Blast-Induced Traumatic Brain Injury Triggered by Moderate Intensity Shock Wave Using a Modified Experimental Model of Injury in Mice / 中华医学杂志(英文版)

<p><b>Background</b>The increasing frequency of explosive injuries has increased interest in blast-induced traumatic brain injury (bTBI). Various shock tube models have been used to study bTBI. Mild-to-moderate explosions are often overlooked because of the slow onset or mildness of the symptoms. However, heavy gas cylinders and large volume chambers in the model may increase the complexity and danger. This study sought to design a modified model to explore the effect of moderate explosion on brain injury in mice.</p><p><b>Methods</b>Pathology scoring system (PSS) was used to distinguish the graded intensity by the modified model. A total of 160 mice were randomly divided into control, sham, and bTBI groups with different time points. The clinical features, imaging features, neurobehavior, and neuropathology were detected after moderate explosion. One-way analysis of variance followed by Fisher's least significant difference posttest or Dunnett's t 3-test was performed for data analyses.</p><p><b>Results</b>PSS of mild, moderate, and severe explosion was 13.4 ± 2.2, 32.6 ± 2.7 (t = 13.92, P < 0.001; vs. mild group), and 56.6 ± 2.8 (t = 31.37, P < 0.001; vs. mild group), respectively. After moderate explosion, mice showed varied symptoms of malaise, anorexia, incontinence, apnea, or seizure. After bTBI, brain edema reached the highest peak at day 3 (82.5% ± 2.1% vs. 73.8% ± 0.6%, t = 7.76, P < 0.001), while the most serious neurological outcomes occurred at day 1 (Y-maze: 8.25 ± 2.36 vs. 20.00 ± 4.55, t = -4.59, P = 0.048; 29.58% ± 2.84% vs. 49.09% ± 11.63%, t = -3.08, P = 0.008; neurologic severity score: 2.50 ± 0.58 vs. 0.00 ± 0.00, t = 8.65, P = 0.016). We also found that apoptotic neurons (52.76% ± 1.99% vs. 1.30% ± 0.11%, t = 57.20, P < 0.001) and gliosis (2.98 ± 0.24 vs. 1.00 ± 0.00, t = 14.42, P = 0.021) in the frontal were significantly higher at day 3 post-bTBI than sham bTBI.</p><p><b>Conclusions</b>We provide a reliable, reproducible bTBI model in mice that can produce a graded explosive waveform similar to the free-field shock wave in a controlled laboratory environment. Moderate explosion can trigger mild-to-moderate blast damage of the brain.</p>

Effect of Shouwu Shudi Yin on dopaminegic neurons in MPTP induced Parkinson's disease mouse model / 中国中药杂志

In order to investigate the effect of Shouwu Shudi Yin on dopaminegic neurons in MPTP induced Parkinson's disease mouse model and the possible mechamism, the experimental mice were randomly divided into 4 groups: control, Shouwu Shudi Yin, MPTP and the treatment (MPTP+Shouwu Shudi Yin) groups. The number of tyrosine hydroxylase (TH) positive cells in the substantia nigra was measured by immunohistochemistry, and mRNA expression of TH and glutathione peroxidase (GPX) were detected by PCR. The results showed that the number of TH positive cells and mRNA expression of TH were significantly reduced in MPTP group compared with the control (P<0.05), and pretreated with Shouwu Shudi Yin didn't show protective effect. Compared to MPTP group, the mRNA expression of four subtypes of GPX were increased in various degrees in the treatment group pretreated with Shouwu Shudi Yin, although the difference was not statistically significant. These indicated that the preventive medication of Shouwu Shudi Yin don't have protective effect on the mice with Parkinson' s disease induced by MPTP, but it may enhance the antioxidant capacity through increasing the expression of GPX.

Reprogramming of adult human neural stem cells into induced pluripotent stem cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Since an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases, here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors.</p><p><b>METHODS</b>NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients. When combined with four factors (OCT3/4, SOX2, KLF4, and c-MYC), iPSCs colonies were successfully obtained.</p><p><b>RESULTS</b>Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties, which include the ability to differentiate into all three germ layers both in vitro and in vivo.</p><p><b>CONCLUSION</b>Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.</p>

Detection of neural stem cells function in rats with traumatic brain injury by manganese-enhanced magnetic resonance imaging / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previously we had successfully tracked adult human neural stem cells (NSCs) labeled with superparamagnetic iron oxide particles (SPIOs) in host human brain after transplantation in vivo non-invasively by magnetic resonance imaging (MRI). However, the function of the transplanted NSCs could not be evaluated by the method. In the study, we applied manganese-enhanced MRI (ME-MRI) to detect NSCs function after implantation in brain of rats with traumatic brain injury (TBI) in vivo.</p><p><b>METHODS</b>Totally 40 TBI rats were randomly divided into 4 groups with 10 rats in each group. In group 1, the TBI rats did not receive NSCs transplantation. MnCl2·4H2O was intravenously injected, hyperosmolar mannitol was delivered to disrupt rightside blood brain barrier, and its contralateral forepaw was electrically stimulated. In group 2, the TBI rats received NSCs (labeled with SPIO) transplantation, and the ME-MRI procedure was same to group 1. In group 3, the TBI rats received NSCs (labeled with SPIO) transplantation, and the ME-MRI procedure was same to group 1, but diltiazem was introduced during the electrical stimulation period. In group 4, the TBI rats received phosphate buffered saline (PBS) injection, and the ME-MRI procedure was same to group 1.</p><p><b>RESULTS</b>Hyperintense signals were detected by ME-MRI in the cortex areas associated with somatosensory in TBI rats of group 2. These signals, which could not be induced in TBI rats of groups 1 and 4, disappeared when diltiazem was introduced in TBI rats of group 3.</p><p><b>CONCLUSION</b>In this initial study, we mapped implanted NSCs activity and its functional participation within local brain area in TBI rats by ME-MRI technique, paving the way for further pre-clinical research.</p>

Polymorphisms in the glutathione peroxidase-1 gene associated with increased risk of Keshan disease / 中华预防医学杂志

<p><b>OBJECTIVE</b>To assess the association of blood selenium and polymorphism of glutathione peroxidase-1 (GPx-1) genes in patients with Keshan Disease (KD) and provide genetic evidence for KD susceptibility.</p><p><b>METHODS</b>The levels of whole blood selenium and the activity of GPx-1 were measured with spectrophotometric and enzymatic method among 71 KD patients and 290 controls (including 78 internal controls and 212 external controls). The genotype of GPx-1 at 198 site was analyzed by sequencing and PCR-RFLP. The functions of two GPx-1 variants were studied by rat neonatal cardiomyocytes transfection and expression plasmid.</p><p><b>RESULTS</b>Blood level of selenium in KD patients was (0.8 ± 0.2) µmol/L, the internal controls' was (0.9 ± 0.2) µmol/L, and the external controls' was (1.2 ± 0.2) µmol/L (F = 4.888, P < 0.001).GPx-1 activity of KD patients was (73.0 ± 12.6) × 10(-10)U/RBC, internal controls' was (80.9 ± 9.2) × 10(-10)U/RBC, and external controls' was (115.8 ± 21.1) × 10(-10)U/RBC (F = 5.324, P < 0.001). Those of KD patients were significantly lower than controls. The polymorphism (Pro198Leu) of GPx-1 were identified; the frequency of Pro198Leu of KD patients was 21.1%, the frequency of controls was 10.7% (χ(2) = 5.588, P = 0.018). The level of blood selenium in variant subgroup (Pro198Leu or Leu198Leu) was (0.9 ± 0.2) µmol/L, and its in non-variant subgroup was (1.1 ± 0.3) µmol/L (t = 3.183, P < 0.01); The GPx-1 activity in variant subgroup was (86.1 ± 23.0) × 10(-10)U/RBC, and its in non-variant subgroup was (101.8 ± 25.9) × 10(-10)U/RBC (t = 5.784, P < 0.01). Further analysis revealed a synergistic-multiplicative interaction between presence of GPx-1 codon198 alleles and low blood selenium level. Over-expression of GPx-1 (198Leu) in rat cardiomyocytes caused 30% lower enzyme activity and less response to increasing concentrations of selenium than with over-expression of GPx-1 (198Pro).</p><p><b>CONCLUSION</b>Low blood selenium in carriers with the 198Leu-susceptible genotype of GPx-1 is associated with low GPx-1 activity, synergistic-multiplicative interaction was found between these two factors. And these two factors may increase the risk of KD.</p>

Investigation and analysis of Keshan disease status and associated factors in Shaanxi Province in 2006 / 中国地方病学杂志

Objective To know the prevalence tendency of Keshan disease(KSD) under control after 10 years in Shaanxi Province, the factors that causes or relative to the disease, to provide scientific reference for disease's prevention and control. Methods Through stratified cluster sampling, based on the severity of KSD in endemic area of Shaanxi Province, 12 villages from 6 counties were randomly selected as investigation points in 2006. The people older than 3 year-old were chosen to do clinical check up and electrocardiogram tracing. Among them, suspicious or abnormal cases were asked to take chest X-ray and cardiac ultrasound. Maize and rice, hair and whole blood were randomly collected to test the selenium content, the activity of Glutathione peroxidase (GSH-Px). Results The total detection rate of potential or chronic KSD was 2.44%(139/5694), the detection rate of abnormal ECG was 9.19% (523/5692), the detection rate of cardiac enlargement from chest X-ray and cardiac ultrasound were 45.6%(72/158) and 34.5%(59/171) respectively. The average content of selenium in staple foods(wheat and corn) were[(0.045±0.036), (0.035±0.025)mg/kg, respectively]. The level of hair selenium in patients and healthy people were [(0.376±0.091), (0.384±0.077)mg/kg, respectively], with non-significant different (u=0.77, P>0.05). There were significant differences in whole blood selenium of patients, healthy people in KSD areas and healthy people in non-KSD areas[(0.071±0.017), (0.077±0.017), (0.090±0.016)mg/L, respectively; F=4.55, P<0.05), the whole blood selenium in patients lower than in healthy people in KSD areas (P<0.05), in healthy people in KSD areas lower than in non-KSD areas (P<0.05). Conclusions After the KSD condition being controlled, the situation in Shaanxi Province has become stable and exhibited a decreasing tendency. The selenium level of both internal and external environment in the endemic area increased significantly, that is the main factors of controlling disease.

Electrocardiography analysis of residents in Keshan disease area in Shaanxi Province / 中国地方病学杂志

Objective To explore the Electrocardiography (ECG) changes of residents in Keshan disease area and the status of growth and decline of Keshan disease in Shaanxi Province. Methods Using stratified randomized sampling method,2 mild,2 moderate and 2 serious disease counties were selected respectively in 2005 and 2006. A total of 6 counties were sampled,2 villages,one with severe disease and one with mild,were selected from each sampled county. A total of 12 villages were selected. The clinical examination and ECG were conducted in 3-year old children of agricultural population of the selected villages. Results ECG of 5692 cases were performed in the selected 12 village in the 6 counties,in which 4917 cases showed normal electrocardiogram,up to 86.38% (4917/5692). Two hundred and fifty-two cases showed roughly normal electrocardiograms,up to 4.43%(252/5692). Five hundred and twenty-three cases had abnormal electrocardiogram,accounting for 9.19% (523/5692). Among them,the abnormal electrocardiogram rates in mild,moderate and serious disease areas were 7.07% (144/2036), 11.41%(167/1646) and 10.54%(212/2010),respectively. Atrioventricular block was the major abnormal electrocardiogram change,followed by arrhythmia,ST-T changes,and low voltage. One hundred and thirty-nine cases were confirmed as latent and chronic Keshan diseases. One hundred and thirty-one cases were latent Keshan, and detection rate was 2.30%(131/5692). Eight cases were chronic Keshan,and the detective rate was 0.14% (8/5692). Complete right bundle branch block [37.06% (63/170) ],ST-T changes [22.35% (38/170) ],multiple premature ventricular beats [12.94% (22/170)] were the major abnormal electrocardiogram change of Keshan patients. Conclusions Atrioventricular block and arrhythmia are the major abnormal electrocardiogram changes. Keshan disease incidences are controlled under a stable condition.

Measurement and analysis of blood plasma brain matriuretic peptide in Keshan disease patients / 中国地方病学杂志

Objective To investigate the relationship and clinical significance of blood plasma brain natriuretic peptide (BNP) and Keshan Disease (KD). Methods Seventy KD patients and 30 healthy volunteers in endemic area were investigated with Doppler Echocardiography for the measurement of left ventricular end-diastolic diameter(LVEDD) and left ventricular ejection fraction (LVEF), and the plasma BNP levels were determined with microparticle enzyme immunoassay. Results The BNP levels in plasma in KD patients [(444.61±102.31), (87.21±23.15)ng/L] were significantly higher than that of healthy volunteers [(34.91±15.21)ng/L],the differencesbeing statistical significant (q=39.74,5.82,P<0.01). The BNP levels in chronic KD patients were higher than that of latent KD patients (q=37.62,P<0.01). The plasma BNP levels in KD patients with LVEDD 60 nun [(928.80±134.27)ng/L] were significantly higher than those of patients with LVEDD 55～60 mm [(89.24±52.31)ng/L] and LVEDD<55 nun [(67.14±6.92)ng/L],the differencesbeing statistical significant (q=44.30,48.16, P<0.01), The plasma BNP levels in KD patients with LVEF<35%[(1654.21±421.35) ng/L] were significantly higher than those of patients with 35% ~ 50%[(421.54±112.32)ng/L] and50% [ (81.21±72.85 ng/L)], the differencesbeing statistical significant(q=24.91,72.66, P<0.01), The BNP levels in LVEF 35%～50% were higher than that of 50% (q=11.84,P<0.01). Conclusion The plasma BNP levels were important for the diagnosis, grouping, therapeutic effect and prognostic evaluation of KD.

Epigenetics and neural stem cell commitment / 神经科学通报·英文版

Neural stem cell is presently the research hotspot in neuroscience. Recent progress indicates that epigenetic modulation is closely related to the self-renewal and differentiation of neural stem cell. Epigenetics refer to the study of mitotical/meiotical heritage changes in gene function that cannot be explained by changes in the DNA sequence. Major epigenetic mechanisms include DNA methylation, histone modification, chromatin remodeling, genomic imprinting, and non-coding RNA. In this review, we focus on the new insights into the epigenetic mechanism for neural stem cells fate.

Stem cells tropism for malignant gliomas / 神经科学通报·英文版

Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas, making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells. However, little is known about the mechanisms underlying the glioma-induced tropism of stem cells. Soluble factors including chemokines or growth factors released and expressed by glioma cells at least mediate the tropism of stem cells for gliomas. Here we review the possible mechanisms of stem cells tropism for malignant gliomas.

The study on relation of HLA-DRB1 gene polymorphism to Keshan disease and its association and linkage in the core families / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate HLA-DRB1 gene polymorphism in patients with Keshan disease (KD) in the north of China, and its relation to KD in the core families.</p><p><b>METHODS</b>Polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method was used to determine HLA-DRB1 genotypes in 118 KD patients, including 63 with latent KD and 55 with chronic KD. Sixty-five normal from the same area were selected as controls. The haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) methods were used to analyze the genetic association and linkage of HLA-DRB1 with KD in 18 KD core families.</p><p><b>RESULTS</b>(1) Thirteen kinds of alleles of HLA-DRB1 gene were found in all patients and the controls. (2) The distributive frequency of DR7 allele was significantly lower in chronic KD patients than that in controls (P< 0.01, OR is 0.1695). (3) The distributive frequency of DR7 allele was statistically lower in chronic KD (P< 0.01, OR is 0.091) and showed no differences in latent KD patients as compared with the controls. (4) DR15 allele of HLA-DRB1 gene showed significant association (chi square is 9.32, P< 0.01) and linkage (chi square is 7.40, P< 0.01) with KD patients in the core families.</p><p><b>CONCLUSION</b>The results show that there might be the genetic susceptibility in the pathogenesis of KD. DR7 allele of HLA-DRB1 gene might be the protective gene of KD. Patients with DR7 allele might be more difficult to become to chronic KD. DR15 allele of HLA-DRB1 gene might be linked to the susceptive site of KD.</p>

Effect of Cleaning Intestinal Tract on Jaundice in Premature Infant / 实用儿科临床杂志

Objective To study the effect of cleaning intestinal tract on treatment jaundice in premature infants.Methods We randomly assigned 48 premature infants from January to December in 2004.In the treatment group the intestinal tract was cleaned with 30～40 mL NS once daily and 3～4 days.The through cutis bilirubin(TCB),the times of blue light,me conium exhustion and feeding toleration were recorded.Results 1.The TCB was obviously descented about 34.2 ?mol/L and the time of blue light was shortened by 20 h in treated group(P