The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

Study on Influence Factors of Pressure Injury Risk in the Elderly Inpatients with Kidney Disease Based on LASSO Regression

Objective: This paper aims to explore clinical status and related influence factors of pressure injury (PI) in the elderly inpatients with kidney disease, so as to provide reference for the prevention and treatment of PI in the elderly inpatients with kidney disease. Methods: Retrospective collection method is adopted to collect 158 clinical cases of the elderly inpatients with kidney disease aged ≥ 60 in the Nephrology Department, the First Affiliated Hospital of Jinan University from January 2017 to December 2019, and then least absolute shrinkage and selection Operator (LASSO) regression analysis is used to analyze 17 possible influence factors;finally Logistic regression model is established to analyze and screen influence factors of risk. Results: 1) Among 158 elderly inpatients with medium and high risk of PI, the incidence of PI is 20.25%;the most common stage of injury is stage I (42.5%);sacrococcygeal (60%) is the high-risk site of pressure injury. 2) LASSO regression analysis shows that history of present respiratory infection/respiratory failure (β = 1.2714. P < 0.05) and hospitalization time (β = 0.4177. P < 0.05) are independent factors influencing PI risk in the elderly inpatients with kidney disease. Conclusion: The elderly patients with kidney disease and PI risk are the high incidence population of hospital acquired PI;for the elderly inpatients with kidney disease and having respiratory infection history or respiratory failure, prolonged hospitalization will significantly increase the risk of PI. Therefore, targeted preventive and control measures should be taken to reduce the incidence of PI.

Alterations in gut microbiota are related to metabolite profiles in spinal cord injury

Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8–T10 traumatic spinal cord injury. We used 16 S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids(L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.

The therapeutic mechanism of dexamethasone in lung injury induced by hydrogen sulfide

The lung is one of the primary target organs of hydrogen sulfide(H2S),as exposure to H2S can cause acute lung injury(ALI)and pulmonary edema.Dexamethasone(Dex)exerts a protective effect on ALI caused by exposure to toxic gases and is commonly used in the clinic;however,the underlying mechanisms remain elusive,and the dose is unclear.Methods:In vivo experiments:divided C57BL6 mice into 6 groups at random,12 in each group.The mice were exposed to H2S for 3 h and 5 or 50 mg/kg Dex pretreated before exposure,sacrificed 12 h later.The morphological changes of HE staining and the ultrastructural changes of lungs under transmission electron microscopy were evaluated.The wet/dry ratio of lung tissue was measured.Bronchial alveolar lavage fluid(BALF)protein content and lung permeability index were detected.The expression of AQP5 protein was measured by immunohistochemistry and Western Blot(WB).In vitro experiments:divided human lung adenocarcinoma cell line A549 into 4 groups.1μmol/L dexamethasone was added to pre-incubation.The WB analyzed the protein of p-ERK1/2,p-JNK,and p-p38 in MAPK pathway after 1 h of NaHS exposure;six hours after NaHS exposure,the AQP5 protein was measured by WB.Results:Dex treatment could significantly attenuate the H2S-induced destruction to the alveolar wall,increase the wet-to-dry weight ratio and decrease pulmonary permeability index,with high-dose dexamethasone seemingly functioning better.Additionally,our previous studies showed that aquaporin 5(AQP 5),a critical protein that regulates water flux,decreased both in a mouse and cell model following the exposure to H2S.This study indicates that tThe decrease in AQP 5 can be alleviated by Dex treatment.Additionally,the mitogen activated protein kinase(MAPK)pathway may be involved in the protective effects of Dex in ALI caused by exposure to H2S since H2Sinduced MAPK activation could be inhibited by Dex.Conclusion:The present results indicate that AQP 5 may be considered a therapeutic target for Dex in H2S or other hazardous gases-induced ALI.

黄芪甲苷对高剂量S-氯胺酮诱导PC12细胞损伤的保护作用

以高剂量S-氯胺酮(S-ketamine, SK)诱导PC12细胞构建体外神经损伤模型,探究黄芪甲苷(astragaloside IV,ASⅣ)对高剂量SK诱导PC12细胞损伤的保护作用及其机制。采用CCK-8法测定细胞活力,并以此确定SK的最佳造模浓度和ASⅣ的最佳治疗浓度;流式细胞术测定细胞凋亡率;DCFH-DA荧光探针法检测细胞内活性氧(ROS)的含量;qPCR法检测目的基因的表达;Western blot技术检测目的蛋白的表达。结果显示,SK的最佳造模浓度为450μg/mL,ASⅣ的最佳治疗浓度为25μmol/L;与对照组相比,SK组细胞凋亡率、ROS含量、Caspase-9和Cytochrome C mRNA表达水平均显著升高(P<0.05),Bax、Pro-Caspase-9、Cleaved-Caspase-9和Cytochrome C蛋白表达量同样显著上升(P<0.05),而Bcl-2/Bax mRNA表达水平比值、Bcl-2蛋白表达量显著下降(P<0.05);ASⅣ治疗后,明显逆转了高剂量SK诱导引起的各项指标变化(P<0.05)。这说明黄芪甲苷可以减轻高剂量S-氯胺酮所致PC12细胞损伤,其机制可能与抑制线粒体凋亡途径有关。

高热惊厥患儿外周血NLR和H_(2)S水平变化及与脑损伤的相关性

目的探讨高热惊厥患儿外周血中性粒细胞/淋巴细胞比值(NLR)和硫化氢(H_(2)S)水平变化及与脑损伤的相关性。方法选取2021年1月至2023年1月期间本院收治的高热惊厥患儿共220例,其中单纯性153例纳入单纯性组,复杂性67例纳入复杂性组,同期选取高热无惊厥患儿109例纳入对照组。所有患儿均检测外周血NLR和H_(2)S水平,采用受试者工作特征(ROC)曲线鉴别单纯性及复杂性高热惊厥患儿。根据高热惊厥患儿有无脑损伤发生情况分为脑损伤组及无脑损伤组,收集两组高热惊厥患儿临床资料,采用多因素Logistic回归模型分析影响高热惊厥患儿脑损伤的独立危险因素。结果与对照组比较,单纯性组及复杂性组外周血NLR水平升高,H_(2)S水平降低(P<0.05),与单纯性组比较,复杂性组外周血NLR水平升高,H_(2)S水平降低(P<0.05)。ROC分析结果显示,外周血NLR、H_(2)S单独检测及二者联合检测鉴别单纯性及复杂性高热惊厥患儿的AUC值(95%CI)分别为0.615(0.547~0.680)、0.731(0.667~0.788)、0.827(0.771~0.875),NLR、H_(2)S联合检测的预测效能高于单独检测(Z=4.488、2.161,P<0.05)。脑损伤组惊厥时体温≥40℃、复杂性高热惊厥、惊厥发作次数≥2次、惊厥持续时间≥15 min例数占比、外周血NLR水平均高于无脑损伤组,H_(2)S水平低于无脑损伤组(P<0.05)。多因素Logistic回归模型分析结果显示,复杂性高热惊厥、惊厥发作次数≥2次,惊厥持续时间≥15 min、外周血NLR高水平及H_(2)S低水平是影响高热惊厥患儿发生脑损伤的独立危险因素(P<0.05)。结论高热惊厥患儿外周血NLR水平升高,H_(2)S水平降低,外周血NLR、H_(2)S水平对于高热惊厥患儿分型具有重要的鉴别价值,且与高热惊厥患儿脑损伤的发生密切相关。

Post electrical or lightning injury syndrome: a proposal for an American Psychiatric Association's Diagnostic and Statistical Manual formulation with implications for treatment

In the past, victims of electrical and lightning injuries have been assessed in a manner lacking a system- atic formulation, and against ad hoc criteria, particularly in the area of neuropsychological disability. In this manner patients have, for example, only been partially treated, been poorly or incorrectly diagnosed, and have been denied the full benefit of compensation for their injuries. This paper contains a proposal for diagnostic criteria particularly for the neuropsychological aspects of the post injury syndrome. It pays attention to widely published consistent descriptions of the syndrome, and a new cluster analysis of post electrical injury patients. It formulates a proposal which could be incorporated into future editions of the American Psychiatric Association＇s Diagnostic and Statistical Manual （DSM）. The major neuropsycholog- ical consequences include neurocognitive dysfunction, and memory subgroup dysfunction, with ongoing consequences, and sometimes including progressive or delayed psychiatric, cognitive, and/or neurological symptoms. The proposed diagnostic criteria insist on a demonstrated context for the injury, both specifying the shock circumstance, and also physical consequences. It allows for a certain delay in onset of symptoms. It recognizes exclusory conditions. The outcome is a proposal for a DSM classification for the post electrical or lightning injury syndrome. This proposal is considered important for grounding patient treatment, and for further treatment trials. Options for treatment in electrical or lightning injury are summarised, and future trials are foreshadowed.

Nationwide trends and predictors of inpatient mortality in 83884 transjugular intrahepatic portosystemic shunt

AIM: To evaluate and validate the national trends and predictors of in-patient mortality of transjugular intrahepatic portosystemic shunt (TIPS) in 15 years.METHODS: Using the National Inpatient Sample which is a part of Health Cost and Utilization Project, we identified a discharge-weighted national estimate of 83884 TIPS procedures performed in the United States from 1998 to 2012 using international classification of diseases-9 procedural code 39.1. The demographic, hospital and co-morbility data were analyzed using a multivariant analysis. Using multi-nominal logistic regression analysis, we determined predictive factors related to increases in-hospital mortality. Comorbidity measures are in accordance to the Comorbidity Software designed by the Agency for Healthcare Research and Quality.RESULTS: Overall, 12.3% of patients died during hospitalization with downward trend in-hospital mortality with the mean length of stay of 10.8 &#x000b1; 13.1 d. Notable, African American patients (OR = 1.809 vs Caucasian patients, P &#x0003c; 0.001), transferred patients (OR = 1.347 vs non-transferred, P &#x0003c; 0.001), emergency admissions (OR = 3.032 vs elective cases, P &#x0003c; 0.001), patients in the Northeast region (OR = 1.449 vs West, P &#x0003c; 0.001) had significantly higher odds of in-hospital mortality. Number of diagnoses and number of procedures showed positive correlations with in-hospital death (OR = 1.249 per one increase in number of procedures). Patients diagnosed with acute respiratory failure (OR = 8.246), acute kidney failure (OR = 4.359), hepatic encephalopathy (OR = 2.217) and esophageal variceal bleeding (OR = 2.187) were at considerably higher odds of in-hospital death compared with ascites (OR = 0.136, P &#x0003c; 0.001). Comorbidity measures with the highest odds of in-hospital death were fluid and electrolyte disorders (OR = 2.823), coagulopathy (OR = 2.016), and lymphoma (OR = 1.842).CONCLUSION: The overall mortality of the TIPS procedure is steadily decreasing, though the length of stay has remained relatively constant. Specific patient ethnicity, location, transfer status, primary diagnosis and comorbidities correlate with increased odds of TIPS in-hospital death.

S100B protein in serum is elevated after global cerebral ischemic injury

BACKGROUND:S100B protein in patients with cardiac arrest,hemorrhagic shock and other causes of global cerebral ischemic injury will be dramatically increased.Ischemic brain injury may elevate the level of serum S100 B protein and the severity of brain damage.METHODS:This article is a critical and descriptive review on S100 B protein in serum after ischemic brain injury.We searched Pubmed database with key words or terms such as "S100B protein", "cardiac arrest", "hemorrhagic shock" and "ischemia reperfusion injury" appeared in the last five years.RESULTS:S100B protein in patients with cardiac arrest,hemorrhagic shock and other causes of ischemic brain injury will be dramatically increased.Ischemic brain injury elevated the level of serum S100 B protein,and the severity of brain damage.CONCLUSION:The level of S100 B protein in serum is elevated after ischemic brain injury,but its mechanism is unclear.

Non-Hodgkin's Lymphoma Primarily Presenting with Fanconi Syndrome and Acute Kidney Injury

KIDNEY involvement is common in non-Hodgkin＇s lymphoma （NHL） with incidence up to 30%-40% in autopsy studies. However, it us- ually occurs late in the course of the diseaseand is clinically silent. Clinically overt renal disease including acute kidney injury （AKI） as its primary manifestation is rarely reported, moreover, Fanconi syndrome （FS） is extremely rare as the main manifestation in NHL. In this report, we presented a case of NHL primarily presenting with FS and AKI due to diffuse interstitial infiltration of NHL cells and emphasized the important role of renal biopsy, especially renal immunohistochemical analysis in the diagnosis of renal diffuse lymphoma.

Early electrical field stimulation prevents the loss of spinal cord anterior horn motoneurons and muscle atrophy following spinal cord injury

Our previous study revealed that early application of electrical field stimulation（EFS） with the anode at the lesion and the cathode distal to the lesion reduced injury potential, inhibited secondary injury and was neuroprotective in the dorsal corticospinal tract after spinal cord injury（SCI）. The objective of this study was to further evaluate the effect of EFS on protection of anterior horn motoneurons and their target musculature after SCI and its mechanism. Rats were randomized into three equal groups. The EFS group received EFS for 30 minutes immediately after injury at T_（10）. SCI group rats were only subjected to SCI and sham group rats were only subjected to laminectomy. Luxol fast blue staining demonstrated that spinal cord tissue in the injury center was better protected; cross-sectional area and perimeter of injured tissue were significantly smaller in the EFS group than in the SCI group. Immunofluorescence and transmission electron microscopy showed that the number of spinal cord anterior horn motoneurons was greater and the number of abnormal neurons reduced in the EFS group compared with the SCI group. Wet weight and cross-sectional area of vastus lateralis muscles were smaller in the SCI group to in the sham group. However, EFS improved muscle atrophy and behavioral examination showed that EFS significantly increased the angle in the inclined plane test and Tarlov＇s motor grading score. The above results confirm that early EFS can effectively impede spinal cord anterior horn motoneuron loss, promote motor function recovery and reduce muscle atrophy in rats after SCI.

Amyloid beta-peptide worsens cognitive impairment following cerebral ischemia-reperfusion injury

Amyloid 13-peptide, a major component of senile plaques in Alzheimer＇s disease, has been implicated in neuronal cell death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer＇s disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries; meanwhile, fibrillar amyloid [3-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid 13-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 313 were significantly stronger in cerebral ischemia-reperfusion injury rats subjected to amyloid [3-peptide administration than those undergo- ing cerebral ischemia-repetfusion or amyloid 13-peptide administration alone. Conversely, the activ- ity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloid 13-peptide administration. These findings suggest that amyloid 13-peptide can potentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cognitive impairment.

Glial fibrillary acidic protein levels are associated with global histone H4 acetylation after spinal cord injury in rats

Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity-a wellknown process that markedly influences the tissue remodeling after a central nervous system injury-is crucial for tissue remodeling after spinal cord injury（SCI）. However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein（GFAP） and S100 calcium-binding protein B（S100B）（astrocytic reactivity classical markers） and global histone H4 acetylation levels. Sixty-one male Wistar rats（aged ~3 months） were divided into the following groups： sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases（first phase： no changes in the 6, 24 and 48 hours post-SCI groups; second phase： increased levels in the 72 hours post-SCI group; and a third phase： return to levels similar to control in the 7 days post-SCI group）. Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.

Ursolic acid induces neural regeneration after sciatic nerve injury

In this study, we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve. BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis at 0.5 cm below the ischial tuber-osity. The successful y generated model mice were treated with 10, 5, or 2.5 mg/kg ursolic acid via intraperitoneal injection. Enzyme-linked immunosorbent assay results showed that serum S100 protein expression level gradual y increased at 1-4 weeks after sciatic nerve injury, and significantly decreased at 8 weeks. As such, ursolic acid has the capacity to significantly increase S100 protein expression levels. Real-time quantitative PCR showed that S100 mRNA expression in the L 4-6 segments on the injury side was increased after ursolic acid treatment. In addition, the muscular mass index in the soleus muscle was also increased in mice treated with ursolic acid. Toluidine blue staining revealed that the quantity and average diameter of myelinated nerve fibers in the injured sciatic nerve were significantly increased after treatment with ursolic acid. 10 and 5 mg/kg of ursolic acid produced stronger effects than 2.5 mg/kg of ursolic acid. Our findings indicate that ursolic acid can dose-dependently increase S100 expression and promote neural regeneration in BALB/c mice fol owing sciatic nerve injury.

Acute effects of human protein S administration after traumatic brain injury in mice

Despite years of effort,no effective acute phase treatment has been discovered for traumatic brain injury.One impediment to successful drug development is entangled secondary injury pathways.Here we show that protein S,a natural multifunctional protein that regulates coagulation,inflammation,and apoptosis,is able to reduce the extent of multiple secondary injuries in traumatic brain injury,and therefore improve prognosis.Mice subjected to controlled cortical impact were treated acutely(10–15 minutes post-injury)with a single dose of either protein S(1 mg/kg)or vehicle phosphate buffered saline via intravenous injection.At 24 hours post-injury,compared to the non-treated group,the protein S treated group showed substantial improvement of edema and fine motor coordination,as well as mitigation of progressive tissue loss.Immunohistochemistry and western blot targeting caspase-3,B-cell lymphoma 2(Bcl-2)along with terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay revealed that apoptosis was suppressed in treated animals.Immunohistochemistry targeting CD11 b showed limited leukocyte infiltration in the protein S-treated group.Moreover,protein S treatment increased the ipsilesional expression of aquaporin-4,which may be the underlying mechanism of its function in reducing edema.These results indicate that immediate intravenous protein S treatment after controlled cortical impact is beneficial to traumatic brain injury prognosis.Animal Use Protocols(AUPs)were approved by the University Committee on Animal Resources(UCAR)of University of Rochester Medical Center(approval No.UCAR-2008-102 R)on November 12,2013.

Dementia in military and veteran populations:a review of risk factors—traumatic brain injury,post-traumatic stress disorder,deployment,and sleep

The military population face a unique set of risk factors that may increase the risk of being diagnosed with dementia.Traumatic brain injury(TBI)and post-traumatic stress disorder(PTSD)have a higher prevalence in this group in comparison to the civilian population.By delving into the individual relationships between TBI and dementia,and PTSD and dementia,we are able to better explore dementia in the military and veteran populations.While there are some inconsistencies in results,the TBI-dementia association has become more widely accepted.Moderate-tosevere TBI has been found to increase the risk of being diagnosed with Alzheimer’s disease.A correlation between PTSD and dementia has been established,however,whether or not it is a causal relationship remains unclear.Factors such as blast,combat and chemical exposure may occur during a deployment,along with TBI and/or PTSD diagnosis,and can impact the risk of dementia.However,there is a lack of literature exploring the direct effects of deployment on dementia risk.Sleep problems have been observed to occur in those following TBI,PTSD and deployment.Poor sleep has been associated with possible dementia risk.Although limited studies have focused on the link between sleep and dementia in military and veteran populations,sleep is a valuable factor to study due to its association and interconnection with other military/veteran factors.This review aims to inform of various risk factors to the cognitive health of military members and veterans:TBI,PTSD,deployment,and sleep.

Prevention of shoulder dystocia related birth injuries: Myths and facts

Traditionally, brachial plexus damage was attributed to excessive traction applied on the fetal head at delivery. Recently, it was proposed that most injuries occur spontaneously in utero. The author has studied the mechanism of neurological birth injuries based on 338 actual cases with special attention to(1) fetal macrosomia;(2) maternal diabetes; and(3) methods of delivery. There was a high coincidence between use of traction and brachial plexus injuries. Instrumental extractions increased the risk exponentially. Erb's palsy following cesarean section was exceedingly rare. These facts imply that spontaneous neurological injury in utero is extremely rare phenomenon. Literary reports show that shoulder dystocia and its associated injuries increased in the United States several-fold since the introduction of active management of delivery in the 1970's. Such a dramatic change in a stable population is unlikely to be caused by incidental spontaneous events unrelated to external factors. The cited investigations indicate that brachial plexus damage typically is traction related. The traditional technique which precludes traction is the optimal method for avoiding arrest of the shoulders and its associated neurological birth injuries. Effective prevention also requires meticulous prenatal care and elective abdominal delivery of macrosomic fetuses in carefully selected cases.

Hypoxia inducible factor-1 alpha stabilization for regenerative therapy in traumatic brain injury

Mild traumatic brain injury（TBI）, also called concussion, initiates sequelae leading to motor deficits, cognitive impairments and subtly compromised neurobehaviors. While the acute phase of TBI is associated with neuroinflammation and nitroxidative burst, the chronic phase shows a lack of stimulation of the neurorepair process and regeneration. The deficiency of nitric oxide（NO）, the consequent disturbed NO metabolome, and imbalanced mechanisms of S-nitrosylation are implicated in blocking the mechanisms of neurorepair processes and functional recovery in the both phases. Hypoxia inducible factor-1 alpha（HIF-1α）, a master regulator of hypoxia/ischemia, stimulates the process of neurorepair and thus aids in functional recovery after brain trauma. The activity of HIF-1α is regulated by NO via the mechanism of S-nitrosylation of HIF-1α. S-nitrosylation is dynamically regulated by NO metabolites such as S-nitrosoglutathione（GSNO） and peroxynitrite. GSNO stabilizes, and peroxynitrite destabilizes HIF-1α. Exogenously administered GSNO was found not only to stabilize HIF-1α and to induce HIF-1α-dependent genes but also to stimulate the regeneration process and to aid in functional recovery in TBI animals.

Prevention of grafted liver from reperfusive injury

INTRODUCTIONThe incidence of primary non-function(PNF)of grafted liver in the early postoperative stage is 2%-23%[1-4],its main cause is the ischemic-rechemic injure[5,6].In this experiment,anisodamine was added into the preserving fluid and the grafted liver was rewarmed at different temperatures to protect the cell membranc and prevent ischemic-reperfusive injury.

Japanese herbal medicine, Saiko-keishi-to, prevents gut ischemia/reperfusion-induced liver injury in rats via nitric oxide

AIM:To determine whether Saiko-keishi-to(TJ-10),a Japanese herbal medicine,could protect liver injury induced by gut ischemia/reperfusion(I/R),and to investigate the role of NO. METHODS:Male Wistar rats were exposed to 30-min gut isohemia followed by 60 min of reperfusion.Intravital microscopy was used to monitor leukocyte recruitment.Plasma tumor necrosis factor(TNF)levels and alanine aminotransferase (ALT)activities were measured.TJ-10 1 g/(kg.d)was intragastrically administered to rats for 7 d.A NO synthase inhibitor was administered. RESULTS:In control rats,gut I/R elicited increases in the number of stationary leukocytes,and plasma TNF levels and ALT activities were mitigated by pretreatment with TJ-10.Pretreatment with the NO synthase inhibitor diminished the protective effects of TJ-10 on leukostasis in the liver,and the increase of plasma TNF levels and ALT activities.Pretreatment with TJ-10 increased plasma nitrite/nitrate levels. CONCLUSION:TJ-10 attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential hepatocellular injury via enhancement of NO production.