Objective To examine cerebrovascular reactivity to CO2 inhalation in mice. Methods In vivo Two-Pho?ton imaging technique was used to record the reaction of cerebral cortical vessels including penetrating artery, surface vein and capillary in 5 male C57 mice after CO2 inhalation under a thinned-skull cranial window. Nitric oxide syntheses inhibitor L-NAME and Prostaglandin syntheses inhibitor Indomethacin were used to block different vasodilator pathways, respectively. Results Different mouse cortical vessels displayed different degrees of dilation to 1-minute 5%CO2 inhala?tion. The penetrating artery exhibited the most obvious dilation (45.01%±4.45%). L-NAME intervention significantly di?minished cerebravascular CO2 reactivity(P<0.05). Indomethacin significantly attenuated the dilation of artery but not capillary comparing with L-NAME intervention(P<0.05). Conclusions Different vessels react differently to CO2 inhala?tion in which postaglandins and NO signal pathways are involved.

Objective To investigate the effects of insulin on vascular diameter of the peri -infarct region and infarct volume after cerebral infarction in mice. Methods Forty male C57/BL6j mice w ere randomly divided into a control group ( n = 5), a cerebral infarction group ( n = 15), a cerebral insulin resistance group (n = 5), and a cerebral insulin resistance infarction group ( n = 15). A model of cerebral infarction w as induced by the photochemical method. A model of cerebral insulin resistance w as induced by intracerebroventricular injection of streptozocin. Tw o -photon confocal microscope w as used to in vivo evaluate the changes of vascular diameter in the peri-infarct region at 20 min after insulin injection into the cerebelomedulary cistern. After modeling of cerebral infarction, artificial cerebrospinal fluid or insulin (10 ng/ml) w as immediately injected into the cerebelomedulary cistern, and the effect of insulin on cerebral infarct volume w as evaluated at 24 h after infarction. Results Insulin did not have significant effect on various types of cerebral vascular diameters in the normal control group, but it significantly contracted cerebral arteries ( -23.16% ±6.86% and -23.32% ±6.40%, respectively; al P <0.001) and penetrating arteries ( -15.20% ±5.51% and -16.40% ±4.27%, respectively; al P < 0.001) in the cerebral insulin resistance group and the cerebral insulin resistance infarction group, but it did not have any effect on the diameters of the cerebral veins. There w ere no significant differences in the vasoactive effects of insulin betw een the cerebral infarction group and the normal control group, as w el as betw een the cerebral insulin resistance group and the cerebral insulin resistance infarction group. Insulin significantly reduced the volume of cerebral infarction in the cerebral infarction group (9.0 ±1.0 mm3 vs.6.0 ±1.2 mm3; t = 4.294,P =0.002), and it did not have significant effect on the volume of cerebral infarction in the cerebral insulin resistance infarction group ( 12.6 ±2.3 mm3 vs.11.6 ±1.7 mm3; t = 0.782, P = 0.456). Conclusions Insulin can reduce ischemic brain injury in normal mice and can not affect the cerebrovascular diameter of the peri-infarct region. The neuroprotective effect of insulin is not significant in cerebral insulin resistance in mice, and it may be associated w ith the vasoconstrictor effects of insulin in the peri -infarct region.

OBJECTIVETo investigate the role of different immunoglobulin- like receptor (KIR)haplotypes in haplo- identical hematopoietic stem cell transplantation (HSCT).

METHODKiller cell KIR genotyping was performed on 468 individuals from 156 unrelated families by PCR-SSP. A total of 624 KIR haplotypes from the parents were used for haplotype analysis. Ninety-two patients received haplo-identical HSCT from one of the parents.

RESULTSThe family study showed segregation of one A haplotype and at least 20 unique B haplotypes. The frequency of haplotype A was 72.92% (455/624). The most commonly observed haplotypes in group B were B1, B2, and B3, present at a frequency of 10.26%, 5.77%, and 4.48%, respectively. Compared to KIR gene matched donors (n=17), grafts from KIR gene mismatched donors (n= 14) had a positive effect on survival after haplo- identical HSCT for AML/MDS patients (OS: 88.2%vs 42.9%,P=0.015; RFS: 88.2%vs 35.7%,P=0.007). No effect was observed for ALL/NHL patients (OS: 76.0%vs 75.0%,P=0.727; RFS: 68.0%vs 65.0%,P=0.866). A significantly lower survival rate was observed for transplants from AA (n=52) and AB1/AB2 donors (n=15), compared to other group Bx donors (n=25) (OS: 53.3%vs 96.0%,P=0.017; RFS: 53.3%vs 92.0%,P=0.019). Meanwhile, the risk of relapse was much higher in AA group (n=52) compared to Bx group (n=40) (25.0%vs 5.0%,P=0.009). A higher risk of TRM was observed in AB1/AB2 group (P=0.012). In addition, transplant from donors carried Cen-B was associated with an increased survival compared with Cen-A homozygous donors (OS: 94.7%vs 68.5%,P=0.036; RFS: 89.5%vs 64.4%,P=0.045).

CONCLUSIONOverall, KIR genotyping and haplotype analyses should be useful for selection of the most optimal donors with favorable KIR gene grafts. KIR gene mismatch donors should be preferred for AML/MDS patients. Selecting donors carried Cen- B and avoiding the selection of donors of KIR genotype AA/AB1/AB2 was strongly advisable for haplo-identical HSCT.

Chronic Disease ; Genotype ; Haplotypes ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute ; therapy ; Neoplasm Recurrence, Local ; Receptors, KIR ; genetics ; Survival Rate ; Tissue Donors

Huntington's disease (HD) is an autosomal dominant inherited disease with insidious onset and slow progression, mainly characterized by chorea-like symptom, intelligence decline, and psychiatric abnormalities. Cause of the disease is abnormal expansion of CAG trinucleotide repeat sequences in the first exon of the Huntington gene (HTT) on chromosome 4. Despite the clear etiology, currently, no effective therapeutic measures to control the disease progress is noted, and symptomatic treatment is still the main treatment in clinical practice. This article provides a brief overview of the current clinical trials, clinical challenges, and future development of HD gene therapy to provide references for subsequent related research.

Objective: To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin’s lymphoma (CHL) to further determine their clinical role and prognostic significance. Methods: The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed. Results: This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL. Conclusions This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.