UBC9-mediated SUMOylation of Lamin B1 enhances DNA-damage-induced nuclear DNA leakage and autophagy after spinal cord injury.

Recent studies have shown that nucleophagy can mitigate DNA damage by selectively degrading nuclear components protruding from the nucleus. However, little is known about the role of nucleophagy in neurons after spinal cord injury (SCI). Western blot analysis and immunofluorescence were performed to evaluate the nucleophagy after nuclear DNA damage and leakage in SCI neurons in vivo and NSC34 expression in primary neurons cultured with oxygen-glucose deprivation (OGD) in vitro, as well as the interaction and colocalization of autophagy protein LC3 with nuclear lamina protein Lamin B1. The effect of UBC9, a Small ubiquitin-related modifier (SUMO) E2 ligase, on Lamin B1 SUMOylation and nucleophagy was examined by siRNA transfection or 2-D08 (a small-molecule inhibitor of UBC9), immunoprecipitation, and immunofluorescence. In SCI and OGD injured NSC34 or primary cultured neurons, neuronal nuclear DNA damage induced the SUMOylation of Lamin B1, which was required by the nuclear Lamina accumulation of UBC9. Furthermore, LC3/Atg8, an autophagy-related protein, directly bound to SUMOylated Lamin B1, and delivered Lamin B1 to the lysosome. Knockdown or suppression of UBC9 with siRNA or 2-D08 inhibited SUMOylation of Lamin B1 and subsequent nucleophagy and protected against neuronal death. Upon neuronal DNA damage and leakage after SCI, SUMOylation of Lamin B1 is induced by nuclear Lamina accumulation of UBC9. Furthermore, it promotes LC3-Lamin B1 interaction to trigger nucleophagy that protects against neuronal DNA damage.

The impact and distinction of 'lipid healthy but obese' and 'lipid abnormal but not obese' phenotypes on lumbar disc degeneration in Chinese.

BACKGROUND: Lipid abnormality and obesity have been proposed to be associated with lumbar disc degeneration, but little is known about the effect of 'lipid healthy but obese' (LH-O) and 'lipid abnormal but not obese' (LA-NO) phenotypes on lumbar disc degeneration in Chinese. The study aims to determine the impact and distinction of LH-O and LA-NO phenotypes on lumbar disc degeneration in Chinese, and to identify the association of related factors with risk of lumbar disc degeneration. METHODS: A total of 678 individuals were included with lumbar magnetic resonance imaging, serum lipid levels and anthropometric measurements. Obesity was defined on the basis of body mass index or waist to hip ratio (WHR). Pfirrmann score and Weishaupt's scale were utilized to assess the degree of disc degeneration and facet joint degeneration. RESULTS: The incidence of the LH-O and LA-NO phenotypes were 11.4% and 18.1%, respectively. LA-NO phenotype demonstrates a high incidence for disc degeneration (P < 0.05), while LH-O phenotype confers a severe disc degeneration grade (P < 0.05). No statistical difference in the percentage of severe facet joint degeneration grade in each group (P > 0.05). Elevated triglycerides and greater WHR may be the risk factors for lumbar disc degeneration in Chinese. CONCLUSION: LH-O and LA-NO phenotypes are common with different status of disc degeneration in Chinese. Elevated triglycerides and abdominal obesity appear to play crucial roles in the development of lumbar disc degeneration.

Does anxiety influence the prognosis of percutaneous transforaminal endoscopic discectomy in the treatment of lumbar disc herniation? A preliminary propensity score matching analysis.

PURPOSE: Previous reports revealed a correlation between psychological problems and spinal surgery. There is a lack of knowledge on the effect of anxiety on the percutaneous transforaminal endoscopic discectomy (PTED) outcome at the two year follow-up. The purpose of this study is to investigate changes in anxiety after PTED among patients with lumbar disc herniation (LDH), to compare the effect of anxiety on the prognosis using propensity score matching analysis, and to identify the related parameters of anxiety. METHODS: A total of 145 patients with LDH requiring PTED surgery were included. Twenty-six LDH patients with anxiety were matched with 26 control patients utilizing propensity score matching analysis. The demographic and peri-operative data were collected and analyzed. A correlation analysis was utilized. RESULTS: Both groups achieved significant improvements in visual analogue scale (VAS) scores for pain, Japanese Orthopedic Association (JOA) scores for neurological deficit, and 36-item Short-Form Health Survey (SF-36) scores and Oswestry Disability Index (ODI) scores for quality of life. A statistical difference was detected between the pre-operative and the post-operative Zung Self-Rating Anxiety Scale scores in the anxiety cohort. However, the difference between the anxiety group and the control group was statistically significant in the aforementioned parameters. The VAS, JOA, ODI and the SF-36 scores, and the disease duration were associated with pre-operative anxiety. CONCLUSION: PTED may provide significant improvements in clinical outcomes and symptoms of anxiety. A negative impact on the patient's prognosis may be caused by the presence of anxiety. Pain severity, neurological deficit, disease duration, and quality of life were associated with anxiety.

Risk factors for urban road traffic injuries in Hangzhou, China.

OBJECTIVE: To investigate factors that most influence urban road traffic injuries (RTI) mortality and morbidity. METHODS: The study used linked police and hospital records of RTI patients in the city of Hangzhou during the 3-year period 2004-2006. Three RTI outcome groups were included: (1) fatally injured; (2) severely injured; and (3) mildly injured persons. RESULTS: High risks for fatal road traffic accidents (RTA) were found on urban links, over weekend, during night hours, in male drivers who drove old vehicles without using seat belts, and at exceeding speeds, or with night time accidents and bad weather condition. In case of higher risk for all urban road users on urban junctions, the numbers on mildly injury cases were increasing. The highest combined risk for dying or being severely injured was found in male drivers driving at excessive speed, on urban links, and with night time accidents. CONCLUSIONS: Intensifying safety education of motor vehicle drivers, enhancing traffic management and keeping balance of "person-vehicle-road" system will greatly reduce the urban traffic accidents and casualties.

[Analysis of clinical risk factors in progression from acute lung injury to acute respiratory distress syndrome in severe trauma patients].

OBJECTIVES: To investigate the potential risk factors of affecting progression from acute lung injury (ALI) to acute respiratory distress syndrome in severe trauma population. METHODS: Twenty potential risk factors of affecting progression of acute lung injury were examined by univariate and multivariate logistic analyses among the severe trauma patients in a retrospective study. RESULTS: All of 375 specially severe trauma patients with ALI were included for analysis. The six risk factors that affected the progression from acute lung injury to acute respiratory distress syndrome were sepsis, duration of trauma, APACHE II score, DIC, aspiration of gastric contents, and advanced age. Specific risk factors also affected different patient subpopulations at different degrees. CONCLUSION: Impact of sepsis, DIC and duration of trauma that predict progression of ALI exists throughout the entire treatment period while aspiration of gastric contents and APACHE II score might affect aggravation of ALI only during the early period; due to deterioration of pulmonary function and severely traumatic injury, advanced age is still an independent risk factor; patients with these risk factors need aggressive supportive cares as early as possible in order to prevent further aggravations.

Risk factors of mortality in road traffic injury patients with acute respiratory distress syndrome.

BACKGROUND: Among the deaths due to trauma, about one half of the patients suffer from road traffic injury (RTI). Most of RTI patients complicate acute respiratory distress syndrome (ARDS) and severe multiple injuries. ARDS is a major contributor to morbidity and mortality in trauma patients. Although many injuries and conditions are believed to be associated with ARDS independent risk factors in trauma patients, their relative importance in development of the syndrome are undefined. We hypothesize that not all of the traditional risk factors impacting mortality are independently associated with patients strictly identified by traffic injury. This study aimed to sieve distinctive risk factors in our RTI population, meanwhile, we also hypothesize that there may exist significantly different risk factors in these patients. METHODS: This was a retrospective cohort study regarding RTI as a single cause for emergency intensive care unit (EICU) admission. Patients identified as severe RTI with post-traumatic ARDS were enrolled in a prospectively maintained database between May 2002 and April 2007 and observed. Twenty-three items of potential risk impacting mortality were calculated by univariate and multivariate Logistic analyses in order to find distinctive items in these severe RTI patients. RESULTS: There were 247 RTI patients with post-traumatic ARDS admitted to EICU during the study period. The unadjusted odds ratio (OR) and 95% confidence intervals (CI) of mortality were associated with six risk factors out of 23: APACHE II score, duration of trauma factor, pulmonary contusion, aspiration of gastric contents, sepsis and duration of mechanical ventilation. The adjusted ORs with 95% CI were denoted with respect to surviving beyond 96 hours EICU admission (APACHE II score, duration of trauma factor, aspiration of gastric contents), APACHE II score beyond 20 EICU admission (duration of trauma factor, sepsis, duration of mechanical ventilation) and mechanical ventilation beyond 7 days EICU admission (duration of trauma factor and sepsis). CONCLUSIONS: We have retrospectively demonstrated an adverse effect of six different risk factors out of 23 items in mortality of post-traumatic ARDS within severe RTI patients and, moreover, gained distinct outcomes in stratified patients under real emergency trauma circumstance. An impact of APACHE II score and pulmonary contusion contributing to prediction of mortality may exist in prophase after traffic injury. Sepsis is still a vital risk factor referring to systemic inflammatory response syndrome, infection, and secondary multiple organs dysfunction. Eliminating trauma factors as early as possible becomes the critical therapeutic measure. Aspiration of gastric contents could lead to incremental mortality due to severe ventilation associated pneumonia. Long-standing mechanical ventilation should be constrained on account of severe refractory complications.

[Risk factors affecting the survival rate in serious multiple trauma patients associated with acute lung injure/acute respiratory distress syndrome].

OBJECTIVE: To investigate risk factors affecting the survival rate in serious multiple traumatic patients associated with acute lung injure (ALI)/acute respiratory distress syndrome (ARDS). METHODS: The clinical data of 76 serious multiple trauma patients associated with ALI and 95 cases in ARDS, totally 171 patients associated with ALI/ARDS, were retrospectively studied, and stepwise logistic regression analysis was used to analyze 20 possible risk factors affecting survival rate. RESULTS: The risk factors affecting survival rate in the ALI group: included smoking (B = -5.235, OR = 0.005, P = 0.001), sepsis secondary to trauma (B = -2.753, OR = 0.064, P = 0.031), and gastrointestinal hemorrhage (B = -2.876, OR = 0.056, P = 0.033). The risk factors affecting survival rate in the ARDS group included the time of induction factor persisting to attacking (B = 3.524, OR = 33.933, P = 0.008), sepsis secondary to trauma (B = -5.183, OR = 0.006, P = 0.004); renal insufficiency(B = -4.745, OR = 0.009, P = 0.009), and gastrointestinal hemorrhage (B = -6.335, OR = 0.002, P = 0.007). CONCLUSION: Different from the results of study of traditional risk factors affecting survival rate in ALI/ARDS, this study reveals that smoking may be an independent risk factor; the earlier ALI/ARDS appears, the lower the predictable survival rate in condition of serious multiple trauma; MODS is easily induced in the course of complicating renal insufficiency during the time of lung injury; sepsis and gastrointestinal hemorrhage are still the infective factors or infection inducing factors affecting the survival rate after trauma; and the primary disease causing infection must be treated actively.

[Expression and significance of substance P, neurofilament-H in glomus tumors with chronic pain].

OBJECTIVE: To observe the expression and distribution of substance P (SP), neurofilament-H (NFH) in glomus tumors with chronic pain, and to discuss the process of chronic pain and the relationship with pain degree. METHODS: Twenty-seven patients diagnosed as glomus tumor with chronic pain were enrolled as case group, and divided into light pain symptomatic group (LPSG) (n = 12) and severe pain symptomatic group (SPSG) (n = 15) according to clinical manifestations. Control group (CG) were enrolled by 30 patients with amputated extremities or hands after trauma. Immunohistochemical methods were used to determine the expression of SP, NFH which were detected quantitatively by computer graph analysis system too. RESULTS: The positive expression and distribution of SP, NFH existed in all the three groups and SPSG expression level was the highest [Grayscale Value(SP) (143.3 +/- 7.5), Grayscale Value(NFH) (167.7 +/- 4.4)], LPSG followed [Grayscale Value(SP) (156.2 +/- 8.2), Grayscale Value(NFH) (194.8 +/- 4.0)], control group was the third [Grayscale Value(SP) (208.2 +/- 16.6), Grayscale Value(NFH) (225.1 +/- 8.3)]; The difference of expression level among three groups was significant [SPSG vs LPSG (P(SP) = 0.002, P(NFH) < 0.0001), SPSG vs CG (P(SP) < 0.0001, P(NFH) < 0.0001), LPSG vs CG (P(SP) < 0.0001, P(NFH) < 0.0001)]. The findings of Pearson product-moment correlation analysis between quantitative grayscale value of SP, NFH respectively and pain score in all the patients with glomus tumor showed linear negative correlation (r(SP) = -0.8974, P(SP) = 0.000001; r(NFH) = -0.6545, P(NFH) = 0.000212). CONCLUSION: SP is the mainly afferent pain transmitter in the process of chronic pain in glomus tumor, and NFH plays an important role in pain-transmitted activities.

Patterns of polymorphism and divergence in the VP1 gene of enterovirus 71 circulating in the Asia-Pacific region between 1994 and 2013.

Enterovirus 71 has been implicated in several outbreaks of hand, foot and mouth disease in the Asia-Pacific region. The present study aimed to achieve comprehensive evolutionary dynamic aspects of EV71 during 1994-2013, based on phylogenetic analyses of the VP1 sequences. The results indicated that 4 genotypes, namely C4, C1, C2 and B4 are the predominant strains, especially in Southeast Asian countries. No common ancestor was shared in different countries. Fourteen sites of substitutions were detected in the VP1 gene sequences; including the most common sites related to neutralization at position V249I [47.1% (189/401)] and A289T [42.6% (171/401)]. However, the sites Q22H and Q22R associated with increased virulence were recognized only in 13.7% (55/401) and 18% (72/401), respectively. None of the above mutations seemed to become fixed because the ratio of Ka/Ks was greater than 1.0. Mutations K43E, A58T, S184T, and T240S could possibly change the spatial structure. Two mutations, G145E and T240S, could obviously affect the hydrophobicity of VP1 and thus alter the EV71 immunoreactivity. In conclusion, the VP1 gene of EV71 strains circulating in the Asia-Pacific region during 1994-2013, showed polymorphisms and divergence with very slow evolution rate, which may be one of the reasons for periodic outbreaks in this area.

Management of traumatic hemothorax by closed thoracic drainage using a central venous catheter.

OBJECTIVE: To evaluate the efficacy and safety of the treatment of traumatic hemothorax by closed pleural drainage using a central venous catheter (CVC), compared with using a conventional chest tube. METHODS: A prospective controlled study with the Ethics Committee approval was undertaken. A total of 407 patients with traumatic hemothorax were involved and they were randomly assigned to undergo closed pleural drainage with CVCs (n=214) or conventional chest tubes (n=193). The Seldinger technique was used for drainage by CVC, and the conventional technique for drainage by chest tube. If the residual volume of the hemothorax was less than 200 ml after the daily volume of drainage decreased to below 100 ml for two consecutive days, the treatment was considered successful. The correlative data of efficacy and safety between the two groups were analyzed using t or chi-squared tests with SPSS 13.0. A P value of less than 0.05 was taken as indicating statistical significance. RESULTS: Compared with the chest tube group, the operation time, fraction of analgesic treatment, time of surgical wound healing, and infection rate of surgical wounds were significantly decreased (P<0.05) in the CVC group. There were no significant differences between the two groups in the success rate of treatment and the incidence of serious complications (P>0.05), or in the mean catheter/tube indwelling time and mean medical costs of patients treated successfully (P>0.05). CONCLUSIONS: Management of medium or large traumatic hemothoraxes by closed thoracic drainage using CVC is minimally invasive and as effective as using a conventional large-bore chest tube. Its complications can be prevented and it has the potential to replace the large-bore chest tube.

[Influence of pedicle screws with different insertion depth on neighboring uninfused segments in a goat lumbar spinal fusion model].

OBJECTIVE: To observe the influences of pedicle screws in various insertion depth on the adjacent segment disc degeneration following lumbar spinal fusion. To explore the relationship between the internal fixation rigidity and incidence of adjacent segment disease. METHODS: Sixteen hybrid male Bohr goats of 10 months old, weighting between 25 and 30 kg, were randomly devided into a control group (N group), and 3 experimental groups, each group had 4 goats. The L4 vertebra of each goat in the experimental groups was fractured, L3-L5 segments were internal fixed with pedicle screws followed by intervertebral joint fusion by a posterior approach. Three experimental groups were devided according to the length of pedicle screws applied, vertebras of goats in L group were internal fixed by the screws at the length of 25 mm, for M group and S group, 20 mm and 15 mm, accordingly. The goats in the control group were treated without any operation. Biomechanical changes and MRI index of upper unfused segment (L2) were measured 24 weeks after operation, and histological changes were observed as well. RESULTS: The pressure and straining of L2 vertebral body and intervertebral disc of L group increased more than N group (P < 0.05), and degenerated cell counting in nucleus pulposus increased as well (P < 0.05). However, MRI index remain unchanged (P > 0.05). CONCLUSIONS: Rigid internal fixation increases the pressure and straining of vertebral body and intervertebral disc of upper adjacent segment, accelerating the degeneration process following lumbar spinal fusion in goats.

Effect of cholinesterase inhibitor galanthamine on circulating tumor necrosis factor alpha in rats with lipopolysaccharide-induced peritonitis.

BACKGROUND: The nervous system, through the vagus nerve and its neurotransmitter acetylcholine, can down-regulate the systemic inflammation in vivo, and recently, a role of brain cholinergic mechanisms in activating this cholinergic anti-inflammatory pathway has been indicated. Galanthamine is a cholinesterase inhibitor and one of the centrally acting cholinergic agents available in clinic. This study aimed to evaluate the effect of galanthamine on circulating tumor necrosis factor alpha (TNF-alpha) in rats with lipopolysaccharide-induced peritonitis and the possible role of the vagus nerve in the action of galanthamine. METHODS: Rat models of lipopolysaccharide-induced peritonitis and bilateral cervical vagotomy were produced. In the experiment 1, the rats were randomly divided into control group, peritonitis group, and peritonitis groups treated with three dosages of galanthamine. In the experiment 2, the rats were randomly divided into sham group, sham plus peritonitis group, sham plus peritonitis group treated with galanthamine, vagotomy plus peritonitis group, and vagotomy plus peritonitis group treated with galanthamine. The levels of plasma TNF-alpha were determined in every group. RESULTS: The level of circulating TNF-alpha was significantly increased in rats after intraperitoneal injection of endotoxin. Galanthamine treatment decreased the level of circulating TNF-alpha in rats with lipopolysaccharide-induced peritonitis, and there was significant difference compared with rats with lipopolysaccharide-induced peritonitis without treatment. The 3 mg/kg dosage of galanthamine had the most significant inhibition on circulating TNF-alpha level at all the three tested doses. Galanthamine obviously decreased the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with sham operation, but could not decrease the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with vagotomy. CONCLUSION: Cholinesterase inhibitor galanthamine has an inhibitory effect on TNF-alpha release in rats with lipopolysaccharide-induced peritonitis, and the vagus nerve plays a role in the process of the action of galanthamine.