Human umbilical cord mesenchymal stem cells-derived exosomal circDLGAP4 promotes angiogenesis after cerebral ischemia-reperfusion injury by regulating miR-320/KLF5 axis.

Accumulating evidence suggests that human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSCs-Exos) are a promising therapeutic strategy for cerebral ischemia-reperfusion injury (CIRI). However, the underlying mechanism remains unclear. hUC-MSCs-Exos were identified by electron microscopy, NTA, and Western blotting. In the hypoxia/reoxygenation (H/R) cell model, human brain microvascular endothelial cells (HBMECs) were cocultured with hUC-MSCs-Exos. Then, cell viability, migration, apoptosis, and tube formation were measured by MTT, flow cytometry, transwell, and tube formation assays. RT-qPCR and Western blotting were used to detect the changes in RNA and protein. RNA pull-down and dual luciferase reporter assays confirmed the relationship between circDLGAP4, miR-320, and KLF5. Ischemia-reperfusion (I/R) rat model was established for in vivo experiments. hUC-MSCs-Exos increased the expression levels of circDLGAP4 and KLF5 but decreased miR-320 in H/R-treated HBMECs by transferring exosomal circDLGAP4. Knockdown of circDLGAP4 in hUC-MSCs-Exos reversed the promoting effects of hUC-MSCs-Exos on cell viability, migration, and tube formation in H/R-treated HBMECs in vitro and also abolished the protective effects of hUC-MSCs-Exos on cerebrovascular injury in I/R rats. Mechanistically, exosomal circDLGAP4 negatively regulated miR-320 in HBMECs, which directly bound to KLF5. In addition, the downregulation of miR-320 could reverse the regulatory effect of exosomal shcircDLGAL5 in H/R-treated HBMECs by upregulating KLF5. hUC-MSCs-Exos-derived circDLGAP4 reduced cerebrovascular injury by regulating miR-320/KLF5 signaling. These results provide a stem cell-based approach to treat CIRI.

Three Polyoxometalate-Based Ag-Organic Compounds as Heterogeneous Catalysts for the Synthesis of Benzimidazoles.

Three new POM-based compounds, with formulae [Na0.63Ag3(Htba)2.37(tba)0.63(H2O)2(PMo12O40)]·4H2O (Ag3PMo), [Ag4(Htba)4(H2O)2(PMo12O40)](NO3)·H2O (Ag4PMo), and [Ag3(Htba)2(tba)(PW12O40)0.5](NO3)0.5·13H2O (Ag3PW), were prepared with a 3-(4H-1,2,4-triazol-4-yl)benzoic acid (Htba) ligand, Keggin-type anions ([PMo12O40]3-/[PW12O40]3-), and a silver ion (Ag+). The structural features of these compounds are particularly different from the multinuclear subunits, which are [Ag3(tba)3] clusters in Ag3PMo, [Ag4(tba)3] chains in Ag4PMo, and [Ag3(tba)3]2 clusters in Ag3PW, connected by multidonor atom tba ligands and Ag+ ions. Meanwhile, in these compounds, polyanions act as polydentate ligands to link adjacent Ag-tba metal-organic units and expand their spatial dimensions. These compounds, as heterogeneous catalysts, exhibit high stability and excellent catalytic activity to construct benzimidazoles. Ag3PMo could efficiently catalyze the condensation of benzene-1,2-diamines and benzaldehydes and produce benzimidazoles in good yields. In addition, Ag3PMo could be reused up to 7 times and was suitable for gram-scale reactions.

Hydrophilic Sulfonated 2,9-Diamide-1,10-phenanthroline Endowed with a Highly Effective Ligand for Separation of Americium(III) from Europium(III): Extraction, Spectroscopy, and Density Functional Theory Calculations.

The design and development of a water-soluble heterocyclic ligand are believed to be an alternative way for improving the separation efficiency of actinides from lanthanides. Herein, we designed and synthesized a novel hydrophilic multidentate ligand: disulfonated N,N'-diphenyl-2,9-diamide-1,10-phenanthroline (DS-Ph-DAPhen) with soft and hard donor atoms, as a masking agent in aqueous solutions for Am(III) separation. The combination of N,N,N',N'-tetraoctyldiglycolamide in kerosene and DS-Ph-DAPhen in aqueous phases could separate Am(III) from Eu(III) across a range of nitric acid concentrations with very high selectivity. The coordination behaviors of Eu(III) with DS-Ph-DAPhen in aqueous solutions were studied by UV-vis titration, electrospray ionization mass spectrometry, and Fourier transform infrared spectra. The results indicated that Eu(III) ions could form both 1:1 and 1:2 complexes with the DS-Ph-DAPhen ligand in aqueous solution. Density functional theory calculation suggests that there are more covalent characters for Am-N bonds than that for Eu-N bonds in the complexes, which supports the better selectivity of the DS-Ph-DAPhen ligand toward Am(III) over Eu(III). This work demonstrates a feasible alternative approach to separating trivalent actinides from lanthanides with high selectivity.

Orexins alleviate motor deficits via increasing firing activity of pallidal neurons in a mouse model of Parkinson's disease.

Orexin is a peptide neurotransmitter released in the globus pallidus. Morphological evidence reveals that both orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) exist in the globus pallidus. Here we showed that bilateral microinjection of both orexin-A and orexin-B into the globus pallidus alleviated motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice. Further in vivo extracellular single-unit recording revealed that the basal spontaneous firing rate of the globus pallidus neurons in MPTP parkinsonian mice was slower than that of normal mice. Application of orexin-A or orexin-B significantly increased the spontaneous firing rate of pallidal neurons. The influx of Ca2+ through the L-type Ca2+ channel is the major mechanism involved in orexin-induced excitation in the globus pallidus. Orexin-A-induced increase in firing rate of pallidal neurons in MPTP parkinsonian mice was stronger than that of normal mice. Orexin-A exerted both electrophysiological and behavioral effects mainly via OX1R, and orexin-B exerted the effects via OX2R. Endogenous orexins modulated the excitability of globus pallidus neurons mainly through OX1R. The present behavioral and electrophysiological results suggest that orexins ameliorate parkinsonian motor deficits through increasing the spontaneous firing of globus pallidus neurons.

Coronary Artery Diameter is Inversely Associated with the Severity of Coronary Lesions in Patients Undergoing Coronary Angiography.

BACKGROUND: The diameters of the coronary arteries have been suggested to be a potential predictor of coronary artery disease (CAD). However, whether the diameters of the coronary arteries are associated with the coronary lesion severity on angiography has not been determined. METHODS: One hundred sixty-seven consecutive adult patients (109 men and 58 women) aged 31-84 years who underwent coronary angiography for suspected or known CAD were enrolled. The known catheter tip diameter was used as the calibration to measure the diameters of coronary arteries, and the severity of coronary lesions was evaluated with the vessel score and Gensini score. RESULTS: In patients with a higher vessel score and Gensini score, the diameters of the left main (LM), left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA) were smaller (all p<0.05) than those in patients with lower scores. Multiple linear regression analysis indicated that the average coronary artery diameter was significantly associated with the Gensini score (ß=-0.444, p<0.00001). Moreover, the diameters of the coronary arteries were potential predictors of CAD, with areas under the receiver operating characteristic curves of 0.268 for average diameter (95% confidence interval [CI]: 0.183-0.353, p<0.00001), 0.356 for the LM diameter (95% CI: 0.266-0.445, p=0.005), 0.214 for the LAD diameter (95% CI: 0.136-0.291, p<0.00001), 0.366 for the LCX diameter (95% CI: 0.271-0.461, p=0.009), and 0.346 for the RCA diameter (95% CI: 0.245-0.447, p=0.003). CONCLUSION: The diameters of coronary arteries are inversely associated with the severity of CAD.

Combination of early constraint-induced movement therapy and fasudil enhances motor recovery after ischemic stroke in rats.

PURPOSE: Constraint-induced movement therapy (CIMT) is a promising technique for the recovery of upper extremity movement in chronic stroke patients. However, the effectiveness of its use in acute ischemia has not been confirmed. Myelin-associated inhibitors, which have upregulated functions in tissues affected by acute focal infarction, limit axonal regeneration via activation of the Rho-Rho-associated protein kinase (ROCK) pathway. The present study examined whether early CIMT combined with the ROCK inhibitor fasudil promotes motor recovery after acute ischemic stroke. MATERIALS AND METHODS: Rats were trained to perform the skilled-reach test and then subjected to middle cerebral artery occlusion (MCAO), producing a stroke affecting the preferred forelimb. Rats were assigned to one of four groups (N = 6/group): (nontreated) Control, CIMT, Fasudil, or CIMT+fasudil. CIMT and/or intraperitoneal infusion of fasudil were initiated 1 day postMCAO. Skilled reach and foot fault test data were collected once before and repeatedly over 4 weeks after the operation. Infarct volumes were calculated. RESULTS: All four groups showed similar forelimb impairment before treatment. The performance of CIMT alone group was similar to that of controls on both tests. Fasudil alone facilitated recovery in the foot-fault test, but not in the skilled-reach test. Rats in the CIMT+fasudil group demonstrated enhanced recovery in both tests, including better performance over time than the Fasudil group on the foot-fault test. Infarct size did not differ significantly between the groups. CONCLUSIONS: Early CIMT promotes motor recovery after acute ischemic stroke when it is administered with fasudil pharmacotherapy, but not without it.

Incidence and survival of lacunar infarction in a southern Chinese population: A 7-year prospective study.

OBJECTIVE: Little attention has been paid to the epidemiological characteristics of lacunar infarction (LAC) in China before. This study aimed to examine the incidence and survival of LAC in a southern Chinese population. METHODS: From 2004-2010 in Changsha, two communities with a registered population of ∼100 000 were selected and data from first-ever ischaemic stroke (IS) cases were prospectively collected. Then the epidemiological characteristics of LAC and non-LAC were evaluated. RESULTS: During the study period, the age-standardized incidence increased at an annual rate of 0.7% (p < 0.001) for LAC and 2.0% (p < 0.001) for non-LAC. The mean annual age-standardized incidence of LAC and non-LAC was 28.2/100 000 and 45.0/100 000, respectively. Compared with non-LAC patients, the prevalence of hypertension, diabetes and hyperlipidemia was significantly higher in patients with LAC (p < 0.05). Although the 30-day fatality rate was significantly lower in patients with LAC than non-LAC (0.5% vs. 14.9%, p < 0.001), there was no significant difference in survival between the two groups (96.7% vs. 95.2%, p = 0.203) after excluding the patients who died within 1 year of stroke onset. CONCLUSION: LAC is a common stroke sub-type in southern China and the long-term prognosis is not benign.

Effect of anti-PMSG on distribution of estrogen receptor alpha and progesterone receptor in mouse ovary, oviduct and uterus.

It is well established that estrogen and progesterone are critical endogenous hormones that are essential for implantation and pregnancy in females. However, the distribution of estrogen receptor α (ERα) and progesterone receptor (PR) in female reproductive tracts is elusive. Herein, we report that after serial treatments with pregnant mare's serum gonadotrophin (PMSG) with or without anti-PMSG (AP), mice could regulate the distribution of ERα and PR in the murine ovary, oviduct and uterus and the level of estradiol in serum. ERα and PR regulation by PMSG and anti-PMSG was estrous cycle-dependent and critical for promoting the embryo-implantation period. Furthermore, our results suggested that AP-42 h treatment is more effective than the other treatments. In contrast, other treatment groups also affected the distribution of ERα and PR in mouse reproductive tracts. Thus, we found that anti-PMSG has the potential to restore the distribution of ERα and PR, which could effectively reduce the negative impact of residual estrogen caused by the normal superovulation effect of PMSG in mice.

Curcumin protects neurons against oxygen-glucose deprivation/reoxygenation-induced injury through activation of peroxisome proliferator-activated receptor-γ function.

The turmeric derivative curcumin protects against cerebral ischemic injury. We previously demonstrated that curcumin activates peroxisome proliferator-activated receptor-γ (PPARγ), a ligand-activated transcription factor involved in both neuroprotective and anti-inflammatory signaling pathways. This study tested whether the neuroprotective effects of curcumin against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury of rat cortical neurons are mediated (at least in part) by PPARγ. Curcumin (10 µM) potently enhanced PPARγ expression and transcriptional activity following OGD/R. In addition, curcumin markedly increased neuronal viability, as evidenced by decreased lactate dehydrogenase release and reduced nitric oxide production, caspase-3 activity, and apoptosis. These protective effects were suppressed by coadministration of the PPARγ antagonist 2-chloro-5-nitrobenzanilide (GW9662) and by prior transfection of a small-interfering RNA (siRNA) targeting PPARγ, treatments that had no toxic effects on healthy neurons. Curcumin reduced OGD/R-induced accumulation of reactive oxygen species and inhibited the mitochondrial apoptosis pathway, as indicated by reduced release of cytochrome c and apoptosis-inducing factor and maintenance of both the mitochondrial membrane potential and the Bax/Bcl-2 ratio. Again, GW9662 or PPARγ siRNA transfection mitigated the protective effects of curcumin on mitochondrial function. Curcumin suppressed IκB kinase phosphorylation and IκB degradation, thereby inhibiting nuclear factor-κ B (NF-κB) nuclear translocation, effects also blocked by GW9662 or PPARγ siRNA. Immunoprecipitation experiments revealed that PPARγ interacted with NF-κB p65 and inhibited NF-κB activation. The present study provides strong evidence that at least some of the neuroprotective effects of curcumin against OGD/R are mediated by PPARγ activation.

TNFSF4 gene polymorphism rs3861950 but not rs3850641 is associated with the risk of cerebral infarction in a Chinese population.

Tumor necrosis factor superfamily member 4 (TNFSF4) plays a key role in the process of atherosclerosis, a common risk factor for both myocardial and cerebral infarctions. Recent studies indicate that the single nucleotide polymorphism (SNP) rs3850641 in TNFSF4 is associated with higher risk of myocardial infarction, but little is known about the association between TNFSF4 variation and cerebral infarction (CI). A case-control study involving 385 CI patients and 385 age-matched, sex-matched non-CI controls was conducted in a Chinese population, only the most common subtype, atherosclerosis CI, was recruited. Two SNPs of TNFSF4, rs3850641 and rs3861950, were genotyped by the TaqMan SNP genotyping method, and verified partly by genomic DNA sequencing. The results revealed a significant allelic association between rs3861950 and CI (Odds ration = 1.733, 95 % confidence interval = 1.333-2.254, P = 0.000). Genotypic association analysis demonstrated that the CC genotype of rs3861950 confers susceptibility to CI (Odds ration = 2.896, 95 % confidence interval = 1.368-6.132), and it was associated with a significantly higher risk of ischemic stroke (Odds ration = 3.520, 95 % confidence interval = 1.546-8.015, P = 0.003) after adjusting for the other confirmed risk factors such as the history of hypertension, diabetes, CAD, smoking and alcohol drinking. While the odds ratio of the T allele to the C allele was 1.733 (95 % confidence interval: 1.333-2.254). However, there was no significant association between rs3850641 and CI (Odds ration = 1.288, 95 % confidence interval = 0.993-1.670, P = 0.056). TNFSF4 gene polymorphism rs3861950, but not rs3850641, is associated with the risk of atherosclerosis CI in a Chinese population.

Public and professional education on urgent therapy for acute ischemic stroke: a community-based intervention in Changsha.

Excessive delay of presentation for stroke in China is reported. In this study, an intervention trial was conducted to promote urgent therapy for acute ischemic stroke. Two communities in Changsha were selected as either intervention or control community from November 2007 to December 2011. Public and professional education was regularly implemented in the intervention community. Publics' knowledge about early identification and urgent therapy of ischemic stroke was surveyed before and after intervention in the two communities. During the intervention period, first-ever ischemic stroke cases occurring in the intervention community (intervention group) and that in the control community (control group) were collected and followed for 90 days. After intervention, the publics' knowledge levels in the intervention community improved significantly. Intervention group' average presentation time was shorter than control group (8.3 ± 5.8 vs. 10.5 ± 6.5 h, P = 0.018). Percentage of presentation time within 3 h (48.0 %), the rate of ambulance use (59.0 %), and thrombolytic therapy (9.3 %) in the intervention group was all obviously higher than that in the control group (21.5, 41.3, and 4.5, respectively). When admitted, the intervention group had lower mean systolic blood pressure (160.8 ± 26.7 vs. 164.7 ± 26.8 mmHg, P = 0.000) than control group. Survivors in the intervention group were more likely to be in higher Barthel index scoring groups than that in the control group at day 90 [(75, 50-100) vs. (65, 35-90), P = 0.035]. Public and professional education may promote prompt presentation and urgent therapy for ischemic stroke, which may be helpful for patients' prognosis.

An inner-filter-effect based ratiometric fluorescent sensor for the detection of uranyl ions in real samples.

In this work, a ratiometric fluorescence system was designed for the detection of trace UO22+ in water based on the inner filter effect (IFE) between gold nanoparticles (AuNPs) and gold nanoclusters (AuNCs). IFE-induced fluorescence quenching was achieved due to the enhanced complementary overlap between the absorption spectra of AuNPs and the emission spectrum of AuNCs after the addition of UO22+. Blue carbon dots (B-CDs) were added to serve as reference fluorophores to expand the color tonality and make human eye recognition easier. The ratiometric fluorescent sensor demonstrated a unique fluorescence color change from red to blue when different doses of UO22+ were added, with a detection limit of 8.4 nM. Furthermore, the ratiometric fluorescent sensor was effectively used for UO22+ determination in real-world water samples, with acceptable recoveries.

Energy restriction induced SIRT6 inhibits microglia activation and promotes angiogenesis in cerebral ischemia via transcriptional inhibition of TXNIP.

Energy restriction (ER) protects against cerebral ischemic injury, but the underlying mechanism remains largely unclear. Here, rats were fed ad libitum (AL) or on an alternate-day food deprivation intermittent fasting (IF) diet for 3 months, followed by middle cerebral artery occlusion (MCAO) surgery. The body weight, infarct volume, and neurological deficit score were accessed at the designated time points. ELISA, qRT-PCR, and Western blotting were used to determine cytokine secretion and the expression of SIRT6, TXNIP, and signaling molecules, respectively. Immunofluorescence evaluated microglial activation and angiogenesis in vivo. For in vitro study, oxygen-glucose deprivation/reoxygenation (OGD/R)-treated cell model was generated. MTT and tube formation assays were employed to determine cell viability and tube formation capability. ChIP assay detected chromatin occupancy of SIRT6 and SIRT6-mediated H3 deacetylation. We found that IF or ER mimetics ameliorated cerebral ischemic brain damage and microglial activation, and potentiated angiogenesis in vivo. ER mimetics or SIRT6 overexpression alleviated cerebral ischemia and reperfusion (I/R)-induced injury in vitro. SIRT6 suppressed TXNIP via deacetylation of H3K9ac and H3K56ac in HAPI cells and BMVECs. Downregulation of SIRT6 reversed ER mimetics-mediated protection during cerebral I/R in vitro. Our study demonstrated that ER-mediated upregulation of SIRT6 inhibited microglia activation and potentiated angiogenesis in cerebral ischemia via suppressing TXNIP.

Efficacy of Getong Tongluo Capsule () for Convalescent-Phase of Ischemic Stroke and Primary Hypertension: A Multicenter, Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION: GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

[Association of single nucleotide polymorphisms of kallikrein 1 gene with cerebral hemorrhage in Changsha Han Chinese].

OBJECTIVE: To explore the association between single nucleotide polymorphisms (SNPs) of KLK1 gene and cerebral hemorrhage in Changsha Han Chinese. METHODS: Two hundred and seventy-three cerebral hemorrhage (CH) patients and 140 healthy controls were collected. The SNPs of rs5516 and rs5517 loci of KLK1 gene were analyzed by SNaPshot methods and direct sequencing. RESULTS: (1)Genotype and allele frequencies in rs5516 locus had no difference between the CH patients and controls (P> 0.05). However, the A allele frequency of the rs5517 locus in CH patients was higher than that in the control group (0.419, 0.321 respectively, P< 0.05). (2)In the control group,the levels of diastolic blood pressure (DBP) of the GA and AA genotype carriers of the rs5517 locus were significantly higher than those of the GG genotype (P< 0.05), while the levels of blood pressure were not significantly different among different genotypes of the rs5516 polymorphism in both CH patients and the control group(P> 0.05). CONCLUSION: Author's preliminary results suggested that the rs5517 polymorphism was associated with cerebral hemorrhage, while the rs5516 polymorphism was not in Changsha Han Chinese.

[Prospective study on associations between levels of total cholesterol, triglyceride and risk of ischemic and hemorrhagic strokes].

OBJECTIVE: To explore associations between levels of total cholesterol (TC), triglyceride (TG) and incidence of ischemic and hemorrhagic strokes in populations. METHODS: Baseline investigations on stroke-related risk factors and physical examinations were performed in 10 093 (> 35 years) stroke-free urban community residents from 5 cities in China during May to July in 1987, follow-up investigations on stroke events were made during 1998 to 2000. The hazard ratios and 95% confidence intervals (CI) of ischemic and hemorrhagic strokes in middle, high tertiles of baseline TC or TG levels were compared with low baseline tertile residents using the Cox regression model. RESULTS: There were 491 first strokes during the 8-years cohort follow-up. Compared with the low tertile, risk of ischemic stroke in the middle and high tertiles of TC level was increased by 61% (HR: 1.61, 95%CI: 1.14-2.27) and 58% (HR: 1.58, 95%CI: 1.12-2.22) after adjustments for DBP, age, sex and other variables in the Cox proportional hazards model. Compared with the low tertile, risk of ischemic stroke in the high tertile of TG level was increased by 43% (HR: 1.43, 95%CI: 1.02-2.00). However, risk of hemorrhagic stroke in the middle and high tertiles of TC level decreased by 12% (HR: 0.88, 95%CI: 0.64-1.22) and 33% (HR: 0.67, 95%CI: 0.48-0.95) compared with the low tertile. CONCLUSIONS: Elevated serum TC and TG are independent risk factors for risk of ischemic stroke. However, low TC was related with increased risk of hemorrhagic stroke.

Muscular involvement of extranodal natural killer/T cell lymphoma misdiagnosed as polymyositis: A case report and review of literature.

BACKGROUND: Natural killer (NK)/T cell lymphoma is a rare and highly aggressive malignant tumor, and is a special form of non-Hodgkin's lymphoma. Although extranodal involvement is frequently found in tissues such as the skin, testicular and gastrointestinal tract etc, its presence in skeletal muscle has scarcely been reported in the literature. CASE SUMMARY: We report a case of extranodal NK/T cell lymphoma with muscle swelling as the first clinical manifestation. A 42-year-old man, who initially presented with localized swelling in the double lower extremities, demonstrated gradual facial and eyelid swelling, and his imaging results showed multiple sites of muscle damage throughout the body. The final pathological results suggested NK/T cell lymphoma, and immunohistochemistry showed CD20 (-), CD3Ɛ (+), CD30 (+), CD56 (-), EBER (+), Ki67 (60%), TIA-1 (+) and CD68 (±) staining. The muscle swelling significantly improved after treatment with chemotherapy regimens. CONCLUSION: This disease is difficult to diagnose and highly invasive, and should be included in the differential diagnosis of unexplained muscle swelling.

Association between Val/Leu(247) polymorphism of apolipoprotein H and cerebral infarction in a Chinese population.

BACKGROUND: Antiphospholipid antibodies (aPL) are considered to be a cause of an acquired hypercoagulable state leading to cerebral infarction (CI). Apolipoprtein H (apoH) is an important target antigen for aPL and thus apoH polymorphisms may influence aPL production and the development of CI. The purpose of this study was to identify associations between the Val/Leu(247) polymorphism of apoH gene and CI in a Chinese cohort. METHODS: This study comprised 130 CI patients and 100 healthy control subjects. Polymorphism assignment was determined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique and DNA sequencing. The presence of aPL was detected by ELISA utilizing irradiated ELISA plates. RESULTS: Our results demonstrated an association between the Val/Leu(247) polymorphism of apoH gene and aPL in CI patients. The frequency of V allele was significantly higher in aPL-positive CI patients compared with control group (chi(2) = 6.864, P < 0.05). VL genotype frequency was also significantly higher in aPL-positive CI group compared with control group (chi(2) = 13.879, P < 0.05) and aPL-negative CI group (chi(2) = 5.567, P < 0.05). CONCLUSIONS: The Val(247) allele of apoH gene is significantly associated with the presence of aPL in Chinese patients with CI.

[Differentiation of hypoxic-ischemic encephalopathy and acute bilirubin encephalopathy with magnetic resonance imaging in neonates].

OBJECTIVE: To investigate the value of conventional magnetic resonance imaging (MRI) and diffusion weighed imaging (DWI) in the differentiation of hypoxic-ischemic encephalopathy (HIE) and acute bilirubin encephalopathy in neonates. METHODS: The MRI findings along with DWI characteristics in 15 neonates with HIE involving basal ganglia and in 18 neonates with acute bilirubin encephalopathy between November 2006 and June 2008 were retrospectively reviewed. RESULTS: On T1WI, only 5 patients presented hyperintensity in the globus pallidus in the HIE group, but 16 in the acute bilirubin encephalopathy group (p<0.01). Nine patients in the HIE group showed hyperintensity in the putamen, but the hyperintensity in the putamen was not found in the acute bilirubin encephalopathy group. The frequency of hyperintensity in the subthalamus in the acute bilirubin encephalopathy group (55.6%) was significantly higher than that in the HIE group (13.3%) (p<0.05). Eight patients in the HIE group showed abnormal signals in the other regions on T1WI, but only two patients in the acute bilirubin encephalopathy group (p<0.05). On DWI, 7 out of 11 patients with HIE presented hyperintensity in the basal ganglia, while all 10 patients of the acute bilirubin encephalopathy group presented normal in the basal ganglia. CONCLUSIONS: Conventional MRI along with DWI is useful in differentiating HIE from acute bilirubin encephalopathy in neonates.

Palmitic and linoleic acids impair endothelial progenitor cells by inhibition of Akt/eNOS pathway.

BACKGROUND: Endothelial progenitor cells (EPCs) are involved in adult neovasculogenesis and maintenance of vascular integrity. Scarce data have been provided for the individual effect of elevated free fatty acids (FFAs) on EPCs. This study was designed to investigate the association between Akt/eNOS signal pathway changes and the proliferation/function of EPCs in the presence of palmitic and linoleic acids. METHODS: After 14-day culture, EPCs were stimulated with different concentrations of palmitic and linoleic acids, with or without SNP, L-NAME, or LY294002. The proliferation and ability of adhesion, migration and tube structure formation of EPCs were observed and the level of phosphorylated Akt protein expression and eNOS protein expression were assayed. RESULTS: Incubation with palmitic and linoleic acids at concentrations of 0.2 muM or higher inhibited EPCs proliferation, significantly reduced migratory rate, reduced adhesion to fibronectin and impaired ability of EPCs to form tube structure in a dose-dependent manner. A simultaneous dose-dependent NO generation and Akt phosphorylation decrease as well as eNOS expression reduction at protein levels were also observed. However, all of the detrimental effects were attenuated by pretreating EPCs with SNP, NO donor. AKT and eNOS inhibitor, LY294002 and L-NAME, respectively, augmented palmitic and linoleic acids inhibitory effects on EPCs. CONCLUSIONS: These findings suggest that palmitic and linoleic acids downregulated AKT/eNOS signal pathway, which contributed to overall poor function and decrease proliferation of EPCs. These changes induced by palmitic and linoleic acids in signaling offer a novel explanation for the overall poor function of EPCs in diabetes mellitus.