Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular factors.Although the spinal cord ...Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular factors.Although the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).展开更多
BACKGROUND Blood glucose and serum albumin have been associated with cardiovascular disease prognosis,but the impact of admission-blood-glucose-to-albumin ratio(AAR)on adverse outcomes in critical ill coronary artery ...BACKGROUND Blood glucose and serum albumin have been associated with cardiovascular disease prognosis,but the impact of admission-blood-glucose-to-albumin ratio(AAR)on adverse outcomes in critical ill coronary artery disease(CAD)patients was not investigated.METHODS Patients diagnosed with CAD were non-consecutively selected from the MIMIC-IV database and categorized into quartiles based on their AAR.The primary outcome was 1-year mortality,and secondary endpoints were in-hospital mortality,acute kidney injury(AKI),and renal replacement therapy(RRT).A restricted cubic splines model and Cox proportional hazard models assessed the association between AAR and adverse outcomes in CAD patients.Kaplan-Meier survival analysis determined differences in endpoints across subgroups.RESULTS A total of 8360 patients were included.There were 726 patients(8.7%)died in the hospital and 1944 patients(23%)died at 1 year.The incidence of AKI and RRT was 63%and 4.3%,respectively.High AAR was markedly associated with in-hospital mortality(HR=1.587,P=0.003),1-year mortality(HR=1.502,P<0.001),AKI incidence(HR=1.579,P<0.001),and RRT(HR=1.640,P<0.016)in CAD patients in the completely adjusted Cox proportional hazard model.Kaplan-Meier survival analysis noted substantial differences in all endpoints based on AAR quartiles.Stratified analysis and interaction test demonstrated stable correlations between AAR and outcomes.CONCLUSIONS The results highlight that AAR may be a potential indicator for assessing in-hospital mortality,1-year mortality,and adverse renal prognosis in critical CAD patients.展开更多
This article,empowered by ChatGPT and through retrieving relevant historical literature,explores how the translator Sun Yat-sen flexibly employed strategies like domestication and foreignization,as well as methods lik...This article,empowered by ChatGPT and through retrieving relevant historical literature,explores how the translator Sun Yat-sen flexibly employed strategies like domestication and foreignization,as well as methods like omission,addition,and modification in his translation of Ambulance Lectures:First Aid to the Injured.Additionally,the research highlights the use of ChatGPT as a tool to assist in the study.While ChatGPT is able to provide comprehensive knowledge quickly and proper translations,improvements are still needed in terms of image accuracy and citation generation.By providing specific context,probing for factual evidence,clarifying the reference objects,and narrowing the scope,prompts can be gradually refined for increasingly satisfactory outcomes.展开更多
Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,mar...Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.展开更多
Neural stem and progenitor cell(NSPC)transpla ntation has emerged as a promising therapeutic strategy for replacing lost neuronal populations and repairing damaged neural circuits following nervous system injury and d...Neural stem and progenitor cell(NSPC)transpla ntation has emerged as a promising therapeutic strategy for replacing lost neuronal populations and repairing damaged neural circuits following nervous system injury and disease.A great deal of experimental work has investigated the biology of NSPC grafting in preclinical animal models;more recently.展开更多
Objective:To investigate the clinical efficacy and safety of percutaneous kyphoplasty at different surgical timings in the treatment of osteoporotic vertebral compression fracture(OVCF)based on the theory of“dynamic-...Objective:To investigate the clinical efficacy and safety of percutaneous kyphoplasty at different surgical timings in the treatment of osteoporotic vertebral compression fracture(OVCF)based on the theory of“dynamic-static integration”.Methods:Patients with OVCF who underwent percutaneous kyphoplasty in our hospital were selected and divided into Groups A,B,and C for those undergoing surgery within 7,7—21,and>21 days of fracture occurrence.The variations in the amount of bone cement injected,pre-and post-operative pain levels,functional activity,deformity correction of the injured vertebrae,bone cement leakage,and vertebral body height loss were compared among the three groups.Results:Regarding pain relief and functional activity,the postoperative Visual Analog Scale and Oswestry Disability Index scores of the three groups significantly improved.Furthermore,the deformities of the injured vertebrae in the three groups were significantly corrected,with Groups A and B exhibiting superior correction compared to Group C.Moreover,the bone cement leakage rates in groups A and C were higher than that in Group B.At the 3-month follow-up,the loss of vertebral height in Group C was significantly higher than those in groups A and B.Conclusion:Kyphoplasty is effective for OVCF treatment.Early surgery can effectively restore the vertebral height of the injured vertebra,reduce kyphosis,and reduce height loss of the injured vertebra after surgery;nevertheless,treatment within 1—3 weeks of the fracture can reduce the occurrence of bone cement leakage,making the surgery safer.Therefore,surgical treatment within 1—3 weeks of fracture is safer and can achieve satisfactory therapeutic effects.From the perspective of traditional Chinese medicine,PKP surgery can transform the fracture end from a micromotion state to a fixed state,which fully embodies the theory of“dynamic-static integration”.展开更多
The germinal matrix being an accumulation of immature blood vessels in the premature infant brain is known to be the main cause of the intracranial hemorrhage. To investigate the injuring mechanism to the blood vessel...The germinal matrix being an accumulation of immature blood vessels in the premature infant brain is known to be the main cause of the intracranial hemorrhage. To investigate the injuring mechanism to the blood vessels of the germinal matrix, a modeling scenario that consists of three basic steps is proposed. First, the cerebral blood flow that depends on autoregulation, CO2 reactivity, and variations of intracranial pressure is modeled. Second, the chaotic blood vessel network of the germinal matrix is generated, and blood pressures in the vessels of this network are computed dependent on the outcome of the first step. In the third step, the pressures computed on the second step are used in finite element simulations of separate blood vessels of the germinal matrix to detect critical values for vessels impairment.展开更多
Objective:To analyze characters of magnetic resonance spectroscopy(MRS) and diffusion tensor imaging(DTI) in the diagnosis of mild trauma brain injuries(MTBI) in frontal lobe and to compare with conventional magnetic ...Objective:To analyze characters of magnetic resonance spectroscopy(MRS) and diffusion tensor imaging(DTI) in the diagnosis of mild trauma brain injuries(MTBI) in frontal lobe and to compare with conventional magnetic resonance imaging(MRI).Methods:A total of 21 patients were selected,who all aged 12-51 years old and had injury within 24 hours.Computer tomography (CT) and the Glasgow Coma Scale were used to evaluate the degree of injury.All patients were diagnosed as MTBI,and 19 had conventional MRI,MRS and DTI.The major parameters of MRS were Probe-P sequence,TE= 144 or 35 ms,and both single voxel spectrum and chemical shift imging were included.The major parameters of DTI were diffusion directions =15,b value = 1000 s/mm^2. Frational anisotropic(FA) map and average ADC map were obtained to evaluate DTI result. Positive deletion ratio was observed and the imaging changes were compared between injured side and normal side.Results:All 21 patients had CT scan and Glasgow scale.A total of 19 patients had conventional MRI.DTI and MRS.Results of CT and conventional MRI showed no significant abnormality in lobe,and Glasgow scale showed mild type.MRS result showed significant decrease in N-acetyl aspartate(NAA) and NAA/creatine(Cr) in 13 cases(68.4%) (P【0.001),and increase in lactic acid(Lac) in 7 cases(36.8%).FA mapping of the frontal lobe displayed significant changes in 7 cases(36.8%),with 5 out of the 7 cases having increase in FA value.And there was no significant difference in average ADC.Conclusions:MRS and DTI might be more sensible than other methods,such as CT and conventional MRI in diagnosis of MTBI.The particular changes were reduced NAA and increased Lac for MRS.and increased FA values for DTI.展开更多
Spinal cord injury （SCI） damages not only the gray matter neurons, but also the white matter axonal tracts that carry signals to and from the brain, re- suiting in permanent loss of function below injury. Neural ste...Spinal cord injury （SCI） damages not only the gray matter neurons, but also the white matter axonal tracts that carry signals to and from the brain, re- suiting in permanent loss of function below injury. Neural stem cells （NSCs） have high therapeutic potential for reconstruction of the injured spinal cord since they can potentially fnrm neuronal relays to bridge functional con-nectivity between separated spinal cord segments. This requires host axonal regeneration into and connectivity with donor neurons, and axonal growth and connectivity of donor neurons to host central nervous system （CNS） circuitry. In this mini-review, we will discuss key studies that explore novel neuronal relay formation by grafting NSCs in models of SCI, with emphasis on long-distance axonal growth and connectivity of NSCs grafted into in-jured spinal cord.展开更多
Objective The microglias is the representative of immune cells in the brain. It plays dual roles of both repairing and damaging in injured nervous system, and works as an inevitable component of the circumstance of in...Objective The microglias is the representative of immune cells in the brain. It plays dual roles of both repairing and damaging in injured nervous system, and works as an inevitable component of the circumstance of injured neurons. This study was aiming at the effects of the microglias on the biological activities of mesenchymal stem cells （MSCs） in the circumstance of injured neurons. Methods MSCs were obtained by primary culture. We adopted PC12 cells （PC12） and BV2 cells （BV2） to substitute for neurons and microglias, respectively. PC12 were injured by aged Aβ1-40 and the supernatant of the injured PC12 was used to set up the circumstance of injured neurons. Transwells were used for co-culture of BV2 and MSCs, which allowed the independent detection of cells after co-culture. Immunofluorescence was used to identify MSCs and neuron-differentiating cells with CD44 and neuron specific enolase （NSE） staining, respectively. MTT assay was adopted to measure the proliferation. Results In the circumstance of both BV2 presence and injured PC 12 supernatant incubation, either the proliferation or the differentiation of MSCs reached the highest, which seemed to be contradictory, but we gave our explanations. With the BV2 co-culture, the proliferation of MSCs tend to be higher, but the neuron-differentiating MSCs were similar to those incubated without BV2 co-culture either in normal or injured in PC12 supernatant. With the incubation of injured PC12 supernatant, the neuron-differentiating cells were significantly higher than that of control （P 〈 0.05）. Conclusion In the circumstance of injured neurons, microlgias tend to promote the MSCs proliferation. Although not helpful in neuron-differentiating, microglias did not exert any negative effect either.展开更多
Liver cirrhosis, a devastating liver fibrosis caused by hepatitis/inflammation or tumors, is a major comorbid factor in known surgery fields, such as cardiovascular and abdominal surgeries. It is important to review p...Liver cirrhosis, a devastating liver fibrosis caused by hepatitis/inflammation or tumors, is a major comorbid factor in known surgery fields, such as cardiovascular and abdominal surgeries. It is important to review possible comorbid results in neurosurgical procedures in cirrhotic patients. In the reviewed literature, ChildPugh and model for end-stage liver disease scores are commonly used in the assessment of surgical risks for cirrhotic patients undergoing abdominal, cardiovascular or neurosurgical procedures. The major categories of neurosurgery are traumatic brain injury(TBI), spontaneous intracranial hemorrhage(SICH), brain tumors, and spinal instrumentation procedures. TBI was reported with surgical mortality as high as 34.5% and a complication rate of 87.2%. For SICH, mortality ranged from 22.7% to 47.0%, while complications were reported to be 43.2%. Less is discussed in brain tumor patients; still the postoperative hemorrhage rate approached 26.7%. In spinal fusion instrumentation procedures, the complication rate was as high as 41.0%. Preoperative assessment and correction could possibly decrease complications such as hemorrhage, wound infection and other cirrhosis-related complications(renal, pulmonary, ascites and encephalopathy). In this study, we reviewed the neurosurgical-related literature with regard to liver cirrhosis as a prognostic factor influencing neurosurgical outcomes.展开更多
This study aimed to investigate the neural differentiation of human umbilical cord mesenchymal stem cells （hUCMSCs） under the induction of injured neural cells. After in vitro isolation and culture, passage 5 hUCMSC...This study aimed to investigate the neural differentiation of human umbilical cord mesenchymal stem cells （hUCMSCs） under the induction of injured neural cells. After in vitro isolation and culture, passage 5 hUCMSCs were used for experimentation, hUCMSCs were co-cultured with normal or AI31.4o-injured PC12 cells, PC12 cell supernatant or PC12 cell lysate in a Transwell co-culture system. Western blot analysis and flow cytometry results showed that choline acetyltransferase and microtubule-associated protein 2, a specific marker for neural cells, were expressed in hUCMSCs under various culture conditions, and highest expression was observed in the hUCMSCs co-cultured with injured PC12 cells. Choline acetyltransferase and microtubule-associated protein 2 were not expressed in hUCMSCs cultured alone （no treatment）. Cell Counting Kit-8 assay results showed that hUCMSCs under co-culture conditions promoted the proliferation of injured PC12 cells. These findings suggest that the microenvironment during neural tissue injury can effectively induce neural cell differentiation of hUCMSCs. These differentiated hUCMSCs likely accelerate the repair of injured neural ceils.展开更多
Electroacupuncture at the head acupoints Baihui（GV20） and Shuigou（GV26） improves recovery of neurological function following ischemic cerebrovascular events,but its mechanism remains incompletely understood.We hyp...Electroacupuncture at the head acupoints Baihui（GV20） and Shuigou（GV26） improves recovery of neurological function following ischemic cerebrovascular events,but its mechanism remains incompletely understood.We hypothesized that the action of electroacupuncture at these acupoints is associated with elevated serum levels of transforming growth factor beta 1（TGF-β1）.To test this,we established a rat model of cerebral ischemia by middle cerebral artery occlusion.Electroacupuncture was performed at Baihui and Shuigou with a “dispersedense” wave at an alternating frequency of 2 and 150 Hz,and at a constant intensity of 3 m A.Each electroacupuncture session lasted 30 minutes and was performed every 12 hours for 3 days.Neurological severity scores were lower in injured rats after acupuncture than in those not subjected to treatment.Furthermore,serum level of TGF-β1 was greater after electroacupuncture than after no treatment.Our results indicate that electroacupuncture at Baihui and Shuigou increases the serum level of TGF-β1 in rats with acute cerebral ischemia/reperfusion injury,and exerts neuroprotective effects.展开更多
Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as ...Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as well as embryonic stem cells and induced plu- ripotent stem cells. In particular, transplants of neural progenitor cells （NPCs） have been shown to limit secondary injury and scar formation and create a permissive environment in the injured spinal cord through the provision of neurotrophic molecules and growth supporting matrices that promote growth of injured host axons. Importantly, transplants of NPC are unique in their poten- tial to replace lost neural cells - including neurons, astrocytes,展开更多
The active ingredient of ginseng,ginsenosides Rg1,has been shown to scavenge free radicals and improve antioxidant capacity.This study hypothesized that ginsenosides Rg1 has a protective role in human neuroblastoma ce...The active ingredient of ginseng,ginsenosides Rg1,has been shown to scavenge free radicals and improve antioxidant capacity.This study hypothesized that ginsenosides Rg1 has a protective role in human neuroblastoma cells injured by H2O2.Ginsenosides Rg1 at different concentrations（50 and 100 μM） was used to treat H2O2（150 μM）-injured SH-SY5 Y cells.Results demonstrated that ginsenoside Rg1 elevated the survival rate of SH-SY5 Y cells injured by H2O2,diminished the amount of leaked lactate dehydrogenase,and increased superoxide dismutase activity.Ginsenoside Rg1 effectively suppressed caspase-3 immunoreactivity,and contributed to heat shock protein 70 gene expression,in a dose-dependent manner.These results indicate that ginsenoside Rg1 has protective effects on SH-SY5 Y cells injured by H2O2 and that its mechanism of action is associated with anti-oxidation and the inhibition of apoptosis.展开更多
Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in...Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase d UTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of Neu N-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.展开更多
Conventional vs. polyethylene glycol （PEG）-fusion tech- nologies to repair severed spinal axons： Most spinal cord injuries （SCIs） involve cutor crush-severance of spinal tract axons in the central nervous system ...Conventional vs. polyethylene glycol （PEG）-fusion tech- nologies to repair severed spinal axons： Most spinal cord injuries （SCIs） involve cutor crush-severance of spinal tract axons in the central nervous system （CNS）. Clinical out- comes after CNS axonal severance is very poor because proximal segments of CNS axons lack a suitable environment for outgrowth （Kakulas, 1999; Fitch and Silver, 2008; Rowland et al., 2008; Kwon et al., 2010） and therefore do not naturally regenerate （Ramon y Caial, 1928）. Current strategies to try to increase behavioral recovery after SCI are focused on en- hancing the environment for axonal outgrowth.展开更多
Immediately after an earthquake a healthcare system within a city, comprising several hospitals, endures an extraordinary demand. This paper proposes a new methodology to estimate whether the hospital network has enou...Immediately after an earthquake a healthcare system within a city, comprising several hospitals, endures an extraordinary demand. This paper proposes a new methodology to estimate whether the hospital network has enough capacity to withstand the emergency caused by an earthquake. The ability of healthcare facilities and to provide a broad spectrum of emergency services immediately after a seismic event is assessed through a metamodel that assumes waiting time as main response parameter to assess the hospital network performance. The First Aid network of San Francisco subjected to a 7.2 Mw magnitude earthquake has been used as case study. The total number of injuries and their distributions among the six major San Francisco’s Emergency Departments have been assessed and compared with their capacity that has been determined using a survey conducted by the medical staff of the hospitals. The numerical results have shown that three of the six considered San Francisco’s hospitals cannot provide emergency services to the estimated injured. Two alternatives have been proposed to improve the performance of the network. The fi rst one redistributes existing resources while the second one considers additional resources by designing a new Emergency Department.展开更多
文摘Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular factors.Although the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).
基金supported by the National Nature Science Foundation of China(No.82370336&No.82330014)the Key Research and Development Plan of Heilongjiang Province(2022ZX06C23&JD2023SJ44)the Research Project of the First Affiliated Hospital of Harbin Medical University(No.2021M19).
文摘BACKGROUND Blood glucose and serum albumin have been associated with cardiovascular disease prognosis,but the impact of admission-blood-glucose-to-albumin ratio(AAR)on adverse outcomes in critical ill coronary artery disease(CAD)patients was not investigated.METHODS Patients diagnosed with CAD were non-consecutively selected from the MIMIC-IV database and categorized into quartiles based on their AAR.The primary outcome was 1-year mortality,and secondary endpoints were in-hospital mortality,acute kidney injury(AKI),and renal replacement therapy(RRT).A restricted cubic splines model and Cox proportional hazard models assessed the association between AAR and adverse outcomes in CAD patients.Kaplan-Meier survival analysis determined differences in endpoints across subgroups.RESULTS A total of 8360 patients were included.There were 726 patients(8.7%)died in the hospital and 1944 patients(23%)died at 1 year.The incidence of AKI and RRT was 63%and 4.3%,respectively.High AAR was markedly associated with in-hospital mortality(HR=1.587,P=0.003),1-year mortality(HR=1.502,P<0.001),AKI incidence(HR=1.579,P<0.001),and RRT(HR=1.640,P<0.016)in CAD patients in the completely adjusted Cox proportional hazard model.Kaplan-Meier survival analysis noted substantial differences in all endpoints based on AAR quartiles.Stratified analysis and interaction test demonstrated stable correlations between AAR and outcomes.CONCLUSIONS The results highlight that AAR may be a potential indicator for assessing in-hospital mortality,1-year mortality,and adverse renal prognosis in critical CAD patients.
基金Research on AI Empowered Bilingual Language Asset Management and English Language Teaching Reform(24JG29)Research on the Digital Empowerment in Business English Major Reform and Innovation in the Context of Language Services(National Higher Education Institutions 202412583HN)Chinese Academic Translation Project of“C-E Translation of The Transformation of Rural China”(21WSHB004)。
文摘This article,empowered by ChatGPT and through retrieving relevant historical literature,explores how the translator Sun Yat-sen flexibly employed strategies like domestication and foreignization,as well as methods like omission,addition,and modification in his translation of Ambulance Lectures:First Aid to the Injured.Additionally,the research highlights the use of ChatGPT as a tool to assist in the study.While ChatGPT is able to provide comprehensive knowledge quickly and proper translations,improvements are still needed in terms of image accuracy and citation generation.By providing specific context,probing for factual evidence,clarifying the reference objects,and narrowing the scope,prompts can be gradually refined for increasingly satisfactory outcomes.
基金supported by NIH grants NIH/NIA R01AG069401(to L.Q.)NIH/NHLBI U54HL165442(to K.T.)P30AR069619(to Penn Center for Musculoskeletal Disorders).
文摘Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.
基金supported by the National Institutes of Health(R01NS116404,to JND)Mission Connect,a program of TIRR Foundation(021-101,to JND)。
文摘Neural stem and progenitor cell(NSPC)transpla ntation has emerged as a promising therapeutic strategy for replacing lost neuronal populations and repairing damaged neural circuits following nervous system injury and disease.A great deal of experimental work has investigated the biology of NSPC grafting in preclinical animal models;more recently.
基金supported by the National Natural Science Foundation of China(82374493).
文摘Objective:To investigate the clinical efficacy and safety of percutaneous kyphoplasty at different surgical timings in the treatment of osteoporotic vertebral compression fracture(OVCF)based on the theory of“dynamic-static integration”.Methods:Patients with OVCF who underwent percutaneous kyphoplasty in our hospital were selected and divided into Groups A,B,and C for those undergoing surgery within 7,7—21,and>21 days of fracture occurrence.The variations in the amount of bone cement injected,pre-and post-operative pain levels,functional activity,deformity correction of the injured vertebrae,bone cement leakage,and vertebral body height loss were compared among the three groups.Results:Regarding pain relief and functional activity,the postoperative Visual Analog Scale and Oswestry Disability Index scores of the three groups significantly improved.Furthermore,the deformities of the injured vertebrae in the three groups were significantly corrected,with Groups A and B exhibiting superior correction compared to Group C.Moreover,the bone cement leakage rates in groups A and C were higher than that in Group B.At the 3-month follow-up,the loss of vertebral height in Group C was significantly higher than those in groups A and B.Conclusion:Kyphoplasty is effective for OVCF treatment.Early surgery can effectively restore the vertebral height of the injured vertebra,reduce kyphosis,and reduce height loss of the injured vertebra after surgery;nevertheless,treatment within 1—3 weeks of the fracture can reduce the occurrence of bone cement leakage,making the surgery safer.Therefore,surgical treatment within 1—3 weeks of fracture is safer and can achieve satisfactory therapeutic effects.From the perspective of traditional Chinese medicine,PKP surgery can transform the fracture end from a micromotion state to a fixed state,which fully embodies the theory of“dynamic-static integration”.
文摘The germinal matrix being an accumulation of immature blood vessels in the premature infant brain is known to be the main cause of the intracranial hemorrhage. To investigate the injuring mechanism to the blood vessels of the germinal matrix, a modeling scenario that consists of three basic steps is proposed. First, the cerebral blood flow that depends on autoregulation, CO2 reactivity, and variations of intracranial pressure is modeled. Second, the chaotic blood vessel network of the germinal matrix is generated, and blood pressures in the vessels of this network are computed dependent on the outcome of the first step. In the third step, the pressures computed on the second step are used in finite element simulations of separate blood vessels of the germinal matrix to detect critical values for vessels impairment.
基金supported by the Science Foundation of Haikou Ilealth Bureau(2010-SWY-13-058)Haikou Science Technology Information Bureu(2009-049-1)
文摘Objective:To analyze characters of magnetic resonance spectroscopy(MRS) and diffusion tensor imaging(DTI) in the diagnosis of mild trauma brain injuries(MTBI) in frontal lobe and to compare with conventional magnetic resonance imaging(MRI).Methods:A total of 21 patients were selected,who all aged 12-51 years old and had injury within 24 hours.Computer tomography (CT) and the Glasgow Coma Scale were used to evaluate the degree of injury.All patients were diagnosed as MTBI,and 19 had conventional MRI,MRS and DTI.The major parameters of MRS were Probe-P sequence,TE= 144 or 35 ms,and both single voxel spectrum and chemical shift imging were included.The major parameters of DTI were diffusion directions =15,b value = 1000 s/mm^2. Frational anisotropic(FA) map and average ADC map were obtained to evaluate DTI result. Positive deletion ratio was observed and the imaging changes were compared between injured side and normal side.Results:All 21 patients had CT scan and Glasgow scale.A total of 19 patients had conventional MRI.DTI and MRS.Results of CT and conventional MRI showed no significant abnormality in lobe,and Glasgow scale showed mild type.MRS result showed significant decrease in N-acetyl aspartate(NAA) and NAA/creatine(Cr) in 13 cases(68.4%) (P【0.001),and increase in lactic acid(Lac) in 7 cases(36.8%).FA mapping of the frontal lobe displayed significant changes in 7 cases(36.8%),with 5 out of the 7 cases having increase in FA value.And there was no significant difference in average ADC.Conclusions:MRS and DTI might be more sensible than other methods,such as CT and conventional MRI in diagnosis of MTBI.The particular changes were reduced NAA and increased Lac for MRS.and increased FA values for DTI.
基金the Veterans Administrationthe Canadian Spinal Research Organizationthe California Institute for Regenerative Medicine
文摘Spinal cord injury （SCI） damages not only the gray matter neurons, but also the white matter axonal tracts that carry signals to and from the brain, re- suiting in permanent loss of function below injury. Neural stem cells （NSCs） have high therapeutic potential for reconstruction of the injured spinal cord since they can potentially fnrm neuronal relays to bridge functional con-nectivity between separated spinal cord segments. This requires host axonal regeneration into and connectivity with donor neurons, and axonal growth and connectivity of donor neurons to host central nervous system （CNS） circuitry. In this mini-review, we will discuss key studies that explore novel neuronal relay formation by grafting NSCs in models of SCI, with emphasis on long-distance axonal growth and connectivity of NSCs grafted into in-jured spinal cord.
文摘Objective The microglias is the representative of immune cells in the brain. It plays dual roles of both repairing and damaging in injured nervous system, and works as an inevitable component of the circumstance of injured neurons. This study was aiming at the effects of the microglias on the biological activities of mesenchymal stem cells （MSCs） in the circumstance of injured neurons. Methods MSCs were obtained by primary culture. We adopted PC12 cells （PC12） and BV2 cells （BV2） to substitute for neurons and microglias, respectively. PC12 were injured by aged Aβ1-40 and the supernatant of the injured PC12 was used to set up the circumstance of injured neurons. Transwells were used for co-culture of BV2 and MSCs, which allowed the independent detection of cells after co-culture. Immunofluorescence was used to identify MSCs and neuron-differentiating cells with CD44 and neuron specific enolase （NSE） staining, respectively. MTT assay was adopted to measure the proliferation. Results In the circumstance of both BV2 presence and injured PC 12 supernatant incubation, either the proliferation or the differentiation of MSCs reached the highest, which seemed to be contradictory, but we gave our explanations. With the BV2 co-culture, the proliferation of MSCs tend to be higher, but the neuron-differentiating MSCs were similar to those incubated without BV2 co-culture either in normal or injured in PC12 supernatant. With the incubation of injured PC12 supernatant, the neuron-differentiating cells were significantly higher than that of control （P 〈 0.05）. Conclusion In the circumstance of injured neurons, microlgias tend to promote the MSCs proliferation. Although not helpful in neuron-differentiating, microglias did not exert any negative effect either.
文摘Liver cirrhosis, a devastating liver fibrosis caused by hepatitis/inflammation or tumors, is a major comorbid factor in known surgery fields, such as cardiovascular and abdominal surgeries. It is important to review possible comorbid results in neurosurgical procedures in cirrhotic patients. In the reviewed literature, ChildPugh and model for end-stage liver disease scores are commonly used in the assessment of surgical risks for cirrhotic patients undergoing abdominal, cardiovascular or neurosurgical procedures. The major categories of neurosurgery are traumatic brain injury(TBI), spontaneous intracranial hemorrhage(SICH), brain tumors, and spinal instrumentation procedures. TBI was reported with surgical mortality as high as 34.5% and a complication rate of 87.2%. For SICH, mortality ranged from 22.7% to 47.0%, while complications were reported to be 43.2%. Less is discussed in brain tumor patients; still the postoperative hemorrhage rate approached 26.7%. In spinal fusion instrumentation procedures, the complication rate was as high as 41.0%. Preoperative assessment and correction could possibly decrease complications such as hemorrhage, wound infection and other cirrhosis-related complications(renal, pulmonary, ascites and encephalopathy). In this study, we reviewed the neurosurgical-related literature with regard to liver cirrhosis as a prognostic factor influencing neurosurgical outcomes.
文摘This study aimed to investigate the neural differentiation of human umbilical cord mesenchymal stem cells （hUCMSCs） under the induction of injured neural cells. After in vitro isolation and culture, passage 5 hUCMSCs were used for experimentation, hUCMSCs were co-cultured with normal or AI31.4o-injured PC12 cells, PC12 cell supernatant or PC12 cell lysate in a Transwell co-culture system. Western blot analysis and flow cytometry results showed that choline acetyltransferase and microtubule-associated protein 2, a specific marker for neural cells, were expressed in hUCMSCs under various culture conditions, and highest expression was observed in the hUCMSCs co-cultured with injured PC12 cells. Choline acetyltransferase and microtubule-associated protein 2 were not expressed in hUCMSCs cultured alone （no treatment）. Cell Counting Kit-8 assay results showed that hUCMSCs under co-culture conditions promoted the proliferation of injured PC12 cells. These findings suggest that the microenvironment during neural tissue injury can effectively induce neural cell differentiation of hUCMSCs. These differentiated hUCMSCs likely accelerate the repair of injured neural ceils.
基金supported by the Key Project Fund of Henan Medical Science and Technology of Henan Province Health Bureau in China,No.200902009
文摘Electroacupuncture at the head acupoints Baihui（GV20） and Shuigou（GV26） improves recovery of neurological function following ischemic cerebrovascular events,but its mechanism remains incompletely understood.We hypothesized that the action of electroacupuncture at these acupoints is associated with elevated serum levels of transforming growth factor beta 1（TGF-β1）.To test this,we established a rat model of cerebral ischemia by middle cerebral artery occlusion.Electroacupuncture was performed at Baihui and Shuigou with a “dispersedense” wave at an alternating frequency of 2 and 150 Hz,and at a constant intensity of 3 m A.Each electroacupuncture session lasted 30 minutes and was performed every 12 hours for 3 days.Neurological severity scores were lower in injured rats after acupuncture than in those not subjected to treatment.Furthermore,serum level of TGF-β1 was greater after electroacupuncture than after no treatment.Our results indicate that electroacupuncture at Baihui and Shuigou increases the serum level of TGF-β1 in rats with acute cerebral ischemia/reperfusion injury,and exerts neuroprotective effects.
基金NIH PO1 NS055976,Craig H.Neilsen Foundation,and Shriner’s Hospital for Children
文摘Cellular transplantation for repair of spinal cord injury is a prom- ising therapeutic strategy that includes the use of a variety of neural and non-neural cells isolated or derived from embryonic and adult tissue as well as embryonic stem cells and induced plu- ripotent stem cells. In particular, transplants of neural progenitor cells （NPCs） have been shown to limit secondary injury and scar formation and create a permissive environment in the injured spinal cord through the provision of neurotrophic molecules and growth supporting matrices that promote growth of injured host axons. Importantly, transplants of NPC are unique in their poten- tial to replace lost neural cells - including neurons, astrocytes,
基金supported by the Research and Development Project Fund of Science and Technology Plan Program of Science and Technology Bureau of Beijing of China,No.Z111107067311022
文摘The active ingredient of ginseng,ginsenosides Rg1,has been shown to scavenge free radicals and improve antioxidant capacity.This study hypothesized that ginsenosides Rg1 has a protective role in human neuroblastoma cells injured by H2O2.Ginsenosides Rg1 at different concentrations（50 and 100 μM） was used to treat H2O2（150 μM）-injured SH-SY5 Y cells.Results demonstrated that ginsenoside Rg1 elevated the survival rate of SH-SY5 Y cells injured by H2O2,diminished the amount of leaked lactate dehydrogenase,and increased superoxide dismutase activity.Ginsenoside Rg1 effectively suppressed caspase-3 immunoreactivity,and contributed to heat shock protein 70 gene expression,in a dose-dependent manner.These results indicate that ginsenoside Rg1 has protective effects on SH-SY5 Y cells injured by H2O2 and that its mechanism of action is associated with anti-oxidation and the inhibition of apoptosis.
基金supported by the National Natural Science Foundation of China,No.81672171,81330042the International Cooperation Program of National Natural Science Foundation of China,No.81620108018+2 种基金a grant from the Ministry of Science and Technology of China,No.2014DFR31210a grant from the Tianjin Science and Technology Committee of China,No.13RCGFSY19000,14ZCZDSY00044the Youth Foundation of Tianjin Medical University General Hospital of China,No.ZYYFY2015008
文摘Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase d UTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of Neu N-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.
基金supported by grants from the Lone Star Paralysis Foundation to GDB and JDPby an NIH grant R01 NS081063 to GD
文摘Conventional vs. polyethylene glycol （PEG）-fusion tech- nologies to repair severed spinal axons： Most spinal cord injuries （SCIs） involve cutor crush-severance of spinal tract axons in the central nervous system （CNS）. Clinical out- comes after CNS axonal severance is very poor because proximal segments of CNS axons lack a suitable environment for outgrowth （Kakulas, 1999; Fitch and Silver, 2008; Rowland et al., 2008; Kwon et al., 2010） and therefore do not naturally regenerate （Ramon y Caial, 1928）. Current strategies to try to increase behavioral recovery after SCI are focused on en- hancing the environment for axonal outgrowth.
基金European Research Council under Grant No.ERC_IDEAL RESCUE_637842 of the project IDEAL RESCUE—Integrated Design and Control of Sustainable Communities during Emergencies
文摘Immediately after an earthquake a healthcare system within a city, comprising several hospitals, endures an extraordinary demand. This paper proposes a new methodology to estimate whether the hospital network has enough capacity to withstand the emergency caused by an earthquake. The ability of healthcare facilities and to provide a broad spectrum of emergency services immediately after a seismic event is assessed through a metamodel that assumes waiting time as main response parameter to assess the hospital network performance. The First Aid network of San Francisco subjected to a 7.2 Mw magnitude earthquake has been used as case study. The total number of injuries and their distributions among the six major San Francisco’s Emergency Departments have been assessed and compared with their capacity that has been determined using a survey conducted by the medical staff of the hospitals. The numerical results have shown that three of the six considered San Francisco’s hospitals cannot provide emergency services to the estimated injured. Two alternatives have been proposed to improve the performance of the network. The fi rst one redistributes existing resources while the second one considers additional resources by designing a new Emergency Department.
