Hippocampus chronic deep brain stimulation induces reversible transcript changes in a macaque model of mesial temporal lobe epilepsy / 中华医学杂志(英文版)

BACKGROUND@#Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level.@*METHODS@#We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses.@*RESULTS@#The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance.@*CONCLUSION@#Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.

Effect of Reduction in Iodine Content of Edible Salt on the Iodine Status of the Chinese Population / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The aim of this study was to evaluate the impact of the revised Chinese National Standard GB26878-2011 'Iodine Content in Edible Salt' on the iodine status among the Chinese population.</p><p><b>METHODS</b>In 2011 and 2014, the probability proportionate to size sampling (PPS) was used in each Chinese province to obtain the representative data. In each sampling unit, school children aged 8-10 years and pregnant women were selected. Key indicators included urinary iodine concentration (UIC), thyroid volume (TV), and the iodine content in edible household salt.</p><p><b>RESULTS</b>The median urinary iodine concentration (MUIC) decreased between 2011 and 2014 from 238.6 to 197.9 µg/L in school-age children. The number of provinces with iodine excess decreased to zero. The proportion of children whose UIC was > 300 µg/L was 18.8% and decreased to 11% compared with 29.8% in 2011. There was no significant difference in UIC < 50 µg/L between 2014 (4.3%) and 2011 (3.7%) (P > 0.05). The MUIC among pregnant women in 2014 was more concentrated between 110 and 230 µg/L. The goiter rate among children aged 8-10 years was unchanged, both the goiter rate of 2011 and 2014 remaining below 5%, in view of the sustainable elimination of iodine deficiency disorders.</p><p><b>CONCLUSION</b>The National Standard GB26878-2011 'Iodine Content in Edible Salt' that was introduced in March 2012 resulted in an overall improvement in iodine status, reducing the risk of excessive iodine intake in the Chinese population.</p>

Serum Thyroglobulin-A Sensitive Biomarker of Iodine Nutrition Status and Affected by Thyroid Abnormalities and Disease in Adult Populations / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the usefulness of the thyroglobulin (Tg) level in adults as a nutritional biomarker of iodine status and to identify the factors related to the serum Tg level.</p><p><b>METHODS</b>A cross-sectional study was conducted in adult populations of areas differing in iodine nutrition from three provinces (Autonomous Region) in China. Serum levels of thyroid hormones and Tg as well as thyroid autoantibodies were measured. The thyroid volume and nodule were measured by ultrasound. A multivariate linear regression analysis was used to assess iodine intake and other indeterminate factors associated with the serum Tg level.</p><p><b>RESULTS</b>A total of 573 adults were recruited for this study. The serum Tg levels differed significantly among the three groups (22.27 μg/L, 9.73 μg/L and 15.77 μg/L in the excess, more-than-adequate, and deficient groups, respectively). The results of multivariate linear regression analysis indicate that excess and deficient iodine intake, goiter, thyroid nodule, hypothyroidism are significantly related with higher Tg level, and TgAb positivity is significantly related with lower serum Tg.</p><p><b>CONCLUSION</b>The serum Tg level reflects abnormal thyroid function and is a sensitive functional biomarker of iodine nutrition status.</p>

Vagus Nerve Stimulation for Pediatric and Adult Patients with Pharmaco-resistant Epilepsy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Over past two decades, vagus nerve stimulation (VNS) has been widely used and reported to alleviate seizure frequency worldwide, however, so far, only hundreds of patients with pharmaco-resistant epilepsy (PRE) have been treated with VNS in mainland China. The study aimed to evaluate the effectiveness of VNS for Chinese patients with PRE and compare its relationship with age cohort and gender.</p><p><b>METHODS</b>We retrospectively assessed the clinical outcome of 94 patients with PRE, who were treated with VNS at Beijing Fengtai Hospital and Beijing Tiantan Hospital between November 2008 and April 2014 from our database of 106 consecutive patients. The clinical data analysis was retrospectively examined.</p><p><b>RESULTS</b>Seizure frequency significantly decreased with VNS therapy after intermittent stimulation of the vagus nerve. At last follow-up, we found McHugh classifications of Class I in 33 patients (35.1%), Class II in 27 patients (28.7%), Class III in 20 patients (21.3%), Class IV in 3 patients (3.2%), and Class V in 11 patients (11.7%). Notably, 8 (8.5%) patients were seizure-free while ≥50% seizure frequency reduction occurred in as many as 60 patients (63.8%). Furthermore, with regard to the modified Engel classification, 12 patients (12.8%) were classified as Class I, 11 patients (11.7%) were classified as Class II, 37 patients (39.4%) were classified as Class III, 34 patients (36.2%) were classified as Class IV. We also found that the factors of gender or age are not associated with clinical outcome.</p><p><b>CONCLUSIONS</b>This comparative study confirmed that VNS is a safe, well-tolerated, and effective treatment for Chinese PRE patients. VNS reduced the seizure frequency regardless of age or gender of studied patients.</p>

Brain stimulation for treatment of refractory epilepsy / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>We review the targets of the deep brain and the responsive neurostimulation system (RNS) to identify the best optimal stimulation parameters and the best mode of stimulation, whether cyclical, continuous, or smarter.</p><p><b>DATA SOURCES</b>This review is based on data obtained from published articles from 1950 to 2013. To perform the PubMed literature search, the following keywords were input: deep brain stimulation (DBS), RNS, and refractory epilepsy.</p><p><b>STUDY SELECTION</b>Articles containing information related to brain stimulation or RNS for the treatment of refractory epilepsy were selected.</p><p><b>RESULTS</b>The currently available treatment options for those patients who resist multiple antiepileptic medications and surgical procedures include electric stimulation, both direct and indirect, of brain nuclei thought to be involved in epileptogenesis. The number of potential targets has increased over the years to include the anterior nucleus of the thalamus, the centromedian nucleus of the thalamus, the hippocampus, the subthalamic nucleus, the caudate nucleus, and the cerebellum, among others. The results of a randomized controlled trial and the RNS trial were published to reveal the effectiveness.</p><p><b>CONCLUSIONS</b>Although statistically significant reductions in seizures have been observed using several different stimulation techniques, including vagus nerve stimulation, DBS, and RNS, these effects are currently only palliative and do not approach the efficacy comparable with that seen in resection in appropriately selected patients. More research is needed to determine optimal stimulation targets and techniques as well as to determine which epilepsy patients will benefit most from this technology.</p>

Inhibition of the reinstatement of morphine-induced place preference in rats by high-frequency stimulation of the bilateral nucleus accumbens / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery. Many studies have identified a central role of the nucleus accumbens (NAc) in addiction. Deep brain stimulation (DBS) has the advantages of being reversible, adjustable, and minimally invasive, and it has become a potential neurobiological intervention for addiction. The purpose of our study was to investigate whether high-frequency DBS in the NAc effectively attenuates the reinstatement of morphine seeking in morphine-primed rats.</p><p><b>METHODS</b>A morphine-dependent group of rats was given increasing doses of morphine during conditioned place preference training. A control group of rats was given equal volumes of saline. After the establishment of this model, withdrawal syndromes were precipitated in these two groups by administering naloxone, and the differences in withdrawal symptoms between the groups were analyzed. Electrodes for DBS were implanted in the bilateral shell of the NAc in the experimental group. The rats were stimulated daily in the NAc for 5 hours per day over 30 days. Changes in the conditioned place preference test and withdrawal symptoms in the rats were investigated and place navigation studies were performed using the Morris water maze. The data were assessed statistically with one-way analysis of variance (ANOVA) followed by Tukey's tests for multiple post hoc comparisons.</p><p><b>RESULTS</b>High-frequency stimulation of the bilateral NAc prevented the morphine-induced reinstatement of morphine seeking in the conditioned place preference test. The time spent in the white compartment by rats following 30 days of DBS ((268.25 ± 25.07) seconds) was not significantly different compared with the time spent in the white compartment after relapse was induced by morphine administration ((303.29 ± 34.22) seconds). High-frequency stimulation of the bilateral NAc accelerated the innate decay of drug craving in morphine-dependent rats without significantly influencing learning and memory.</p><p><b>CONCLUSION</b>Bilateral high-frequency stimulation of the shell of the NAc may be useful as a novel therapeutic modality for the treatment of severe morphine addiction.</p>

Investigation of state and influence factors of children's Kaschin-Beck disease in Xinghai county of Qinghai province in 2009 / 中国地方病学杂志

Objective To investigate the present prevalence state of children's Kaschin-Beck disease (KBD) in Xinghai county of Qinghai province,a relative active KBD area in 2009,and to investigate their nutritional selenium level of local children and the T-2 toxin contamination level in their staple food.Methods Right hand X-ray photographs of children aged 7 - 12 in Shang,Zhong and Xia villages of Tangnaihai countryside in Xinghai county were taken.X-ray diagnosis was carried out according to the Diagnostic Criteria of Kashin Beck Disease (GB 16003-1995 ).Selected samples (children's hair,drinking water and their staple food) were collected according to X-ray film taken.Selenium contents in hair,drinking water and staple food samples were measured by 2,3-diaminonaphthalene fluorescence,and T-2 toxin in staple food sample was detected with enzyme-linked immunosorbent assay(ELISA) kits.ResultsTotal X-ray detection rate of children KBD was 12.20％(31/254) and KBD positive rate of children in Xia village was up to 14.97％(22/147),Shang village was up to 9.52％(6/63),and Zhong village was up to 6.82％ (3/44).The selenium level in children's body and outer environment was very low,namely,the selenium content in hair,drinking water,wheat and flour was (0.250 ± 0.136)mg/kg,(0.156 ± 0.046)μg/L,(0.0045 ± 0.0030)mg/kg,and (0.0067 ± 0.0116)mg/kg,respectively.The T-2 toxin level was relatively high in children's staple food,which was (78.91 ± 46.17)μg/kg in wheat and (47.47 ± 46.47)μg/kg in flour.Conclusions In relative active KBD areas of Xinghai county of Qinghai province,the children's selenium nutritional level is low,and the T-2 toxin contamination level in their staple food is relatively high,which is consistent with the distribution of local children's KBD.

Morphology damages of rat articular cartilage induced by different doses of T-2 toxin / 中国地方病学杂志

Objective To study the damage of rat articular cartilage induced by different doses of T-2 toxin, and to explore the relationship between mini-dose T-2 toxin and articular cartilage damage. Methods A total of 120 Wistar rats, weighing 50 - 70 g, were randomly divided into four groups according to their body weights: T-2 toxin group 0(control), 100, 200, 300 μg/kg, 30 rats in each group. Animals in the control group were fed standard rat chow, and animals in the three T-2 toxin groups were fed T-2-toxin-contaminated chow (the dose was 100, 200, 300 μg/kg, respectively). After 6 months, rats were euthanized by ether asphyxiation. The bilateral knee joints were collected and section prepared. The articular cartilage was examined by light and electronic microscope. Results Light microscope showed, the rat articular chondrocytes were clear and arranged orderliness in the control group. The rat articular chondrocytes were disarranged in 100 μg/kg T-2 toxin group.Degeneration and necrosis were found in 200 μg/kg group. Chondrocytes were shrunken with hypereosinophilia cytoplasm and fragmented pyknotic nuclei, extensive areas of chondrocyte loss and chondrocyte clones were visible in 300 μg/kg group. Scanning electronic micrograph(SEM) showed, the rat articular chondrocytes were clear, well formed and arranged tidy in the control group. The surface of articular cartilage was rough in 100 μg/kg group.Collagen fasciculi ruptured and stacked up in 200 μg/kg group. Presented a typical articular dryness phenomenon,the cartilage surface collapsed and many pits appeared in 300 μg/kg group. Transmission electronic microscope (TEM) showed that chondrocytes were abundant with cytoplasm, well-developed rough endoplasmic reticulum in the control group; agglomerate chromatin scattered along the karyotheca, nuclear membrane was thickening, with vacuolar degeneration of the endoplasmic reticulum in the 100 μg/kg group; endoplasmic reticulum expended, with protein retention and organelles breaks in the 200 μg/kg group. A large number of chondrocytes lost organdles, the membrane structures disrupted and the cartilage matrix stromatolyzed in the 300 μg/kg group. Conclusions Within the range of 100 - 300 μg/kg, T-2 toxin induces dose-related articular cartilage injury, the greater the dose, the more serious damage.

Temporal lobe epilepsy with hypothalamic hamartoma: a rare case / 中华医学杂志(英文版)

Refractory gelastic seizure is one of the most common clinical manifestations in patients with hypothalamic hamartoma (HH) and HH is usually regarded as the epileptogenic focus. A young female patient with a small HH and refractory seizures is reported here. However, both the seizure semiology and results of electroencephalogram monitoring indicated the right temporal region was the epileptogenic focus. Thus a standard right anterior temporal lobectomy was performed while the hamartoma preserved. There was a marked improvement in both seizure frequency and quality of life during a 13-month follow-up. The outcome supported the concept that independent epileptogenic focus outside of the hypothalamus might occur in patients with HH.

Investigation on the selenium and T-2 toxin level in Kaschin-Beck disease relative active regions in Aba state of Sichuan province in 2008 / 中国地方病学杂志

Objective To investigate the children's body environmental Se and T-2 toxin level in their staple food in Kaschin-Beck disease(KBD)relative active regions in Aba state of Sichuan province in 2008.Methods We took X-ray photograph of the right hand on children aged 7-13 years in 48 villages from 11 counties in Aba state.The relative active regions of KBD were chosen according to the X-ray result and historical status of KBD.The children's urine and hair,drinking water and their staple food werr sampled.Selenium contents in urine,hair,water and food samples were determined by naphthalene fluorescence,and T-2 toxin in staple food samples were detected by ELISA kits.Results In 2145 X-ray films,66 films were positive,and the children's KBD positive rate was 3.08%(66/2145).The KBD positive rate was respectively 10.98%(29/264)and 8.52%(19/223)in Maerkang county,Jinchuan county and it was 0.75%(3/400)in Rangtang county,historically serious endemic area.The selenium content in urine of children aged 7-13 years in Maerkang county,Jinchuan county and Rangtang county was (10.41±4.67), (10.11±3.65), (8.42±2.68)μg/g Cr, respectively, there was no statistical difference among three counties(F=0.901, P>0.05). The selenium content in hair of children aged 7-13 years in Maerkang county[(0.18±0.04)mg/kg] was lower than that in Jinchuan county[(0.21±0.04)mg/kg, P<0.05].The selenium content in water in Jinchuan county [(0.225±0.124 )μg/L ] was lower than that in Maerkang county and Rangtang county[(0.320±0.092), (0.339±0.105)μg/L, all P<0.05]. The selenium content in staple food in Jinchuan county(0.0033 mg/kg) was lower than that in Maerkang county and Rangtang county(0.0258,0.0137mg/kg, Z=-6.146,-3.042, all P<0.017). The T-2 toxin level in flour in three counties was 19.60,17.95,26.25 ng/g,respectively,there was no statistical difference among three counties(X2=5.623, P>0.05).The T-2 toxin level in grain Maerkang county (10.72 ng/g) was higher than that in Jinchuan county and Rangtang county (3.74,3.30 ng/g, Z=-6.315,-4.407,all P<0.017). T-2 toxin contamination in flour was more severe than that in grain (Z=-6.690,-5.493,-3.676, all P<0.05). Conclusions In 3 relative active KBD regions of Aba state,the children's selenium nutritional status and the T-2 toxin contamination level in their staple food is consistent with the distribution of KBD.

Investigation of diagnosis and treatment for primary central nervous system lymphoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics of primary central nervous system lymphoma (PCNSL) so as to improve comprehension of that unusual lesions.</p><p><b>METHODS</b>Forty-three cases of immunocompetent patients with a confirmed diagnosis of PCNSL were retrospectively reviewed. The clinical presentation, laboratory examination, imaging characteristics, histopathologic types and treatment were analyzed.</p><p><b>RESULTS</b>Single-locus lesion was found in thirty-six patients and multi-locus lesions were found in seven patients. Forty-seven operations were performed. The main characteristics including increased intracranial pressure in 22 cases (51.2%) followed by hemiparesis, seizure and speech problems in 16 cases (37.2%), disturbance of intellectual function and mental confusion in 10 cases (23.3%), contents of cerebrospinal fluid protein concentrations increased in 8 of 12 tested cases (66.7%). Histopathologic exam showed B-cell lymphoma in 40 (40/41, 97.6%) and T-cell lymphoma in 1 case (1/41, 2.4%). Ki-67 positive expression is 42.8% +/- 23.3% in 3 samples.</p><p><b>CONCLUSIONS</b>CT, MRI and CSF cytological examination are mainly diagnostic methods for PCNSL. Elevated lymphocyte counting in peripheral blood can not be the diagnostic criteria for PCNSL. The purpose of operation is alleviating symptom, increasing quantity of life and making histopathologic diagnosis. Adjuvant chemotherapy plus whole-brain radiation is an efficient treatment for PCNSL.</p>

Three-dimensional computed tomography-guided radiofrequency trigeminal rhizotomy for treatment of idiopathic trigeminal neuralgia / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the effectiveness of three-dimensional computed tomography (3D-CT) guided radiofrequency trigeminal rhizotomy (RF-TR) in treatment of idiopathic trigeminal neuralgia (ITN).</p><p><b>METHODS</b>From 1999 to 2001, 18 patients with ITN were treated with percutaneous controlled RF-TR. Intraoperative 3D-CT scanning was performed to guide the trajectory of the puncture. After correction of the needle tip according to the CT scans and stimulation effects, 2 to 5 lesions were made for a duration of 60-90 seconds at a temperature of 60 degrees C to 75 degrees C depending on the pain distribution and the age of patient.</p><p><b>RESULTS</b>The needles located in foramen ovale. Pain alleviated immediately with no serious complication in all patients. The patients were followed up for an average of 31.5 months (range 24-41 months). Acute pain relief was experienced by 17 patients after the procedure, reaching an initial success rate of 94.4%. Early (< 6 months) pain recurrence was observed in 2 patients (11.1%), whereas late (> 6 months) recurrence was reported in 3 patients (16.7%). Thirteen patients had complete pain control, with no need for medication thereafter. Five cases experienced partial pain relief, but required medication at a lower dose than in the preoperative period.</p><p><b>CONCLUSION</b>3D-CT foramen ovale locations can raise the successful rate of puncture, enhance the safety, and reduce the incidence rate of complication.</p>

The expression of KDR and VEGF in yolk sac and liver of human embryo / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the expression and distribution of KDR, VEGF and CD34 in yolk sac and liver of human embryo at different development stage.</p><p><b>METHODS</b>Yolk sacs and livers of 15 human embryos were analyzed by the immunohistochemical SP kits for the expression of KDR, VEGF and CD34.</p><p><b>RESULTS</b>KDR, VEGF and CD34 were all expressed in yolk sacs and livers of the embryos. In the intermediate liver group, the grey value of KDR and VEGF were 103.8 +/- 6.1 and 96.4 +/- 6.3, respectively, stronger than that in the late liver group which were 90.4 +/- 6.0 and 87.4 +/- 6.3, respectively (P < 0.05). A positive correlation between the levels of KDR and VEGF was observed (P < 0.05).</p><p><b>CONCLUSION</b>The expression of KDR and CD34 in yolk sac and liver of embryo suggests the presence of hemangioblast in these organs. Interaction of KDR and VEGF might relate to survival, proliferation, migration and differentiation of hemangioblasts.</p>