Mn SOD expression and activity was found in Hep G2.215 cells. Moreover, AMPK activation contributed to the up-regulation of Mn SOD. HBx protein was identified to induce the expression of AMPK and Mn SOD. CONCLUSION: Our results suggest that HBV suppresses mitochondrial superoxide level and exerts an antiapoptotic effect by activating AMPK/Mn SOD signaling pathway, which may provide a novel pharmacological strategy to prevent HCC.
