Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hi...Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hibernation techniques,mild hypothermia has preliminarily confirmed its clinical effect on spinal cord injury.However,its technical defects and barriers,along with serious clinical side effects,restrict its clinical application for spinal cord injury.Artificial hibernation is a futureoriented disruptive technology for human life support.It involves endogenous hibernation inducers and hibernation-related central neuromodulation that activate particular neurons,reduce the central constant temperature setting point,disrupt the normal constant body temperature,make the body adapt"to the external cold environment,and reduce the physiological resistance to cold stimulation.Thus,studying the artificial hibernation mechanism may help develop new treatment strategies more suitable for clinical use than the cooling method of mild hypothermia technology.This review introduces artificial hibernation technologies,including mild hypothermia technology,hibernation inducers,and hibernation-related central neuromodulation technology.It summarizes the relevant research on hypothermia and hibernation for organ and nerve protection.These studies show that artificial hibernation technologies have therapeutic significance on nerve injury after spinal co rd injury through inflammatory inhibition,immunosuppression,oxidative defense,and possible central protection.It also promotes the repair and protection of res pirato ry and digestive,cardiovascular,locomoto r,urinary,and endocrine systems.This review provides new insights for the clinical treatment of nerve and multiple organ protection after spinal cord injury thanks to artificial hibernation.At present,artificial hibernation technology is not mature,and research fa ces various challenges.Neve rtheless,the effort is wo rthwhile for the future development of medicine.展开更多
Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduit...Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.展开更多
Objective:To investigate the occurrence of BRAFV600E and RAS mutations in thyroid papillary carcinoma (PTC) and to study their correlation with clinicopathological features of PTC. Methods Relevant information of PTC ...Objective:To investigate the occurrence of BRAFV600E and RAS mutations in thyroid papillary carcinoma (PTC) and to study their correlation with clinicopathological features of PTC. Methods Relevant information of PTC was downloaded and organized from The Cancer Genome Atlas (TCGA) via cBioPortal, then the gene mutation and clinical information of 402 PTC samples were analyzed. The correlation of BRAFV600E and RAS mutations with clinicopathological features and prognosis of PTC were subjected to univariate analysis. Secondly, we use Binary Logistic multivariate analysis to analyze the factors screened above. Results BRAFV600E mutation rate is 48.5% (195/402) and RAS mutation rate is 10.2% (41/402) in 402 cases of PTC. Univariate analysis showed that BRAFV600E mutation has nothing to do with age and sex of the patient. There is a significant correlation among BRAFV600E mutation and lymph node metastasis, extrathyroidal invasion, staging, recurrence, progression and pathological subtypes in PTC. There is no significant correlation among RAS and age, sex, staging, recurrence, progression. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC. Multivariate logistic regression analysis indicated that there is a significant correlation among BRAFV600E mutation and extrathyroidal invasion, pathological subtypes in PTC. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC.ConclusionThe mutation rate of BRAFV600E was significantly higher than that of RAS in PTC. Mutations in BRAFV600E and RAS can be used as predictors of prognosis in PTC.展开更多
There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a prom...There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury.In this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in rats.Composite scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for 2weeks.Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity scores.In addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured area.In conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.展开更多
Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury.To investigate whether injectable collagen scaffol...Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury.To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage,this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion crite ria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People’s Armed Police Force from May 2016 to December 2020.Patients were divided into three groups according to the clinical situation and patient benefit:control(n=18),human umbilical cord-derived mesenchymal stem cells(n=4),and combination(n=8).The control group did not receive any transplantation.The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation.The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells.Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intra cerebral hemorrhage-related encephalomalacia.Severe adve rse events associated with cell transplantation were not observed.Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.展开更多
Cymbopogon citratus in the gramineous family,also known as lemongrass(LG),is a perennial herb.LG,a drug and food homologous medicine,has a widely recorded medicinal value and food applications.To date,158 LG compounds...Cymbopogon citratus in the gramineous family,also known as lemongrass(LG),is a perennial herb.LG,a drug and food homologous medicine,has a widely recorded medicinal value and food applications.To date,158 LG compounds have been reported,including terpenoids,flavonoids,phenolic acids.Pharmacological and clinical studies have indicated that LG has antibacterial,neuroprotective,hypoglycemic,hypotensive,anti-inflammatory,and anti-tumor effects.This article reviews LG in ethnopharmacology,chemical composition,pharmacology,food,medicine,and daily chemical applications to provide a basis for the subsequent development of food and medicine.展开更多
Currently, there is no effective strategy to promote functional recovery after a spinal cord injury. Collagen scaffolds can not only provide support and guidance for axonal regeneration, but can also serve as a bridge...Currently, there is no effective strategy to promote functional recovery after a spinal cord injury. Collagen scaffolds can not only provide support and guidance for axonal regeneration, but can also serve as a bridge for nerve regeneration at the injury site. They can additionally be used as carriers to retain mesenchymal stem cells at the injury site to enhance their effectiveness. Hence, we hypothesized that transplanting human umbilical cord-mesenchymal stem cells on collagen scaffolds would enhance healing following acute complete spinal cord injury. Here, we test this hypothesis through animal studies and a phase I clinical trial.(1) Animal experiments: Models of completely transected spinal cord injury were established in rats and canines by microsurgery. Mesenchymal stem cells derived from neonatal umbilical cord tissue were adsorbed onto collagen scaffolds and surgically implanted at the injury site in rats and canines;the animals were observed after 1 week–6 months. The transplantation resulted in increased motor scores, enhanced amplitude and shortened latency of the motor evoked potential, and reduced injury area as measured by magnetic resonance imaging.(2) Phase I clinical trial: Forty patients with acute complete cervical injuries were enrolled at the Characteristic Medical Center of Chinese People's Armed Police Force and divided into two groups. The treatment group(n = 20) received collagen scaffolds loaded with mesenchymal stem cells derived from neonatal umbilical cordtissues;the control group(n = 20) did not receive the stem-cell loaded collagen implant. All patients were followed for 12 months. In the treatment group, the American Spinal Injury Association scores and activities of daily life scores were increased, bowel and urinary functions were recovered, and residual urine volume was reduced compared with the pre-treatment baseline. Furthermore, magnetic resonance imaging showed that new nerve fiber connections were formed, and diffusion tensor imaging showed that electrophysiological activity was recovered after the treatment. No serious complication was observed during follow-up. In contrast, the neurological functions of the patients in the control group were not improved over the follow-up period. The above data preliminarily demonstrate that the transplantation of human umbilical cord-mesenchymal stem cells on a collagen scaffold can promote the recovery of neurological function after acute spinal cord injury. In the future, these results need to be confirmed in a multicenter, randomized controlled clinical trial with a larger sample size. The clinical trial was approved by the Ethics Committee of the Characteristic Medical Center of Chinese People's Armed Police Force on February 3, 2016(approval No. PJHEC-2016-A8). All animal experiments were approved by the Ethics Committee of the Characteristic Medical Center of Chinese People's Armed Police Force on May 20, 2015(approval No. PJHEC-2015-D5).展开更多
One reason for the poor therapeutic effects of stem cell transplantation in traumatic brain injury is that exogenous neural stem cells cannot effectively migrate to the local injury site,resulting in poor adhesion and...One reason for the poor therapeutic effects of stem cell transplantation in traumatic brain injury is that exogenous neural stem cells cannot effectively migrate to the local injury site,resulting in poor adhesion and proliferation of neural stem cells at the injured area.To enhance the targeted delivery of exogenous stem cells to the injury site,cell therapy combined with neural tissue engineering technology is expected to become a new strategy for treating traumatic brain injury.Collagen/heparan sulfate porous scaffolds,prepared using a freeze-drying method,have stable physical and chemical properties.These scaffolds also have good cell biocompatibility because of their high porosity,which is suitable for the proliferation and migration of neural stem cells.In the present study,collagen/heparan sulfate porous scaffolds loaded with neural stem cells were used to treat a rat model of traumatic brain injury,which was established using the controlled cortical impact method.At 2 months after the implantation of collagen/heparan sulfate porous scaffolds loaded with neural stem cells,there was significantly improved regeneration of neurons,nerve fibers,synapses,and myelin sheaths in the injured brain tissue.Furthermore,brain edema and cell apoptosis were significantly reduced,and rat motor and cognitive functions were markedly recovered.These findings suggest that the novel collagen/heparan sulfate porous scaffold loaded with neural stem cells can improve neurological function in a rat model of traumatic brain injury.This study was approved by the Institutional Ethics Committee of Characteristic Medical Center of Chinese People’s Armed Police Force,China(approval No.2017-0007.2)on February 10,2019.展开更多
BACKGROUND Aneurysm compression,diabetes,and traumatic brain injury are well-known causative factors of oculomotor nerve palsy(ONP),while cases of ONP induced by neurovascular conflicts have rarely been reported in th...BACKGROUND Aneurysm compression,diabetes,and traumatic brain injury are well-known causative factors of oculomotor nerve palsy(ONP),while cases of ONP induced by neurovascular conflicts have rarely been reported in the medical community.Here,we report a typical case of ONP caused by right posterior cerebral artery(PCA)compression to increase neurosurgeons’awareness of the disease and reduce misdiagnosis and recurrence.CASE SUMMARY A 54-year-old man without a known medical history presented with right ONP for the past 5 years.The patient presented to the hospital with right ptosis,diplopia,anisocoria(rt 5 mm,lt 2.5 mm),loss of duction in all directions,abduction,and light impaired pupillary reflexes.Magnetic resonance angiography and computed tomography venography examinations showed no phlebangioma,aneurysm,or intracranial lesion.After conducting oral glucose tolerance and prostigmin tests,diabetes and myasthenia gravis were excluded.Cranial nerve magnetic resonance imaging showed that the right PCA loop was in direct contact with the cisternal segment of the right oculomotor nerve(ON).Microvascular decompression(MVD)of the culprit vessel from the ON through a right subtemporal craniotomy was carried out,and the ONP symptoms were significantly relieved after 3 mo.CONCLUSION Vascular compression of the ON is a rare pathogeny of ONP that may be refractory to drug therapy and ophthalmic strabismus surgery.MVD is an effective treatment for ONP induced by neurovascular compression.展开更多
OBJECTIVE To compare the morphological and compositional characteristics of carotid plaques in two cohorts(2002−2005 and 2012−2015)of Chinese patients using magnetic resonance vessel wall imaging.METHODS Symptomatic p...OBJECTIVE To compare the morphological and compositional characteristics of carotid plaques in two cohorts(2002−2005 and 2012−2015)of Chinese patients using magnetic resonance vessel wall imaging.METHODS Symptomatic patients with carotid atherosclerotic plaques who underwent carotid vessel wall magnetic resonance imaging between 2002−2005 and 2012−2015 were retrospectively recruited.Plaque morphology[including mean wall area,wall thickness,and maximum normalized wall index(NWI)]and composition[including calcification,intraplaque hemorrhage,and lipid-rich necrotic core(LRNC)]in symptomatic carotid arteries were evaluated and compared between patients in these two time periods.RESULTS A total of 258 patients,including 129 patients in the 2002−2005 cohort and 129 patients in the 2012−2015 cohort,were recruited.Statin use(49.6%vs.32.6%,P=0.004)and hypertension(76.0%vs.62.8%,P=0.015)were significantly more common in the 2012-2015 cohort than in the 2002−2005 cohort.Patients in the 2012−2015 cohort also exhibited significantly low plaque burden parameters(all P<0.05),as well as a lower prevalence(68.2%vs.89.9%,P<0.001)and volume percentages of LRNC(11.2%±14.2%vs.25.7%±17.7%,P<0.001).These differences remained significant after adjustment for clinical factors.The differences in the volume percentages of LRNC also remained significant after an additional adjustment for maximum NWI(P<0.001).CONCLUSIONS Patients in the 2012−2015 cohort had a lower plaque burden and volume percentages of LRNC in symptomatic carotid arteries than those in the 2002−2005 cohort.These findings indicate that carotid plaques in the recent cohort had a lower severity and vulnerability.展开更多
Objective: To explore potential genes associated with the formation and rupture of intracranial aneurysms based on the Gene Expression Omnibus (GEO) database. Methods: A total of 133 mRNA microarrays were collected fr...Objective: To explore potential genes associated with the formation and rupture of intracranial aneurysms based on the Gene Expression Omnibus (GEO) database. Methods: A total of 133 mRNA microarrays were collected from the GEO database. Differential mRNA gene analysis was performed on the data of each group in the GEO2R platform, and the common differential genes were screened and the gene ontology enrichment analysis and the Kyoto Gene and Genomic Encyclopedia pathway enrichment analysis were completed. The screened differential genes were introduced into the String online database to obtain the interaction between the proteins encoded by the differential genes. Results: Forty-two common differential genes were screened, and the main biological processes involved included the transcriptional regulation of oxidative stress, the positive regulation of chemokine production, and the positive regulation of autophagy of giant cells by RNA polymerase II promoter. Molecular functions included protein binding, RNA polymerase II transcriptional co-repressor activity, transcriptional activator activity, and protein kinase C binding. The main signal pathways covered included hypoxia-inducible factor-1 signaling pathway, glucagon signaling pathway, and metabolic pathway signaling pathway. Conclusions: The formation and rupture of the intracranial aneurysm may be initially screened with amidoxime reduction component 1, tumor necrosis factor-α-inducible protein 6, haptoglobin, mast cell membrane-expressing protein 1, zipper containing kinase, phospholipase Cβ4 and blood and nervous system expression factor-1. In addition to the previously knownintracranial aneurysms mechanisms, cellular autophagy and hypoxia inducible factor-1 pathway may also be involved in the formation of intracranial aneurysms.展开更多
The gut microbiome shows changes under a plateau environment,while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome(IBS);however,the relationship between ...The gut microbiome shows changes under a plateau environment,while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome(IBS);however,the relationship between the two remains unexplored.In this work,we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA(rRNA)sequencing analysis of their fecal samples.Through evaluating the participants’clinical symptoms,combined with an IBS questionnaire,we screened the IBS sub-population in our cohort.The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora.In addition,we found that the longer the time volunteers spent in the plateau environment,the more similar their gut microbiota composition and abundance became compared to those before entering the plateau,and IBS symptoms were significantly alleviated.Therefore,we speculated that the plateau may be a special environment that induces IBS.The taxonomic units g_Alistipes,g_Oscillospira,and s_Ruminococcus_torques,which had been proved to play important roles in IBS pathogenesis,were also abundant in the IBS cohort at high altitudes.Overall,the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS.Our results prompt further research to elucidate the relevant mechanism.展开更多
The restoration of nerve dysfunction after traumatic brain injury(TBI)faces huge challenges due to the limited self-regenerative abilities of nerve tissues.In situ inductive recovery can be achieved utilizing biologic...The restoration of nerve dysfunction after traumatic brain injury(TBI)faces huge challenges due to the limited self-regenerative abilities of nerve tissues.In situ inductive recovery can be achieved utilizing biological scaffolds combined with endogenous human umbilical cord mesenchymal stem cells(HUCMSCs)-derived exosomes(MExos).In this study,brain-derived neurotrophic factor-stimulated HUCMSCs-derived exosomes(BMExos)were composited with collagen/chitosan by 3D printing technology.3D-printed collagen/chitosan/BMExos(3D-CC-BMExos)scaffolds have excellent mechanical properties and biocompatibility.Subsequently,in vivo experiments showed that 3D-CC-BMExos therapy could improve the recovery of neuromotor function and cognitive function in a TBI model in rats.Consistent with the behavioural recovery,the results of histomorphological tests showed that 3D-CC-BMExos therapy could facilitate the remodelling of neural networks,such as improving the regeneration of nerve fibres,synaptic connections and myelin sheaths,in lesions after TBI.展开更多
To the Editor:Lung fibrosis is characterized by extracellular matrix accumulation and remodeling of the lung interstitium.Although lung fibrosis has been extensively studied,there is still a lack of effective anti-pul...To the Editor:Lung fibrosis is characterized by extracellular matrix accumulation and remodeling of the lung interstitium.Although lung fibrosis has been extensively studied,there is still a lack of effective anti-pulmonary fibrosis drugs at present.The pathogenesis of lung fibrosis involves many aspects in which the lung macrophages play a particularly important role.[1]It has been reported that the manipulation of the monocyte/macrophage phenotype switch might be a potential target for many macrophagemediated inflammatory disorders.In our previous study,mice that were exposed to bleomycin(BLM)showed a dynamic change of mononuclear phagocytes in the circulating system,lung alveoli,and interstitial compartments.The rapid increase of the number of circulating Ly6Chi monocytes after BLM stimulation,followed by the expansion of M2-like alveolar macrophages(AMf)numbers,is closely associated with lung inflammatory response and fibrosis.[2,3]展开更多
The secretome secreted by stem cells and bioactive material has emerged as a promising therapeutic choice for traumatic brain injury(TBI).We aimed to determine the effect of 3D-printed collagen/chitosan/secretome deri...The secretome secreted by stem cells and bioactive material has emerged as a promising therapeutic choice for traumatic brain injury(TBI).We aimed to determine the effect of 3D-printed collagen/chitosan/secretome derived from human umbilical cord blood mesenchymal stem cells scaffolds(3D-CC-ST)on the injured tissue regeneration process.3D-CC-ST was performed using 3D printing technology at a low temperature(20C),and the physical properties and degeneration rate were measured.The utilization of low temperature contributed to a higher cytocompatibility of fabricating porous 3D architectures that provide a homogeneous distribution of cells.Immediately after the establishment of the canine TBI model,3D-CC-ST and 3D-CC(3D-printed collagen/chitosan scaffolds)were implanted into the cavity of TBI.Following implantation of scaffolds,neurological examination and motor evoked potential detection were performed to analyze locomotor function recovery.Histological and immunofluorescence staining were performed to evaluate neuro-regeneration.The group treated with 3D-CC-ST had good performance of behavior functions.Implanting 3D-CC-ST significantly reduced the cavity area,facilitated the regeneration of nerve fibers and vessel reconstruction,and promoted endogenous neuronal differentiation and synapse formation after TBI.The implantation of 3D-CC-ST also markedly reduced cell apoptosis and regulated the level of systemic inflammatory factors after TBI.展开更多
Background:High-frequency irreversible electroporation(H-FIRE)is a novel,next-generation nanoknife technology with the advantage of relieving irreversible electroporation(IRE)-induced muscle contractions.However,the d...Background:High-frequency irreversible electroporation(H-FIRE)is a novel,next-generation nanoknife technology with the advantage of relieving irreversible electroporation(IRE)-induced muscle contractions.However,the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined.This study aimed to compare the efficacy of the two treatments in vivo.Methods:Ten Bamaminiature swinewere divided into two group:five in the 1-day group and five in the 7-day group.The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant(Krans),rate constant(Kep)and extravascular extracellular volume fraction(Ve)value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),size of the ablation zone,and histologic analysis.Each animal underwent the IRE andH-FIRE.Temperatures of the electrodesweremeasured during ablation.DCE-MRI images were obtained 1,4,and 7 days after ablation in the 7-day group.All animals in the two groups were euthanized 1 day or 7 days after ablation,and subsequently,IRE and H-FIRE treated liver tissues were collected for histological examination.Student’s t test or Mann-Whitney U test was applied for comparing any two groups.One-way analysis of variance(ANOVA)test and Welch’s ANOVA test followed byHolm-Sidak’smultiple comparisons test,one-wayANOVAwith repeatedmeasures followed by Bonferroni test,or Kruskal-Wallis H test followed by Dunn’s multiple comparison test was used for multiple group comparisons and post hoc analyses.Pearson correlation coefficient test was conducted to analyze the relationship between two variables.Results:Higher Ve was seen in IRE zone than in H-FIRE zone(0.14±0.02 vs.0.08±0.05,t=2.408,P=0.043)on day 4,but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points(all P>0.05).For IRE zone,the greatest Ktrans was seen on day 7,which was significantly higher than that on day 1(P=0.033).The ablation zone size of H-FIRE was significantly larger than IRE 1 day(4.74±0.88 cm^(2)vs.3.20±0.77 cm^(2),t=3.241,P=0.009)and 4 days(2.22±0.83 cm^(2)vs.1.30±0.50 cm^(2),t=2.343,P=0.041)after treatment.Apoptotic index(0.05±0.02 vs.0.73±0.06 vs.0.68±0.07,F=241.300,P<0.001)and heat shock protein 70(HSP70)(0.03±0.01 vs.0.46±0.09 vs.and 0.42±0.07,F=64.490,P<0.001)were significantly different between the untreated,IRE and H-FIRE zones,but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone(both P>0.05).Electrode temperature variations were not significantly different between the two zones(18.00±3.77℃ vs.16.20±7.45℃,t=0.682,P=0.504).The Ktrans value(r=0.940,P=0.017)and the Kep value(r=0.895,P=0.040)of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.Conclusions:H-FIRE showed a comparable ablation effect to IRE.DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.展开更多
基金supported by the Key Projects of the National Natural Science Foundation of China,No.11932013(to XC)Key Military Logistics Research Projects,No.B WJ21J002(to XC)+4 种基金the Key projects of the Special Zone for National Defence Innovation,No.21-163-12-ZT006002-13(to XC)the National Nature Science Foundation of China No.82272255(to XC)the National Defense Science and Technology Outstanding Youth Science Fund Program,No.2021-JCIQ-ZQ-035(to XC)the Scientific Research Innovation Team Project of Armed Police Characteristic Medical Center,No.KYCXTD0104(to ZL)the National Natural Science Foundation of China Youth Fund,No.82004467(to BC)。
文摘Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hibernation techniques,mild hypothermia has preliminarily confirmed its clinical effect on spinal cord injury.However,its technical defects and barriers,along with serious clinical side effects,restrict its clinical application for spinal cord injury.Artificial hibernation is a futureoriented disruptive technology for human life support.It involves endogenous hibernation inducers and hibernation-related central neuromodulation that activate particular neurons,reduce the central constant temperature setting point,disrupt the normal constant body temperature,make the body adapt"to the external cold environment,and reduce the physiological resistance to cold stimulation.Thus,studying the artificial hibernation mechanism may help develop new treatment strategies more suitable for clinical use than the cooling method of mild hypothermia technology.This review introduces artificial hibernation technologies,including mild hypothermia technology,hibernation inducers,and hibernation-related central neuromodulation technology.It summarizes the relevant research on hypothermia and hibernation for organ and nerve protection.These studies show that artificial hibernation technologies have therapeutic significance on nerve injury after spinal co rd injury through inflammatory inhibition,immunosuppression,oxidative defense,and possible central protection.It also promotes the repair and protection of res pirato ry and digestive,cardiovascular,locomoto r,urinary,and endocrine systems.This review provides new insights for the clinical treatment of nerve and multiple organ protection after spinal cord injury thanks to artificial hibernation.At present,artificial hibernation technology is not mature,and research fa ces various challenges.Neve rtheless,the effort is wo rthwhile for the future development of medicine.
基金supported by the National Natural Science Foundation of China,No.82202718the Natural Science Foundation of Beijing,No.L212050the China Postdoctoral Science Foundation,Nos.2019M664007,2021T140793(all to ZL)。
文摘Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor site.As an alternative,nerve guidance conduits may be used.The ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve regeneration.We designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align them.Subsequently,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber lumen.The presence of aligned fibers on the inner surface can promote the extension of nerve cells along the fibers.The helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide stability.Our novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.
基金National Natural Science Foundation of China.Project No:81302577.
文摘Objective:To investigate the occurrence of BRAFV600E and RAS mutations in thyroid papillary carcinoma (PTC) and to study their correlation with clinicopathological features of PTC. Methods Relevant information of PTC was downloaded and organized from The Cancer Genome Atlas (TCGA) via cBioPortal, then the gene mutation and clinical information of 402 PTC samples were analyzed. The correlation of BRAFV600E and RAS mutations with clinicopathological features and prognosis of PTC were subjected to univariate analysis. Secondly, we use Binary Logistic multivariate analysis to analyze the factors screened above. Results BRAFV600E mutation rate is 48.5% (195/402) and RAS mutation rate is 10.2% (41/402) in 402 cases of PTC. Univariate analysis showed that BRAFV600E mutation has nothing to do with age and sex of the patient. There is a significant correlation among BRAFV600E mutation and lymph node metastasis, extrathyroidal invasion, staging, recurrence, progression and pathological subtypes in PTC. There is no significant correlation among RAS and age, sex, staging, recurrence, progression. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC. Multivariate logistic regression analysis indicated that there is a significant correlation among BRAFV600E mutation and extrathyroidal invasion, pathological subtypes in PTC. There is a significant correlation among RAS and lymph node metastasis, extrathyroidal invasion and pathological subtypes in PTC.ConclusionThe mutation rate of BRAFV600E was significantly higher than that of RAS in PTC. Mutations in BRAFV600E and RAS can be used as predictors of prognosis in PTC.
基金supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development,No.2019ZX09301-147 (to LXZ)。
文摘There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury.In this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in rats.Composite scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for 2weeks.Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity scores.In addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured area.In conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.
基金supported by the National Key Research and Development Plan of China,No.2016YFC1101500 (to ZS)the National Natural Science Foundation of China,Nos.11932013 and 11672332 (both to XYC)。
文摘Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury.To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage,this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion crite ria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People’s Armed Police Force from May 2016 to December 2020.Patients were divided into three groups according to the clinical situation and patient benefit:control(n=18),human umbilical cord-derived mesenchymal stem cells(n=4),and combination(n=8).The control group did not receive any transplantation.The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation.The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells.Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intra cerebral hemorrhage-related encephalomalacia.Severe adve rse events associated with cell transplantation were not observed.Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.
基金supported by the National Key R&D Program of China(No.2022YFC3501805)for financial support.
文摘Cymbopogon citratus in the gramineous family,also known as lemongrass(LG),is a perennial herb.LG,a drug and food homologous medicine,has a widely recorded medicinal value and food applications.To date,158 LG compounds have been reported,including terpenoids,flavonoids,phenolic acids.Pharmacological and clinical studies have indicated that LG has antibacterial,neuroprotective,hypoglycemic,hypotensive,anti-inflammatory,and anti-tumor effects.This article reviews LG in ethnopharmacology,chemical composition,pharmacology,food,medicine,and daily chemical applications to provide a basis for the subsequent development of food and medicine.
基金supported by the National Natural Science Foundation of China,Nos.11932013(to SZ),11672332(to SZ)the National Key Research and Development Plan of China,No.2016YFC1101500(to SZ)+2 种基金the Science and Technology Military-Civilian Integration Project of Tianjin of China,No.18ZXJMTG00260(to XYC)the Key Project of Science and Technology Support Plan of Tianjin of China,No.17YFZCSY00620(to XYC)the Rescue Medical Clinical Center Fund of Tianjin of China,No.15ZXLCSY00040(to XYC)
文摘Currently, there is no effective strategy to promote functional recovery after a spinal cord injury. Collagen scaffolds can not only provide support and guidance for axonal regeneration, but can also serve as a bridge for nerve regeneration at the injury site. They can additionally be used as carriers to retain mesenchymal stem cells at the injury site to enhance their effectiveness. Hence, we hypothesized that transplanting human umbilical cord-mesenchymal stem cells on collagen scaffolds would enhance healing following acute complete spinal cord injury. Here, we test this hypothesis through animal studies and a phase I clinical trial.(1) Animal experiments: Models of completely transected spinal cord injury were established in rats and canines by microsurgery. Mesenchymal stem cells derived from neonatal umbilical cord tissue were adsorbed onto collagen scaffolds and surgically implanted at the injury site in rats and canines;the animals were observed after 1 week–6 months. The transplantation resulted in increased motor scores, enhanced amplitude and shortened latency of the motor evoked potential, and reduced injury area as measured by magnetic resonance imaging.(2) Phase I clinical trial: Forty patients with acute complete cervical injuries were enrolled at the Characteristic Medical Center of Chinese People's Armed Police Force and divided into two groups. The treatment group(n = 20) received collagen scaffolds loaded with mesenchymal stem cells derived from neonatal umbilical cordtissues;the control group(n = 20) did not receive the stem-cell loaded collagen implant. All patients were followed for 12 months. In the treatment group, the American Spinal Injury Association scores and activities of daily life scores were increased, bowel and urinary functions were recovered, and residual urine volume was reduced compared with the pre-treatment baseline. Furthermore, magnetic resonance imaging showed that new nerve fiber connections were formed, and diffusion tensor imaging showed that electrophysiological activity was recovered after the treatment. No serious complication was observed during follow-up. In contrast, the neurological functions of the patients in the control group were not improved over the follow-up period. The above data preliminarily demonstrate that the transplantation of human umbilical cord-mesenchymal stem cells on a collagen scaffold can promote the recovery of neurological function after acute spinal cord injury. In the future, these results need to be confirmed in a multicenter, randomized controlled clinical trial with a larger sample size. The clinical trial was approved by the Ethics Committee of the Characteristic Medical Center of Chinese People's Armed Police Force on February 3, 2016(approval No. PJHEC-2016-A8). All animal experiments were approved by the Ethics Committee of the Characteristic Medical Center of Chinese People's Armed Police Force on May 20, 2015(approval No. PJHEC-2015-D5).
基金supported by the National Natural Science Foundation of China,Nos.11672332,11932013(both to XYC)the National Key Research and Development Plan of China,No.2016YFC1101500(to HTS)the Key Science and Technology Support Foundation of Tianjin of China,No.17YFZCSY00620(to HTS).
文摘One reason for the poor therapeutic effects of stem cell transplantation in traumatic brain injury is that exogenous neural stem cells cannot effectively migrate to the local injury site,resulting in poor adhesion and proliferation of neural stem cells at the injured area.To enhance the targeted delivery of exogenous stem cells to the injury site,cell therapy combined with neural tissue engineering technology is expected to become a new strategy for treating traumatic brain injury.Collagen/heparan sulfate porous scaffolds,prepared using a freeze-drying method,have stable physical and chemical properties.These scaffolds also have good cell biocompatibility because of their high porosity,which is suitable for the proliferation and migration of neural stem cells.In the present study,collagen/heparan sulfate porous scaffolds loaded with neural stem cells were used to treat a rat model of traumatic brain injury,which was established using the controlled cortical impact method.At 2 months after the implantation of collagen/heparan sulfate porous scaffolds loaded with neural stem cells,there was significantly improved regeneration of neurons,nerve fibers,synapses,and myelin sheaths in the injured brain tissue.Furthermore,brain edema and cell apoptosis were significantly reduced,and rat motor and cognitive functions were markedly recovered.These findings suggest that the novel collagen/heparan sulfate porous scaffold loaded with neural stem cells can improve neurological function in a rat model of traumatic brain injury.This study was approved by the Institutional Ethics Committee of Characteristic Medical Center of Chinese People’s Armed Police Force,China(approval No.2017-0007.2)on February 10,2019.
基金Supported by National Natural Science Foundation of China,No.32070791the Key Scientific Research Projects of Military Logistics,No.BWJ20J002.
文摘BACKGROUND Aneurysm compression,diabetes,and traumatic brain injury are well-known causative factors of oculomotor nerve palsy(ONP),while cases of ONP induced by neurovascular conflicts have rarely been reported in the medical community.Here,we report a typical case of ONP caused by right posterior cerebral artery(PCA)compression to increase neurosurgeons’awareness of the disease and reduce misdiagnosis and recurrence.CASE SUMMARY A 54-year-old man without a known medical history presented with right ONP for the past 5 years.The patient presented to the hospital with right ptosis,diplopia,anisocoria(rt 5 mm,lt 2.5 mm),loss of duction in all directions,abduction,and light impaired pupillary reflexes.Magnetic resonance angiography and computed tomography venography examinations showed no phlebangioma,aneurysm,or intracranial lesion.After conducting oral glucose tolerance and prostigmin tests,diabetes and myasthenia gravis were excluded.Cranial nerve magnetic resonance imaging showed that the right PCA loop was in direct contact with the cisternal segment of the right oculomotor nerve(ON).Microvascular decompression(MVD)of the culprit vessel from the ON through a right subtemporal craniotomy was carried out,and the ONP symptoms were significantly relieved after 3 mo.CONCLUSION Vascular compression of the ON is a rare pathogeny of ONP that may be refractory to drug therapy and ophthalmic strabismus surgery.MVD is an effective treatment for ONP induced by neurovascular compression.
基金the National Natural Science Foundation of China(No.82001774&No.81801694)the Beijing National Science Foundation(No.7212100)the Beijing Science and Technology Project(Z161100000516194)。
文摘OBJECTIVE To compare the morphological and compositional characteristics of carotid plaques in two cohorts(2002−2005 and 2012−2015)of Chinese patients using magnetic resonance vessel wall imaging.METHODS Symptomatic patients with carotid atherosclerotic plaques who underwent carotid vessel wall magnetic resonance imaging between 2002−2005 and 2012−2015 were retrospectively recruited.Plaque morphology[including mean wall area,wall thickness,and maximum normalized wall index(NWI)]and composition[including calcification,intraplaque hemorrhage,and lipid-rich necrotic core(LRNC)]in symptomatic carotid arteries were evaluated and compared between patients in these two time periods.RESULTS A total of 258 patients,including 129 patients in the 2002−2005 cohort and 129 patients in the 2012−2015 cohort,were recruited.Statin use(49.6%vs.32.6%,P=0.004)and hypertension(76.0%vs.62.8%,P=0.015)were significantly more common in the 2012-2015 cohort than in the 2002−2005 cohort.Patients in the 2012−2015 cohort also exhibited significantly low plaque burden parameters(all P<0.05),as well as a lower prevalence(68.2%vs.89.9%,P<0.001)and volume percentages of LRNC(11.2%±14.2%vs.25.7%±17.7%,P<0.001).These differences remained significant after adjustment for clinical factors.The differences in the volume percentages of LRNC also remained significant after an additional adjustment for maximum NWI(P<0.001).CONCLUSIONS Patients in the 2012−2015 cohort had a lower plaque burden and volume percentages of LRNC in symptomatic carotid arteries than those in the 2002−2005 cohort.These findings indicate that carotid plaques in the recent cohort had a lower severity and vulnerability.
基金supported by the National Natural Science Foundation of China(Grant No.31200809)Project of Shanghai Hongkou District Health and Family Planning Commission(Grant No.1802-06)"Special Fund Project for Basic Scientific Research Operating Expenses of Central Universities"of Tongji University(Grant No.22120180282).
文摘Objective: To explore potential genes associated with the formation and rupture of intracranial aneurysms based on the Gene Expression Omnibus (GEO) database. Methods: A total of 133 mRNA microarrays were collected from the GEO database. Differential mRNA gene analysis was performed on the data of each group in the GEO2R platform, and the common differential genes were screened and the gene ontology enrichment analysis and the Kyoto Gene and Genomic Encyclopedia pathway enrichment analysis were completed. The screened differential genes were introduced into the String online database to obtain the interaction between the proteins encoded by the differential genes. Results: Forty-two common differential genes were screened, and the main biological processes involved included the transcriptional regulation of oxidative stress, the positive regulation of chemokine production, and the positive regulation of autophagy of giant cells by RNA polymerase II promoter. Molecular functions included protein binding, RNA polymerase II transcriptional co-repressor activity, transcriptional activator activity, and protein kinase C binding. The main signal pathways covered included hypoxia-inducible factor-1 signaling pathway, glucagon signaling pathway, and metabolic pathway signaling pathway. Conclusions: The formation and rupture of the intracranial aneurysm may be initially screened with amidoxime reduction component 1, tumor necrosis factor-α-inducible protein 6, haptoglobin, mast cell membrane-expressing protein 1, zipper containing kinase, phospholipase Cβ4 and blood and nervous system expression factor-1. In addition to the previously knownintracranial aneurysms mechanisms, cellular autophagy and hypoxia inducible factor-1 pathway may also be involved in the formation of intracranial aneurysms.
基金supported by the Research and Innovation Team Topics of Characteristic Medical Center of Chinese People’s Armed Police Force(No.KYCXTD0503)the National Natural Science Foundation of China(No.82170558).
文摘The gut microbiome shows changes under a plateau environment,while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome(IBS);however,the relationship between the two remains unexplored.In this work,we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA(rRNA)sequencing analysis of their fecal samples.Through evaluating the participants’clinical symptoms,combined with an IBS questionnaire,we screened the IBS sub-population in our cohort.The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora.In addition,we found that the longer the time volunteers spent in the plateau environment,the more similar their gut microbiota composition and abundance became compared to those before entering the plateau,and IBS symptoms were significantly alleviated.Therefore,we speculated that the plateau may be a special environment that induces IBS.The taxonomic units g_Alistipes,g_Oscillospira,and s_Ruminococcus_torques,which had been proved to play important roles in IBS pathogenesis,were also abundant in the IBS cohort at high altitudes.Overall,the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS.Our results prompt further research to elucidate the relevant mechanism.
基金supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development(2015ZX09102010).
文摘The restoration of nerve dysfunction after traumatic brain injury(TBI)faces huge challenges due to the limited self-regenerative abilities of nerve tissues.In situ inductive recovery can be achieved utilizing biological scaffolds combined with endogenous human umbilical cord mesenchymal stem cells(HUCMSCs)-derived exosomes(MExos).In this study,brain-derived neurotrophic factor-stimulated HUCMSCs-derived exosomes(BMExos)were composited with collagen/chitosan by 3D printing technology.3D-printed collagen/chitosan/BMExos(3D-CC-BMExos)scaffolds have excellent mechanical properties and biocompatibility.Subsequently,in vivo experiments showed that 3D-CC-BMExos therapy could improve the recovery of neuromotor function and cognitive function in a TBI model in rats.Consistent with the behavioural recovery,the results of histomorphological tests showed that 3D-CC-BMExos therapy could facilitate the remodelling of neural networks,such as improving the regeneration of nerve fibres,synaptic connections and myelin sheaths,in lesions after TBI.
基金supported by a grant from Tianjin Municipal Science and Technology Committee(No.18JCZDJC12000).
文摘To the Editor:Lung fibrosis is characterized by extracellular matrix accumulation and remodeling of the lung interstitium.Although lung fibrosis has been extensively studied,there is still a lack of effective anti-pulmonary fibrosis drugs at present.The pathogenesis of lung fibrosis involves many aspects in which the lung macrophages play a particularly important role.[1]It has been reported that the manipulation of the monocyte/macrophage phenotype switch might be a potential target for many macrophagemediated inflammatory disorders.In our previous study,mice that were exposed to bleomycin(BLM)showed a dynamic change of mononuclear phagocytes in the circulating system,lung alveoli,and interstitial compartments.The rapid increase of the number of circulating Ly6Chi monocytes after BLM stimulation,followed by the expansion of M2-like alveolar macrophages(AMf)numbers,is closely associated with lung inflammatory response and fibrosis.[2,3]
基金supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development(2015ZX09102010).
文摘The secretome secreted by stem cells and bioactive material has emerged as a promising therapeutic choice for traumatic brain injury(TBI).We aimed to determine the effect of 3D-printed collagen/chitosan/secretome derived from human umbilical cord blood mesenchymal stem cells scaffolds(3D-CC-ST)on the injured tissue regeneration process.3D-CC-ST was performed using 3D printing technology at a low temperature(20C),and the physical properties and degeneration rate were measured.The utilization of low temperature contributed to a higher cytocompatibility of fabricating porous 3D architectures that provide a homogeneous distribution of cells.Immediately after the establishment of the canine TBI model,3D-CC-ST and 3D-CC(3D-printed collagen/chitosan scaffolds)were implanted into the cavity of TBI.Following implantation of scaffolds,neurological examination and motor evoked potential detection were performed to analyze locomotor function recovery.Histological and immunofluorescence staining were performed to evaluate neuro-regeneration.The group treated with 3D-CC-ST had good performance of behavior functions.Implanting 3D-CC-ST significantly reduced the cavity area,facilitated the regeneration of nerve fibers and vessel reconstruction,and promoted endogenous neuronal differentiation and synapse formation after TBI.The implantation of 3D-CC-ST also markedly reduced cell apoptosis and regulated the level of systemic inflammatory factors after TBI.
基金This work was supported by a grant from the National Natural Science Foundation of China(No.81771944).
文摘Background:High-frequency irreversible electroporation(H-FIRE)is a novel,next-generation nanoknife technology with the advantage of relieving irreversible electroporation(IRE)-induced muscle contractions.However,the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined.This study aimed to compare the efficacy of the two treatments in vivo.Methods:Ten Bamaminiature swinewere divided into two group:five in the 1-day group and five in the 7-day group.The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant(Krans),rate constant(Kep)and extravascular extracellular volume fraction(Ve)value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),size of the ablation zone,and histologic analysis.Each animal underwent the IRE andH-FIRE.Temperatures of the electrodesweremeasured during ablation.DCE-MRI images were obtained 1,4,and 7 days after ablation in the 7-day group.All animals in the two groups were euthanized 1 day or 7 days after ablation,and subsequently,IRE and H-FIRE treated liver tissues were collected for histological examination.Student’s t test or Mann-Whitney U test was applied for comparing any two groups.One-way analysis of variance(ANOVA)test and Welch’s ANOVA test followed byHolm-Sidak’smultiple comparisons test,one-wayANOVAwith repeatedmeasures followed by Bonferroni test,or Kruskal-Wallis H test followed by Dunn’s multiple comparison test was used for multiple group comparisons and post hoc analyses.Pearson correlation coefficient test was conducted to analyze the relationship between two variables.Results:Higher Ve was seen in IRE zone than in H-FIRE zone(0.14±0.02 vs.0.08±0.05,t=2.408,P=0.043)on day 4,but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points(all P>0.05).For IRE zone,the greatest Ktrans was seen on day 7,which was significantly higher than that on day 1(P=0.033).The ablation zone size of H-FIRE was significantly larger than IRE 1 day(4.74±0.88 cm^(2)vs.3.20±0.77 cm^(2),t=3.241,P=0.009)and 4 days(2.22±0.83 cm^(2)vs.1.30±0.50 cm^(2),t=2.343,P=0.041)after treatment.Apoptotic index(0.05±0.02 vs.0.73±0.06 vs.0.68±0.07,F=241.300,P<0.001)and heat shock protein 70(HSP70)(0.03±0.01 vs.0.46±0.09 vs.and 0.42±0.07,F=64.490,P<0.001)were significantly different between the untreated,IRE and H-FIRE zones,but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone(both P>0.05).Electrode temperature variations were not significantly different between the two zones(18.00±3.77℃ vs.16.20±7.45℃,t=0.682,P=0.504).The Ktrans value(r=0.940,P=0.017)and the Kep value(r=0.895,P=0.040)of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.Conclusions:H-FIRE showed a comparable ablation effect to IRE.DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.