Nasal Administration of bFGF-Loaded Nanoliposomes Attenuates Neuronal Injury and Cognitive Deficits in Mice with Vascular Dementia Induced by Repeated Cerebral Ischemia‒Reperfusion.

Introduction: Basic fibroblast growth factor (bFGF) shows great potential for preventing vascular dementia (VD). However, the blood‒brain barrier (BBB) and low bioavailability of bFGF in vivo limit its application. The present study investigated how nasal administration of bFGF-loaded nanoliposomes (bFGF-lips) affects the impaired learning and cognitive function of VD mice and the underlying mechanism involved. Methods: A mouse model of VD was established through repeated cerebral ischemia‒reperfusion. A Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and cognitive function of the mice. Hematoxylin and eosin (HE) staining, Nissl staining and TUNEL staining were used to evaluate histopathological changes in mice in each group. ELISA and Western blot analysis were used to investigate the molecular mechanism by which bFGF-lips improve VD incidence. Results: Behavioral and histopathological analyses showed that cognitive function was significantly improved in the bFGF-lips group compared to the VD and bFGF groups; in addition, abnormalities and the apoptosis indices of hippocampal neurons were significantly decreased. ELISA and Western blot analysis revealed that bFGF-lips nasal administration significantly increased the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), bFGF, B-cell lymphoma 2 (Bcl-2), phosphorylated protein kinase B (PAKT), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1) and haem oxygenase-1 (HO-1) in the hippocampus of bFGF-lips mice compared with the VD and bFGF groups. Furthermore, the concentrations of malondialdehyde (MDA), caspase-3 and B-cell lymphoma 2-associated X (Bax) were clearly lower in the bFGF-lips group than in the VD and bFGF groups. Conclusion: This study confirmed that the nasal administration of bFGF-lips significantly increased bFGF concentrations in the hippocampi of VD mice. bFGF-lips treatment reduced repeated I/R-induced neuronal apoptosis by regulating apoptosis-related protein concentrations and activating the phosphatidylinositol-3-kinase (PI3K)/(AKT)/Nrf2 signaling pathway to inhibit oxidative stress.

[Effect of acupuncture on analgesia and sedation in elderly patients with severe pneumonia during invasive mechanical ventilation].

OBJECTIVE: To observe the analgesic and sedative effects of acupuncture in elderly patients with severe pneumonia during invasive mechanical ventilation. METHODS: A total of 188 elderly patients with severe pneumonia were randomly divided into an observation group and a control group, 94 cases in each group. Both groups were treated with routine nursing and treatment of severe pneumonia such as invasive mechanical ventilation, analgesia and sedation. Based on these, the observation group was treated with acupuncture at Neiguan (PC 6), Hegu (LI 4), Yintang (GV 29) and Baihui (GV 20), twice a day until the mechanical ventilation was offline. The critical care pain observation tool (CPOT) score and Richmond agitation-sedation score (RASS) were observed before treatment and 0.5 h after analgesia and sedation; the average time of reaching the standard, the reaching standard rate of shallow sedation and analgesia within 0.5 h and 72 h as well as the dosage of analgesic and sedative drugs and compilations were compared between the two groups. The mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR) and blood oxygen saturation (SpO2) were observed before treatment and 0.5 h, 1 h and 2 h after analgesia and sedation. The levels of partial pressure of blood oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and lactic acid (Lac) were observed before treatment and 12 h, 24 h, 48 h, 72 h, 96 h, 120 h and 144 h after analgesia and sedation. The white blood cell (WBC), neutrophil percentage (NEUT%), high-sensitivity C-reactive protein (hs-CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine (Cr) were observed before treatment and 72 h after analgesia and sedation. The tracheal intubation time and ICU hospitalization time were compared between two groups. RESULTS: At the time point of 0.5 h after treatment, the CPOT and RASS scores in the two groups were lower than those before treatment (P<0.05); the average time of reaching the standard in the observation group was shorter than that in the control group (P<0.01); the 30 min reaching standard rates of CPOT and RASS scores as well as the rate of reaching the shallow sedation and analgesia within 72 h in the observation group were higher than those in the control group (P<0.01, P<0.05). The dosage and duration of dexmedetomidine, propofol and butorphanol in the observation group were less than those in the control group (P<0.05), and the occurrence times of hypotension, respiratory depression, bradycardia, constipation as well as average tracheal intubation time and average ICU hospitalization time in the observation group were less than those in the control group (P<0.05). After 0.5 h, 1 h and 2 h of treatment, the HR and RR were lower than those before treatment in the two groups (P<0.05), MAP and SpO2 were higher than those before treatment in the two groups (P<0.05); the MAP 0.5 h after treatment in the observation group was higher than that in the control group (P<0.05); the HR after 1 h and 2 h of treatment in the observation group was lower than that in the control group (P<0.05). Compared before treatment, the levels of PaCO2 and Lac were reduced and the levels of PaO2 were increased 12 h, 24 h, 48 h, 72 h, 96 h, 120 h and 144 h after treatment in both groups (P<0.05); compared before treatment, the WBC, NEUT%, hs-CPR, ALT and Cr were reduced 72 h after treatment in the two groups (P<0.05), and the hs-CRP in the observation group was lower than that in the control group (P<0.05). CONCLUSION: Acupuncture has analgesic and sedative effect in elderly patients with severe pneumonia during invasive mechanical ventilation, which could reduce the dosage of sedative and analgesic drugs and the occurrence of complications, improve blood oxygen, and has good safety.

Association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China.

BACKGROUND: Genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediators of ischemic stroke. This study aimed to explore the association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China. METHODS: This case-control study consisted of 690 patients with ischemic stroke and 690 controls. Polymorphisms of ALOX5 rs2029253 A/G, LTA4H rs6538697 T/C, and LTC4S rs730012 A/C were genotyped by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. The multivariate logistic regression model was used to exclude the effects of conventional risk factors on ischemic stroke. RESULTS: Carriers of C allele in rs730012 were more susceptible to ischemic stroke (OR: 1.37; 95%CI: 1.08-1.73; P=0.009). The rs2029253 GG genotype showed a risk-reducing effect on ischemic stroke (OR: 0.72; 95%CI: 0.55-0.93; P=0.013) while the rs6538697 CC genotype had an increased risk of ischemic stroke (OR: 1.77; 95%CI: 1.09-2.89; P=0.022). The rs730012 variant was not associated with ischemic stroke risk after adjusting confounding factors (P>0.05). CONCLUSION: The present study suggested that gene polymorphisms in the leukotrienes pathway may exert influences, with independent genetic effects, on ischemic stroke susceptibility in a cohort of Chinese in east China.