Subcapsular renal haematoma after ureteroscopic lithotripsy: a single-centre, retrospective study in China.

OBJECTIVES: To investigate the incidence, predisposing factors, diagnosis and management of subcapsular renal haematoma (SRH) after ureteroscopic lithotripsy (URSL). DESIGN: Retrospective observational study. SETTING: Shandong Provincial Hospital, a 4500-bed tertiary hospital in China. PARTICIPANTS: The data from 1535 consecutive patients treated with URSL (including rigid URSL and flexible URSL) between January 2015 and October 2020 were retrospectively analysed. MAIN OUTCOME MEASURES: SRH after URSL confirmed via CT. The characteristics, operative data and outcomes of these patients were documented and compared. RESULTS: Six patients were confirmed to have an SRH after URSL on CT. The total incidence of SRH after URSL was 0.39%. The incidences of SRH after rigid URSL and flexible URSL were 0.38% and 0.41%, respectively. Unendurable ipsilateral flank pain and a significant decrease in haemoglobin after surgery were the typical clinical manifestations of SRH after URSL. There were no significant differences in age, sex, history of diabetes mellitus, preoperative hypertension, body mass index, stone laterality or perfusion pressure (p>0.05). However, SRH was significantly associated with the stone size, stone location, degree of hydronephrosis and operative duration (p<0.01). One patient was managed conservatively without further intervention, percutaneous drainage was performed in four patients and one patient underwent emergency angiography. No patients died of SRH. CONCLUSIONS: SRH is a rare but potentially serious complication of URSL. Severe hydronephrosis and a thin renal cortex preoperatively and prolonged operative duration are strong predisposing factors for SRH. Laparoscopic ureterolithotomy should be considered as an alternative surgery for patients with severe ureteral tortuosity. SRH is treated based on patients' clinical manifestations. Most patients can be managed with conservative treatment or percutaneous drainage alone.

Green tea improves cognitive function through reducing AD-pathology and improving anti-oxidative stress capacity in Chinese middle-aged and elderly people.

Background: Numerous benefits of green tea have been reported. However, the effects of green tea on cognitive function remain disputable and the mechanism is still unclear. Objective: To investigate the relationship of green tea consumption with cognitive function and related blood biomarkers among Chinese middle-aged and elderly people. Methods: A total of 264 participants aged 50-70 years old were enrolled from Zhongnan Hospital of Wuhan University. They were interviewed about green tea consumption patterns and underwent neuropsychological tests covering five main cognitive domains to assess cognition including Montreal Cognitive Assessment (MoCA) and the other 10 scales. Then we detected serum oxidative stress biomarkers including Superoxide Dismutase (SOD), Malondialdehyde (MDA), Glutathione Peroxidase (GPx), Glutathione Reductase (GR), and Alzheimer's disease (AD) markers including ß-amyloid (Aß)40, Aß42, and phosphorylated tau-181 (pTau181). Results: In the tea-consuming group, the MoCA scores (P = 0.000), Hopkins Verbal Learning Test (HVLT) immediate recall (P = 0.012) and delayed recall (P = 0.013) were significantly higher while Trail Making Test-B (P = 0.005) and Victoria Stroop test interference (P = 0.000) were lower. In terms of oxidative stress markers, the tea-consuming group had lower serum MDA levels (P = 0.002) and higher serum SOD (P = 0.005) and GPx (P = 0.007) levels. In terms of AD markers, serum pTau181 (P < 0.000), Aß42 (P = 0.019) and total Aß levels (P = 0.034) but not serum Aß40 levels, were lower in the tea-consuming group. In the logistic regression analysis, there was a significant negative correlation between green tea consumption and cognitive impairment (OR = 0.26, 95 % CI 0.13 0.52 for high group). Conclusion: Regular green tea consumption is associated with better cognitive function among Chinese middle-aged and elderly people, mainly reflected in memory and executive function. It may achieve protective effects by reducing AD-related pathology and improving anti-oxidative stress capacity and higher levels of tea consumption have a stronger protective effect.

Clinical Characteristics and Factors Associated with Disease Progression of Mild to Moderate COVID-19 Patients in a Makeshift (Fangcang) Hospital: A Retrospective Cohort Study.

OBJECTIVE: Information regarding the epidemiology and clinical features of mild to moderate patients caused by COVID-19 in Fangcang Hospital is scarce. Through a retrospective cohort study, the clinical characteristics of COVID-19 patients in Dongxihu Fangcang shelter hospitals were analyzed, and the factors that affected the disease progression of COVID-19 patients were explored. METHODS: The clinical characteristics of 714 patients with COVID-19 were retrospectively analyzed at Dongxihu Fangcang Hospital between February 7 and March 8, 2020. We described the clinical characteristics and distribution of discharge or transfer times for each patient. According to the disease progression of COVID-19 patients, we divided all patients into Non-Deteriorated group and Deteriorated group. Furthermore, binary logistic regression was used for a single outcome and multiple response variables. RESULTS: We treated 789 patients with mild and moderate COVID-19, of which 714 were included in this study, which included 326 (45.66%) deteriorated patients and 388 (54.34%) non-deteriorated patients. The mean age of the study population was 48.16±12.44 years. Of all patients, 319 (44.7%) were men and 395 (55.3%) were women. The average length of the patient's stay was 16.08±5.13 days. The most common clinical feature on admission was fever (593 of 714, 83.05%). It is worth noting that 80 (11.20%) of the 714 patients were asymptomatic from exposure to admission. Multivariate logistic regression analysis showed that gender, age, diabetes, respiratory system disease, fever, dyspnea, and nasal congestion were risk factors associated with deterioration in cases with COVID-19 patients, and asymptomatic (OR: 0.058; 95% CI: 0.022-0.155; P<0.001) was the protective factor for deterioration of COVID-19 patients. CONCLUSION: Accompanied by chronic diseases, old age, fever, nasal congestion, and dyspnea were factors that influenced the aggravation of COVID-19 patients, and more attention and treatment should be given to these patients.

RT-PCR Combined with CT Examination in the Diagnosis and Prognosis Evaluation of COVID-19 Patients in Fangcang Hospital: A Case Series.

RATIONALE: Currently, the "gold standard" is real-time reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of the viral DNA for diagnosis of COVID-19 infection. However, early reports of test performance in the Wuhan outbreak showed variable sensitivities. Therefore, the simple use of RT-PCR as a discharge standard for COVID-19 patients may be risky. Early discussions suggested that CT should be the preferred modality for the diagnosis of COVID-19. However, the use of CT for COVID-19 discharge is controversial. In the Fangcang hospital, we performed multiple nucleic acid tests and chest CT examinations in all patients. For discharged patients, we performed multiple nucleic acid tests and chest CT scans on the basis of discharge standards to minimize the incidence of false negatives in nucleic acid tests. PATIENT CONCERNS: Two 42-year-old male patients with mild to moderate COVID-19 were treated in the Fangcang Hospital According to the treatment, one patient was cured and discharged, while the other patient was sent to a higher-level hospital for further treatment. DIAGNOSES: Real-time reverse transcriptase-polymerase chain reaction amplification of the viral DNA for diagnosis of COVID-19 infection. INTERVENTIONS: The patients received Chinese medicine and antiviral treatment in the Fangcang Hospital. OUTCOMES: At follow-up, both patients were cured after treatment and returned to normal life after 2 weeks of home isolation and a negative nucleic acid test. LESSONS: The use of nucleic acid testing combined with chest CT examination can quickly diagnose patients with COVID-19 infection and evaluate their treatment in the Fangcang Hospital.

The Emerging Roles of Ferroptosis in Vascular Cognitive Impairment.

Vascular cognitive impairment (VCI) is a clinical syndrome that encompasses all forms of cognitive deficits caused by cerebrovascular disease, from mild cognitive impairment to dementia. Vascular dementia, the second most common type of dementia after Alzheimer's disease (AD), accounts for approximately 20% of dementia patients. Ferroptosis is a recently defined iron-dependent form of cell death, which is distinct from apoptosis, necrosis, autophagy, and other forms of cell death. Emerging evidence suggests that ferroptosis has significant implications in neurological diseases such as stroke, traumatic brain injury, and AD. Additionally, ferroptosis inhibition has an obvious neuroprotective effect and ameliorates cognitive impairment in various animal models. Here, we summarize the underlying mechanisms of ferroptosis and review the close relationship between ferroptosis and VCI.

Neuropsychiatric Symptoms and Cognitive Impairment in Chinese Patients with Parkinson's Disease in Han and Hui Ethnicity.

Neuropsychiatric symptoms are common in patients with Parkinson's disease (PD) and they are likely to outweigh the motor symptoms and become a major factor affecting the quality of life of PD patients. However, the studies focusing on the non-motor symptoms in Chinese PD patients from different ethnicity are scarce. The aim of this retrospective study was to investigate neuropsychiatric symptoms and cognitive impairment in Chinese PD patients from Han and Hui populations from central China. Seventy-two Han Chinese PD patients (Han PD group) and 71 age-and sex-matched Hui Chinese PD patients (Hui PD group) were enrolled from Zhongnan Hospital of Wuhan University between Sept. 2011 and Aug. 2014 in the study. The neuropsychiatric symptoms and cognitive impairment were assessed using Neuropsychiatric Inventory (NPI) and Mini Mental State Examination (MMSE). We found that the proportion of depression, anxiety, apathy, irritability, euphoria and night time behavior disturbances were higher in the Han PD group than in the Hui PD group (P<0.05 or P<0.01). But the proportion of delusion, hallucination, agitation, disinhibition, aberrant motor behavior and change in appetite were not significantly different between the Han PD group and the Hui PD group (P>0.05). The total mean scores of the MMSE from patients in the Han PD group were similar to those in the Hui PD group (P>0.05). However, the subscale scores of recall domain and language domain in the Han PD group were significantly different from those in the Hui PD group (P<0.05). No significant difference was noted in the orientation, memory and calculation domains between the two PD groups (P>0.05). This study first showed the recall domain and language domain were different between the Han PD patients and the Hui PD patients. Depression, anxiety, apathy, irritability, euphoria and night time behavior disturbances were less presented in the Hui PD patients. All these differences may be related to the different ethnicity, which would be helpful for clinical physicians to recognize the different non-motor symptoms in Chinese PD patients with different ethnicity.

Postoperative intermittent fasting prevents hippocampal oxidative stress and memory deficits in a rat model of chronic cerebral hypoperfusion.

PURPOSE: Whether intermittent fasting (IF) treatment after stroke can prevent its long-term detrimental effects remains unknown. Here, we investigate the effects of postoperative IF on cognitive deficits and its underlying mechanisms in a permanent two-vessel occlusion (2VO) vascular dementia rat model. METHODS: Rats were subjected to either IF or ad libitum feeding 1 week after 2VO surgery. The cognition of rats was assessed using the novel object recognition (NOR) task and Morris water maze (MWM) 8 weeks after surgery. After behavioral testing, hippocampal malondialdehyde (MDA) and glutathione (GSH) concentrations, superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes, inflammatory protein levels, and microglia density were determined. RESULTS: Postoperative IF significantly ameliorated the cognitive performance of 2VO rats in the NOR and MWM tests. Cognitive enhancement paralleled preservation of the PSD95 and BDNF levels in the 2VO rat hippocampus. Mechanistically, postoperative IF mitigated hippocampal oxidative stress in 2VO rats, as indicated by the reduced MDA concentration and mRNA and the protein levels of the reactive oxygen species-generating enzyme nicotinamide adenine dinucleotide phosphate oxidase 1. IF treatment also preserved the GSH level and SOD activity, as well as the levels of their upstream regulating enzymes, resulting in preserved antioxidative capability. In addition, postoperative IF prevented hippocampal microglial activation and elevation of sphingosine 1-phosphate receptor 1 and inflammatory cytokines in 2VO rats. CONCLUSIONS: Our results suggest that postoperative IF suppresses neuroinflammation and oxidative stress induced by chronic cerebral ischemia, thereby preserving cognitive function in a vascular dementia rat model.

Cognitive impairment correlates with serum carbonyl compound profiles in subclinical carotid atherosclerosis.

Current evidence indicates that carotid atherosclerosis is an independent risk factor for cognitive impairment. Serum metabolomic analysis holds significant promise for uncovering the relationship between carotid atherosclerosis and cognitive impairment. In this study, we aimed to evaluate the profiling of serum carbonyl compounds in subclinical carotid atherosclerosis (SCA) patients and to explore the relationship between serum carbonyl compounds and cognitive performance. We enrolled 51 SCA patients and 45 healthy control individuals using carotid ultrasound assessment. All the participants were subjected to a neuropsychological assessment and their fasting serum samples were collected for untargeted stable isotope-labeling strategy combined with liquid chromatography-double precursor ion scan-mass spectrometry analysis. Compared with the control, the SCA group showed lower scores in global cognition, immediate memory, verbal fluency, executive function, and visual attention. For the isotope-labeling strategy combined with liquid chromatography-double precursor ion scan-mass spectrometry analysis, 149 potential carbonyl candidates were discovered in the pooled serum. In the SCA serum, 41 carbonyl compounds showed significantly increased levels and 14 carbonyl compounds showed significantly decreased levels. In addition, six carbonyl compounds involved in the oxidation of polyunsaturated fatty acids and vitamin E were correlated with cognitive performance. A negative correlation was observed between cognitive performance and the levels of octanal, nonanal, α-tocopherolquinone, and heptanal, respectively. A positive correlation was observed between cognitive performance and the levels of acetophenone and 1-(3-aminopropyl)-4-aminobutanal, respectively. In summary, the SCA individuals have poor cognitive performance, which may be reflected by aberrant serum carbonyl compound profiles.

Postischemic Housing Environment on Cerebral Metabolism and Neuron Apoptosis after Focal Cerebral Ischemia in Rats.

The purpose of this study was to evaluate the roles of different housing environments in neurological function, cerebral metabolism, cerebral infarction and neuron apoptosis after focal cerebral ischemia. Twenty-eight Sprague-Dawley rats were divided into control group (CG) and cerebral ischemia group, and the latter was further divided into subgroups of different housing conditions: standard environment (SE) subgroup, individual living environment (IE) subgroup, and enriched environment (EE) subgroup. Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO). Beam walking test was used to quantify the changes of overall motor function. Cerebral infarction and cerebral metabolism were studied by in vivo magnetic resonance imaging and 1H-magnetic resonance spectra, respectively. Neuron necrosis and apoptosis were detected by hematoxylin-eosin and TUNEL staining methods, respectively. The results showed that performance on the beam-walk test was improved in EE subgroup when compared to SE subgroup and IE subgroup. Cerebral infarct volume in IE subgroup was significantly larger than that in SE subgroup (P<0.05) and EE subgroup (P<0.05) on day 14 after MCAO. NAA/Cr and Cho/Cr ratios were lower in MCAO groups under different housing conditions as compared to those in CG (P<0.05). NAA/Cr ratio was lower in IE subgroup (P<0.05) and higher in EE subgroup (P<0.05) than that in SE subgroup. NAA/ Cr ratio in EE was significantly higher than that in IE subgroup (P<0.05). Cho/Cr ratio was decreased in MCAO groups as compared to that in CG (P<0.05). A significant decrease in normal neurons in cerebral cortex was observed in MCAO groups as compared to CG (P<0.05). The amount of normal neurons was less in IE subgroup (P<0.05), and more in EE subgroup (P<0.05) than that in SE subgroup after MCAO. The amount of normal neurons in EE subgroup was significantly more than that in IE subgroup after MCAO (P<0.05). The ratio of TUNEL-positive neurons in EE was significantly lower than that in SE subgroup (P<0.05) and IE subgroup (P<0.05). Correlation analysis showed that the beam walking test was negatively correlated with NAA/Cr ratio (P<0.05). Cerebral infarct volume was negatively correlated with both NAA/Cr ratio (P<0.01) and Cho/Cr ratio (P<0.01). The amount of normal cortical neurons was positively correlated with both NAA/Cr ratio (P<0.01) and Cho/Cr ratio (P<0.05). The TUNEL-positive neurons showed a negative correlation with both NAA/Cr ratio (P<0.01) and Cho/Cr ratio (P<0.01). This study goes further to show that EE may improve neurological functional deficit and cerebral metabolism, decrease cerebral infarct volume, neuron necrosis and apoptosis, while IE may aggravate brain damage after MCAO.

Adiponectin Attenuates Streptozotocin-Induced Tau Hyperphosphorylation and Cognitive Deficits by Rescuing PI3K/Akt/GSK-3ß Pathway.

Clinical studies have demonstrated that decreased adiponectin is associated with the development of Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). We focused on determining the neuroprotective effect offered by adiponectin against streptozotocin-induced brain damage in ICV-STZ rat model. We found that adiponectin supplements significantly restored the cognitive deficits in ICV-STZ rat model including shorter escape latency, more crossing times and increased time spent in the target quadrant. Adiponectin supplements also increased number of dendritic branches and mushroom percentage. In addition, adiponectin supplements attenuated tau hyperphosphorylation at multiple AD-related sites through activation of protein Ser9-phosphorylated glycogen synthase kinase-3ß (Ser9-GSK-3ß) with increased the Akt and PI3K activity. Our data suggest that adiponectin supplements have neuroprotective effects on the ICV-STZ rat model, which may be mediated by the activation of the PI3K/Akt/GSK-3ß signaling pathway.

ZNF300 tight self-regulation and functioning through DNA methylation and histone acetylation.

BACKGROUND: Accumulating evidence demonstrates that the KRAB-ZNFs involve in various biological processes. As a typical member of KRAB-ZNFs, dysregulation of ZNF300 contributes to multiple pathologies such as leukemia and cancer. However, mechanisms underlying ZNF300 tight regulation and its pathophysiological function remain largely unknown. METHODS: The effect of ZNF300ZFR on gene transcriptional activity was measured by Dual luciferase reporter system. ChIP-PCR assay were performed to detect the enrichment of ZNF300 protein and H3K9Ac in the ZNF300 gene. Co-immunoprecipitation assays followed by western blot were performed to detect the interaction between ZNF300 and KAP1. The DNA methylation in the ZNF300 gene promoter was analyzed by BSP. ZNF300 function on K562 cell differentiation was analyzed by flow cytometry. RESULTS: In this study, we found that the zinc finger domain-encoding region (ZFR) of ZNF300 functioned as a repressor possibly by mediating DNA methylation and ZNF300 bound to its ZNF300ZFR, suggesting a potential auto-inhibition mechanism. To support this, DNA methylation inhibition upregulated ZNF300 expression and ZNF300 overexpression inhibited endogenous ZNF300 expression. More importantly, DNA methylation inhibition restored megakaryocyte differentiation in K562 cells suppressed by ZNF300 downregulation, suggesting an important role of DNA methylation in ZNF300 function. Interestingly, ZNF300 knockdown restored global H3K9Ac that was reduced in K562 cells undergoing megakaryocyte differentiation. CONCLUSIONS: Our study revealed novel features of ZNF300 that possibly mediate its regulation and function by modulating epigenetic modifications.

Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion.

Background: Whether intermittent fasting (IF) pretreatment can prevent vascular cognitive dysfunction remains unknown to our knowledge.Objective: We investigated the effects and underlying mechanisms of IF pretreatment on cognitive dysfunction in a permanent 2-vessel occlusion (2VO) vascular dementia rat model.Methods: Male Wistar rats weighing 200 g were subjected to either IF or ad libitum feeding for 12 wk before 2VO surgery. Rats in the IF protocol underwent alternative-day feed deprivation (FD). Memory of the animals was assessed by using the Morris water maze (MWM) and the novel object recognition (NOR) test 6 wk after the surgery. After behavioral testing, malondialdehyde and glutathione concentrations, superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes, inflammatory protein concentrations, and microglia density were determined in the hippocampus of rats.Results: 2-vessel occlusion operation ad libitum (2VO-AL) rats had significantly longer escape latencies on day 4 of the training phase and spent a lower percentage of time in the target quadrant (25% compared with 38% and 41%) in the MWM, and had lower discrimination ratios (47% compared with 65% and 67%) in the NOR test than 2-vessel operation and alternate-day feed deprivation (2VO-FD) and sham operation ad libitum (Sham-AL) rats, respectively (P < 0.05). This indicates that IF helps to prevent vascular cognitive deficits. 2VO-AL rats also had higher malondialdehyde (3.54 compared with 2.15 and 1.66 nmol/mg protein) and lower glutathione concentrations (53.25 compared with 66.41 and 91.71 nmol/mg protein), lower SOD activity (100.1 compared with 133.3 and 138.5 U/mg protein), lower gene expression of antioxidative enzymes, higher expression of inflammatory proteins, and higher microglia density in the hippocampus than 2VO-FD and Sham-AL rats, respectively (P < 0.05). This suggests that IF has antioxidative and anti-inflammatory effects.Conclusions: IF pretreatment provided sustained neuroprotection in a rat model of vascular dementia. These effects were associated with reduced oxidative stress and neuroinflammation.

Comparative analysis of general characteristics of ischemic stroke of BAD and non-BAD CISS subtypes.

Based on the recently proposed Chinese ischemic stroke subclassification (CISS) system, intracranial branch atheromatous disease (BAD) is divided into large artery atherosclerosis (LAA) and penetrating artery disease (PAD). In the current retrospective analysis, we compared the general characteristics of BAD-LAA with BAD-PAD, BAD-LAA with non-BAD-LAA and BAD-PAD with non-BAD-PAD. The study included a total of 80 cases, including 45 cases of BAD and 35 cases of non-BAD. Subjects were classified using CISS system: BAD-LAA, BAD-PAD, non-BAD-LAA and non-BAD-PAD. In addition to analysis of general characteristics, the correlation between the factors and the two subtypes of BAD was evaluated. The number of cases included in the analysis was: 32 cases of BAD-LAA, 13 cases of BAD-PAD, 21 cases of non-BAD-LAA, and 14 cases of non-BAD-PAD. Diabetes mellitus affected more non-BAD-LAA patients than BAD-LAA patients (P=0.035). In comparison with non-BAD-PAD, patients with BAD-PAD were younger (P=0.040), had higher initial NIHSS score (P<0.001) and morbidity of ischemic heart disease (P=0.033). Within patients with BAD, the PAD subtype was associated with smoking (OR=0.043; P=0.011), higher low-density lipoprotein (OR=5.339; P=0.029), ischemic heart disease (OR=9.383; P=0.047) and diabetes mellitus (OR=12.59; P=0.020). It was concluded that large artery atherosclerosis was the primary mechanism of BAD. The general characteristics showed no significant differences between the CISS subtypes of LAA and PAD within BAD, as well as between the BAD and non-BAD within LAA subtype. Several differences between PAD subtypes of BAD and non-BAD were revealed.

Triptolide attenuates cerebral ischemia and reperfusion injury in rats through the inhibition the nuclear factor kappa B signaling pathway.

Inflammation plays critical roles in the acute progression of the pathology of ischemic injury. Previous studies have shown that triptolide interferes with a number of pro-inflammatory mechanisms. In this study, we investigated whether triptolide has protective effects during acute cerebral ischemia/reperfusion (I/R) injury. Male Sprague Dawley rats received triptolide or vehicle at the onset of reperfusion following middle cerebral artery occlusion. Twenty-four hours after reperfusion, we evaluated neurological injuries, the expression of pro-inflammatory markers, and NF-κB activation. I/R rats treated with triptolide showed significantly better neurological deficit scores, decreased neural apoptosis, and reduced cerebral infarct volume and brain edema, and triptolide treatment suppressed the activation of NF-κB following I/R injury. Furthermore, the expression levels of pro-inflammatory cytokines at both the mRNA and protein levels were significantly decreased in rats receiving triptolide. These results indicate that the neuroprotective effects of triptolide during acute cerebral I/R injury are possibly related to the inhibition of both the NF-κB signaling pathway and inflammation.

Efficacy of Rho kinase inhibitor on cognitive impairment induced by chronic cerebral hypoperfusion in rats.

This work aims to explore the efficacy of Rho kinase inhibitor Fasudil on cognitive impairment induced by chronic cerebral hypoperfusion in rats. A total of 32 male adult Sprague Dawley (SD) rats were randomly divided into three groups: treatment group, control group and sham-operated group for severe carotid artery stenosis model. After two weeks, 8.35 mg/kg Fasudil and physiological saline were intraperitoneally applied twice per day in treatment group and control group, respectively. Morris water maze test was performed in each group to detect the changes of cognitive function and observe the hippocampal pathomorphology in rats after eight weeks. The average escape latency distinctly shortened (P < 0.01) and the percentage of swimming distance in the platform quadrant significantly increased (P < 0.01) in treatment group compared with those at corresponding time points in control group. The rate of carotid artery stenosis in rats had no statistical difference between treatment and control groups (P > 0.05). Fasudil effectively improved hippocampal pathomorphology. Rho kinase inhibitor obviously ameliorated cognitive impairment induced by chronic cerebral hypoperfusion in rats.

Post-occlusion administration of sodium butyrate attenuates cognitive impairment in a rat model of chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) has been commonly associated with Alzheimer's disease and other types of dementia, but therapies that can improve cerebral blood flow displayed little effect on impaired cognition. Epigenetic intervention with histone deacetylase inhibitors, such as sodium butyrate (SB), on the other hand has been shown to improve cognition in several animal models of dementia. To investigate the effect of SB on cognitive impairment induced by CCH in rats, adult male SD rats were given intraperitoneal injections of SB at a daily dose of 840mg/kg for 4weeks, from the 29th day after permanent occlusion of bilateral common carotid arteries (2VO). Learning and memory were assessed by Morris water maze and novel object recognition. Following behavioral tests, western blotting of histone acetylation, of transcription factors, of neuronal/synaptic proteins, were performed using rat hippocampus and cortex. The data showed that SB treatment alleviated hippocampal dependent spatial learning disability in 2VO rats, and altered HDAC1/2 mRNA level, histone H4 acetylation and Nrf2 transcriptional activation in rat hippocampus. Accordingly, cognition-protective effect of SB appeared to be partially mediated by enhancing histone acetylation and hence by facilitating the transcription of Nrf2 downstream genes in the hippocampus. Thus, SB might be considered for putative treatment for CCH-related cognitive impairment.

Changes of c-fos, malondialdehyde and lactate in brain tissue after global cerebral ischemia under different brain temperatures.

Under global cerebral ischemia, the effect of different brain temperature on cerebral ischemic injury was studied. Male Sprague-Dawley rats were divided into normothermic (37-38°C) ischemia, mild hypothermic (31-32°C) ischemia, hyperthermic (41-42°C) ischemia and sham-operated groups. Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model and brain temperature was maintained at defined level for 60 min after 20-min ischemia. The expression of c-fos protein and the levels of malondialdehyde (MDA) and lactate in brain regions were detected by immunochemistry and spectrophotometrical methods, respectively. C-fos positive neurons were found in the hippocampus and cerebral cortex after cerebral ischemia reperfusion. Mild hypothermia increased the expression of c-fos protein in both areas, whereas hyperthermia decreased the expression of c-fos protein in the hippocampus at 24 h reperfusion, and the cerebral cortex at 48 h reperfusion when compared to normothermic conditions. In normothermic, mild hypothermic and hyperthermic ischemia groups, the levels of MDA and lactate in brain tissue were increased at 24, 48 and 72 h reperfusion following 20-min ischemia as compared with the sham-operated group (P<0.01). The levels of MDA and lactate in mild hypothermic group were significantly lower than those in normothermic group (P<0.01). It is suggested that brain temperature influences the translation of the immunoreactive protein product of c-fos after global cerebral ischemia, and MDA and lactate are also affected by hypothermia and hyperthermia.

PI3K/Akt signal pathway involved in the cognitive impairment caused by chronic cerebral hypoperfusion in rats.

Chronic cerebral hypoperfusion (CCH) is a common pathophysiological state that usually occurs in conditions such as vascular dementia and Alzheimer's disease, both of which are characterized by cognitive impairment. In previous studies we found that learning capacity and memory were gradually impaired with CCH, which altered the expression of synaptophysin, microtubule associated protein-2, growth associated protein-43, brain-derived neurotrophic factor, nerve growth factor, N-methyl-D-aspartate receptor subunit 1, cAMP response element-binding protein and tau hyperphosphorylation in the hippocampus. However, the molecular basis of cognitive impairment in CCH remains obscure. Here we explore the hypothesis that the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signal pathway is involved in this type of cognitive impairment. In order to determine if the expression of PI3K, Akt and phosphorylated Akt (p-Akt) proteins are altered at different stages of CCH with differing levels of cognitive impairment. we performed permanent, bilateral occlusion of the common carotid arteries (2-VO) to induce CCH. Adult male SD rats were randomly divided into sham-operated group, 2-VO 1 week group, 2-VO 4 weeks group and 2-VO 8 weeks group. Behavior tests were utilized to assess cognitive abilities, while western blots were utilized to evaluate protein expression. Rats in the 2-VO groups spent less time exploring novel objects than those in the sham-operated group, and the discrimination ratio of the 2-VO 8 weeks group and the sham-operated group were higher than chance (0.50). Escape latencies in the Morris water maze task in the 2-VO 1 week group were longer than those in the sham-operated group on day 4 and day 5, while escape latencies in the 2-VO 4 weeks group were longer than those in the sham-operated group from day 3 to day 5. Escape latencies in 2-VO 8 weeks group were longer than those in the sham-operated group from day 2 to day 5. NE (northeast) square swimming times in the 2-VO 1 week group, 2-VO 4 weeks group and 2-VO 8 weeks group were shorter than that in the sham-operated group. Western blotting showed that the PI3K expression in the 2-VO 1 week group was lower than that in sham-operated group, while p-Akt expression in the 2-VO 8 weeks group was higher than that in the sham-operated group. There was a linear relationship between the PI3K expression and the discrimination ratio, as well as a linear relationship between the PI3K and NE square swimming time. Thus, we propose that the PI3K/Akt signal pathway is an important cell pathway that is associated with the cognitive impairment following CCH.

[Association of estrogen receptor ß gene polymorphisms with hypertension in postmenopausal women].

OBJECTIVE: To explore the association between estrogen receptor ß (ERß) gene polymorphisms and hypertension in postmenopausal women. METHODS: The relationship of two polymorphisms (rs944050 and rs4986938) with hypertension was examined in 71 postmenopausal women with hypertension and 50 healthy age-matched controls. RESULTS: In hypertension and control groups, the ERß allelic frequencies of A and G were 0.500, 0.500, 0.540, 0.460; 0.077, 0.923, 0.170, 0.830 respectively. The genotypic distributions of both polymorphisms stayed within Hardy-Weinberg equilibrium. For polymorphism rs4986938, statistical difference existed between the wild-type genotype and a combination of heterozygous and homozygous variant genotypes (P < 0.05). The variant allele A of rs4986938 in ERß gene decreased the risk of hypertension (OR = 0.41, 95%CI 0.18-0.92). CONCLUSION: The polymorphism rs4986938 in ERß gene was associated with an elevated risk of hypertension in Chinese Han postmenopausal women.