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Objective To explore the clinical and neuroimaging features in a Chinese family with hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) caused by mutation of the colony stimulating factor 1 receptor gene (CSF1R). Methods The proband and another patient from a HDLS pedigree were assessed respectively through standardized clinical evaluation (medical history inquiry, physical examination),neuropsychology assessment,MRI,genetic sequencing, as well as brain PET imaging with carbon11-labelled Pittsburgh compound-B(11C-PIB). Results A HDLS pedigree with three patients was recruited to this study. Apathy, memory decline, slow behavior were the first symptoms for two of the patients. Being bedridden, urinary incontinence and epilepsy were developed at the later stage. A missense mutation c. 2381T>C(p. I794T) in exon 18 of the CSF1R gene of chromosome 5 was identified in the proband. The brain DWI illustrated multiple patchy high signal in periventricular white matter and centrum semiovale which was characterized by persistence, and the corpus callosum was affected in the early stage. Conclusion The multiple patchy high signal with persistence in periventricular white matter and centrum semiovale of DWI is helpful for the early diagnosis of HDLS.
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Objective To assess the effectiveness of long-term prescriptions of hypertensive and diabetic drugs in family doctor contracted service.Methods A survey on long-term prescription in family doctor contract service was conducted from November 2015 to December 2015 in Shanghai Changning district.Ten center managers,101 family doctors and 208 contracted patients from 10 community health service centers were surveyed with 3 different types of questionnaires,respectively.The relevant information of long-term prescription,including medication information,health management,contracted service,patient's acceptance and performance status were collected and assessed.Results The 1-month and 2-month prescriptions accounted for 76.5％ (156/204) and 13.2％ (27/204),respectively.The survey showed that 87.1％ (88/101) of family doctors were willing to make long-term prescriptions;95.6％ (195/204) of patients felt convenience of long-term prescription;88.1％ (89/101) of family doctors affirmed that long-term prescriptions effectively reduced the number of re-visits;93.6％ (191/204) of patients thought that long-term prescriptions reduced the visit number and 60.8％ (124/204) thought that it reduced medical expenses.The main factors influencing family doctors' choice of long-term prescription were the stability of disease condition (72.3％,73/101),the compliance of patients (68.3％,69/101),the accurate diagnosis (50.5％,51/101) and long-term regular medication (45.5％,46/101);70.6％ (144/204) of patients thought that the hypertensive and diabetic drugs included in the tong-term prescription catalogue met their needs.Conclusion The long-term prescriptions can effectively reduce the re-visits and medical expenses of patients,which is highly recognized and accepted by both family doctors and patients.
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Objective To investigate expression of β-site APP-cleaving enzymel(BACE1) and Aβ in brain of diabetes mellitus of Wistar rats,to study pathophysiological mechanism of Alzheimer disease from diabetic metabolic disorder. Methods Animal model of diabetes mellitus was established by streptozocin with intraperitoneal injection. Wistar rats were randomly divided into normal group (N), sham-operation group (S), 4 weeks diabetes mellitus model group (M4), 6 weeks diabetes mellitus model group (M6) and 8 weeks diabetes mellitus model group (M8). Behaviour was tested with Morris water maze and shuttle box test. Expression of Aβ was measured by enzyme linked immunosorbent assay and BACE1 by immunohistochemistry, enzyme linked immunosorbent assay, Western blotting and RT-PCR. The absorbance value was measured by imaging analysis. Results The electric times and latancy of memory and study were more increased in model group than that in N and S group but the times of escape more decreased(P<0.01). The expression of Aβ_(1-40) increased from (64.13±6.76)pg/mg in normal group to (86.43±7.03)pg/mg in model group by ELISA(P<0.001) and Aβ_(1-42) from (67.43±5.12 )pg/mg in normal group to (89.45±5.28) pg/mg (P<0.001) in model group. The expression of BACE1 increased from (116.46±8.10)pg/mg in normal group to (158.73±6.24)pg/mg in model group by ELISA and from 0.61±0.11 in normal group to 1.52±0.16 by Western blotting absorbance valule and from 1.62±0.26 in normal group to 3.61±0.32 by RT-PCR absorbance valule and from 0.81±0.21 in normal group to 2.01±0.36 by immunohistochemistry absorbance valule (P<0.001). The expression of BACE1 and Aβ in MT group was higher than that of in N and S group (P<0.01). The level of BACE1 and Aβ had positive correlation with cognitive impairment.Conclusion The expression of BACE1 and Aβ is increased in diabetes mellitus rats. Diabetes mellitus contributes to Alzheimer diseases that.
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Objective To investigate the effect of phosphatidylinesitol-3 kinase/serine threonine kinase (PI3K/Akt) signaling pathway on expression of beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) in the hippocampus neurons of rat brain. Methods Forty SD rats were randomly divided into 4 groups: blank control group, sham-operated group, insulin group and wortmannin group. Insulin or the specific inhibitor of PI3K, wortmannin was injected into hippocampus neurons to activate or inhibit the signaling pathway in insulin group or wortmannin group, respectively. Immunoprecipitation and Western blot were used to analyze the proteins levels of PI3K/Akt and BACE1. Results In insulin treatment group,among the proteins downstream of signaling pathway, expression of Akt increased (0. 952±0.060 vs 0.835±0.029,t=4.9150, P=0.0001), phospho-Akt set473 increased (0.800±0.075 vs 0.657± 0.025,t=4.5598, P=0.0002), phospho-GSK-3α decreased (0.604±0.062 vs 0.726±0.041, t= 3.5871, P=0.0018 ), and the expression of mature BACE1 and β-CTF significantly decreased. In wortmannin group, the expression of Akt and phospho-Akt ser473 were inhibited; phospho-GSK-3α increased ; mature BACEI (1.004±0.096) and β-CTF (1.031±0.048) increased (t=11.5980, P= 0.0000 and t =4.2194, P =0.0004, respectively). Conclusions PI3K/Akt signaling pathway might effect the expression of BACE1, in which impaired signaling pathway may cause the amyloid precursor protein to be easily processed by BACE1, and thus involves the pathology of Alzheimer' s disease.