The pathological presentation of Alzheimer disease (AD), the leading cause of senile dementia, involves regionalized neuronal death and an accumulation of intraneuronal and extracellular filaments termed neurofibrillary tangles and senile plaques, respectively. One of the ?-amyloid peptides (A?), the A?1-42 form, is primarily responsible for neuronal damage and cell death that is the main component in the senile plaques. Over the past twenty years, the amyloid hypothesis has been strongly supported by a wealth of evidence, including data from genetic studies of Alzheimer disease. Amyloid cascade hypothesis states that the accumulation and deposition of fibrillar A? is the primary driver of neurodegeneration and cognitive decline leading to dementia. AD is a clinicopathological syndrome in which different gene defects can lead--directly or indirectly--to alter APP expression or proteolytic processing as such to change A? stability or aggregation. These result in a chronic imbalance between A? production and clearance. Gradual accumulation of aggregated A? initiates a complex, multistep cascade that includes gliosis, inflammatory changes, neuritic/synaptic change, tangles and transmitter loss. The evidence that links A? to the pathogenesis of AD is substantial, but the means by which these peptides exert their toxic effects, and where in neuronal cells they act, is far from clear. The up-to-date proceeding in the molecular mechanism of ?-amyloid peptides is overviewed.

Objective To investigate the antithrombosis effects of Buyang Huanwu Decoction(BHD) and its active fractions on cultured vascular endothelial cells(VEC) following the stimulation of thrombin and their mechanism.Methods The human umbilicus vein endothelial cells(ECV 304) were cultured in media containing 10 U/mL thrombin and different dosese of drugs.The levels of tPA and PAI-1 were detected by ELISA,the expression of TF,TFPI,and TM mRNA was measured by RT-PCR,and the expression of PKC? was examined by immunohistochemical staining 24 h later.Results Compared to the control without any treatment,the release of tPA was increased evidently(P0.05).Compared to the data after the mere stimulus of thrombin,each dose of BHD increased the release of tPA(P0.05);And glycoside(1.25 mg/mL) increased the release of tPA(P

Objective To study the effect of different approaches of Cage bone graft combined with pedicle screw fixation fusion in trea-ting lumbar spondylolisthesis. Methods From January 2011 to December 2012,120 patients with lumbar spondylolisthesis in our hospital were randomly divided into anterior lumbar interbody fusion (ALIF) group(n=40),postero lateral fusion (PLF) group(n=40) and posteri-or lunbar interbody fusion (PLIF) group(n=40). The related index and body’s function were observed. Results In PLIF group,the opera-tion time was(82. 3 ± 12. 1) h,intraoperative bleeding volume was (60. 3 ± 9. 5) mL,postoperative ambulation time was (5. 5 ± 0. 7) d, NRS score was(1. 5 ± 0. 2),ODI score 3,6,9,12 months after operation were respectively (24. 1 ± 3. 4),(19. 4 ± 3. 1),(13. 5 ± 2. 5), (9. 8 ± 1. 6),which was significantly lower than ALIF group and PLF group;the intervertebral height(9. 3 ± 1. 2)mm were significantly high-er than those of ALIF group and PLF group. Conclusion PLIF has positive clinical value in treating lumbar spondylolisthesis as it can re-duce the operation wound,promote postoperative recovery,and improve the long-term function of body.

Objective To evaluate the expression of substance P (SP) and caltenin gene related peptide (CGRP) in esophagueal mucosa from patients with non-erosive gnstroesophageal reflux disease (NERD) and reflux esophagitis (RE) and to explore their role in the development of NERD. Methods Fif-ty-one patients with typical symptoms of gnstroesophageal reflux disease (GERD) were evaluated with reflux disease questionnaire (RDQ), PPI test, endoscopy and 24hr esophageal pH monitoring. The patients were then divided into RE group (n = 21), NERD group with acid refluux (NERD+, n = 12) and NERD group without acid reflux (NERD-, n = 18) according to the evaluation results. The expression of SP and CGRP in esophagus mucosa from these patients and 10 healthy control subjects were assayed by immunohistochemis-try, and the stain positive index (PI) was calculated by Color patho-image analysis software and compared. Results The PIs of SP and CGRP in NERD- group were 96.77±31.74 and 24.76±29.15, respectively, which were significantly higher than those of NERD+ group (73.64±31.38, 9.78±10.30, respectively, P < 0.05), RE group (67.56±34.62, 9.61±6.20, respectively, P < 0.05) and control group (59.82± 46.15, 8.64±12.12, respectively, P < 0.05). Conclusion Expressions of SP and CGRP in esophagus mucosa from NERD patients without detectable acid reflux are significantly increased, they may play an im-portant role in esophageal visceral sensitivity.

Objective To explore the roles of PKCθ(protein kinase Cθ)signaling pathway on the activation,proliferation and TH1/TH2 cytokines production of the γδT lymphocytes stimulated by Mycobacterium tuberculosis antigen(Mtb-Ag) in vitro.Methods Peripheral blood mononuclear cells(PBMC)were pretreated with or without Rottlerin at 5.0 μmol/L,and stimulated with Mtb-Ag and cultured in rhIL-2 containing medium.After different time of culture,activation molecules and cytokines production of γδT cells were measured by flow cytometry.The proliferation proportion and the percentage of each generation of γδT cells were determined by carboxylfluoreseein diacetate succinmidyl ester(CFSE)labeling technique and flow cytometry.Results After 3d of stimulation with Mtb-Ag,the expression rates of CD69 and CD25 of γδT cells were 46.2%and 45.6%,respectively.Pretreatment of 5.0 μmol/L Rottlerin markedly inhibited the both expressions of CD69 and CD25 in γδT cells(P＜0.01).After stimulation and expansion in vitro for 5,10,and 15 d,the percentages of the γδT cell were 9.6%,54.6%and 82.4%,respectively.There was a few γδT cells in propagation on the 5th day of culture,and almost all γδT cell divisions were above 6 generations on the 10th and 15th day of culture.Pretreatment of the Rotflerin significantly suppressed the γδT cell proliferation,but after 10 d culture,there were still a few parts of γδT cells in propagation.Meanwhile,after 7,14,and 21d of culture,upon stimulation with PMA+Ionomycin,the IFN-γ producing-γδT cells were about 80%at all times.But only after 21d culture,IL-4-producing γδT cells was 2.6%.,The percentage of IFN-γ producing γδT cells markedly reduced in Rottlerin group(P＜0.01).IL-4 secretion of the γδT cells was almost completely blocked.Conclusion PKCO signal pathway involves in activation,proliferation and differentiation of the γδT lymphocytes stimulated by Mtb-Ag.

Objective To evaluate the efficacy and safety of endovascular mechanical thrombectomy in patients with anterior circulation stroke. Methods PubMed, EMBASE, Cochrane database, Clinical Trials and the related supplement resources were retrieved. The randomized controled trials for comparing intravenous thrombolysis and endovascular mechanical thrombectomy in patients with anterior circulation stroke were selected. The bias risk assessment was performed. The basic characteristics of studies and the clinical outcome data at day 90, including good outcome (defined as the modified Rankin scale score 0-2), death and symptomatic intracranial hemorrhage (sICH) were extracted. Review Manager 5.3 software was used to conduct the statistical analysis. Results A total of 10 articles were enroled, including 1 557 patients in the endovascular mechanical thrombectomy group and 1 359 in the intravenous thrombolysis group. The overal quality of the included trials was higher. The risk of bias was lower. The good outcome rate in the endovascular mechanical thrombectomy group was significantly higher than that in the intravenous thrombolysis group (odds ratio [ OR] 2. 15, 95% confidence interval [ CI] 1. 34-3. 46; P < 0. 01). The death risk at day 90 was significantly lower than that in the intravenous thrombolysis group (OR 0. 86, 95% CI 0. 69-1. 06; P = 0. 16), and there was borderline statistical significance for the risk of sICH (OR 1. 35, 95% CI 1. 00- 1. 84; P = 0. 05 ). Conclusions The effectiveness of the endovascular mechanical thrombectomy is superior to the intravenous thrombolysis in patients with anterior circulation stroke;however, in terms of safety, further evaluation is needed.

Objective To explore the role of the computerized 3D reconstruction in studying the anatomy of the jugular foramen. Methods Plastination was used to make equidistant serial thin sections with 1^2*!mm in thickness.A SGI workstation was employed to reconstruct the jugular foramen and relative structures in three-dimensions. Results The computerized 3D-reconstruction could clearly display the important nerves and vessels of the jugular foramen,delineate the relationships between the internal carotid artery,internal jugular vein,the bundle of glossopharyngeal,vagus and accessory nerve and the skull base.All structures reconstructed can be represented individually or jointly and rotated continuously in any plane.Any diameter and angle of the structures reconstructed could be measured conveniently.Conclusion The computerized 3D-reconstruction possesses important value in studying the anatomy of the jugular foramen.

OBJECTIVE: To investigate the resting-state functional connectivity in patients with schizophrenia and healthy controls using multivoxel pattern analysis, and to find out the abnormal functional connectivity in patients. METHODS: Twenty two patients with schizophrenia and 22 matched controls were given resting state functional magnetic resonance brain scan. We used the high functional connectivity as features, reduced the dimensionality by 3 methods, and classified the features. RESULTS: The principal component analysis achieved the best generalization performance, whose classification rate was 86.4%. Most features were the functional connectivity within or between the visual cortex network and the pre- and post-central and temporal lobe connectivity. CONCLUSION Patients with schizophrenia can be identified with multivoxel pattern analysis based on the functional magnetic resonance imaging, and visual cortex network may play an important role in physiological explanation of the syndrome of schizophrenia.
Adolescent ; Adult ; Brain ; physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Principal Component Analysis ; Schizophrenia ; diagnosis ; physiopathology ; Signal Processing, Computer-Assisted ; Visual Cortex ; physiopathology ; Young Adult

Objective: To report a family diagnosed with Allan-Herndon-Dudley syndrome (AHDS) due to SLC16A2 gene mutation and to summarize the phenotypes, genotypes, diagnosis, treatment, and prognosis. Methods: The clinical features of a family of AHDS diagnosed in Xiangya Hospital of Central South University in November 2017 were analyzed. Related literature was searched at Online Mendelian Inheritance in Man (OMIM), PubMed, CNKI and Wanfang database (from the establishment of databases to June 2018) by using "Allan-Herndon-Dudley syndrome" , and "AHDS" as keywords and the case reports from April 2013 to June 2018 were reviewed. Results: The proband was a boy aged 8 months who presented with global developmental retardation, inability to hold up the head, disability to sit independently or grab, no language development, elongated face, big ears, esotropia, scoliosis, hypotonia in the trunk, hypertonia in extremities, and hyperreflexia. Brain magnetic resonance imaging (MRI) showed widening of the extracerebral space and delayed myelination. Thyroid function tests revealed increased FT3, decreased FT4 and normal TSH. Whole exome sequencing (WES) revealed the SLC16A2 gene c.431-1 (IVS1) G>C hemizygous mutation. The infant's mother and grandmother are carriers, but whose father had no related mutation. One uncle from maternal side had severe psychomotor retardation as well as dystonia and died at one year of age with unknown etiology. A total of 97 articles were retrieved in which 19 case reports were reviewed. Forty-two cases (22 from 8 families and 20 sporadic) were reported. Among these 42 cases (all males), all of them presented with moderate to severe cognitive dysfunction, 15 with seizures; 36 were bedridden, only 4 could walk; 31 had no language development, 2 could speak sentences, 4 could speak few words, 1 had babbling sounds. Furthermore,16 had microcephaly, 18 had facial dysmorphism, 6 had esotropia, 2 had hearing loss,14 had scoliosis, 11 had joint contracture, 30 had low body weight/muscle wasting, 37 had hypotonia in trunk or extremities, 32 had progressive spastic paraplegia or hypertonia. In terms of thyroid function, 33 had abnormal results, within whom 30 had increased T3, 25 had decreased T4 and 3 had increased TSH. Brain MRI showed delayed myelination in 22 cases, within which one normalized with development. Genetic tests showed that 31 had missense mutation (14 sporadic), 5 had deletion mutation (3 sporadic, and 1 due to frameshift mutation), 5 had insertion mutation (2 sporadic), and 1 had repeated mutation. The prognosis was poor as patients often died of recurrent respiratory tract infection. Conclusions The main clinical manifestations of AHDS are severe global developmental retardation, hypotonia, spastic paraplegia, abnormal serum levels of thyroid hormone and delayed brain myelination. SLC16A2 c. 431-1 (IVS1) G > C mutation is accountable for this disease.

Objective: To explore the relationship of sleep with C reactive protein (CRP) abnormality and hyperinsulinemia in adolescents, and to provide reference for early prevention of metabolic disorders. Methods: Based on the Chinese Metabolic Syndrome Cohort Study in Anhui Province, a total of 653 adolescents aged 12 to 19 were selected to examine the relationship between wakeup time, bedtime, sleep disordered breathing (SDB) and CRP abnormality as well as hyperinsulinemia. Results: Later wakeup time (OR=1.68, 95%CI=1.03-2.75) was positively correlated with a higher risk of fasting hyperinsulinemia. Late bedtime (OR=1.96, 95%CI=1.29-2.99) was associated with 2 h postprandial hyperinsulinemia. Among those with high CRP concentration, late wakeup time and late bedtime were positely associated with hyperinsulinemia than those with normal CRP concentration; and the correlation between SDB and hyperinsulinemia was observed. Conclusion Later wakeup and late bedtime may be risk factors for hyperinsulinemia in adolescents. High concentrations of CRP may further increase the risk of hyperinsulinemia, a condition associated with sleep problems.Teenagers should get up and go to bed as early as possible.