Amelioration of Cognitive Dysfunction in Diabetic Rats by Jianpi Qinghua Prescription / 中国实验方剂学杂志

ObjectiveTo explore the amelioration of cognitive dysfunction in diabetes mellitus （DM） by Jianpi Qinghua prescription （JPQH） based on type 2 diabetes （T2DM） model rats. MethodFifty healthy male Wistar rats of SPF grade were randomly divided into control group （n=10） and experimental group （n=40）. The rats in the control group were fed conventionally， while those in the experimental group were fed on a high-sugar， high-fat diet for six weeks and administered with streptozotocin （STZ） for the induction of the DM model. The model rats were randomly divided into model group， sitagliptin group （1.2 g·L-1）， pioglitazone group （0.8 g·L-1）， and JPQH group （1.3 g·mL-1）， with 10 rats in each group. After six weeks of drug intervention， the changes in body weight， blood glucose， and other related indexes of each group were recorded. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the peripheral blood and brain. The Morris water maze test was used to evaluate the cognitive function in rats. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the hippocampal CA region. The amyloid β-protein 40 （Aβ40） level was detected by immunohistochemistry. The protein expression of t-tau and p-tau in hippocampal neurons of rats was detected by Western blot. ResultCompared with blank group， the body weight of model group was significantly decreased （P<0.05）， blood glucose level was significantly increased （P<0.01）， inflammatory cytokines TNF-α and IL-1β were increased （P<0.05）， learning and spatial ability were significantly decreased （P<0.01）， the arrangement of hippocampal cells was loose and disordered， and the intercellular space was significantly increased. The number of cells decreased significantly， and the expression of Aβ40 increased significantly. and increased t-tau and p-tau protein content in the hippocampus （P<0.01）. Compared with model group， the JPQH group showed reduced blood glucose （P<0.01）， decreased TNF-α and IL-1β levels in the peripheral blood and cerebrospinal fluid （P<0.05）， a downward trend of IL-6 without a statistical difference， improved learning and spatial memory ability （P<0.01）， densely arranged cells in the hippocampal CA1 area， increased cell number， reduced Aβ40 expression， and decreased p-tau protein expression （P<0.05）. ConclusionJPQH can prevent cognitive dysfunction in DM by reducing inflammatory factor levels， decreasing neurotoxicity caused by Aβ40 deposition， and inhibiting hyperphosphorylation of tau protein in DM rats.

Alterations of gut microbiota composition and cogni-tive behavior in APP/PS1/tau triple-transgenic mouse model of Alzheimer's disease / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)is a progressive neurological disease.Given the important role of gut microbiota composition in AD pathology,the observed perturbation in the microbiota composition and diversity may serve as the mechanisms underlying age-dependent APP/PS1/tau triple-transgenic mouse(3×Tg-AD)mice amyloid deposition and memory deficits.Here-in,we intended to investigate the gut microbiota and as-sessed its relationship with the triggering and develop-ment of cognitive impairment of AD.METHODS This study involves the comparative assessment of spatial learning,amyloid β-protein(Aβ)accumulation,and fecal microbiota alterations in 3×Tg-AD mice from three age groups:AD asymptomatic stage(3 m),presymptomatic stage(6 m),and the symptomatic stage of AD(9 m).RE-SULTS We demonstrate that spatial memory deficits,brain Aβ accumulation,and weight gain in 3×Tg-AD mice gradually appear after 6 months of age.However,the total gut bacterial counts underwent changes from 3 to 6 months of age and were further altered at 9 months of age.Importantly,changes in gut bacteria abundance of Desulfobacterota and Actinobacteriota phylain 6-month-old mice preceded apparent spatial memory deficits.CONCLUSION Changes in the gut microbial community are one of the mechanisms of early AD pathology.

Effect of Clkl gene on level of Aβ-induced autophagy in Alzheimer's disease / 中国药理学通报

Aim To investigate the effect of siRNA transfection of silencing Clkl gene on autophagy levels in AD model cells. Methods The Clkl gene was silted using siRNA transfection techniques. MTT was used to observe the effects of Aβ

Ginsenoside Rg_1 protects PC12 cells against Aβ-induced injury through promotion of mitophagy by PINK1/parkin activation / 中国中药杂志

Amyloid β-protein(Aβ) deposition in the brain is directly responsible for neuronal mitochondrial damage of Alzheimer's disease(AD) patients. Mitophagy, which removes damaged mitochondria, is a vital mode of neuron protection. Ginsenoside Rg_1(Rg_1), with neuroprotective effect, has displayed promising potential for AD treatment. However, the mechanism underlying the neuroprotective effect of Rg_1 has not been fully elucidated. The present study investigated the effects of ginsenoside Rg_(1 )on the autophagy of PC12 cells injured by Aβ_(25-35) to gain insight into the neuroprotective mechanism of Rg_1. The autophagy inducer rapamycin and the autophagy inhi-bitor chloroquine were used to verify the correlation between the neuroprotective effect of Rg_1 and autophagy. The results showed that Rg_1 enhanced the viability and increased the mitochondrial membrane potential of Aβ-injured PC12 cells, while these changes were blocked by chloroquine. Furthermore, Rg_(1 )treatment increased the LC3Ⅱ/Ⅰ protein ratio, promoted the depletion of p62 protein, up-regulated the protein levels of PINK1 and parkin, and reduced the amount of autophagy adaptor OPTN, which indicated the enhancement of autophagy. After the silencing of PINK1, a key regulatory site of mitophagy, Rg_1 could not increase the expression of PINK1 and parkin or the amount of NDP52, whereas it can still increase the LC3Ⅱ/Ⅰ protein ratio and promote the depletion of OPTN protein which indicated the enhancement of autophagy. Collectively, the results of this study imply that Rg_1 can promote autophagy of PC12 cells injured by Aβ, and may reduce Aβ-induced mitochondrial damage by promoting PINK1-dependent mitophagy, which may be one of the key mechanisms of its neuroprotective effect.

Effects of on behavior and blood-brain barrier in Alzheimer's disease mice / 浙江大学学报·医学版

To investigate the effects of on behavior and blood brain barrier (BBB) in Alzheimer's disease mice. Thirty-eight 4-month-old APP/PS1 double transgenic mice were randomly divided into three groups: model group, low-dose group and high-dose group. Saline, and 12 g·kg·d were given to each group by continuous gavage once a day for respectively. The changes in activities of daily live and fear conditioning memory behavior of mice were examined by nesting behavior test and fear conditioning test, respectively. The β-amyloid protein (Aβ) depositions in cortex and hippocampal CA1 area of mice were detected by thioflavin T staining. The CD34 and activities fibrinogen (Fib) immunofluorescence double staining were used to determine the vascular endothelial integrity and BBB exudation. Compared with model mice, activities of daily live were significantly improved in low-dose and high-dose groups (both <0.01), the fear memory ability was significantly increased in high-dose group (<0.01). The amount of Aβ deposition in cortex and hippocampal CA1 decreased significantly in high-dose group, the area ratio decreased significantly; the area ratio of Aβ deposition in hippocampal CA1 region in low-dose group also decreased (all <0.05). The proportions of CD34 positive area of cortex in low and high dose groups increased, the percentage of fibrinogen positive area decreased (all <0.05). The proportion of CD34 positive area in hippocampal CA1 region in high-dose group was significantly increased, the percentage of fibrinogen positive area decreased significantly (both <0.05). especially high-dose can improve the activities of daily live and fear conditioning memory function of APP/PS1 mice, reduce the deposition of Aβ in brain. The mechanism may be related to the reduction of BBB permeability and the protection of the integrity of BBB.

Protective effect of baicalein on injured PC12 cell induced by Aβ and its mechanism / 国际中医中药杂志

Objective:To investigate the protective effect of baicalein on injured PC12 cell induced by Aβ and explore its mechanism.Methods:The method of MTT was used to detect the cell activity of each group and screened the concentration of baicalein. The PC12 cells were randomly divided into the blank group, the Aβ group, the baicalin group and the estradiol group. 24 hours after inoculation, baicalein group was intervened with 1×10 -6 mol/L baicalein solution, and estradiol group was intervened with 1×10 -5 mol/L estradiol solution. Two hours later, except the blank group, the other groups were added with 1.5×10 -4 mol/L Aβ to make the model. MTT assay was used to detect the cell viability of each group after 24 hours of cultivation. Then used oxidation kit to detect the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and lactate dehydrogenase (LDH) in each group. And the level of caspase-3 mRNA was detected by Real-time Quantitative PCR (RT-PCR). Then the Western blot method was used to detect the expressions of p-PI3K, p-AKT and caspase-3. Results:Compared with the Aβ group, the PC12 cell viability [(96.348 ± 0.571)%, (97.183 ± 0.714)% vs. (86.922 ± 0.429)%] in the baicalin group and the estradiol group significantly increased( P<0.01). The activities of SOD [(54.31 ± 1.34) U/mgprot, (57.38 ± 2.25) U/mgprot vs. (36.18 ± 2.24) U/mgprot] and GSH-PX [(4.46 ± 0.23) U/mgprot, (4.72 ± 0.31) U/mgprot vs. (2.05 ± 0.37) U/mgprot] significantly increased, and the level of LDH [(85.43 ± 0.92) nmol/ml, (82.46 ± 0.27) nmol/ml vs. (99.17 ± 0.52) nmol/ml] significantly decreased ( P<0.01). The expression of caspase-3 mRNA (2.24 ± 0.64, 2.33 ± 0.75 vs. 3.46 ± 0.46) and p-PI3K (0.46 ± 0.03, 0.44 ± 0.06 vs. 0.66 ± 0.09), p-AKT (0.43 ± 0.05, 0.41 ± 0.02 vs. 0.58 ± 0.03), caspase-3 (0.61 ± 0.03, 0.56 ± 0.53 vs. 0.92 ± 0.07) protein significantly decreased ( P<0.01). Conclusion:Baicalein could slow down cell apoptosis and oxidative reaction, reduce the damage of Aβ to PC12 cells by inhibiting the expression of PI3K/AKT pathway.

Effects of Effective Part of Tinospora sinensis on Hippocampus Proteomics of AD Rats Induced by Beta-amyloid Protein and D-galactose / 中国药学杂志

OBJECTIVE: To investigate the effect of the 80% ethanol elution part of Tinospora sinensis macroporous resin extract on the expression of hippocampus proteome in Alzheimer′s disease (AD) model rats induced by D-galactose combined with Aβ2535. METHODS: The AD rats model replicated by D-galactose combined with Aβ2535, The AD rat model was replicated by D-galactose combined with Aβ2535, and randomly divided into sham operation group, model group, Donepezil group (donepezil, 6.0 mg•kg-1), and 80% extraction of Tinospora sinensi group (crude drug 6 g•kg-1). Donepezil group: donepezil 0.1 mL•10 g-1 ig. 80% extraction of Tinospora sinensi group: Tinospora sinensis effective part extraction 0.1 mL•10 g-1 ig. Model group and sham-operation group: physiological saline 0.1 mL•10 g-1 ig. Once a day, continuous administration for 15 d. Separating the hippocampus and extracting the protein, take the system test with nanol-ESI liquid-mass spectrometry, protein discovery software was used for identification, and qualitative analysis different groups of hippocampal proteins by SIEVE software. Take the GO analysis on differential protein with the ANTHER classification system and use IPAD to enrich the pathway. RESULTS: Compared with the model group, the drug-administered group had 66 differential proteins, including tubulin, heat shock proteins, energy metabolism-related proteins, vesicle production/transport related proteins, and brain protection-related proteins, which are closely related to AD. The above differential proteins involve a total of 21 signaling pathways. CONCLUSION: Tinospora sinensis may promote the synthesis and release of neurotransmitters by up-regulating clathrin and vesicle-forming transport and neurotransmitter release, and improve the function of cholinergic function in the brain to achieve the pathological process of AD.

Progress in interventional mechanism of paeoniflorin on Alzheimer’s disease / 中草药

Alzheimer’s disease (AD) is one of the main pathogenies of the cognitive decline in aging population. Paeoniflorin is a water-soluble monoterpene isolated from the roots of Paeonia lactiflora or P. suffruticosa, which are both in the family Ranunculaceae. Paeoniflorin has the effect of improving the cognitive ability, sedative, anti-inflammatory, analgesic, and spasmolytisch activities. It could also regulate hyperphosphorylation of Tau and Aβ proteins; Paeoniflorin can restore the balance of neurotransmitter and neurotransmitter receptors including acetylcholine, nerve growth factor, calcium ion, α7 nicotinic acetylcholine receptor and adenosine receptors, and reduce inflammation, oxidative stress and neuron apoptosis in AD animal and cell models. This paper reviewed relevant research in the past decade about the effect of paeoniflorin on AD, which may provide theoretical basis to use agent from Chinese medicine for AD prevention and treatment.

Rho-associated coiled coil protein kinase 1 involved in amyloid β-protein-induced damage in primary neurons of rats / 上海交通大学学报（医学版）

Objective • To investigate the role of Rho-associated coiled coil protein kinase 1 (ROCK1) in amyloid β-protein (Aβ) induced damage of rat hippocampal neurons. Methods • The rat primary neurons were treated with Aβ40 oligopeptides to establish a neurotoxicity model. Western blotting was used to detect the protein expression of ROCK1. Its activity was detected by the kit. Confocal laser scanning was used to observe the calcium signal in neurons, and apoptosis of neurons was detected by TUNEL assay. Y-27632, an inhibitor of ROCK1, was added into the culture medium in order to observe its effect on Aβ40. Results • Aβ40 (10 μmol/L) could significantly induce calcium overload, increase ROCK1 expression and activity, and promote apoptosis in primary neurons. Furthermore, ROCK1 inhibitor could decrease all the effect induced by Aβ40. Conclusion • ROCK1 is involved in both Aβ- induced neuronal calcium overload and neurotoxicity, and ROCK1 inhibitor can antagonize the toxic effects of Aβ.

Effects of Chinese traditional medicine-selected recipe Q0409 on ability of learning and memory in SAM-P/8 mice / 中国病理生理杂志

AIM:To investigate the effects of Chinese traditional medicine-selected recipe Q0409 on the ability of learning and memory in SAM-P/8 mice. METHODS:Total 91 mice (4-month-old SAM-P/8 mice, SAM-R/1 mice and Kunming mice) were used in the study, in which the male and female animals were labeled separately. According to the performance of Morris water maze test, the mice were divided into 5 groups randomly. The mice were fed with different drugs or distilled water for 60 d (from 4 months to 6 months). The mice were fed with the drugs from 61 d to 65 d, and 1 h later each time, the Morris water maze test was carried out. After this Morris test were finished at 65 d, the mice were killed immediately and their hippocampal tissues were isolated. Half of the hippocampal tissues were added with precooled normal saline and made into 10% (g/mL) homogenate for detecting the protein content and acetyl cholinesterase (AChE) activity. The other half was fixed with 4% paraformaldehyde and embedded with paraffin for immunohistochemical staining of amyloid β-protein (Aβ). RESULTS:Compared with model group, the results of navigation training and spatial probe training in Morris water maze test were significantly improved (P<0.05), and the activity of AChE in the hippocampal ho-mogenate was significantly decreased (P<0.05) in Q0409 treatment group. No difference in Q0409 group was observed compared with control group and positive drug (huperzine A) group. Immunohistochemical staining showed no typical "se-nile plaques" in the male mice of Q0409 group, while there was shallower and smaller brown staining in the hippocampus of the female mice of Q0409 group. The positive area of Aβ deposition decreased in the CA1 area of hippocampal tissues in Q0409 group. These results were similar to those in positive drug group. CONCLUSION:Q0409 improves the ability of learning and memory in SAM-P/8 mice, which is related to the inhibition of AChE activity and the reduction of Aβ protein deposition in the hippocampus. The effects is similar to those of huperzine A.

Changes in histopathology and ultrastructure of corneal epithelium in TgAPPswePS1 transgenic mice / 眼科新进展

Objective To investigate the histopathological and ultrastructural changes in the corneal epithelium in TgAPPswePS1 transgenic mice.Methods TgAPPswePS1 transgenic mice were randomly divided into experimental group (A and B sub-group) and control group.There were 15 APPswe/PSEN1dE9 transgenic mice (15-18 months old) with Alzheimer's disease (AD) in the experimental A group,and 15 APPswe/PSEN1 dE9 transgenic AD mice (8 months old) mice in the experimental B group,as well as 10 wild-type mice (8 months old) in the control group.Then,the histopathological and ultrastructural changes and the expression of amyloid β-protein (Aβ) in the corneal epithelium of the mice were detected,and finally,the apoptosis of corneal epithelial cells were observed by TUNEL assay.Results The thickness of corneal epithelium in the control group,A and B sub-group of the experimental group was (23.567 ± 2.123) μm,(15.456 ± 1.439) μm and (20.104 ± 1.763) μm,respectively.Meanwhile,murine corneal epithelial cells presented the histopathological changes of disorderly arrangement,decreased layers of cells and irregular morphology in the experimental group compared with the control group.Under transmission electron microscope,the microvilli on the surface of corneal epithelium was flat and significantly decreased in the A and B sub-group when compared with the control group.Moreover,Aβ positive expression in the experimental group was significantly upregulated compared with the control group;and the apoptotic number of the corneal epithelium in the B sub-group [(5.631 ± 2.471) cells] was smaller than that in the A sub-group [(16.329 ±3.542) cells],with the significant difference(P ＜ 0.05).Conclusion There are changes in the histopathology and ultrastructure of the corneal epithelium and the expression of Aβ in TgAPPswePS1 transgenic mice compared with wild-type mice,which are associated with the age of mice.

Effect and its mechanism of Linagliptin on mild cognitive impairment in elderly type 2 diabetes mellitus patients / 中华老年医学杂志

Objective To investigate the effect and its underlying mechanism of Linagliptin on mild cognitive impairment (MCI) in elderly type 2 diabetes mellitus (T2DM) patients.Methods Montreal Cognitive Assessment(MoCA)scale was used to prospectively screen T2DM patients for MCI in our hospital from December 2016 to June 2017,and a total of 98 elderly T2DM patients with MCI were recruited.They were randomly divided into the linagliptin group(Linagliptin + metformin,n=50)and the non-linagliptin group(gliclazide + metformin,n =48).Serum fasting plasma glucose (FPG),glycosylated hemoglobin(HbAlc),blood lipids and amyloid β-protein 1-42 (Aβ1-42) levels were determined,and MoCA score and homeostasis model assessment of insulin resistance(HOMA-IR)were calculated,and were compared between the two groups before and after 24 weeks of treatment.Results In the linagliptin group,serum FPG,HbA1c,HOMA-IR,Aβ1-42 levels were significantly decreased and MoCA score was increased after 24 weeks of treatment as compared with pre-treatment [(7.29± 1.00) mmol/L vs.(9.16 ± 1.60) mmol/L,(7.19 ± 0.99) ％ vs.(9.36 ± 1.07) ％,(3.05 ± 1.12) vs.(4.05±1.30),(0.463±0.093)g/L vs.(0.528±0.110)g/L,(24.48± 1.18) vs.(23.22± 1.37),all P＜0.05].In the non-linagliptin group as control,FPG and HbA1c levels were decreased after 24 weeks of treatment as compared with pre-treatment[(7.23±1.09)mmol/L vs.(9.20± 1.75) mmol/L,(7.23±1.03)％ vs.(9.69± 1.18)％,both P ＜ 0.05],while there was no significant difference in HOMA IR,Aβ1-42 level and MoCA score[(3.95 ± 1.00) vs.(4.19± 1.13),(0.517± 0.113)g/L vs.(0.526±0.119)g/L,(23.21±1.18) vs.(23.00±1.32),all P＞0.05].It is worth to pay close attention to the key discovery of this paper that HOMA-IR and Aβ1-42 levels were significantly lower and MoCA score was significantly higher in the linagliptin group than in the non-linagliptin group after 24 weeks of treatment(all P＜0.05).Conclusions Linagliptin as one of DPP-4 enzyme inhibitors can improve the cognitive function in elderly patients with T2DM,which might be relevant to reducing serum Aβ level and improving HOMA-IR.DPP-4 enzyme inhibitor may be a good option for treatment of mild cognitive dysfunction in T2DM patients in the future.

Effects of multiple monitoring of total intravenous anesthesia on postoperative cognitive dysfunction in ;elderly patients / 临床麻醉学杂志

Objective To observe the effect of multiple monitoring of total intravenous anes-thesia on postoperative cognitive function in elderly patients.Methods Elective 100 patients undergo-ing general anesthesia for abdominal operation,56 males,44 females,aged 65-80 years,ASA physi-cal status Ⅱ or Ⅲ.All patients were divided into multiple monitoring group (group M)and routine monitoring group (group R)by random digital table method,n =50 each.In group M,the anesthesi-ologists modulated anesthetic drugs to make NTI of 37-56 and rSO 2 higher than 50% or not lower than the baseline value by 20%,while in group R the infusion rate of propofol,remifentanil and cisa-tracurium was adjusted by anesthesiologists according to anesthesiologist’s experiences by the pa-tients’monitoring index.Cognitive function of patients in the two groups were evaluated using MMSE 1 d before surgery and 1 d,3 d,7 d,1 month and 3 months after surgery.The occurrence of cognitive dysfunction 7 d,1 month and 3 months after surgery,the postoperative recovery and the dosage of propofol,remifentanil and cisatracurium were recorded.Blood was randomly selected from each group to determine the serum content of S100βand Aβ1-42 by ELISA method at the time point of before surgery (T0 ),one hour after starting surgery (T1 ),the end of surgery (T2 )and postopera-tive 24 hours (T3 ).Results The incidence of postoperative cognitive decline in group M on 1 d (8%vs.22%),3 d (2% vs.1 6%)after surgery were significantly lower than that in group R (P <0.05). Postoperative cognitive dysfunction between the two groups 7 d and 1 month,3 months after surgery has no statistical significance.The dose of propofol [(3.3 ± 0.8)mg · kg-1 · h-1 vs.(3.7 ± 0.7 ) mg·kg-1 ·h-1 ,P < 0.05 ] and cisatracurium [(104 ± 47 )μg · kg-1 · h-1 vs.(124 ± 68 )μg·kg-1 ·h-1 ,P <0.05]in group M was less than that in group R.The time of eye-opening [(10 ±3)min vs.(1 6±6)min,P <0.01],extubation [(13±3)min vs.(22±7)min,P <0.01]and lo-cation [(1 7±4)min vs.(27 ±9)min,P <0.01 ]was shorter in group M.Compared with T0 ,the serum level of S100βprotein was significantly increased in group M at T1 ,T2 and group R at T1-T3 (P <0.05);The level of serum S100βprotein in group M was significantly lower than that in group R (P <0.05).Compared with T0 ,Aβ1-42 protein level was significantly reduced in two groups at T1 and T2 (P <0.05),but there was no significant difference between the two groups.Conclusion Total intravenous anesthesia with multiple monitoring can reduce neural injury and reduce the incidence of early postoperative cognitive decline in elderly patients with abdominal surgery,but has no significant effect on the incidence of POCD.

Effects of Remifentanil-induced Controlled Hypotension on Postoperative Cognitive Dysfunction and Se-rum S100βProtein in Elderly Patients Underwent Spinal Surgery and Relationship Analysis / 中国药房

OBJECTIVE:To observe the effects of remifentanil-induced controlled hypotension (CH) on postoperative cogni-tive dysfunction (POCD) and serum S100β protein in elderly patients underwent spinal surgery,and to investigate their relation-ship. METHODS:Sixty elderly patients undergoing selective laminectomy decompression internal fixation of lumbar or thoracic fractures under general anesthesia were selected prospectively from orthopedics department of our hospital during Jan. 2014-Dec. 2015,and then divided into CH group and non-CH group in accordance with random number table,with 30 cases in each group. Both groups received general anesthesia of injection and inhalation via endotracheal intubation. Mean arterial pressure (MAP) of CH group were reduced to 70%-80%of the basic values by adjusting remifentanil infusion rate;those of non-CH group were main-tained at basic level. Surgery duration,anesthesia duration,intraoperative blood loss,the incidence of POCD and serum concentra-tion of S100β protein were observed in 2 groups. The relationship of serum concentration of S100β protein with POCD was ana-lyzed,and the occurrence of ADR was recorded. RESULTS:The intraoperative blood loss of CH group was significantly less than that of non-CH group,with statistical significance (P0.05). The incidence of POCD and serum concentration of S100β protein in CH group were significantly higher than in non-CH group on the 2nd and 3rd day after surgery,with statistical significance(P<0.05). The serum concentration of S100β protein may be related to the incidence of POCD (r=0.992 7,P=0.001 3). CONCLU-SIONS:Remifentanil CH used in elderly patients underwent spinal surgery can reduce intraoperative blood loss,but increase the se-rum concentration of S100βprotein and the incidence of POCD at early stage.

Clinical evaluation of Kudiezi injection in acute cerebral infarction and its effects on serum VEGF, S-100βand MMP-9 levels / 中国生化药物杂志

Objective To investigate clinical evaluation of Kudiezi injection in treatment of acute cerebral infarction and its effects on serum vascular endothelial growth factor(VEGF), S-100β, matrix metalloproteinases(MMP)-9 levels.Methods 98 patients of acute cerebral infarction who received therapy from October 2014 to October 2016 in our hospital were selected.Those patients were randomly divided into the observation group and the control group with 48 cases in each group.The control group was treated with routine treatment, while the observation group was treated with Kudiezi injection.After treatment of 14 days, the clinical curative effect, serum VEGF, S-100β, MMP-9, National institutes of health stroke scale (NIHSS) and Barthel index were compared.Results After treatment, the total effective rate in the observation group 87.75%(43/49) was significantly higher than that of the control group 65.31%( 32/49 ) , the difference was statistically significant ( P<0.05 ) , the level of VEGF in the observation group was significantly higher than that of the control group, and the S-100βand MMP-9 were significantly lower than that of the control group, the difference was statistically significant (P<0.05), the NIHSS score in the observation group was significantly lower than that of the control group, the difference was statistically significant (P<0.05), the Barthel index in the observation group was significantly higher than that of the control group, the difference was statistically significant (P<0.05).Conclusion Kudiezi injection is well for acute cerebral infarction, which can effectively improve the serum levels of VEGF, S-100β, MMP-9, and can improve the therapeutic effect, promote the recovery of neurological function and improve the quality of life.

Effect of Early Moxibustion Intervention on the Expression of Amyloid β-protein1-40 in 5XFAD Transgenic Mice / 上海针灸杂志

Objective To explore effect of early moxibustion intervention on cerebral Aβ1-40 in a mouse model of Alzheimer disease (AD) and the mechanism of action of moxibusion in preventing and treating AD.Method Gene phenotype in transgenic AD passage mice was identified using PCR. One and a half-month-old female Tg6799 transgenic mice were randomly allocated, including nine mice to a model group and eight mice to a treatment group. Nine C57BL/6J wild type female mice of the same age and background constituted a normal control group. Wheat-grain-sized moxa cone moxibustion on bilateral points Xinshu(BL15) and Shenshu(BL23) was given to the treatment group. After the completion of treatment, Aβ1-40 expression in mouse frontal cortex and hippocampal region was determined using the immunohistochemical method.Result Aβ1-40 expression in mouse frontal cortex and hippocampal region decreased significantly in the treatment group compared with the model group (P<0.01,P<0.05). Conclusion Early moxibustion intervention can decrease cerebral Aβ1-40 expression and delay AD pathological process in a mouse model of AD.

Effect of Early Moxibustion Intervention on the Expression of Amyloid β-protein1-40 in 5XFAD Transgenic Mice / 上海针灸杂志

Objective To explore effect of early moxibustion intervention on cerebral Aβ1-40 in a mouse model of Alzheimer disease (AD) and the mechanism of action of moxibusion in preventing and treating AD.Method Gene phenotype in transgenic AD passage mice was identified using PCR. One and a half-month-old female Tg6799 transgenic mice were randomly allocated, including nine mice to a model group and eight mice to a treatment group. Nine C57BL/6J wild type female mice of the same age and background constituted a normal control group. Wheat-grain-sized moxa cone moxibustion on bilateral points Xinshu(BL15) and Shenshu(BL23) was given to the treatment group. After the completion of treatment, Aβ1-40 expression in mouse frontal cortex and hippocampal region was determined using the immunohistochemical method.Result Aβ1-40 expression in mouse frontal cortex and hippocampal region decreased significantly in the treatment group compared with the model group (P<0.01,P<0.05). Conclusion Early moxibustion intervention can decrease cerebral Aβ1-40 expression and delay AD pathological process in a mouse model of AD.

Protective effect of total alkaloids of Corydalis Ochotensis on rats with Alzheimer's disease induced by β-amyloid protein / 吉林大学学报(医学版)

Objective:To explore the influence of total alkaloids of Corydalis Ochotensis(TAOCO) on the behavior and pathomorphology of brain tissue of the rats with Alzheimer's disease(AD) induced by β-amyloid protein 25-35(Aβ25-35),and to clarify its therapeutic effects on the AD rats.Methods:The Wistar rats were divided into mormal control group(treated with 0.5 mL·100 g-1 distilled water) (n=9),model group(treated with 0.5 mL·100 g-1 distilled water)(n=9),positive drug group(treated with 1.75 mg·kg-1 donepezil hydrochloride)(n=9),and low,middle and high doses (treated with 2.0,4.0 and 8.0 mg·kg-1) of TAOCO groups(n=8,n=9,n=9).The rat AD models were made by injecting Aβ25-35 into hippocampus.On the 14th day after operation,the rats were administered for 7 d.Morris water maze test was used to detect the spatial learning and memory ability of the rats;dark avoidance task was used to observe the passive avoidance ability of the rats;the pathomorphology of the cerebral cortex and hippocampus of the rats were detected.Results:The Morris water maze test results showed that compared with model group,the latency to platform of the rats in low dose of TAOCO group was decreased on the 4th and 5th days(P0.05).Compared with model group,there was no obvious improvement of the cerebral cortex and hippocampus injury of the rats in low and middle doses of TAOCO groups.In high dose of TAOCO group,the cerebral cortex and hippocampus injury of the rats were significantly improved.Conclusion:TAOCO can improve the learning and memory function of the AD rats and reduce the pathological injury of brain tissue of AD rats.

Effect of Electro-acupuncture on Behavior Alterations in Mice with Isoflurane-induced Alzheimer's Disease and Its Mechanism / 广州中医药大学学报

Objective To investigate the effect of electro-acupuncture on behavior alterations,the expression of amyloid precursor protein(APP),amyloid β-protein(Aβ) proteins and neuroapoptosis in the cerebral cortex in the APPswe/PS1dE9 double transgenic mice with Alzheimer's disease (AD) induced by isoflurane.Methods Sixmonth-old AD mice and wild-type mice at the same age were randomly divided into wile-type control group,AD group,isoflurane group,electro-acupuncture group (N =8).The mice were given pretreatment with electro-acupuncture at Baihui(GV20) acupoint and Yongquan(KI 1) acupoint once a day for 3 successive days,15 min each time.And then the mice in electro-acupuncture group and isoflurane group were exposed to a box full of 1.2％ isoflurane for 4 hours.Morris water maze was used to test the learning and memory abilities of the mice,Western blotting method was used to detect the expression of APP-C83,APP-C99 and Aβ,and terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL) was used to detect neuroapoptosis in the cerebral cortex.Results The escape latency of AD group was longer than that of wild-type mice group(P＜0.05),and the latency of isoflurane group was longer than that of AD group (P ＜ 0.05),while the latency of electro-acupuncture group was shorter than that of isoflurane group(P ＜ 0.05).The percentage of retention time in the target quadrant and the times for crossing the target quadrant in isoflurane group were lower than those of AD group (P ＜ 0.05),but were higher in electro-acupuncture group than those in isoflurane group (P ＜ 0.05).APPC83 expression level in isoflurane group was significantly lower than that in AD group (P ＜ 0.05),while APP-C83 expression level in electro-acupuncture group was higher than that in isoflurane group (P ＜ 0.05).APP-C99 expression level in isoflurane group was significantly higher than that in AD group (P ＜ 0.05),and APP-C99 expression level in electro-acupuncture group was lower than that in isoflurane group (P ＜ 0.05).The cortical apoptosis index in isoflurane group was significantly higher than that in AD group (P ＜ 0.05),and the cortical apoptosis index in electro-acupuncture group was lower than that in isoflurane group (P ＜ 0.05).The expression level of Aβ in AD group,isoflurane group and electro-acupuncture group was significantly higher than wild-type control group (P ＜ 0.05).Conclusion Electro-acupuncture can relieve the AD-like neurotoxicity induced by isoflurane and inhibit the decline of learning and memory abilities of AD mice,and the mechanism is probably related with suppressing the overexpression of APP-C99 and reducing the production and accumulation of Aβ,thereby alleviating the neuroapoptosis.

Effect of ulinastatin on serum concentration of S100βprotein and NSE in patients undergoing supratento-rial tumor resection / 临床麻醉学杂志

Objective To observe the serum concentration of S100βprotein (S100β)and neuron specific enolase (NSE)in patients undergoing supratentorial tumor resection with ulinastatin treat-ment.Methods Twenty-four patients with supratentorial tumor resection,aged 18-65 years,ASA Ⅰor Ⅱ,were randomly divided into the control group (group A,n =12)and ulinastatin group (group U,n =12).Patients in group U received ulinastatin (2 kU/kg)at the beginning of the surgery,with the continuous dose of 1 kU·kg-1 ·h-1 till the end of the operation.Group A received equivalent volume of saline solution as the vehicle control.Blood samples were taken from the artery and jugular venous bulb before induction of anesthesia (T1 ),skin incision (T2 ),1 h after dura openning (T3 ),at the closure of dura (T4 ),at the end of operation (T5 )and 24 h after operation (T6 )to analyze the concentration of S100β and NSE.The concentration of S100β and NSE were determined by ELISA. Results The concentration of serum S100β and NSE increased more significantly higher at T3-T6 in group A than group U (P <0.01).The concentration of serum S100βand NSE in group U were lower than those in group A at T3-T5 (P < 0.01 ).Conclusion Ulinastatin reduces the concentration of serum S100βand NSE during surgery,indicating it alleviates brain injury during supratentorial tumor resection.