Chronic spinal cord compression associated with intervertebral disc degeneration in SPARC-null mice

Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in rodents,and therefore establishing a chronic spinal cord compression(CSCC)animal model is of crucial importance to explore the pathogenesis and treatment of CSCC.The absence of secreted protein,acidic,and rich in cysteine(SPARC)leads to spontaneous intervertebral disc degeneration in mice,which resembles human disc degeneration.In this study,we evaluated whether SPARC-null mice may serve as an animal model for CSCC.We performed rod rotation test,pain threshold test,gait analysis,and Basso Mouse Scale score.Our results showed that the motor function of SPARC-null mice was weakened,and magnetic resonance images revealed compression at different spinal cord levels,particularly in the lumbar segments.Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes,activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype;it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway.Notably,these findings are characteristics of CSCC.Therefore,we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

Macrophage migration inhibitory factor facilitates astrocytic production of the CCL2 chemokine following spinal cord injury

Spinal cord injury causes accumulation of a large number of leukocytes at the lesion site where they contribute to excessive inflammation.Overproduced chemokines are responsible for the migratory process of the leukocytes,but the regulatory mechanism underlying the production of chemokines from resident cells of the spinal cord has not been fully elucidated.We examined the protein levels of macrophage migration inhibitory factor and chemokine C-C motif chemokine ligand 2 in a spinal cord contusion model at different time points following spinal cord injury.The elevation of macrophage migration inhibitory factor at the lesion site coincided with the increase of chemokine C-C motif chemokine ligand 2 abundance in astrocytes.Stimulation of primary cultured astrocytes with different concentrations of macrophage migration inhibitory factor recombinant protein induced chemokine C-C motif chemokine ligand 2 production from the cells,and the macrophage migration inhibitory factor inhibitor 4-iodo-6-phenylpyrimidine attenuated the stimulatory effect.Further investigation into the underlying mechanism on macrophage migration inhibitory factor-mediated astrocytic production of chemokine C-C motif chemokine ligand 2 revealed that macrophage migration inhibitory factor activated intracellular JNK signaling through binding with CD74 receptor.Administration of the macrophage migration inhibitory factor inhibitor 4-iodo-6-phenylpyrimidine following spinal cord injury resulted in the reduction of chemokine C-C motif chemokine ligand 2-recruited microglia/macrophages at the lesion site and remarkably improved the hindlimb locomotor function of rats.Our results have provided insights into the functions of astrocyte-activated chemokines in the recruitment of leukocytes and may be beneficial to develop interventions targeting chemokine C-C motif chemokine ligand 2 for neuroinflammation after spinal cord injury.

Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos

The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributo rs to the failure of sensory and motor functional recovery following spinal cord injury.Heat shock transcription factor 1(HSF1),a master regulator of the heat shock response,plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous system.However,the underlying mechanism has not been fully elucidated.In the present study,we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1(gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord injury.gHSF1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail amputation.gHSF1 ove rexpression in gecko primary neuro ns significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3,and fa cilitated neuro nal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B pathways.Furthermore,gHSF1 efficiently inhibited the macrophagemediated inflammatory response by inactivating 1kappa B-alpha/NF-kappaB signaling.Our findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation,and provide new avenues of investigation for promoting spinal co rd injury repair in mammals.

China cardiovascular diseases report 2015： a summary

1 Introduction Major and profound changes have taken place in China over the past 30 years. An epidemic of cardiovascular diseases （CVD） in China is emerging as a result of lifestyle changes, urbanization, and the accelerated process of aging. The incidence of CVD is continuously increasing and will remain an upward trend in the next decade. Since 2005,

China cardiovascular diseases report 2018: an updated summary

1 Introduction Rapid socioeconomic progress has greatly affected the lifestyle in China.Consequently,owing to lifestyle changes,urbanization,and accelerated population aging,the risk of cardiovascular diseases(CVD)has increased.The incidence of CVD has been increasing continuously and this upward trend is projected to continue in the next decade.The growing burden of CVD has become a major public health issue.

High mobility group box 1 mediates inflammatory response of astrocytes via cyclooxygenase 2/prostaglandin E2 signaling following spinal cord injury

High mobility group box 1(HMGB1) interacts with pattern-recognition receptors of immune cells to activate the inflammatory response. Astrocytes play a positive role in the inflammatory response of the central nervous system by expressing a broad range of patternrecognition receptors. However, the underlying relationship between HMGB1 and the inflammatory reaction of astrocytes remains unclear. In this study, we established rat models of spinal cord injury via laminectomy at the T8–10 level, and the injured spinal cord was subjected to transcriptome sequencing. Our results showed that the HMGB1/Toll-like receptor 4(TLR4) axis was involved in the activation of astrocyte inflammatory response through regulation of cyclooxygenase 2(COX2)/prostaglandin E2(PGE2) signaling. Both TLR4 and COX2 were distributed in astrocytes and showed elevated protein levels following spinal cord injury. Stimulation of primary astrocytes with recombinant HMGB1 showed that COX2 and microsomal PGE synthase(mPGES)-1, rather than COX1, mPGES-2, or cytosolic PGE synthase, were significantly upregulated. Accordingly, PGE2 production in astrocytes was remarkably increased in response to recombinant HMGB1 challenges. Pharmacologic blockade of TLR2/4 attenuated HMGB1-mediated activation of the COX2/PGE2 pathway. Interestingly, HMGB1 did not impact the production of tumor necrosis factor-α or interleukin-1β in astrocytes. Our results suggest that HMGB1 mediates the astrocyte inflammatory response through regulating the COX2/PGE2 signaling pathway. The study was approved by the Laboratory Animal Ethics Committee of Nantong University, China(approval No. 20181204-001) on December 4, 2018.

Neurological recovery and antioxidant effects of resveratrol in rats with spinal cord injury: a meta-analysis

Objective:To critically assess the neurological recovery and antioxidant effects of resveratrol in rat models of spinal cord injury.Data sources:Using“spinal cord injury”,“resveratrol”and“animal experiment”as the main search terms,all studies on the treatment of spinal cord injury in rats by resveratrol were searched for in PubMed,EMBASE,MEDLINE,Web of Science,Science Direct,China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases by computer.The search was conducted from their inception date to April 2017.No language restriction was used in the literature search.Data selection:The methodological quality of each study was assessed by the initial Stroke Therapy Academic Industry Roundtable recommendations.Two reviewers independently selected studies according to the title,abstract and full text.The risk of bias in the included studies was also evaluated.Meta-analyses were performed with Review Manager 5.3 software.Outcome measures:Neurological function was assessed by the Basso,Beattie,and Bresnahan scale score,inclined plane score and Gale’s motor function score.Molecular-biological analysis of antioxidative effects was conducted to determine superoxide dismutase levels,malondialdehyde levels,nitric oxide synthase activity,nitric oxide levels,xanthine oxidase and glutathione levels in spinal cord tissues.Results:The methodological quality of the 12 included studies was poor.The results of meta-analysis showed that compared with the control group,resveratrol significantly increased the Basso,Beattie,and Bresnahan scale scores after spinal cord injury(n=300,mean difference(MD)=3.85,95%confidence interval(CI)[2.10,5.59],P<0.0001).Compared with the control group,superoxide dismutase levels were significantly elevated(n=138,standardized mean difference(SMD)=5.22,95%CI[2.98,7.45],P<0.00001),but malondialdehyde levels were significantly diminished(n=84,SMD=–3.64,95%CI[–5.84,–1.43],P=0.001)in the spinal cord of the resveratrol treatment group.Conclusions:Resveratrol promoted neurological recovery and exerted antioxidative effects in rat models of spinal cord injury.The limited quality of the included studies reduces the application of this meta-analysis.Therefore,more high-quality studies are needed to provide more rigorous and objective evidence for the pre-clinical treatment of spinal cord injury.

Effect of docosahexaenoic acid on the recovery of motor function in rats with spinal cord injury: a meta-analysis

Objective:Studies have shown that docosahexaenoic acid(DHA)has a beneficial effect in the treatment of spinal cord injury.A meta-analysis was used to study the effect of DHA on the neurological recovery in the rat spinal cord injury model,and the relationship between the recovery of motor function after spinal cord injury and the time and method of administration and the dose of DHA.Data source:Published studies on the effect of DHA on spinal cord injury animal models from seven databases were searched from their inception to January 2019,including PubMed,MEDLINE,EMBASE,the China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases.The search terms included“spinal cord injury”“docosahexaenoic acid”,and“rats”.Data selection:Studies that evaluated the influence of DHA in rat models of spinal cord injury for locomotor functional recovery were included.The intervention group included any form of DHA treatment and the control group included treatment with normal saline,vehicle solution or no treatment.The Systematic Review Centre for Laboratory animal Experimentation’s risk of bias assessment tool was used for the quality assessment of the included studies.Literature inclusion,quality evaluation and data extraction were performed by two researchers.Meta-analysis was then conducted on all studies that met the inclusion criteria.Statistical analysis was performed on the data using RevMan 5.1.2.software.Outcome measures:The primary outcome measure was the score on the Basso,Beattie,and Bresnahan scale.Secondary outcome measures were the sloping plate test,balance beam test,stair test and grid exploration test.Results:A total of 12 related studies were included,3 of which were of higher quality and the remaining 9 were of lower quality.The highest mean Basso,Beattie,and Bresnahan scale score occurred at 42 days after DHA treatment in spinal cord injury rats.At 21 days after treatment,the mean difference in Basso,Beattie,Bresnahan scores between the DHA group and the control group was the most significant(pooled MD=4.14;95%CI=3.58–4.70;P<0.00001).In the subgroup analysis,improvement in the Basso,Beattie,and Bresnahan scale score was more significant in rats administered DHA intravenously(pooled MD=2.74;95%CI=1.41–4.07;P<0.0001)and subcutaneously(pooled MD=2.99;95%CI=2.29–3.69;P<0.00001)than in the groups administered DHA orally(pooled MD=3.04;95%CI=–1.01 to 7.09;P=0.14).Intravenous injection of DHA at 250 nmol/kg(pooled MD=2.94;95%CI=2.47–3.41;P<0.00001]and 1000 nmol/kg[pooled MD=3.60;95%CI=2.66–4.54;P<0.00001)significantly improved the Basso,Beattie,and Bresnahan scale score in rats and promoted the recovery of motor function.Conclusion:DHA can promote motor functional recovery after spinal cord injury in rats.The administration of DHA by intravenous or subcutaneous injection is more effective than oral administration of DHA.Intravenous injection of DHA at doses of 250 nmol/kg or 1000 nmol/kg is beneficial.Because of the small number and the low quality of the included studies,more high-quality research is needed in future to substantiate the results.

Epigenetic inactivation of secreted frizzled-related protein 2 in esophageal squamous cell carcinoma

AIM： To investigate the expression and methylation status of the secreted frizzled-related protein 2 （SFRP2） in esophageal squamous cell carcinoma （ESCC） and ex- plore its role in ESCC carcinogenesis.METHODS： Seven ESCC cell lines （KYSE 30, KYSE150, KYSE410, KYSE510, EC109, EC9706 and TE-1） and one immortalized human esophageal epithelial cell line （Het- 1A）, 20 ESCC tissue samples and 20 paired adjacent non-tumor esophageal epithelial tissues were analyzed in this study. Reverse-transcription polymerase chain reaction （RT-PCR） was employed to investigate the expression of SFRP2 in cell lines, primary ESCC tumor tissue, and paired adjacent normal tissue. Methylation status was evaluated by methylation-specific PCR and bisulfite sequencing. The correlation between expres- sion and promoter methylation of the SFRP2 gene was confirmed with treatment of 5-aza-2＇-deoxycytidine. To assess the potential role of SFRP2 in ESCC, we es-tablished stable SFRP2-transfected cells and examined them with regard to cell proliferation, colony formation, apoptosis and cell cycle in vivo and in vitro.RESULTS： SFRP2 mRNA was expressed in the im- mortalized normal esophageal epithelial cell line but not in seven ESCC cell lines. By methylation-specific PCR, complete methylation was detected in three cell lines with silenced SFRP2 expression, and extensive methylation was observed in the other four ESCC cell lines. 5-aza-2＇-deoxycytidine could restore the expres- sion of SFRP2 mRNA in the three ESCC cell lines lack- ing SFRP2 expression. SFRP2 mRNA expression was obviously lower in primary ESCC tissue than in adjacent normal tissue （0.939 ± 0.398 vs 1.51 ± 0.399, P 〈 0.01）. SFRP2 methylation was higher in tumor tissue than in paired normal tissue （95% vs 65%, P 〈 0.05）. The DNA methylation status of the SFRP2 correlated inversely with the SFRP2 expression. To assess the potential role of SFRP2 in ESCC, we established stable SFRP2 transfectants and control counterparts by in- troducing pcDNA3.1/v5 hisA -SFRP2 or pcDNA3.1/v5 hisA -empty vector into KYSE30 cells lacking SFRP2 expression. After transfection, the forced-expression of SFRP2 was confirmed by the RT-PCR. In comparison with the control groups, stably-expressed SFRP2 in KYSE 30 cells significantly reduced colony formation in vitro （47.17% 4± 15.61% vs 17% ：1： 3.6%, P = 0.031） and tumor growth in nude mice （917.86：1：249.35 mm3 vs 337.23 ± 124.43 mm3, P 〈 0.05）. Using flow cytom- etry analysis, we found a significantly higher number of early apoptotic cells in SFRP2-transfected cells than in the control cells （P = 0.025）. The mean cell number in the S and G2-M phases of the cell cycle was also significantly lower in SFRP2-transfected KYSE30 cells compared with mock transfected counterparts. CONCLUSION： Silencing of SFRP2 expression through promoter hypermethylation may be a factor in ESCC carcinogenesis through loss of its tumor-suppressive activity.

Metformin improves boar sperm quality via 5′-AMPactivated protein kinase-mediated energy metabolism in vitro

Sperm are specialized cells that require adenosine triphosphate(ATP) to support their function.Maintaining sperm energy homeostasis in vitro is vitally important to improve the efficacy of boar sperm preservation. Metformin can activate 5′-AMPactivated protein kinase(AMPK) to improve metabolic flexibility and maintain energy homeostasis. Thus, the aim of the present study was to investigate whether metformin can improve boar sperm quality through AMPK mediation of energy metabolism. Sperm motility parameters, membrane integrity,acrosomeintegrity,mitochondrial membrane potential(ΔΨm), ATP content, glucose uptake,and lactate efflux were analyzed.Localization and expression levels of AMPK and phospho-Thr172-AMPK(p-AMPK) were also detected by immunofluorescence and western blotting. We found that metformin treatment significantly increased sperm motility parameters, ΔΨm, and ATP content during storage at 17 ℃. Moreover, results showed that AMPK was localized at the acrosomal region, connecting piece, and midpiece of sperm and p-AMPK was distributed at the post-acrosomal region, connecting piece, and midpiece. When sperm were incubated with metformin for 4 h at 37 ℃, sperm motility parameters, ΔΨm, ATP content,p-AMPK, glucose uptake, and lactate efflux all significantly increased, whereas the addition of Compound C treatment, an inhibitor of AMPK,counteracted these positive effects. Together, our results suggest that metformin promotes AMPK activation, which contributes to the maintenance of energy hemostasis and mitochondrial activity,thereby maintaining boar sperm functionality and improving the efficacy of semen preservation.

Mechanism of resveratrol on the promotion of induced pluripotent stem cells

OBJECTIVE： To investigate the effects of resveratrol （RV） in reprogramming mouse embryonic fibroblasts （MEFs） into induced pluripotent stem cells （iPSCs） and the related mechanism. METHODS： Primary MEFs were isolated from E13.5 embryos and used within three passages. Retroviruses expressing Sox2 and Oct4 were produced by transfecting GP2-293t cells with recombinant plasmids murine stern cell virus （MSCV）-Sox2 and MSCV-Oct4. Supernatants containing retroviruses were obtained after 48-hour transfection and MEFs were then infected. Different concentrations （0, 5, 10 and 20 IJmol/L） of RV were added to embryonic stem cell （ESC） medium to culture MEFs 48 h post-infection, iPSC clones emerged and were further cultured. Expression of pluripotent markers of iPSCs was identified by cell immunofluorescence and reverse transcription-polymerase chain reaction. Both cytotoxicity and cell proliferation were assayed by Western blot analysis after RV was added into ESC medium. The ultrastructure change of mitochondria was observed by electron microscopy. RESULTS： More than 2.9-fold and 1.3-fold increases in colony number were observed by treatment with RV at 5 and 10 pmol/L, respectively. The reprogramming efficiency was significantly decreased by treatment with 20 pmol/L RV. The proliferation effect on MEFs or MEFs infected by two factors Sox2/Oct4 （2 factors-MEFs, 2F-MEFs） was investigated after RV treatment. At 20 pmol/L RV, induced cell apoptosis and proliferation inhibition were more obvious than those of 5 and 10 IJmol/L treatments. Clones were selected from the 10 pmol/L RV-treated group and cultured. Green fluorescent protein expression from one typical clone was silenced one month later which expressed ESC-associated marker genes Gdf3, Nanog, Ecatl, Fgf4 and Foxd3. Electron transmission microscope showed obvious cavitations in mitochondria. The expression of hypoxia-inducible factor-la was up-regulated when 2F-MEFs were treated with RV compared to the control group. CONCLUSION： RV improved the efficiency of reprogramming 2F-MEFs into iPSCs at low and moderate concentrations （5 and 10 pmol/L）. The effect of 10 pmol/L RV on reprogramming was much greater than that of 5 pmol/L RV. However, high concentration of RV （20 pmol/L） led to more severe cavitations in mitochondria and caused cytotoxic effects. Taken together, these findinqs suqclest that RV mimics hypoxia in cells and promotes reprogramming at a low concentration.

Predictors for malignant potential and deep submucosal invasion in colorectal laterally spreading tumors

BACKGROUND Colorectal laterally spreading tumors(LSTs)with malignant potential require en bloc resection by endoscopic submucosal dissection(ESD),but lesions with deep submucosal invasion(SMI)are endoscopically unresectable.AIM To investigate the factors associated with high-grade dysplasia(HGD)/carcinoma and deep SMI in colorectal LSTs.METHODS The endoscopic and histological results of consecutive patients who underwent ESD for colorectal LSTs in our hospital from June 2013 to March 2019 were retrospectively analyzed.The characteristics of LST subtypes were compared.Risk factors for HGD/carcinoma and deep SMI(invasion depth≥1000μm)were determined using multivariate logistic regression.RESULTS A total of 323 patients with 341 colorectal LSTs were enrolled.Among the four subtypes,non-granular pseudodepressed(NG-PD)LSTs(85.5%)had the highest rate of HGD/carcinoma,followed by the granular nodular mixed(G-NM)(77.0%),granular homogenous(29.5%),and non-granular flat elevated(24.2%)subtypes.Deep SMI occurred commonly in NG-PD LSTs(12.9%).In the adjusted multivariate analysis,NG-PD[odds ratio(OR=16.8,P<0.001)and G-NM(OR=7.8,P<0.001)subtypes],size≥2 cm(OR=2.2,P=0.005),and positive non-lifting sign(OR=3.3,P=0.024)were independently associated with HGD/carcinoma.The NG-PD subtype(OR=13.3,P<0.001)and rectosigmoid location(OR=8.7,P=0.007)were independent risk factors for deep SMI.CONCLUSION Because of their increased risk for malignancy,it is highly recommended that NG-PD and G-NM LSTs are removed en bloc through ESD.Given their substantial risk for deep SMI,surgery needs to be considered for NG-PD LSTs located in the rectosigmoid,especially those with positive nonlifting signs.

Analysis of Translocation of the CagA Protein and Induction of a Scattering Phenotype in AGS Cells Infected with Helicobacter pylori

Objective To investigate whether the presence of structured CagA proteins in Western- and Eastern-type Helicobacter pylori （H. pylori） induces different incidences of gastric diseases. Methods CagA and phosphorylatd CagA were expressed in AGS gastric epithelial cells infected with wild type and mutant strains. The ability of individual CagA was determined by immunoprecipitation and Western blot assay. Morphological changes of these cells were observed under microscope to evaluate the appearance of elongation hummingbird phenotype. Results The sizes of CagA proteins in different strains were different, and no phosphorylated CagA proteins were detected in wild-type strains. Meanwhile, the kinetics of CagA status in AGS infected with H. pylori was detected. The molecular weight of phosphorylated CagA with the same size of CagA proteins in H. pylori was different in infections with different wild-type strains. CagA and phosphorylated CagA increased in a time-dependent manner after the infection. The hummingbird phenotype with H. pylori for time-course was observed under microscope. Instead of HPK5 strain, the wild-type 26695 strain induced hummingbird phenotype in a time-dependent manner. Conclusion Translocation and phosphorylation of CagA are necessary, but not sufficient, for the induction of hummingbird phenotype in AGS cells.

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis

OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injuries","brain hemorrhage, traumatic","acute brain injury","dizocilpine maleate","dizocilpine","MK-801","MK801","rat","rats","rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform(VJIP) and SinoMed databases were searched from their inception dates to March 2018.DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P < 0.00001) and degree of cerebral edema(5 studies, n = 75, MD =-1.21, 95% CI:-1.50 to-0.91;P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test(2 studies, n = 60, MD =-10.88, 95% CI:-20.75 to-1.00;P = 0.03) and neurological function 24 hours after brain injury(11 studies, n = 335, MD =-1.04, 95% CI:-1.47 to-0.60;P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.

Crushing behaviors of buckling-induced metallic meta-lattice structures

Thin-walled lattice materials can be applied as energy absorbers in protective structures of civil defense. In this paper, quasi-static in-plane crushing tests were carried out to investigate the crushing behavior and energy absorption of buckling induced meta-lattice structures (BIMSs) with different central angles made of plastic iron material DT3 and formed by wire cutting technique. Three crushing patterns were revealed and analyzed. The test results clearly show that the initial peak force (IPF), the crushing force efficiency (CFE), the specific energy absorption (SEA) and the mean crushing force (MCF) can be substantially improved by introducing buckling pattern into the straight-walled lattice structure. The MCF of the BIMS was consistently predicted based on the simplified super folding element (SSFE) and the flattening element.

Association between antiplatelet medication and cerebral microbleeds in stroke-free population

BACKGROUND Cerebral microbleeds(CMBs)may increase the risk of future intracerebral hemorrhage and ischemic stroke.However,It is unclear whether antiplatelet medication is associated with CMBs.This study aimed to investigate the association between antiplatelet medication and CMBs in a community-based stroke-free population.METHODS In this cross-sectional study,stroke-free participants aged 18-85 years were recruited from a community in Beijing,China.Demographic,clinical,and antiplatelet medication data were collected through a questionnaire,and all participants underwent blood tests and brain magnetic resonance imaging at 3.0T.The presence,count,and location of CMBs were evaluated using susceptibility-weighted imaging.The association between antiplatelet medication and the presence of CMBs was analyzed using multivariable logistic regression.The associations between antiplatelet medication and CMBs by location(lobar,deep brain or infratentorial,and mixed regions)were also analyzed using multinomial logistic regression.A linear regression analysis was conducted to determine the association between antiplatelet medication and the log-transformed number of CMBs.RESULTS Of the 544 participants(mean age:58.65±13.66 years,217 males),119 participants(21.88%)had CMBs,and 64 participants(11.76%)used antiplatelet medication.Antiplatelet medication was found to be associated with CMBs at any location[odds ratio(OR)=2.39,95%CI:1.24-4.58]and lobar region(OR=2.83,95%CI:1.36-5.86),but not with the number of CMBs(β=0.14,95%CI:-0.21-0.48).Among antiplatelet medications,aspirin use was found to be associated with any CMB(OR=3.17,95%CI:1.49-6.72)and lobar CMBs(OR=3.61,95%CI:1.57-8.26).CONCLUSIONS Antiplatelet medication was associated with CMBs in stroke-free participants,particularly lobar CMBs.Among antiplatelet medications,aspirin use was associated with any CMB and lobar CMBs.Our findings suggest that it might be essential to optimize the management of antiplatelet medication in the stroke-free population with a higher burden of vascular risk factors to reduce the potential risk of CMBs.

Essen score in the prediction of cerebrovascular events compared with cardiovascular events after ischaemic stroke or transient ischaemic attack:a nationwide registry analysis

BACKGROUND The Essen risk score improves stratification of patients with acute ischemic stroke by early stroke recurrence.Recent study showed it could also predict myocardial infarction(MI).This study aimed to compare the Essen score’s ability to predict cerebrovascular events with compared cardiovascular events.METHODS We included patients with acute ischaemic stroke or transient ischaemic attack within seven days from the Third China National Stroke Registry.One-year cumulative event rates of combined vascular events(a composite of MI,stroke recurrence or vascular death)and cardiac events(a composite of MI,heart failure or cardiac death)was estimated using the Kaplan-Meier met-hod.The predictive value of the Essen score was assessed with C-statistics.In multivariate Cox regression analyses,we assessed whether Essen score,etiological subtype and imaging parameters were associated with outcomes.RESULTS Of 13,012 patients were included,the cumulative one-year event rates were 10.03%for combined vascular events and 0.77%for cardiac events,respectively.Compared with those with an Essen score<3,patients with an Essen score≥3 were more likely to have a subsequent combined vascular event[hazard ratio(HR)=1.39,95%CI:1.24−1.55]and cardiac events(HR=2.30,95%CI:1.53−3.44).The score tended to be more predictive of the risk of MI(C-statistic=0.63,95%CI:0.55−0.71)and cardiac events(C-statistic=0.62,95%CI:0.56−0.67)than stroke recurrence(C-statistic=0.55,95%CI:0.54−0.57)and combined vascular events(C-statistic=0.56,95%CI:0.54−0.57).In multivariable analysis after adjusted Essen score,patients with multiple acute in-farctions or single acute infarctions and large artery atherosclerosis subtype were independently associated with an increased risk of combined vascular events.While the cardioembolism subtype was associated with an increased risk of cardiac events.CONCLUSIONS The Essen score is potentially more suitable for risk stratification of cardiovascular events than cerebrovascular events.Moreover,future predictive tools should take brain imaging findings and cause of stroke into consideration.

The HMGB1 signaling pathway activates the inflammatory response in Schwann cells

Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1（HMGB1）, is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schwann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products（RAGE）, but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.

Research progress of non-specific neck pain in traditional Chinese medicine and western medicine

Non-specific neck pain is a common disease in clinic,and its pathogenesis is not clear.With the progress of the times and the change of living and working habits,the incidence of non-specific neck pain is increasing year by year,which has a great impact on people’s physical and mental health,work and life.Traditional Chinese medicine mainly treats non-specific neck pain by acupuncture and massage,while western medicine generally uses exercise and manipulation therapy,but the quality of clinical evidence of all kinds of therapy is not high,which needs to be verified.This paper summarizes the research progress of traditional Chinese medicine and western medicine in the treatment of non-specific neck pain from the aspects of pathogenesis,etiology and pathogenesis of traditional Chinese medicine,and treatment of traditional Chinese medicine and western medicine,so as to provide reference for doctors in clinical treatment of this disease.

Beyond low-density lipoprotein cholesterol levels:Impact of prior statin treatment on ischemic stroke outcomes

Although essential for cardiovascular therapy,the pleiotropic effects of statins on ischemic stroke lack clinical evidence.This study examined the effects of statins beyond low-density lipoprotein cholesterol(LDL-C)levels on mortality and stroke severity.A total of 825,874 patients with ischemic stroke were included in this study,of whom 125,650 statin users were 1:1 matched with non-users based on their LDL-C levels(±0.05 mmol/L),forming the LDL-C-matched cohort.Associations between preceding statin treatment,in-hospital mortality,and stroke severity(National Institutes of Health Stroke Scale scoreR16)were estimated by multivariate and conditional logistic regression models in overall cohort and LDL-C-matched cohort,respectively.