We measured the levels of High-Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child-care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme-linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)-17, IL-6, transforming growth factor ß (TGF-ß), IL-10, and NT-proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P < .05). In patients with SPE with AHF, plasma HMGB1 was positively correlated with RAGE, Th17, Th17/Treg, IL-17, and IL-6 and was negatively correlated with TGF-ß and IL-10 (P < .05). Our findings revealed that patients with SPE with AHF had elevated levels of HMGB1 and RAGE while exhibiting Th17/Treg immune imbalance, suggesting that the abnormal expression of these indicators may be involved in the pathogenesis of SPE with AHF.
HMGB1 Protein , Pre-Eclampsia , Female , Humans , Pregnancy , Cytokines , Glycation End Products, Advanced/metabolism , HMGB1 Protein/metabolism , Hypertension/metabolism , Interleukin-10/metabolism , Interleukin-6 , Pre-Eclampsia/metabolism , Receptor for Advanced Glycation End Products/metabolism , T-Lymphocytes, Regulatory/metabolism , Transforming Growth Factor beta/metabolism
Objective:To explore the clinical characteristics of Diamond-Blackfan anemia (DBA) in children caused by RPL5 gene mutation, thus improving the understanding of the etiology of DBA.Methods:The clinical data and sequencing results of a child with DBA caused by RPL5 gene mutation treated in the Children′s Hospital of Fudan University were analyzed.In addition, through literature review of reported DBA cases at domestic and home, summarized the clinical features of DBA.Results:The patient was an 8-year-old male child.Bone marrow puncture examination of the child showed DBA, and a heterozygous mutation of RPL5 gene c. 657C>G, p.Y219X was identified for the first time in the DBA case.A total of 47 cases of DBA were retrieved from the online databases plus the one reported in this study (48 cases in total), and their clinical features were summarized as follows: the incidence of DBA was similar in men and women.The number of DBA patients in Asia was lower than that in Europe and the United States.DBA was mainly a sporadic disease.Among the exon mutations in European and American cases of DBA, 43.0% of them had mutations in Exon3.The malformation rate of DBA patients with RPL5 mutation was 81.3% (39/48 cases, excluding short stature cases), which was higher than that of patients with other mutation types.The response rate of glucocorticoid therapy for DBA was 46.0%, which was lower than that of the overall response rate.Conclusions:chr1: 93303142(c.657 C>G, p.Y219X) is a newly detected mutation of RPL5 gene in the DBA case, which expands the pathogenic gene spectrum of DBA.Patients with RPL5 mutation have higher rates of teratogenicity and multiple teratogenicity, and a lower response rate to hormone therapy.
Objective:To investigate the effects of cattle encephalon glycoside and ignotin(CEGI)on the expression of glial fibrillary acidic protein(GFAP)and neuronal nuclear antigen(NeuN)in the brain of APP/PS1 model mice of Alzheimer's disease.Methods:A total of 36 5-month-old APP/PS1 dual-transgenic model mice were randomly divided into 3 groups: the model group(normal saline 6.6 ml·kg -1·d -1), CEGI group(CEGI 6.6 ml·kg -1·d -1)and donepezil group(donepezil 2 mg·kg -1·d -1), with 12 in each group.Twelve C57BL/6J mice of the same age were used as the normal control group.All mice were given drugs for 6 weeks consecutively.Brain tissue was collected for immunohistochemical staining to detect the expression of amyloid β-protein(Aβ), GFAP and NeuN, which were then analyzed quantitatively. Results:The results of immunohistochemical staining indicated that levels of Aβ and GFAP were higher and levels of NeuN were lower in the model group than in the normal control group(0.147±0.068% vs.0%, 61.750±22.020 vs.26.000±4.598, 0.021±0.002 vs.0.032±0.003, P<0.05). Levels of Aβ and GFAP were lower and levels of NeuN were higher in the CEGI group and the donepezil group than in the model group(0.058±0.055 % vs.0.057±0.045 %, 38.250±5.418 vs.36.130±5.963, 0.029±0.004 vs.0.027±0.003, P<0.05). There was no significant difference in the expression of Aβ, GFAP and NeuN between the CEGI group and the donepezil group( P>0.05). Conclusions:CEGI has multi-target neuroprotective effects via down-regulating the expression of Aβ and GFAP and up-regulating the expression of NeuN.
Objective To study the pathological features of argyrophilic grains in normal aging brain, AD, PD and progressive superior nuclear paralysis patients. Methods Brain tissue samples taken from 5 AD, 3 PD, 2 progressive superior nuclear paralysis patients with complete clinico-pathological data and 4 normal aging brain subjects were stained with HE, Luxol fast blue and Gallyas-Braak silver respectively. Aβ, tau, α-synuclein and P62 antibodies were detected by microscopy with immunohistochemical staining. The pathological features of argyrophilic grains were recorded. Results The Gallyas-Braak silver staining showed argyrophilic grain structure in 4 out of the 14 amygdaloid nucleus tissue samples (2 from AD patients, 1 from progressive superior nuclear paralysis patients and 1 from normal aging brain patients) with a positive rate of 28.6％. The immunohistochemical staining showed positive tau and P62 antibodies. Conclusion Argyrophilic grain lesion is not uncommon in aging-related neurodegenerative diseases such as normal aging brain, AD and progressive superior nuclear paralysis and can thus produce its superposition effect on the clinical symptoms of cognitive impairment in AD and progressive superior nuclear paralysis patients.
Postsynaptic density protein 95(PSD-95) ,the most abundant and significant synapse scaffolding protein at excitatory synapses ,is a hallmark of synaptic function. Proteins palmitoylation is one of the important post-translational modifications ,which is occurred more frequently in the nervous system than in other organs. Palmitoylation-dependent regulation of PSD-95 has become a research hotspot in the fields of neuroplasticity and neuropsychiatric diseases.
Objective@#To search for biomarkers for human familial prion disease.@*Methods@#Two-dimensional differential gel electrophoresis (2D-DIGE) proteomic analysis has been performed in frontal lobe tissues of 3 patients suffering from human familial prion disease (PrP) and 3 age-and sex-matched patients suffering from sudden death due to heart failure without neurological disease.@*Results@#The maps revealed 14 polypeptide chains differentially modulated in the PrP samples, among those, 7 could be identified upon digestion and MALDI-TOF/MS analysis, of which 6 appeared to be up-regulated, 1 being down-regulated.@*Conclusions@#We highlight Galectin-1(Gal-1), ryanodine receptor 2 (RyR2), ubiquitin, Rab-interacting lysosomes protein-like protein 1 (RILPL-1) profillin 2 (PFN2), in the differential map. These proteins are related to neurogenesis, the clearance of misfolded proteins, stasis of calium channel, myoclonus and so on. These proteins are potential biomarkers or targets for treatment of prion disease.
BACKGROUND/AIMS: The relationship between C-peptide levels and gastrointestinal (GI) symptoms in type 2 diabetic patients is not clear. The purpose of this study is to examine the association between fasting C-peptide and GI symptoms of gastroparesis in type 2 diabetic patients. METHODS: We recruited 333 type 2 diabetic patients into the present study. All patients filled out questionnaires of gastroparesis cardinal symptom index (GCSI) to evaluate GI symptoms. Hospital anxiety and depression scale were adopted to define anxiety and depression. Patients with GCSI scores ≥ 1.9 were regarded as having symptoms of gastroparesis. RESULTS: In our study, 71 (21.3%) type 2 diabetic patients had GCSI scores ≥ 1.9. In comparison to patients with scores < 1.9, those with scores ≥ 1.9 had significantly lower fasting c-peptide levels (1.49 ng/mL vs 1.94 ng/mL, P < 0.001), higher prevalence of depression (40.9% vs 18.3%, P < 0.001) and anxiety (28.2% vs 13.0%, P = 0.002). Multivariate logistic regression revealed that fasting C-peptide was still significantly associated with symptoms of gastroparesis (odds ratio, 0.67; 95% confidence intervals, 0.48–0.94; P = 0.021), even after adjustments for age, sex, body mass index, HbA1c, current smoking and drinking status, anxiety, and depression. Furthermore, linear regressions showed that fasting C-peptide was independently and negatively related to GCSI scores (standardized regression coefficient, −0.29; P < 0.001) in patients with at least one GI symptom. CONCLUSION: GI symptoms of diabetic gastroparesis affect approximately 20% of type 2 diabetes patients and are associated with lower fasting C-peptide levels independent of depression and anxiety status.
Humans , Anxiety , Anxiety Disorders , Body Mass Index , C-Peptide , Depression , Depressive Disorder , Diabetes Mellitus , Drinking , Fasting , Gastroparesis , Linear Models , Logistic Models , Prevalence , Smoke , Smoking
<p><b>OBJECTIVE</b>To investigate histopathology and proteinopathy in the spinal cord of patients with common neurodegenerative diseases.</p><p><b>METHODS</b>Spinal cord tissues from clinically and neuropathologically confirmed neruodegnerative diseases were enrolled in this study, including 3 cases of multiple system strophy, 4 cases of amyotrophic lateral sclerosis, 5 cases of Alzheimer's disease (AD, included 2 cases of AD combined with Parkinson's disease), 2 cases of progressive supranuclear palsy, 1 case of dementia with lewy body and 1 case of corticobasal degeneration from 1955 to 2013 at Chinese People's Liberation Army General Hospital. Four normal control cases were also included. Routine HE and Gallyas-Braak staining, and immunohistochemical stainings for anti-PHF tau (AT8), anti-α-synuclein, anti-TDP-43 and anti-ubiquitin were performed.</p><p><b>RESULTS</b>Examination of the spinal cord in 3 cases with multiple system strophy revealed severe neuron loss in the intermediolateral nucleus of thoracic segment and Onuf's nucleus of the sacral segment, along with moderate neuron loss in the anterior horn of the cervical segment and mild myelin pallor in the anterior funiculus and anterolateral funiculus in the cervical and thoracic segments. Large amount of argentophilic, ubiquitin and synuclein positive oligodendroglial cytoplasmic inclusions were found widely distributed in the anterior horn and the anterior funiculus and anterolateral funiculus of the full spinal cord. Severe neuron loss and several morphological changes with gliosis in the anterior horn and severe loss of myelin in the anterior funiculus and anterolateral funiculus of the full spinal cord were observed in 4 cases of amyotrophic lateral sclerosis, 2 of which were found with Bunina bodies in neurons of the anterior horn. Three amyotrophic lateral sclerosis cases had ubiquitin-positive neuronal inclusions and TDP-43 positive neuronal and glial inclusions in the anterior horn at cervical and lumbar segments. A few argentophilic, tau positive neurofibrillary tangles (NFTs) and neuropil threads in the anterior horn at cervical and lumbar segments were found in 4 AD cases. Examination of spinal cord in 2 cases with Parkinson's disease combined with AD and 1 case with dementia with lewy body revealed severe neuron loss in the intermediolateral nucleus of thoracic segment, and a few synuclein positive lewy bodies and neuritis were also observed. There was mild neuron loss in the anterior horn at cervical and lumbar segments, along with some argentophilic, tau positive globous NFTs and many argentophilic, tau positive neutrophil threads were observed in 2 progressive supranuclear palsy cases and 1 corticobasal degeneration case.</p><p><b>CONCLUSION</b>Each common neurodegenerative diseases of the spinal cord including multiple system strophy, amyotrophic lateral sclerosis and Parkinson's disease has its own specific histopathology and proteinopathy characteristics.</p>
Humans , Alzheimer Disease , Pathology , Amyotrophic Lateral Sclerosis , Pathology , DNA-Binding Proteins , Metabolism , Immunohistochemistry , Inclusion Bodies , Pathology , Neurodegenerative Diseases , Pathology , Neurofibrillary Tangles , Pathology , Neurons , Pathology , Parkinson Disease , Pathology , Spinal Cord , Pathology , Ubiquitin , Metabolism , alpha-Synuclein , Metabolism
Objective To study the effect of revised trauma score (RTS) in the rescue of patients with multiple trauma emergency application. Methods According to the admission time, 56 multiple trauma patients were assigned into the control group, and another 58 into the observation group. The control group was treated with traditional pre-hospital and hospital emergency care. The observation group with pre-hospital emergency care and hospital based on the RTS results. The two groups were compared in terms of effective treatment time and complications. Result The effective rescue time of the observation group was significantly shorter than that of the control group (P<0.001) and the complication rate was significantly lower than that of the control group (P<0.05). Conclusion Based on the integrated emergency rescue measures on the basis of RTS scores, accurate condition judgment can be made in a short time so that consistent care can be given to the patients and the success rate can be improved , and the occurrence of complications can be reduced and the rescue success rate can be increased.
Objective To investigate the change of genomic DNA of liver and spleen tissue for different age of the elderly,and provide the experimental data for aging-related research. Methods 35 livers and 33 spleens of autopsied samples preserved in refrigerator at-80 ℃ were divided into 3 groups according to age:age 65y to 79y,age 80y to 89y,age≥90y. The content of DNA in liver and spleen was determined by ultraviolet absorbent method. Results Compaired with age 80y to 89y (0. 310 ± 0. 286)mg/mL,the content of DNA in liver was significant higher at age 65y to 79y (1.464 ±0.488)mg/mL and age ≥90y(1.147 ±0.333)mg/mL(P<0.05);Compared with age 80y to 89y(0. 938 ± 0. 589)mg/mL,the content of DNA in spleen was significant higher at age 65y to 79y(1. 723 ± 0. 726)mg/mL and age≥90y(1. 688 ± 0. 963)mg/mL(P<0. 05). The content of DNA was significant lower in liver (0. 856 ± 0. 658)mg/mL than that in spleen (1. 414 ± 0. 852)mg/mL. Conclusion The content of DNA in human liver and spleen tissue may be decrease along with aging. The content of DNA in the group at age≥90y may be increase. There were some differences between different viscera tissue in content of DNA.
Objective:To analyze the expression profile of miRNA-34c in cervical cancer tissue and identify its novel target gene. Methods:The expression levels of miRNA-34c were detected in 34 paired cervical cancer tissues and normal paraneoplastic tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Polo-like kinase 4 (PLK4) is a target gene of miRNA-34c pre-dicted in the miRNA Target Database. Luciferase vector containing the binding site of miRNA-34c to PLK4 3'UTR and miRNA-34c mimic or negative control were co-transfected into HEK293T cells, and luciferase expression was examined. The miRNA-34c mimic or negative control was transfected into SiHa cells, and the mRNA or protein expression of PLK4 was detected via qRT-PCR or Western blot, respectively. Results:MiRNA-34c expression was lower in cervical cancer tissues than in normal paraneoplastic tissues. The miR-NA-34c mimics significantly inhibited luciferase activation in the HEK293T cells (P<0.01) and significantly decreased the mRNA and protein expression levels of PLK4 in the SiHa cells (P<0.01). Conclusion:MiRNA-34c is significantly decreased in cervical cancer tis-sues. Moreover, miRNA-34c can significantly repress the mRNA and protein expression levels of PLK4 by directly targeting the 3'UTR.
Objective To establish a new method to analyze the position accuracy of multileaf collimator (MLC) in the dynamic mode.Methods The MLC test sequence was created in a field,where intentional leaf positional errors ranging from 0.1 to 1 mm per centimeter were introduced.In order to establish the relationship between the ion chamber readings and leaf position,whose slope indicated the leaf position error per centimeter,a two-dimensional ion chamber array was used to measure absorbed dose while leaves were moving at dose rates of 100,300 and 600 MU/min,respectively.For routine test,leaf position error was easily found via dose profile in y direction of the field created by dynamic leaves,where the position error could be quantitatively calculated as the slope of absorbed dose line of x direction of the same field.Results The error of 0.2 mm or more per centimeter was obviously shown through y dose profile.The calibration curve was linear at different dose rates.At 600 MU/min,a 0.1 mm leaf position error corresponded to a slope variation of 0.74％,and the differences between the tested errors and the introduced errors were within 0.1 mm.Conclusions The simple and reliable method is helpful to establish the intensity modulated radiation therapy (IMRT) quality control (QC) system.
<p><b>OBJECTIVE</b>To recognize relationship of protein related neurodegeneration abnormal aggregation in the aged brains with their cognitive and motor functions.</p><p><b>METHODS</b>Brain tissues from the consecutive autopsy cases of the aged from January 2005 to December 2006 in PLA General Hospital were carried out for immunohistochemical staining with beta amyloid, tau, α-synuclein and ubiquitin antibodies. The consortium to establish a registry for Alzheimer's disease (CERAD) was used to semi-quantitatively analyze Aβ positive core plaques density and Braak staging for tau positive neurofibrillary tangles (NFTs) and α-synuclein positive Lewy bodies. In addition, Aβ positive cerebral amyloid angiopathy (CAA), neuritic plaques and various ubiquitin positive structures were also observed. The relationship of these protein abnormal depositions in the aged brains with cognitive and motor functions were analyzed.</p><p><b>RESULTS</b>In brain tissues of 16 consecutive autopsy cases of the aged from 78 to 95 years, there were 13 cases with Aβ positive core plaques, their density was 2 cases with sparse, 2 cases with moderate and 9 cases with frequent, respectively, according to CREAD.Eight cases with Aβ positive CAA were found, including 6 cases of mild CAA and 2 cases of severe CAA. There were 12 cases with tau positive NFTs, including 6 cases with Braak stageI-II, 4 cases with stage III-IV and 2 cases with stage V-VI. There were 5 cases with frequent Aβ core plaques, meanwhile existing numerous tau/ubiquitin positive neuritic plaques and Braak stage IV-VI of tau positive NFTs, all of them presented cognitive dysfunction. Among 4 other cases with frequent Aβ core plaques, only one case coexisted α-synuclein positive Lewy bodies showed moderate cognitive impairment, remaining 3 cases did not present cognitive dysfunction. There were 4 cases with α-synuclein positive Lewy bodies in the brainstem, and all of these cases presented parkinsonian motor dysfunction. 13 cases with ubiquitin positive structures were found.</p><p><b>CONCLUSIONS</b>Beta amyloid protein positive deposit in the aged brain is an important marker of normal brain aging and cognitive impairment; frequent Aβ core plaques in the neocortex plus Braak IV and above tau positive NFTs are closely related to cognitive dysfunction of Alzheimer's disease; α-synuclein positive Lewy bodies in the brainstem is one of the important pathological markers of parkinsonian motor disorders; ubiquitin deposition involves the development of some characteristic structures of several neurodegenerative diseases.</p>
Aged , Humans , Alzheimer Disease , Metabolism , Pathology , Amyloid beta-Peptides , Autopsy , Brain , Pathology , Brain Chemistry , Cerebral Amyloid Angiopathy , Neurofibrillary Tangles , Chemistry , Pathology , Plaque, Amyloid , Ubiquitin , alpha-Synuclein , tau Proteins
<p><b>OBJECTIVE</b>To assess the association of vitamin D receptor (VDR) gene Fok I and Bsm I polymorphisms with dyslipidemia in elderly male patients with type 2 diabetes of Han nationality.</p><p><b>METHODS</b>A total of 328 elderly male residents of Han nationality in Beijing, including 237 type 2 diabetic patients and 91 healthy control subjects, were enrolled in this study. The diabetic patients were divided into non-dyslipidemia group (DO group, n=134) and dyslipidemia group (DH group, n=103). All the participants were genotyped for Fok I and Bsm I polymorphisms in VDR gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing technology, and the results were compared with their clinical characteristics.</p><p><b>RESULTS</b>For Fok I, the frequency of F allele was significantly higher in the diabetic patients than in the control group (Χ(2)=3.873, P=0.049, OR=1.439, 95% CI: 1.001-2.071). In the dominant model, the frequency of FF genotype was significantly higher in the diabetic group (Χ(2)=5.057, P=0.025, OR=1.756, 95% CI: 1.072-2.875) as well as in DH group (Χ(2)=6.168, P=0.013, OR=2.06, 95% CI: 1.161-3.663) than in the control group. There was no significant differences in the genotype frequency or allele distribution in other paired groups (P>0.05). Compared with Ff + ff genotype, FF genotype was associated with a significantly decreased average diastolic blood pressure (P=0.039) but significantly increased postprandial blood glucose (P=0.035), triglycerides (P=0.049) and uric acid (P=0.031). No significant difference was detected in genotype frequency or allele distribution of Bsm I polymorphisms between the groups (P>0.05); serum creatinine levels were significantly higher in bb genotype than in BB + Bb genotype group (P=0.011).</p><p><b>CONCLUSION</b>VDR gene Fok I polymorphisms may be a risk factor for dyslipidemia in elderly male patients with type 2 diabetes among Chinese Han population, where Bsm I polymorphisms are not associated with diabetic dyslipdiemia.</p>
Aged , Humans , Male , Alleles , Blood Glucose , Blood Pressure , Case-Control Studies , Diabetes Mellitus, Type 2 , Genetics , Dyslipidemias , Genetics , Ethnicity , Genotype , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Receptors, Calcitriol , Genetics , Risk Factors , Triglycerides , Blood
Objective To investigate the condition of nutrition in child with cerebral palsy (CP) and the effect of nutritional intervention. Methods 49 CP children and other 60 health children (controls) were measured their bodies, hemoglobin, serum trace elements, and bone mineral density (with ultrasonic), and the feeding behavior was also investigated. Results The incidence of malnutrition was 48.97%, in which 26.53%for low weight. The levels of serum iron and zinc were poor in the CP children, and the incidence of iron deficiency anemia was 34.67%in the CP children, different from the controls (P0.05). Feeding problems were found in 44.9%of CP children. About 50%of malnutrition was cor-rected, especially the body weight after 4 months of Intervention, with anemia corrected in 88.2%, and bone mineral density recovered in 50%. Conclusion It is a problem for many CP children with malnutrition and nutritional disorders, and need nutrition intervention as the content of the rehabilitation.
<p><b>OBJECTIVE</b>To investigate the effect of intensive rosuvastatin therapy on adhesion molecules in patients with peripheral atherosclerosis and explore the possible upstream mechanism.</p><p><b>METHODS</b>Twenty asymptomatic patients with peripheral atherosclerosis were enrolled and given 5-20 mg/day rosuvastatin for 3 months. Before and after the treatment, the lipid profile and plasma vascular cell adhesion molecule-1 (VCAM-1) levels were examined. The expression of intercellular adhesion molecule-1 (ICAM-1) in the mononuclear cells was measured using flow cytometry, and the mRNA and protein expressions of peroxisome proliferator-activated receptor γ (PPARγ) were detected using RT-PCR and Western blotting, respectively.</p><p><b>RESULTS</b>Compared with the baseline levels, ICAM-1 expression decreased and PPARγ protein expression increased in the lymphocytes. Rosuvastatin therapy did not produce obvious effects on plasma VCAM-1 level or ICAM-1 expression in the monocytes in these patients.</p><p><b>CONCLUSION</b>Rosuvastatin produces anti-inflammatory effects by decreasing the expression of ICAM-1 in mononuclear cells, and its upstream mechanism may involve the PPARγ pathway.</p>
Female , Humans , Male , Middle Aged , Atherosclerosis , Drug Therapy , Metabolism , Cell Adhesion Molecules , Metabolism , Fluorobenzenes , Therapeutic Uses , Intercellular Adhesion Molecule-1 , Metabolism , Monocytes , Metabolism , PPAR gamma , Metabolism , Pyrimidines , Therapeutic Uses , Rosuvastatin Calcium , Sulfonamides , Therapeutic Uses , Vascular Cell Adhesion Molecule-1 , Metabolism
Gamma-glutamyl hydrolase (GGH) plays an important role in methotrexate (MTX)polyglutarmation. High level of GGH has been associated with cellular resistance to MTX. Recent studies have demonstrate that some polymorphisms of GGH could change the expression and catalytic activity of the enzyme,causing interindividual difference in MTX cytotoxicity. No study about GGH was reported in Chinese population. This paper reviewed the advances about the structure and function of GGH and its gene, and the advances in associations between polymorphisms of GGH and MTX sensitivity.
Objective To study the neuropathological characteristics of late-onset Alzheimer' s disease (LOAD) in Chinese people, to ensure correct diagnosis of LOAD.Methods Choosing cerebral cortex of temporal layer of 8 cases of LOAD and 5 cases of age-matched normal control group by autopsy.Histopathologlc diagnosis was established in all these 13 cases.Cerebral cortex were taken from temporal layer in 13-101 hours after death and were fixed with 40 g/L paraformaldehyde, followed by paraffin-embedding and serial sectioning with 6 μm thickness.Brain tissue was analyzed neuropatholically by using immunohistochemical staining for β-amyloid (Aβ) and AT8 on these cases.Positive distribution of temporal layer was observed under light microscope.Results The results of immunohistochemical stainings of Aβ and AT8 were positive in all of LOAD.Aβ immunoreactant located in the cerebral cortex.The diffuse plaques, primitive plaques and burn-out plaques of senile plaques were displayed clearly by immunohistochcmical stainings of Aβ.AT8 immunoreactants showed neurofibrillary tangles, neuropil thread and senile plaques in nerve cell of cerebral cortex in different degree respectively.The positive rate Aβ and AT8 were both 8/8 by semiquantitative analysis in AD group.As the normal aging control group, which was 0 and 1/5 respectively.There was significant difference of the positive rate Aβ and AT8 in two groups(χ2 = 13.000,P=0.001; χ2=9.244,P=0.007).Conclusions Sensitive immunnhistochemical technique was significant to display senile plaques and neurofibrillary tangles.The findings demonstrate that immunohistochemistry staining of Aβ and AT8 can display senile plaques and neurofibrillary tangles clearly.The connection of the 2 different methods might improve diagnose accordance rate of AD.
@#Objective To investigate the effect of anisodamine on calbindin-D28K(CaBP) expression in the ethanol-induced brain damage in rat cerebellum.Methods2 months aged male Sprague-Dawley rats were injected intraperitoeally with ethanol,normal saline,saline+anisodamine and ethanol+anisodamine respectively for 8 d.They were evaluated with Morris water maze.The counts,average area and density of CaBP positive neurons in cerebellum were measured with immunohistochemical technique and image analytical system.Results The latency of Morris water maze was significantly longer in the ethanol group than in the others(P<0.05),while the distance was significantly longer in the ethanol group than in the saline group and saline+anisodamine group(P<0.05).There is not significant difference between ethanol group and ethanol+anisodamine group(P>0.05),but is seemed some longer.The counts,average area and density of CaBP positive Purkinje cell were all significantly less in ethanol group than in the others(P<0.05).There Pwas not significant difference among ethanol+anisodamine group,saline group and saline+anisodamine group(P>0.05) in the counts,but the average areas and density in ethanol+anisodamine group were less than those in saline group and saline+anisodomine group(P<0.05).Conclusion The ethanol can reduce the CaBP expression in the Purkinje cells of the rats cerebellum.Anisodamine can protect the rats cerebellum from it.
BACKGROUND: It is found reported that polymorphism of Fok 1 restriction endonuclease cut site on exon 2 of 5' end start codon of 5' end start codon (SC), which affected the structure of VDR amino acids,and was relative related to bone mineral density(BMD).OBJECTIVE: To analyze the association between Vitamin D receptor gene (Fok 1) polymorphisms and osteoporosis in the elderly men.DESIGN: case-controlled trialstudy.SETTING: Institute of Gerontology, Chinese PLA General Hospital and Department of Endocrinology,Second Artillery General Hospital of Chinese PLA.PARTICIPANTS: A total of 26 elderly men with osteoporosis at out-patients clinic of Chinese PLA General Hospital and Department of Endocrinology,Second Artillery General Hospital of Chinese PLA from January 2002 to June 2002 were selected involved as osteoporosis case group,with and the average age of was (70±5) years, and BMD in osteoporosis group was 2.0-2.5 SD lower than 2.0-2.5 SD of the peak of BMD. Totally 66 healthy men with average age of (70±5)years were selected as control group during at the same time. All the subjects signed the informed consent,who were Beijing inhabitants of Han nationality, and there was no blood relationship among them.METHODS:VDR-Fok1 genotypes in both groups were detected with by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),and distributiondistribution of VDR-Fok 1 genotypes were analyzedanalyzed.MAIN OUTCOME MEASURES: distribution Distribution of VDR-Fok1genotypes in both each groups.RESULTS: Totally 66 healthy elderly men and 26 elderly men with osteoporosis entered analysis of results. The frequencies of FF, Ff and ff genotype were found to be 42%, 42% and 15% in control group, and 15%,50%,35% in osteoporosis group, respectively,and there was significantly different between two groups(x2=12.078,P ＜ 0.01).Frequency of allele were significantly different between control group and osteoporosis group (64%,36% vs 40%,60%, x2=8.232,P ＜ 0.01).CONCLUSION: There is a significant difference in the frequency distrinution of VDR gene start codon polymorphism between healthy elderly men and those with osteoporosis.
