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 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 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 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

Clinical data of a child with high blood ammonia and suspected argininosuccinate synthetase deficiency (ASSD) in Hunan Children′s Hospital were retrospectively analyzed, including data of mass spectra for blood amino acids and acyl carnitine, urine organic acid analysis and whole exome sequencing.After the exact diagnosis of ASSD and being approved by the Administrative Regulation for Import Medical Devices Urgently Needed in Boao Lecheng International Medical Tourism Pilot Zone of Hainan Free Trade Port, the patient was medicated with Glyceryl phenylbutyrate (GPB) and followed up.The patient was a boy aged 7 years and 8 months, who presented at the Neurology Department of Hunan Children′s Hospital for sleepiness, abnormal mental behavior and personality change for 1 week on December 2, 2021.Before GPB treatment, the highest blood ammonia, alanine aminotransferase and aspartate transaminase were 325.2 μmol/L, 465.7 IU/L and 277.3 IU/L, respectively.Genetic metabolism assay of blood and urine showed a significantly increased citrulline at 697.42 μmol/L; urine organic acid analysis showed increased urinary orotic acid at 144.2 μmol/L, and increased uracil at 65.1 μmol/L.A pure heterozygous variant of the ASS1 gene (c.1087C>T, p.R363W) was detected.After GPB treatment, the blood ammonia levels were 21.3 μmol/L, 54.6 μmol/L and 62.4 μmol/L on the 41 st, 90 th and 146 th days, respectively.Until July 20, 2022 follow-up visit, the patient recovered well without adverse events.This was the first ASSD child in China who was treated with GPB.This case report provided therapeutic experience of ASSD in our country.ASSD has a high mortality rate and unexplained abnormal mental behavior.It is necessary to timely measure blood ammonia, and a series of urea cycle disorders should be well concerned.The diagnosis and management of ASSD rely on the data of metabolism examination and genetic testing.

OBJECTIVE: To explore the clinical phenotype and genetic basis of a child with early onset neurodevelopmental disorder with involuntary movement (NEDIM). METHODS: A child who presented at Department of Neurology of Hunan Children's Hospital on October 8, 2020 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was searched from the CNKI, PubMed and Google Scholar databases to summarize the clinical phenotypes and genetic variants of the patients. RESULTS: This child was a 3-year-and-3-month boy with involuntary trembling of limbs and motor and language delay. WES revealed that the child has harbored a c.626G>A (p.Arg209His) variant of the GNAO1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant had been reported in HGMD and ClinVar databases, but not in the dbSNP, ExAC and 1000 Genomes databases. Prediction with SIFT, PolyPhen-2, and Mutation Taster online software suggested that the variant may be deleterious to the protein function. By UniProt database analysis, the encode amino acid is highly conserved among various species. Prediction with Modeller and PyMOL software indicated that the variant may affect the function of GαO protein. Based on the guideline of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. CONCLUSION The GNAO1 gene c.626G>A (p.Arg209His) variant probably underlay the NEDIM in this child. Above finding has expanded the phenotypic spectrum of GNAO1 gene c.626G>A (p.Arg209His) variant and provided a reference for clinical diagnosis and genetic counseling.
Humans ; Computational Biology ; Genetic Counseling ; Genomics ; Mutation ; Neurodevelopmental Disorders/genetics* ; Dyskinesias ; GTP-Binding Protein alpha Subunits, Gi-Go