Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a...Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.展开更多
Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration...Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.展开更多
This paper explores the association between intestinal microecology and digestive health and disease recovery in children with pneumonia.Intestinal microecological imbalance is common in children with pneumonia,which ...This paper explores the association between intestinal microecology and digestive health and disease recovery in children with pneumonia.Intestinal microecological imbalance is common in children with pneumonia,which is closely associated with digestive health and disease recovery.Intestinal microecological imbalance may affect digestive enzyme activity,intestinal mucosal barrier function,and nutrient absorption,which in turn affects digestive health.In addition,intestinal microecological imbalances may be associated with immune regulation,inflammatory responses,and pathogen suppression,affecting disease recovery.Strategies to regulate intestinal microecology include probiotic supplementation,dietary modification,and pharmacological treatment.Currently,the study of intestinal microecology in children with pneumonia faces challenges,and there is a need for improved research methods,individualized treatment strategies,and the development of novel probiotics.In conclusion,the intestinal microecology of children with pneumonia is closely related to digestive health and disease recovery,and the regulation of intestinal microecology is of great significance to the treatment of children with pneumonia.Furthermore,future research should further explore the application of the microecology of the intestinal microecology in the treatment of children with pneumonia.展开更多
Objective:Despite trials and programs for the prevention of childhood mortality due to pneumonia,Ethiopia is among the top five countries with the highest number of deaths due to pneumonia.Although the prevalence of p...Objective:Despite trials and programs for the prevention of childhood mortality due to pneumonia,Ethiopia is among the top five countries with the highest number of deaths due to pneumonia.Although the prevalence of pneumonia has increased in the abovementioned trials,little is known about the recovery time from severe pneumonia and its predictors in the study area.Therefore,this study aimed to assess the time to recovery from severe pneumonia and its predictors among pediatric patients admitted to Mizan-Tepi University Teaching Hospital,Ethiopia,in 2022.Methods:A total of 591 children admitted for severe pneumonia were selected using simple random sampling.Data were entered into Epi-data version 4.4.2.1 and expor ted to STATA version 14 for analysis,and the assumptions of Cox propor tional hazard models and goodness of fit were assessed through Shoenfeld residual and Cox-Snell residual,respectively.Bivariate and multivariable Cox regression models were used to identify the predictors of mor tality.Results:This study revealed that 91.54%(95%confidence interval[CI]:89.00–93.53)of participants recovered with an incidence rate of 24.10(95%CI:22.15–26.21)per 100 person-day–observations.The hmedian recovery time of children was 4 days(95%CI:2–6).Children who were not exclusively breastfed(AHR=1.3;95%CI:1.03–1.66),who had a history of inability to suck/feed(AHR=0.81;95%CI:0.65–0.99)were independent predictors of the time to recovery.Conclusions:Children with severe pneumonia who had not exclusively breastfed and who had a history of inability to suck/feed were independent predictors of time to recovery.Therefore,all stakeholders and concerned health care providers should focus more on early diagnosis and management and hasten early recovery based on the identified factors.展开更多
After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for man...After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for many central nervous system diseases,including traumatic brain injury and Alzheimer's disease.However,whether it can play a role in the treatment of spinal cord injury remains unclear.In this study,the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression.We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators,including tumor necrosis factor-α,interleukin-6 and interleukin-1β.It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype,and reduced the amount of reactive oxygen species in the acute phase.Furthermore,the survival of residual neural cells around the injury epicenter,and neuronal and axonal regeneration were also markedly enhanced,which promoted locomotor recovery in the model rats.Collectively,our findings support the conclusion that tau inhibition can attenuate neuroinflammation,alleviate oxidative stress,protect residual cells,facilitate neurogenesis,and improve the functional recovery after spinal cord injury,and thus suggest that tau could be a good molecular target for spinal cord injury therapy.展开更多
Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promo...Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.展开更多
Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes af...Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.展开更多
Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactiv...Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.展开更多
BACKGROUND This study aimed to evaluate the safety of enhanced recovery after surgery(ERAS)in elderly patients with gastric cancer(GC).AIM To evaluate the safety of ERAS in elderly patients with GC.METHODS The PubMed,...BACKGROUND This study aimed to evaluate the safety of enhanced recovery after surgery(ERAS)in elderly patients with gastric cancer(GC).AIM To evaluate the safety of ERAS in elderly patients with GC.METHODS The PubMed,EMBASE,and Cochrane Library databases were used to search for eligible studies from inception to April 1,2023.The mean difference(MD),odds ratio(OR)and 95%confidence interval(95%CI)were pooled for analysis.The quality of the included studies was evaluated using the Newcastle-Ottawa Scale scores.We used Stata(V.16.0)software for data analysis.RESULTS This study consists of six studies involving 878 elderly patients.By analyzing the clinical outcomes,we found that the ERAS group had shorter postoperative hospital stays(MD=-0.51,I2=0.00%,95%CI=-0.72 to-0.30,P=0.00);earlier times to first flatus(defecation;MD=-0.30,I²=0.00%,95%CI=-0.55 to-0.06,P=0.02);less intestinal obstruction(OR=3.24,I2=0.00%,95%CI=1.07 to 9.78,P=0.04);less nausea and vomiting(OR=4.07,I2=0.00%,95%CI=1.29 to 12.84,P=0.02);and less gastric retention(OR=5.69,I2=2.46%,95%CI=2.00 to 16.20,P=0.00).Our results showed that the conventional group had a greater mortality rate than the ERAS group(OR=0.24,I2=0.00%,95%CI=0.07 to 0.84,P=0.03).However,there was no statistically significant difference in major complications between the ERAS group and the conventional group(OR=0.67,I2=0.00%,95%CI=0.38 to 1.18,P=0.16).CONCLUSION Compared to those with conventional recovery,elderly GC patients who received the ERAS protocol after surgery had a lower risk of mortality.展开更多
Knee osteoarthritis is a degenerative disorder of the knee,which leads to joint pain,stiffness,and inactivity and significantly affects the quality of life.With an increased prevalence of obesity and greater life expe...Knee osteoarthritis is a degenerative disorder of the knee,which leads to joint pain,stiffness,and inactivity and significantly affects the quality of life.With an increased prevalence of obesity and greater life expectancies,total knee arthroplasty(TKA)is now one of the major arthroplasty surgeries performed for knee osteoarthritis.When enhanced recovery after surgery(ERAS)was introduced in TKA,clinical outcomes were enhanced and the economic burden on the healthcare system was reduced.ERAS is an evidence-based scientific protocol aimed at ameliorating the surgical stress response.ERAS aims to enhance the recovery phase,which encompasses multidisciplinary strategies at every step of perioperative care,including the rehabilitation phase.Implementation of ERAS in TKA aids in reducing the length of hospital stay,improving pain management,reducing perioperative complications,and enhancing patient satisfaction.Multidisciplinary collaboration,integrating the expertise of anesthesiologists,orthopedic surgeons,nursing personnel,and other healthcare professionals,is the cornerstone of ERAS in patients undergoing TKA.展开更多
Emulsification is one of the important mechanisms of surfactant flooding. To improve oil recovery for low permeability reservoirs, a highly efficient emulsification oil flooding system consisting of anionic surfactant...Emulsification is one of the important mechanisms of surfactant flooding. To improve oil recovery for low permeability reservoirs, a highly efficient emulsification oil flooding system consisting of anionic surfactant sodium alkyl glucosyl hydroxypropyl sulfonate(APGSHS) and zwitterionic surfactant octadecyl betaine(BS-18) is proposed. The performance of APGSHS/BS-18 mixed surfactant system was evaluated in terms of interfacial tension, emulsification capability, emulsion size and distribution, wettability alteration, temperature-resistance and salt-resistance. The emulsification speed was used to evaluate the emulsification ability of surfactant systems, and the results show that mixed surfactant systems can completely emulsify the crude oil into emulsions droplets even under low energy conditions. Meanwhile,the system exhibits good temperature and salt resistance. Finally, the best oil recovery of 25.45% is achieved for low permeability core by the mixed surfactant system with a total concentration of 0.3 wt%while the molar ratio of APGSHS:BS-18 is 4:6. The current study indicates that the anionic/zwitterionic mixed surfactant system can improve the oil flooding efficiency and is potential candidate for application in low permeability reservoirs.展开更多
BACKGROUND We report a rare case of full neurological recovery from severe nonexertional heat stroke in a 67-year-old woman with an initial Glasgow Coma Scale of 3.This report raises awareness among doctors that when ...BACKGROUND We report a rare case of full neurological recovery from severe nonexertional heat stroke in a 67-year-old woman with an initial Glasgow Coma Scale of 3.This report raises awareness among doctors that when heatstroke is diagnosed,comprehensive treatment should be implemented as soon as possible.Moreover,targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.CASE SUMMARY A previously healthy 67-year-old woman with an initial Glasgow Coma Scale of 3 was found lying prone on the road at noon on a summer day.Laboratory tests revealed multiorgan failure.As soon as heatstroke was diagnosed,comprehensive treatment was implemented.On hospital Day 3,the patient was extubated.Her initial Sequential Organ Failure Assessment score at hospitalization was 14 and decreased to 2 on hospital Day 4.On the seventh day following hospital admission,as the patient’s general condition improved,the levels of laboratory test findings decreased rapidly.Finally,the patient gradually recovered with no other neurological symptoms(the Glasgow Coma Scale at discharge was 15,and her ability to walk independently was restored).CONCLUSION This case demonstrated that targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.展开更多
For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein th...For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.展开更多
基金supported by the Stem Cell and Translation National Key Project,No.2016YFA0101403(to ZC)the National Natural Science Foundation of China,Nos.82171250 and 81973351(to ZC)+6 种基金the Natural Science Foundation of Beijing,No.5142005(to ZC)Beijing Talents Foundation,No.2017000021223TD03(to ZC)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,No.CIT&TCD20180333(to ZC)Beijing Municipal Health Commission Fund,No.PXM2020_026283_000005(to ZC)Beijing One Hundred,Thousand,and Ten Thousand Talents Fund,No.2018A03(to ZC)the Royal Society-Newton Advanced Fellowship,No.NA150482(to ZC)the National Natural Science Foundation of China for Young Scientists,No.31900740(to SL)。
文摘Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
基金Shandong Province Traditional Chinese Medicine Science and Technology Project"Efficacy Evaluation of Acupoint Application Synergy Model Intervention in Bronchoscopic Treatment of Severe Mycoplasma Pneumonia in Children"(Project No.2020M177)。
文摘This paper explores the association between intestinal microecology and digestive health and disease recovery in children with pneumonia.Intestinal microecological imbalance is common in children with pneumonia,which is closely associated with digestive health and disease recovery.Intestinal microecological imbalance may affect digestive enzyme activity,intestinal mucosal barrier function,and nutrient absorption,which in turn affects digestive health.In addition,intestinal microecological imbalances may be associated with immune regulation,inflammatory responses,and pathogen suppression,affecting disease recovery.Strategies to regulate intestinal microecology include probiotic supplementation,dietary modification,and pharmacological treatment.Currently,the study of intestinal microecology in children with pneumonia faces challenges,and there is a need for improved research methods,individualized treatment strategies,and the development of novel probiotics.In conclusion,the intestinal microecology of children with pneumonia is closely related to digestive health and disease recovery,and the regulation of intestinal microecology is of great significance to the treatment of children with pneumonia.Furthermore,future research should further explore the application of the microecology of the intestinal microecology in the treatment of children with pneumonia.
文摘Objective:Despite trials and programs for the prevention of childhood mortality due to pneumonia,Ethiopia is among the top five countries with the highest number of deaths due to pneumonia.Although the prevalence of pneumonia has increased in the abovementioned trials,little is known about the recovery time from severe pneumonia and its predictors in the study area.Therefore,this study aimed to assess the time to recovery from severe pneumonia and its predictors among pediatric patients admitted to Mizan-Tepi University Teaching Hospital,Ethiopia,in 2022.Methods:A total of 591 children admitted for severe pneumonia were selected using simple random sampling.Data were entered into Epi-data version 4.4.2.1 and expor ted to STATA version 14 for analysis,and the assumptions of Cox propor tional hazard models and goodness of fit were assessed through Shoenfeld residual and Cox-Snell residual,respectively.Bivariate and multivariable Cox regression models were used to identify the predictors of mor tality.Results:This study revealed that 91.54%(95%confidence interval[CI]:89.00–93.53)of participants recovered with an incidence rate of 24.10(95%CI:22.15–26.21)per 100 person-day–observations.The hmedian recovery time of children was 4 days(95%CI:2–6).Children who were not exclusively breastfed(AHR=1.3;95%CI:1.03–1.66),who had a history of inability to suck/feed(AHR=0.81;95%CI:0.65–0.99)were independent predictors of the time to recovery.Conclusions:Children with severe pneumonia who had not exclusively breastfed and who had a history of inability to suck/feed were independent predictors of time to recovery.Therefore,all stakeholders and concerned health care providers should focus more on early diagnosis and management and hasten early recovery based on the identified factors.
基金supported by the National Natural Science Foundation of China,No.81801907(to NNC)Shenzhen Commitiee of Science and Technology,No.JCYJ20180307145215811(to NNC)+1 种基金Sun Yat-sen University Youth Teacher Training Project,No.19ykpy11(to NNC)Sanming Project of Medicine in Shenzhen,No.SZSM201911002(to SYL)。
文摘After spinal cord injury,the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase,and levels of both correlate with injury severity.Tau inhibition is considered effective therapy for many central nervous system diseases,including traumatic brain injury and Alzheimer's disease.However,whether it can play a role in the treatment of spinal cord injury remains unclear.In this study,the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression.We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators,including tumor necrosis factor-α,interleukin-6 and interleukin-1β.It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype,and reduced the amount of reactive oxygen species in the acute phase.Furthermore,the survival of residual neural cells around the injury epicenter,and neuronal and axonal regeneration were also markedly enhanced,which promoted locomotor recovery in the model rats.Collectively,our findings support the conclusion that tau inhibition can attenuate neuroinflammation,alleviate oxidative stress,protect residual cells,facilitate neurogenesis,and improve the functional recovery after spinal cord injury,and thus suggest that tau could be a good molecular target for spinal cord injury therapy.
基金supported by the National Natural Science Foundation of China,Nos.81801169 (to LXX),82071404 (to HC),81870952 (to HMW)。
文摘Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.
基金supported by NIH grants RF1 AG069466(to JL and LDM),R01 NS099628(to JL),and AG069466(to JL and LDM)the American Heart Association award 20POST35180172(to FB)。
文摘Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.
基金supported by the National Natural Science Foundation of China,Nos.81941011(to XL),31771053(to HD),31730030(to XL),31971279(to ZY),31900749(to PH),31650001(to XL),31320103903(to XL),31670988(to ZY)the Natural Science Foundation of Beijing,Nos.7222004(to HD)+1 种基金a grant from Ministry of Science and Technology of China,Nos.2017YFC1104002(to ZY),2017YFC1104001(to XL)a grant from Beihang University,No.JKF-YG-22-B001(to FH)。
文摘Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.
基金Supported by Chongqing Medical University Program for Youth Innovation in Future Medicine,No.W0190.
文摘BACKGROUND This study aimed to evaluate the safety of enhanced recovery after surgery(ERAS)in elderly patients with gastric cancer(GC).AIM To evaluate the safety of ERAS in elderly patients with GC.METHODS The PubMed,EMBASE,and Cochrane Library databases were used to search for eligible studies from inception to April 1,2023.The mean difference(MD),odds ratio(OR)and 95%confidence interval(95%CI)were pooled for analysis.The quality of the included studies was evaluated using the Newcastle-Ottawa Scale scores.We used Stata(V.16.0)software for data analysis.RESULTS This study consists of six studies involving 878 elderly patients.By analyzing the clinical outcomes,we found that the ERAS group had shorter postoperative hospital stays(MD=-0.51,I2=0.00%,95%CI=-0.72 to-0.30,P=0.00);earlier times to first flatus(defecation;MD=-0.30,I²=0.00%,95%CI=-0.55 to-0.06,P=0.02);less intestinal obstruction(OR=3.24,I2=0.00%,95%CI=1.07 to 9.78,P=0.04);less nausea and vomiting(OR=4.07,I2=0.00%,95%CI=1.29 to 12.84,P=0.02);and less gastric retention(OR=5.69,I2=2.46%,95%CI=2.00 to 16.20,P=0.00).Our results showed that the conventional group had a greater mortality rate than the ERAS group(OR=0.24,I2=0.00%,95%CI=0.07 to 0.84,P=0.03).However,there was no statistically significant difference in major complications between the ERAS group and the conventional group(OR=0.67,I2=0.00%,95%CI=0.38 to 1.18,P=0.16).CONCLUSION Compared to those with conventional recovery,elderly GC patients who received the ERAS protocol after surgery had a lower risk of mortality.
文摘Knee osteoarthritis is a degenerative disorder of the knee,which leads to joint pain,stiffness,and inactivity and significantly affects the quality of life.With an increased prevalence of obesity and greater life expectancies,total knee arthroplasty(TKA)is now one of the major arthroplasty surgeries performed for knee osteoarthritis.When enhanced recovery after surgery(ERAS)was introduced in TKA,clinical outcomes were enhanced and the economic burden on the healthcare system was reduced.ERAS is an evidence-based scientific protocol aimed at ameliorating the surgical stress response.ERAS aims to enhance the recovery phase,which encompasses multidisciplinary strategies at every step of perioperative care,including the rehabilitation phase.Implementation of ERAS in TKA aids in reducing the length of hospital stay,improving pain management,reducing perioperative complications,and enhancing patient satisfaction.Multidisciplinary collaboration,integrating the expertise of anesthesiologists,orthopedic surgeons,nursing personnel,and other healthcare professionals,is the cornerstone of ERAS in patients undergoing TKA.
基金financially supported by National Natural Science Foundation of China(No.22302229)Beijing Municipal Excellent Talent Training Funds Youth Advanced Individual Project(No.2018000020124G163)。
文摘Emulsification is one of the important mechanisms of surfactant flooding. To improve oil recovery for low permeability reservoirs, a highly efficient emulsification oil flooding system consisting of anionic surfactant sodium alkyl glucosyl hydroxypropyl sulfonate(APGSHS) and zwitterionic surfactant octadecyl betaine(BS-18) is proposed. The performance of APGSHS/BS-18 mixed surfactant system was evaluated in terms of interfacial tension, emulsification capability, emulsion size and distribution, wettability alteration, temperature-resistance and salt-resistance. The emulsification speed was used to evaluate the emulsification ability of surfactant systems, and the results show that mixed surfactant systems can completely emulsify the crude oil into emulsions droplets even under low energy conditions. Meanwhile,the system exhibits good temperature and salt resistance. Finally, the best oil recovery of 25.45% is achieved for low permeability core by the mixed surfactant system with a total concentration of 0.3 wt%while the molar ratio of APGSHS:BS-18 is 4:6. The current study indicates that the anionic/zwitterionic mixed surfactant system can improve the oil flooding efficiency and is potential candidate for application in low permeability reservoirs.
文摘BACKGROUND We report a rare case of full neurological recovery from severe nonexertional heat stroke in a 67-year-old woman with an initial Glasgow Coma Scale of 3.This report raises awareness among doctors that when heatstroke is diagnosed,comprehensive treatment should be implemented as soon as possible.Moreover,targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.CASE SUMMARY A previously healthy 67-year-old woman with an initial Glasgow Coma Scale of 3 was found lying prone on the road at noon on a summer day.Laboratory tests revealed multiorgan failure.As soon as heatstroke was diagnosed,comprehensive treatment was implemented.On hospital Day 3,the patient was extubated.Her initial Sequential Organ Failure Assessment score at hospitalization was 14 and decreased to 2 on hospital Day 4.On the seventh day following hospital admission,as the patient’s general condition improved,the levels of laboratory test findings decreased rapidly.Finally,the patient gradually recovered with no other neurological symptoms(the Glasgow Coma Scale at discharge was 15,and her ability to walk independently was restored).CONCLUSION This case demonstrated that targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.
基金supported by Hong Kong Spinal Cord Injury Fund (HKSCIF),China (to HZ)。
文摘For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.
