Risk factors for acute kidney injury following coronary artery bypass graft surgery in a Chinese population and development of a prediction model

BACKGROUND Acute kidney injury(AKI)after coronary artery bypass graft(CABG)surgery is associated with significant morbidity and mortality.This retrospective study aimed to establish a risk score for postoperative AKI in a Chinese population.METHODS A total of 1138 patients undergoing CABG were collected from September 2018 to May 2020 and divided into a derivation and validation cohort.AKI was defined according to the Kidney Disease Improving Global Outcomes(KDIGO)criteria.Multivariable logistic regression analysis was used to determine the independent predictors of AKI,and the predictive ability of the model was determined using a receiver operating characteristic(ROC)curve.RESULTS The incidence of cardiac surgery–associated acute kidney injury(CSA-AKI)was 24.17%,and 0.53%of AKI patients required dialysis(AKI-D).Among the derivation cohort,multivariable logistic regression showed that age≥70 years,body mass index(BMI)≥25 kg/m2,estimated glomerular filtration rate(eGFR)≤60 mL/min per 1.73 m2,ejection fraction(EF)≤45%,use of statins,red blood cell transfusion,use of adrenaline,intra-aortic balloon pump(IABP)implantation,postoperative low cardiac output syndrome(LCOS)and reoperation for bleeding were independent predictors.The predictive model was scored from 0 to32 points with three risk categories.The AKI frequencies were as follows:0-8 points(15.9%),9-17 points(36.5%)and≥18 points(90.4%).The area under of the ROC curve was 0.730(95%CI:0.691-0.768)in the derivation cohort.The predictive index had good discrimination in the validation cohort,with an area under the curve of 0.735(95%CI:0.655-0.815).The model was well calibrated according to the Hosmer-Lemeshow test(P=0.372).CONCLUSION The performance of the prediction model was valid and accurate in predicting KDIGO-AKI after CABG surgery in Chinese patients,and could improve the early prognosis and clinical interventions.

Panax notoginseng saponins improve recovery after spinal cord transection by upregulating neurotrophic factors

Saponins extracted from Panax notoginseng are neuroprotective, but the mechanisms underlying this effect remain unclear. In the present study, we established a rat model of thoracic（T10） spinal cord transection, and injected Panax notoginseng saponins（100 mg/kg） or saline 30 minutes after injury. Locomotor functions were assessed using the Basso, Beattie, and Bresnahan（BBB） scale from 1 to 30 days after injury, and immunohistochemistry was carried out in the ventral horn of the spinal cord at 1 and 7 days to determine expression of nerve growth factor（NGF） and brain-derived neurotrophic factor（BDNF）. Our results show that at 7–30 days post injury, the BBB score was higher in rats treated with Panax notoginseng saponins than in those that received saline. Furthermore, at 7 days, more NGF- and BDNF-immunoreactive neurons were observed in the ventral horn of the spinal cord of rats that had received Panax notoginseng saponins than in those that received saline. These results indicate that Panax notoginseng saponins caused an upregulation of NGF and BDNF in rats with spinal cord transection, and improved hindlimb motor function.

Glial cell line-derived neurotrophic factor as a treatment after spinal cord injury

Spinal cord injury（SCI）is a devastating trauma that currently affects 54 people out of every million,which is approximately 270,000people in the United States（National Spinal Cord Injury Statistical Center,2013）.The effects of such an injury can cause a loss of both motor and sensory function below the injury site,normally leaving the patient unable to care for themselves entirely and relying on family and friends to provide personal care.Currently there are no.

Examining the properties and therapeutic potential of glial restricted precursors in spinal cord injury

In the aftermath of spinal cord injury,glial restricted precursors（GRPs） and immature astrocytes offer the potential to modulate the inflammatory environment of the injured spinal cord and promote host axon regeneration.Nevertheless clinical application of cellular therapy for the repair of spinal cord injury requires strict quality-assured protocols for large-scale production and preservation that necessitates long-term in vitro expansion.Importantly,such processes have the potential to alter the phenotypic and functional properties and thus therapeutic potential of these cells.Furthermore,clinical use of cellular therapies may be limited by the inflammatory microenvironment of the injured spinal cord,altering the phenotypic and functional properties of grafted cells.This report simulates the process of large-scale GRP production and demonstrates the permissive properties of GRP following long-term in vitro culture.Furthermore,we defined the phenotypic and functional properties of GRP in the presence of inflammatory factors,and call attention to the importance of the microenvironment of grafted cells,underscoring the importance of modulating the environment of the injured spinal cord.

Human umbilical cord blood stem cells and brainderived neurotrophic factor for optic nerve injury: a biomechanical evaluation

Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10^6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

Distribution of paired immunoglobulin-like receptor B in the nervous system related to regeneration difficulties after unilateral lumbar spinal cord injury

Paired immunoglobulin-like receptor B（Pir B） is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of Pir B on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of Pir B（via immunofluorescence） in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for Pir B increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, Pir B was mainly distributed along neuronal and axonal membranes. Pir B was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunoreactivity for Pir B was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the findings suggest a pattern of Pir B immunoreactivity in the nervous system after unilateral spinal transection injury, and also indicate that Pir B may suppress repair after injury.

Vascular endothelial growth factor induced angiogenesis following focal cerebral ischemia/reperfusion injury in rabbits

BACKGROUND： Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor （VEGF） on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic. OBJECTIVE： To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia /reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia. DESIGN： A randomized controlled animal tria SETTNG： Department of Medical Imaging, Second Hospital of Hebei Medical University MATERIALS： Sixty-five healthy male New Zealand rabbits of clean degree, weighing （2.6±0.2） kg, aged 4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia （Beijing Zhongshan Company）, recombinant VEGF165 （Peprotech Company, USA）, biotinylated second antibody and ABC compound （Wuhan Boster Company） were applied. METHODS： The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy, Second Hospital of Hebei Medical University from May to August in 2005. （1） The rabbits were randomly divided into three groups： sham-operated group （n=15）, control group （n=25） and VEGF-treated group （n=-25）. In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion （MCAO） induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165 （2.5 mg/L） was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabbits in the sham-operated group were only drilled but not administrated. （2） The experimental indexes were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The brain tissues in the surrounding regions of the infarcted sites were collected. The positive expressions of the factors of vascular pseudohemophilia in vascular endothelial cells were analyzed with immunohistochemical method. The microvessels in unit statistical field were counted with the imaging analytical software. MAIN OUTCOME MEASURES： The changes of microvascular density in the brain tissue and the positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of the infarcted sites were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment. RESULTS： All the 65 New Zealand rabbits were involved in the analysis of results without deletion. Changes of the number of microvessels at different time points in each group： There were no obvious changes at different time points in the sham-operated group. The numbers of microvessels at 7 and 14 days were obviously more in the control group than in the sham-operated group [（6.0±1.1）, （9.0±0.9） microvessels; （3.0±1.1）, （3.0±1.1） microvessels; P〈 0.05-0.01], and those at 3, 7, 14 and 28 days were obviously more in the VEGF-treated group than in the control group [（8.3±2.0）, （13.4±1.4）, （15.5±2.3）, （6.8± 1.0） microvessels; （3.4±0.6）, （6.0±1.1）, （9.0±0.9）, （3.2±0.8） microvessels; P 〈 0.01]. （2） Positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of infarcted sites： There were no obvious changes at different time points in the sham-operated group. In the control group, the changing law of the expressions was the same as that for the number of microvessels that the expression began to mildly increase at 7 days, reached the peak value at 14 days, and began to reduce at 28 days. In the VEGF-treated group, the expression was obviously increased at 3 days, also reached the peak value at 14 days, and reduced to the normal level at 70 days, but the expressions were obviously stronger than those in the control group at the same time points. CONCLUSION： Angiogenesis can be obviously induced in rabbits after the focal cerebral ischemia/reperfusion injury is treated with VEGF for 18 days.

Changes of norepinephrine and tumor necrosis factor in submandibular gland of rats with sympathetic nerve injury and the protective effect of 17 beta-estradiol

BACKGROUND： Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotective effects. OBJECTIVE： To observe the effect of 17 beta-estradiol on the content of norepinephrine （NE） and level of tumor necrosis factor （TNF） in submandibular glands of rats with sympathetic nerve injury, and analyze the dose-dependence and pathway of action. DESIGN： A randomized control animal study SETTINGS： Department of Hand Surgery, the 252 Hospital of Chinese PLA; Department of Hand Surgery Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology. MATERIALS： Fifty healthy female Wistar rats were randomly divided into 5 groups with 10 rats in each group： sham-operated group, ovariectomy＋6-OHDA＋saline group, ovariectomy＋6-OHDA＋17β-estradiol 50, 200 and 500 μg/kg groups. METHODS： The experiments were carried out in Tongji Medical College, Huazhong University of Science and Technology between October 2005 and March 2006. Bilateral ovaries were only exposed but not resected for the rats in the sham-operated group, but bilateral ovaries were resected in all the other groups. In the ovariectomy＋6-OHDA＋176-estradiol 50, 200 and 500 μg/kg groups, the rats were administrated with intraperitoneal injection of 6-OHDA （8 mg/kg）, and then immediately given 176-estradiol of corresponding dosages respectively, once a day for 10 days continuously. Rats in the sham-operated group and ovariectomy＋6-OHDA＋saline group were administrated with saline of the same volume. After administration, 5 rats in each group were killed to determine the NE contents in bilateral submandibular glands with high performance liquid chromatography-electrochemical detector （HPLC-ECD）, and the other 5 rats were used to determine the TNF levels in submandibular glands with enzyme-linked immunosorbant assay. MAIN OUTCOME MEASURES： The NE contents and TNF levels in submandibular glands of rats in each group were observed. RESULTS： All the 50 rats were involved in the analysis of results. （1） The NE content was obviously lower in the ovariectomy＋6-OHDA＋saline group than in the sham-operated group [（1 035±196）, （1 823±314） ng/g, P 〈 0.05], there were no significant differences between the ovariectomy＋6-OHDA＋17β-estradiol 50 μg/kg group and ovariectomy＋6-OHDA＋saline group [（1 004±253）, （1 035±196） ng/g, P 〉 0.05], but obviously higher in the ovariectomy＋6-OHDA＋17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy＋6-OHDA＋saline group [（1 487±268）, （1 939±274）, （1 035±196） ng/g, P 〈 0.05]. （2） The TNF level was obviously higher in the ovariectomy＋6-OHDA＋saline group than in the sham-operated group [（3.498±0.792）, （1.893±0.533） ng/g, P 〈 0.05], there were no significant differences between the ovariectomy＋ 6-OHDA＋17β-estradiol 50 μg/kg group and ovariectomy＋6-OHDA＋saline group [（3.328 ±0.712）, （3.498±0,792） ng/g, P 〉 0.05], but obviously lower in the ovariectomy＋6-OHDA＋17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy＋6-OHDA＋saline group [（2.639±0.438）, （2.016±0.619）, （3.498＋0.792） ng/g, P 〈 0.05]. CONCLUSION： Estrogen has obvious protective effect dose-dependently on 6-OHDA induced chemical sympathetic nerve terminal injury in rats, and it may play its protective role by reducing TNF level and ameliorating inflammatory reaction.

Brain-derived neurotrophical factor after olfactory ensheathing cells transplantation in spinal cord injury of rats

Objective To observe the expression of brain - derived neurotrophical factor ( BDNF) in injury spinal cord after transplantation olfactory ensheathing cells ( OECs) , and to investigate the mechanism of OECs repairing spinal cord injury. Methods OECs from GFP transgenic rats were separated and cultured for transplantation. Spinal cord injury rats were separated two groups by

Non-viral liposome-mediated transfer of brain-derived neurotrophic factor across the blood-brain barrier

Brain-derived neurotrophic factor（BDNF） plays an important role in the repair of central nervous system injury,but cannot directly traverse the blood-brain barrier.Liposomes are a new type of non-viral vector,able to carry macromolecules across the blood-brain barrier and into the brain.Here,we investigate whether BDNF could be transported across the blood-brain barrier by tail-vein injection of liposomes conjugated to transferrin（Tf） and polyethylene glycol（PEG）,and carrying BDNF modified with cytomegalovirus promoter（pC MV） or glial fibrillary acidic protein promoter（p GFAP）（Tf-p CMV-BDNF-PEG and Tf-p GFAP-BDNF-PEG,respectively）.Both liposomes were able to traverse the blood-brain barrier,and BDNF was mainly expressed in the cerebral cortex.BDNF expression in the cerebral cortex was higher in the Tf-p GFAP-BDNF-PEG group than in the Tf-p CMV-BDNF-PEG group.This study demonstrates the successful construction of a non-virus targeted liposome,Tf-p GFAP-BDNF-PEG,which crosses the blood-brain barrier and is distributed in the cerebral cortex.Our work provides an experimental basis for BDNF-related targeted drug delivery in the brain.

Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve:viscoelasticity characterization

The optic nerve is a viscoelastic solid-like biomaterial.Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury.We hypothesized that stress relaxation and creep properties of the optic nerve change after injury.Moreover,human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal.To validate this hypothesis,a rabbit model of optic nerve injury was established using a clamp approach.At 7 days after injury,the vitreous body received a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells.At 30 days after injury,stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly,with pathological changes in the injured optic nerve also noticeably improved.These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves,and thereby contributes to nerve recovery.

Does glioblastoma cyst fluid promote sciatic nerve regeneration?

Glioblastoma cyst fluid contains growth factors and extracellular matrix proteins which are known as neurotrophic and neurite-promoting agents. Therefore, we hypothesized that glioblastoma cyst fluid can promote the regeneration of injured peripheral nerves. To validate this hypothesis, we transected rat sciatic nerve, performed epineural anastomosis, and wrapped the injured sciatic nerve with glioblastoma cyst fluid- or saline-soaked gelatin sponges. Neurological function and histomorphological examinations showed that compared with the rats receiving local saline treatment, those receiving local glioblastoma cyst fluid treatment had better sciatic nerve function, fewer scars, greater axon area, counts and diameter as well as fiber diameter. These findings suggest that glioblastoma cyst fluid can promote the regeneration of injured sciatic nerve and has the potential for future clinical application in patients with peripheral nerve injury.

Risk factors of acute renal injury in patients with acute left heart failure

Objective To investigate the risk factors of acute renal injury(acute kidney injury)in patients with acute left heart failure.Methods Clinical data of 188 patients with acute left heart failure who were admitted to our hospital were retrospectively analyzed.Logistic regression analysis was used to assess the risk factors for AKI.

Incidence,prevalence,and causes of spinal injuries in China,1990-2019:Findings from the Global Burden of Disease Study 2019

Background:Spinal injuries are an urgent public health priority;nevertheless,no China-wide studies of these injuries exist.This study measured the incidence,prevalence,causes,regional distribution,and annual trends of spinal injuries in China from 1990 to 2019.Methods:We used data from the Global Burden of Diseases,Injuries,and Risk Factors Study 2019 to estimate the incidence and prevalence of spinal injuries in China.The data of 33 provincial-level administrative regions(excluding Taiwan,China)provided by the National Center for Chronic and Noncommunicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention(CDC)were use to systematically analyze the provincial etiology,geographical distribution,and annual trends of spinal injuries.The Bayesian meta-regression tool DisMod-MR 2.1 was used to ensure the consistency among incidence,prevalence,and mortality rates in each case.Results:From 1990 to 2019,the number of living patients with spinal injuries in China increased by 138.32%,from 2.14 million to 5.10 million,while the corresponding age-standardized prevalence increased from 0.20%(95%uncertainty interval[UI]:0.18-0.21%)to 0.27%(95%UI:0.26-0.29%).The incidence of spinal injuries in China increased by 89.91%(95%UI:72.39-107.66%),and the prevalence increased by 98.20%(95%UI:89.56-106.82%),both the most significant increases among the G20 countries;71.00%of the increase could be explained by age-specific prevalence.In 2019,the incidence was 16.47(95%UI:12.08-22.00,per 100,000 population),and the prevalence was 358.30(95%UI:333.96-386.62,per 100,000 population).Based on the data of 33 provincial-level administrative regions provided by CDC,age-standardized incidence and prevalence were both highest in developed provinces in Eastern China.The primary causes were falls and road injuries;however,the prevalence and specific causes differed across provinces.Conclusions:In China,the overall disease burden of spinal injuries increased significantly during the past three decades but varied considerably according to geographical location.The primary causes were falls and road injuries;however,the prevalence and specific causes differed across provinces.

ENDOTOXIN-INDUCED LIVER INJURY AND CHANGES IN THE LEVELS OF PLASMA TUMOR NECROSIS FACTOR-α AND INTERLEUKIN-6 IN RABBITS

ELISA was employed to detect changes in plasma TNF-α and IL-6 level in rabbits having endotoxin-induced generalized Shwartzman reaction. Liver injury was assessed by the increase of serum ALT and hepatic histopathologic changes. The results showed that plasma TNF-α and IL-6 levels increased remarkably 12h after intravenous injection of endotoxin twice at a 24h interval, and these changes corresponded with the degree of liver injury. Coinjection of dexamethasone and endotoxin partly prevented the elevation of TNF-α and IL-6 levels and reduced liver injury. These results indicated that TNF-α and IL-6 were involved in endotoxin-induced liver injury.

Comparative study of the effect of basic fibroblast growth factor and vascular endothelial growth factor on limb ischemia/reperfusion injury of rats

Objective To investigate the effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on limb ischemia/reperfusion injury of rats and the mechanism Methods The hind limb ischemia/reperfusion injury of male SD rats was induced by tourniquet for 2 hours and then reperfusing for 12 hours with administration of different agents Animals were divided into control, bFGF 10 and bFGF 50, VEGF 10 and VEGF 50 group by infusing physiological saline, 10 and 50?μg/kg bFGE, 10 and 50?μg/kg VEGF, respectively Blood was collected to determine malonyldialdehyde (MDA), and the ischemic reperfused gastrocnemius muscle and the contralateral control one were harvested together for measurement of tissue viability, water content, myeloperoxidose (MPO) activity, ATP and MDA concentration Results Compared with control group, tissue viability of ischemia/reperfusion limb in bFGF 10 and bFGF 50 group increased by 16 0% ( P <0 05) and 32 8% ( P <0 01), ATP content increased by 14 8% and 35 6% ( P <0 01), and plasma MDA level decreased by 45 2% and 56 2% ( P <0 01) 10?μg/kg bFGF had no significant effect on tissue water content, MPO activity, MDA concentration of ischemia/reperfusion limb, while 50?μg/kg of bFGF lowered these values by 15 7%, 32 5% and 13 6% ( P <0 05) and 14 7% ( P <0 01), MPO activity augmented by 44 9% and 96 1% ( P <0 01), ATP content decreased by 13 1% ( P <0 05) and 33 3% ( P <0 01) Plasma and tissue MDA concentrations in VEGF 10 group had no significant changes ( P >0 05), while in VEGF 50 group, these values were elevated by 46 4% and 38 6% ( P <0 01) Conclusion bFGF attenuated, while VEGF exacerbated ischemia/reperfusion injury of rat limb significantly, the mechanism of which was probably related to preventing or enhancing lipid peroxide, and increasing or decreasing energy store