Cell-specific IL-1R1 regulates the regional heterogeneity of microglial displacement of GABAergic synapses and motor learning ability.

Microglia regulate synaptic function in various ways, including the microglial displacement of the surrounding GABAergic synapses, which provides important neuroprotection from certain diseases. However, the physiological role and underlying mechanisms of microglial synaptic displacement remain unclear. In this study, we observed that microglia exhibited heterogeneity during the displacement of GABAergic synapses surrounding neuronal soma in different cortical regions under physiological conditions. Through three-dimensional reconstruction, in vitro co-culture, two-photon calcium imaging, and local field potentials recording, we found that IL-1ß negatively modulated microglial synaptic displacement to coordinate regional heterogeneity in the motor cortex, which impacted the homeostasis of the neural network and improved motor learning ability. We used the Cre-Loxp system and found that IL-1R1 on glutamatergic neurons, rather than that on microglia or GABAergic neurons, mediated the negative effect of IL-1ß on synaptic displacement. This study demonstrates that IL-1ß is critical for the regional heterogeneity of synaptic displacement by coordinating different actions of neurons and microglia via IL-1R1, which impacts both neural network homeostasis and motor learning ability. It provides a theoretical basis for elucidating the physiological role and mechanism of microglial displacement of GABAergic synapses.

Case report about a successful full robotic radical gastric cancer surgery with intracorporeal robot-sewn anastomosis in a patient with situs inversus totalis and a two-and-a-half-year follow-up study.

BACKGROUND: During the last decade, total laparoscopic and laparoscopic-assisted distal gastrectomy for gastric cancer patients has been developed as alternatives to open resection. In recent years, this minimally invasive surgery has been extended using robotic-assisted surgery. CASE PRESENTATION: Here, we report a surgical intervention using a Da Vinci surgical robot in which a lower two-third stomach resection with subsequent Billroth II gastrojejunostomy was performed. The patient was a 53-year-old male with complete situs inversus gastric cancer who had received 2 cycles of neo-adjuvant oxaliplatin combined with S-1 medication. The operation took 3 h in total without complications. The amount of bleeding was about 50 mL, and on day 5 after the operation, the patient was discharged. CONCLUSIONS: This is the first report of a successful robot-assisted gastric cancer resection of advanced gastric cancer in a patient with the anatomical abnormality of situs inversus totalis.

Long-Term Changes in Drug Craving and Nutritional Status of Opioid Addicts with Nucleus Accumbens Ablative Stereotactic Neurosurgery at Five Years Postoperatively.

BACKGROUND: The nucleus accumbens (NAcc) has been proven to be associated with drug and food craving. NAcc ablative neurosurgery has been suggested to modulate the balance of the brain reward system and thus alleviate drug dependence in patients. It has been hypothesized that it would also alleviate food craving in patients as well as altering their nutritional status. AIMS: This study aimed to estimate the effect of NAcc neurosurgery on drug craving and nutritional status in patients with drug dependence at 5 years postoperatively. METHODS: The study included 100 patients with NAcc surgery and 92 patients without surgery. Body mass index (BMI) and body fat percentage (BF%) were examined to assess nutritional status, and questionnaires were administered to assess drug craving. RESULTS: Compared with the nonsurgery group and the relapse patients from the surgery group, the nonrelapse patients from the surgery group had higher BMI and BF% but lower drug craving. There were no significant differences between the nonsurgery group and the relapse patients in BMI, but the relapse patients had higher drug craving than the nonsurgery group. CONCLUSIONS: Long-term follow-up suggested that NAcc ablative neurosurgery would alleviate drug craving and yield a better nutritional status if individuals sustained abstinence. It would increase drug craving but would not ruin the nutritional status of patients even when individuals relapsed postoperatively.

Hydrogen sulphide and mild hypothermia activate the CREB signaling pathway and prevent ischemia-reperfusion injury.

BACKGROUND: Both hydrogen sulphide (H2S) and mild hypothermia have been reported to prevent brain damage caused by reperfusion assault through regulating the N-methyl-D-aspartate receptor (NMDAR). However, the relationship between the two treatments and how they exert neuro-protective effects through NMDARs remain to be elucidated. METHODS: Transient cerebral ischemia was induced using the Pulsinelli four-vessel occlusion method. We used sodium hydrosulphide (NaHS) as the H2S donor. We randomly divided 100 Sprague-Dawley rats into five groups of 20: Sham operation group (Sh), normothermic (36-37 °C) ischemia group (NT), mild hypothermic (32-33 °C) ischemia group (mHT), normothermic ischemia combined with NaHS treatment group (NT + NaHS), and mild hypothermic ischemia combined with NaHS treatment group (mHT + NaHS). After 6 hrs of reperfusion, rats were decapitated and hippocampus samples were immediately collected. We measured NR2A (GluN1), NR2B (GluN2) and p-CREB protein levels using western blotting. We further analyzed BDNF mRNA expression by real-time PCR. Hematoxylin and eosin (HE) staining was used to examine pyramidal cell histology at the CA1 region. All statistical analyses were carried out by ANOVA and LSD t-test as implemented by the SPSS 13.0 software. RESULTS: In the four test groups with ischemia-reperfusion, hippocampal H2S concentration increased following treatment, and administration of NaHS further increased H2S levels. Moreover, administration of both NaHS and mild hypothermia resulted in up-regulation of NR2A and NR2B protein expressions, as well as p-CREB protein and BDNF mRNA levels. At the cellular level, NaHS and mild hypothermia groups exhibited lower damage caused by ischemia-reperfusion in the CA1 region of the hippocampus. The strongest protective effect was observed in rats treated with combined NaHS and mild hypothermia, suggesting their effects were additive. CONCLUSION: Our results support previous findings that hydrogen sulphide and mild hypothermia can prevent ischemia-reperfusion injury. Both treatments caused an up-regulation of NMDA receptors, as well as an elevation in p-CREB protein and BDNF mRNA levels. Thus, hydrogen sulphide and mild hypothermia may provide neuro-protective effect through activating the pro-survival CREB signaling pathway.

Activation of glutamatergic neurons in the somatosensory cortex promotes remyelination in ischemic vascular dementia.

Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.

Human PARP1 substrates and regulators of its catalytic activity: An updated overview.

Poly (ADP-ribose) polymerase 1 (PARP1) is a key DNA damage sensor that is recruited to damaged sites after DNA strand breaks to initiate DNA repair. This is achieved by catalyzing attachment of ADP-ribose moieties, which are donated from NAD+, on the amino acid residues of itself or other acceptor proteins. PARP inhibitors (PARPi) that inhibit PARP catalytic activity and induce PARP trapping are commonly used for treating BRCA1/2-deficient breast and ovarian cancers through synergistic lethality. Unfortunately, resistance to PARPi frequently occurs. In this review, we present the novel substrates and regulators of the PARP1-catalyzed poly (ADP-ribosyl)ation (PARylatison) that have been identified in the last 3 years. The overall aim is the presentation of protein interactions of potential therapeutic intervention for overcoming the resistance to PARPi.

Resolvin D1 Attenuates Innate Immune Reactions in Experimental Subarachnoid Hemorrhage Rat Model.

Excessive inflammation is a major cause contributing to early brain injury (EBI) and is associated with negative or catastrophic outcomes of subarachnoid hemorrhage (SAH). Resolvin D1 (RvD1) exerts strong anti-inflammatory and pro-resolving effects on either acute or chronic inflammation of various origin. Henceforth, we hypothesized that RvD1 potentially attenuates excessive inflammation in EBI following SAH. Therefore, we generated a filament perforation SAH model and administered 3 different doses (0.3, 0.6, and 1.2 nmol) of RvD1 after experimental SAH. Neurological scores, brain edema, and blood-brain barrier integrity were evaluated; besides, neutrophil infiltration, neuronal deaths, and microglial pro-inflammatory polarization were observed using histopathology or immunofluorescence staining, western blots, and qPCR. After confirming the effectiveness of RvD1 in SAH, we administered the FPR2-specific antagonist Trp-Arg-Trp-Trp-Trp-Trp-NH2 (WRW4) 30 min before SAH establishment to observe whether this compound could abolish the anti-inflammatory effect of RvD1. Altogether, our results showed that RvD1 exerted a strong anti-inflammatory effect and markedly reduced neutrophil infiltration and microglial pro-inflammatory activation, leading to remarkable improvements in neurological function and brain tissue restoration. After addition of WRW4, the anti-inflammatory effects of RvD1 were abolished. These results indicated that RvD1 could exert a good anti-inflammatory effect and alleviate EBI, which suggested that RvD1 might be a novel therapeutic alternative for SAH-induced injury.

Role of epithelial-to-mesenchymal transition in the pulmonary fibrosis induced by paraquat in rats.

BACKGROUND: This study aims to explore the characteristics of the epithelial-to-mesenchymal transition (EMT) process and its underlying molecular mechanisms in the period of paraquat (PQ)-induced pulmonary fibrosis (PF). METHODS: Picrosirius red staining and collagen volume fraction were utilized to evaluate the pathological changes of PQ-induced PF in rats. Immunohistochemistry, Western blot, and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were used to measure the protein and gene expression of EMT markers, EMT-associated transcription factors, and regulators of EMT-related pathways, respectively. RESULTS: The collagen deposition in the alveolar septum and increased PF markers were characteristics of pathological changes in PQ-induced PF, reached a peak on day 14 after PQ poisoning, and then decreased on day 21. The protein and gene expression of the fibrosis marker, EMT markers, transcription factors, and regulators of EMT-related signaling pathways significantly increased at different time points after PQ poisoning compared with corresponding controls (P<0.05), and most of them reached a peak on day 14, followed by a decrease on day 21. The gene expression of EMT markers was significantly correlated with PF markers, transcription factors, and regulators of EMT-related signaling pathways (P<0.05). The mRNA expression of transcription factors was significantly correlated with that of TGF-ß1 and Smad2 (P<0.05 or P<0.01), instead of Wnt2 and ß-catenin (P>0.05). CONCLUSIONS: EMT process plays a role in the PQ-induced PF, in which most PF and EMT markers have a peak phenomenon, and its underlying molecular mechanisms might be determined by further studies.

Effects of hydroxysafflor yellow A on the experimental traumatic brain injury in rats.

This paper explores the effects of hydroxysafflor yellow A (HSYA) on traumatic brain injury (TBI). Rats were divided into four groups: control, TBI, TBI combined with HSYA, and TBI combined with nimodipine. Saline, HSYA, or nimodipine was i.v. injected at 30 min before and 6 h after the onset of TBI. The contusion volume of brain, mitochondrial ATPase activity, brain malondialdehyde (MDA) content, and the concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in the blood plasma were investigated. The results showed that the inhibitory rate of HSYA at a dose of 4 mg/kg was 59.2% compared with the TBI group. After the insult by TBI for 48 h, the activity of Na(+), K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase decreased to 31, 35, and 38% of control group. HSYA increased these ATPase activities by 162, 96, and 131% of TBI group. HSYA also increased superoxide dismutase activity and decreased MDA content in the right parietal lobe adjacent to contusion foci in TBI rats. HSYA enhanced the t-PA activity by 64.64%, decreased the PAI-1 activity by 71.88%, and decreased the MMP-9 expression to 49.11% in the hippocampus of the TBI group at 12 h. In conclusion, HSYA may exert a potential therapeutic strategy to improve the outcome following TBI injury.

Long Noncoding RNA SNHG12 Indicates the Prognosis and Accelerates Tumorigenesis of Diffuse Large B-Cell Lymphoma Through Sponging microR-195.

BACKGROUND: Small nucleolar RNA host gene 12 (SNHG12) expression is associated with multiple cancers, including renal cell carcinoma, prostate cancer, cervical cancer, nasopharyngeal carcinoma, colorectal cancer, and hepatocellular carcinoma. However, SNHG12 biological function is unclear in diffuse large B-cell lymphoma (DLBCL). METHODS: SNHG12 expression and associated clinicopathological characteristics were evaluated in DLBCL tissues. CCK-8 and transwell assay were used to analyze the in vitro role of SNHG12 in DLBCL progression. The xenograft model was used to explore the in vivo role of SNHG12 in DLBCL growth. The physical interaction between SNHG12 and miR-195 was confirmed using bioinformatics analysis and a dual luciferase assay. RESULTS: SNHG12 expression was upregulated in DLBCL tissues and correlated with patients' prognosis. SNHG12 downregulation inhibited cell growth, migration, and invasion of DLBCL cells in vitro, while its overexpression promoted these cellular processes. Moreover, SNHG12 knockdown repressed tumorigenesis of DLBCL cells in vivo. Further experiments demonstrated that miR-195 is a target of SNHG12 in DLBCL and that their expression negatively correlates in DLBCL. SNHG12 functioned as a competing endogenous RNA for miR-195 in DLBCL cells and miR-195 upregulation abolished the effects of SNHG12 on of DLBCL progression. CONCLUSION: SNHG12 predicts poor clinical outcome and serves as a novel oncogene in DLBCL via miR-195 sponging. We also suggest that SNHG12 can be used as a potential therapeutic candidate for DLBCL patients.

Prolonged febrile seizures induce inheritable memory deficits in rats through DNA methylation.

AIMS: Febrile seizures (FSs) are the most common types of seizures in young children. However, little is known whether the memory deficits induced by early-life FSs could transmit across generations or not. METHODS: The memory functions of different generations of FS rats were behaviorally evaluated by morris water maze, inhibitory avoidance task, and contextual fear conditioning task. Meanwhile, molecular biology and pharmacological methods were used to investigate the role of DNA methylation in transgenerational transmission of memory defects. RESULTS: Prolonged FSs in infant rats resulted in memory deficits in adult and transgenerationally transmitted to next generation, which was mainly through mothers. For these two generations, DNA methyltransferase (DNMT) 1 was upregulated, leading to transcriptional inhibition of the synaptic plasticity protein reelin but not the memory suppressor protein phosphatase 1. DNMT inhibitors prevented the high expression of DNMT1 and hypermethylation of reelin gene and reversed the transgenerationally memory deficits. In addition, enriched environment in juvenile rats rescued memory deficits induced by prolonged FSs. CONCLUSIONS: Our study demonstrated early experience of prolonged FSs led to memory deficits in adult rats and their unaffected offspring, which involved epigenetic mechanisms, suggesting early environmental experiences had a significant impact on the transgenerational transmission of neurological diseases.

[Expression and Clinical Significance of Leukemia Stem Cell Antigen in Acute Myeloid Leukemia].

OBJECTIVE: To analyze the expression characteristics of leukemia stem cell (LSC) antigen in acute myeloid leukemia (AML) and to explore the correation of LSC-specific antigens with the subtypes, cytogenetics and clinical efficacy of AML. METHODS: A total of 61 newly diagnosed patients with AML (except M3) hospltalized in Department of Hematology of our hopital were selected from January 2013 to March 2016. The immun phenotypes and expression of Tim-3, CD96 and CD123 on leucamia cells were detected by direct immunofluorescenct flow cytometry. 61 patients were divided into positive expression and megative expression groups according to expression of Tim-3, CD96 and CD123; the correlation of LSC antigen expression level with high WBC count, chromosome and therapeutic efficacy was analyzed. RESULTS: Among 61 newly diagnosed patients with AML (except M3), the expression rate of Tim-3, CD96 and CD123 was 52.45%, 44.26% and 55.73% respectively. The expression rates of Tim-3, CD96 and CD123 between the AML subtypes and total patients was not stetistically different (P>0.05). The high WBC count occurred more easily in AML (except MS) patients with positive expression of Tim-3, CD96 and CD123, but compared with AML patients with negative espression, the difference was not statstically significant (P>0.05). The proportion of chromosone karyotype with poor prognosis detected in patients with positive expression of Tim-3 and CD96 was higher than that in patients with negative expreesion (P<0.05); while the preoprtion of chromosome karyotype with poor prognosis detected in patients with positive and negative expression of CD123 was not significantly different (P>0.05). After 2 courses of chemotherapy, the complete remission (CR) rate in patients with positive expression of Tim-3, CD96 and CD123 was significantly lower than that in patients with negative expression of Tim-3, CD96 and CD123 (P<0.05), the comparison of OS time in patients with positive and negative expression of Tim-3 and CD96 showed the statistical difference (P>0.05), while the difference of OS time in patients with positive and negative expression of CD123 was not significant (P>0.05). CONCLUSION: The expression levels of Tim-3, CD96 and CD123 in newly diagnosed AML (except M3) sybtype patients are not significantly different form those in total patients. The high WBC count ocours more easily in patients with positive expression of Tim-3, CD96 and CD123. After 2 course of chemotherapy, the CR rate in patients with positive expression of Tim-3, CD96 and CD123 was significantly lower than that in patients with negative expression. The proportion of chromsome karyotype with poor prognosis detected in patients with positive expression of Tim-3 and CD96 is high, moreover, OS time in patients with positive expression of Tim-3 and CD96 is shorter than that in patients with negative expression.

[Reversing effect of histamine on neurotoxicity induced by beta-amyloid1-42].

OBJECTIVE: To investigate the effects of histamine on the neurotoxicity induced by beta-amyloid(1-42)(Abeta42) in rat phaeochromocytoma (PC12) cells. METHODS: The in vitro model of Alzheimer's disease was constructed with A beta42-treated PC12 cells. Cell morphology and MTT assay were used to evaluate the cell toxicity and histamine effects. The different histamine antagonists were applied to investigate the involvement of receptor subtypes. RESULT: The neurotoxicity was induced by A beta42 in a concentration-dependent manner, which was reversed by histamine at concentration of 10(-7), 10(-6) mol/L. The effect was reversed by H(2) antagonist zolantidine and H(3)antagonist clobenpropit, but not by H(1) antagonist diphenhydramine. CONCLUSION: Histamine reduces neurotoxicity induced by beta-amyloid(1-42), which may be mediated by H(2) and H(3)receptors.

Mild Hypothermia Combined with Hydrogen Sulfide Treatment During Resuscitation Reduces Hippocampal Neuron Apoptosis Via NR2A, NR2B, and PI3K-Akt Signaling in a Rat Model of Cerebral Ischemia-Reperfusion Injury.

We investigated whether mild hypothermia combined with sodium hydrosulfide treatment during resuscitation improves neuron survival following cerebral ischemia-reperfusion injury beyond that observed for the individual treatments. Male Sprague-Dawley rats were divided into seven groups (n = 20 for each group). All rats underwent Pulsinelli 4-vessel occlusion. Ischemia was induced for 15 min using ligatures around the common carotid arteries, except for the sham group. Immediately after initiating reperfusion, the mild hypothermia (MH), sodium hydrosulfide (NaHS), hydroxylamine (HA), MH + NaHS, MH + HA, and ischemia-reperfusion (I/R) control groups received an intraperitoneal injection of saline, sodium hydrosulfide, hydroxylamine, sodium hydrosulfide, hydroxylamine, and saline, respectively, and mild hypothermia (32 to 33 °C) was induced in the MH, MH + NaHS, and MH + HA groups for 6 h. The levels of NR2A, NR2B, p-Akt, and p-Gsk-3ß in the hippocampus of the MH, NaHS, and MH + NaHS groups were higher than those in the I/R control group, with the highest levels observed in the MH + NaHS group (P < 0.05). Treatment with hydroxylamine reduced the levels of these proteins in the HA and MH + HA groups, compared with the I/R control and MH groups, respectively. The apoptotic index of the CA1 region of the hippocampus was 45.2, 66.5, 63.5, and 84.8 % in the MH + NaHS, MH, NaHS, and I/R control groups, respectively (P < 0.05), indicating that the combination treatment shifted the NR2A/NR2B balance in favor of synaptic neuron stimulation and phosphatidylinositol 3'-kinase (PI3K)/Akt signaling. The combination of mild hypothermia and sodium hydrosulfide treatment for resuscitation following ischemia-reperfusion injury was more beneficial for reducing hippocampal apoptosis and pathology than that of mild hypothermia or hydrogen sulfide treatment alone.

[Reversing effect of histamine on neuron death induced by N-methyl-D-aspartate].

OBJECTIVE: To determine the effect of histamine on N-methyl-D-aspartate (NMDA) induced neuron death and to elucidate its mechanism. METHODS: The primary cortical cell culture was adopted. Neuron morphology and MTT assay were used to evaluate the drugs effects. RESULT: Histamine at doses of 10(-4) 10(-6) 10(-7) 10(-8) mol/L reversed the neuron death induced by NMDA (50 micromol/L) for 3 h. The protection of histamine peaked at doses of 10(-4) mol/L and 10(-7)mol/L. The effect of histamine of 10(-7) mol/L was reversed only by cimetidine an H(2)receptor antagonist. However, the effect of histamine of 10(-4) mol/L was reversed only by pyrilamine but not cimetidine. CONCLUSION: Histamine could reduce neuron death induced by NMDA; its protection at a low dose might be mediated by H(2)receptor, and at a high dose by H(1)receptor.

Use of evidence-based pharmacotherapy for secondary prevention of coronary heart disease: a Chinese medicine hospital versus a general hospital.

OBJECTIVE: To determine differences in adherence to secondary prevention guidelines (pharmacological interventions) among coronary heart disease (CHD) patients between a Chinese medicine (CM) hospital and a general hospital in a Chinese city. METHODS: Medical records of 200 patients consecutively discharged from the CM hospital and the general hospital for CHD were reviewed to determine the proportions of eligible patients who received antiplatelet agents, ß-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and statins at discharge. The effects of patient characteristics and hospital type on the use of these medicines were estimated using logistic regression models. RESULTS: Patients discharged from the CM hospitals were older; more likely females; had greater history of hyperlipidemia, cerebrovascular diseases and less smoker (P<0.01 or P<0.05). They were less likely to receive coronary angiography and percutaneous coronary intervention, and had a longer length of stay than those discharged from the general hospital (P<0.01 or P<0.05). There were no significant differences in antiplatelet agents (96% vs. 100%, P=0.121) or statins (97.9% vs. 100%, P=0.149) use between the CM hospital and the general hospital. In multivariable analyses that adjusted for patient characteristics and hospital type, there was no significant difference in use of ß-blockers between the CM hospital and the general hospital. In contrast, patients discharged from the CM hospital were less likely to receive ACE inhibitors/ARBs compared with those discharged from the general hospital (odds ratio: 0.3, 95% confidence interval: 0.105-0.854). CONCLUSION: In this study, the CM hospital provides the same quality of care in CHD for prescribing evidence-based medications at discharge compared with another general hospital except for ACE inhibitors/ARBs use.

[Prognostic significance of serial determinations of lactate dehydrogenase in follow-up for patients with myelodysplastic syndrome].

This study was aimed to dynamically observe the expression level of lactate dehydrogenase (LDH) in MDS patients and to explore the significance of LDH level for prognostic judgement of MDS patients. The expression level of LDH in 163 confirmedly diagnosed patients from 2001 to 2009 years in our hospital, the changes of LDH level in follow-up patients and relation of the LDH changes to prognosis, survival time and MDS progression, as well as the relation of LDH level to blood cell count, ratio and karyotype of blast cells in bone marrow were analyzed retrospectively. The results showed that the median LDH level in 163 MDS patients at diagnosis was 214 U/L (range 102 - 865 U/L), the median survival time of patients with increased LDH (> 240 U/L) was 25.6 months which was significantly shorter than that of patients with normal LDH level (56.8 months)(p < 0.05). When MDS patients were classified according to IPSS, the increased LDH level in MDS patients was observed in high risk and intermediate II groups (337.20 ± 298.00 U/L and 234.07 ± 216.00 U/L, respectively) which was significantly higher than that in low risk group (154.94 ± 46.08 U/L) (p < 0.05). The LDH level in patients with MDS progression was obviously enhanced while LDH level in patients without progression was not enhanced, mainly maintained in stable level as compared with LDH level at diagnosis and before progression (p < 0.005). By multivariate analysis, the increase of LDH level was found to be an independent prognostic factor. It is concluded that the LDH level may be used as indicator for judging prognosis of MDS patients, which is helpful to early recognition of MDS progression and risk stratification of disease, as well as selection of rational therapy.

Activation of the central histaminergic system is involved in hypoxia-induced stroke tolerance in adult mice.

We hypothesized that activation of the central histaminergic system is required for neuroprotection induced by hypoxic preconditioning. Wild-type (WT) and histidine decarboxylase knockout (HDC-KO) mice were preconditioned by 3 hours of hypoxia (8% O(2)) and, 48 hours later, subjected to 30 minutes of middle cerebral artery (MCA) occlusion, followed by 24 hours of reperfusion. Hypoxic preconditioning improved neurologic function and decreased infarct volume in WT or HDC-KO mice treated with histamine, but not in HDC-KO or WT mice treated with α-fluoromethylhistidine (α-FMH, an inhibitor of HDC). Laser-Doppler flowmetry analysis showed that hypoxic preconditioning ameliorated cerebral blood flow (CBF) in the periphery of the MCA territory during ischemia in WT mice but not in HDC-KO mice. Histamine decreased in the cortex of WT mice after 2, 3, and 4 hours of hypoxia, and HDC activity increased after 3 hours of hypoxia. Vascular endothelial growth factor (VEGF) mRNA and protein expressions showed a greater increase after hypoxia than those in HDC-KO or α-FMH-treated WT mice. In addition, the VEGF receptor-2 antagonist SU1498 prevented the protective effect of hypoxic preconditioning in infarct volume and reversed increased peripheral CBF in WT mice. Therefore, endogenous histamine is an essential mediator of hypoxic preconditioning. It may function by enhancing hypoxia-induced VEGF expression.