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Background/Aims: Chronic psychological stress affects gastrointestinal physiology which may underpin alterations in the immune response and epithelial transport, both functions are partly regulated by enteric nervous system. However, its effects on enteric neuroplasticity are still unclear. This study aims to investigate the effects of chronic unpredictable psychological stress on intestinal motility and prominent markers of enteric function. Methods: Adult male C57BL/6J mice were exposed to 19 day of unpredictable stress protocol schedule of social defeat and overcrowding. We investigated the effects on plasma corticosterone, food intake, and body weight. In vivo gastrointestinal motility was assessed by fecal pellet output and by whole-gastrointestinal transit (using the carmine red method). Tissue monoamine level, neural and glial markers, neurotrophic factors, monoamine signaling, and Toll-like receptor expression in the proximal and distal colon, and terminal ileum were also assessed. Results: Following chronic unpredictable psychological stress, stressed mice showed increased food intake and body weight gain (P < 0.001), and reduced corticosterone levels (P < 0.05) compared to control mice. Stressed mice had reduced stool output without differences in water content, and showed a delayed gastrointestinal transit compared to control mice (P < 0.05). Stressed mice exhibited decreased mRNA expression of tyrosine hydroxylase (Th), brain-derived neurotrophic factor (Bdnf) and glial cell-derived neurotrophic factor (Gdnf), as well as Toll-like receptor 2 (Tlr2) compared to control (P < 0.05), only proximal colon. These molecular changes in proximal colon were associated with higher levels of monoamines in tissue. Conclusion: Unpredictable psychological chronic stress induces region-specific impairment in monoamine levels and neuroplasticity markers that may relate to delayed intestinal transit.

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OBJECTIVES: Management of chronic tendon pain is difficult and controversial. This is due to poor knowledge of the underlying pathophysiology of chronic tendon pain, priorly known as tendinitis but now termed tendinopathy. The objective of this topical review was to synthesize evolving information of mechanisms in tendon pain, using a comprehensive search of the available literature on this topic. CONTENT: This review found no correlations between tendon degeneration, collagen separation or neovascularization and chronic tendon pain. The synthesis demonstrated that chronic tendon pain, however, is characterized by excessive nerve sprouting with ingrowth in the tendon proper, which corresponds to alterations oberserved also in other connective tissues of chronic pain conditions. Healthy, painfree tendons are devoid of nerve fibers in the tendon proper, while innervation is confined to tendon surrounding structures, such as sheaths. Chronic painful tendons exhibit elevated amounts of pain neuromediators, such as glutamate and substance p as well as up-regulated expression and excitability of pain receptors, such as the glutamate receptor NMDAR1 and the SP receptor NK1, found on ingrown nerves and immune cells. Increasing evidence indicates that mast cells serve as an important link between the peripheral nervous system and the immune systems resulting in so called neurogenic inflammation. SUMMARY: Chronic painful tendons exhibit (1) protracted ingrowth of sensory nerves (2) elevated pain mediator levels and (3) up-regulated expression and excitability of pain receptors, participating in (4) neuro-immune pathways involved in pain regulation. Current treatments that entail the highest scientific evidence to mitigate chronic tendon pain include eccentric exercises and extracorporeal shockwave, which both target peripheral neoinnervation aiming at nerve regeneration. OUTLOOK: Potential mechanism-based pharmacological treatment approaches could be developed by blocking promotors of nerve ingrowth, such as NGF, and promoting inhibitors of nerve ingrowth, like semaphorins, as well as blocking glutamate-NMDA-receptor pathways, which are prominent in chronic tendon pain.

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Introduction: Serum levels of pro-B-type natriuretic peptide (BNP) and N-terminal (NT) proBNP are measured at admission to assess the likelihood of acutely decompensated heart failure (ADHF). Elevated NT-proBNP levels on initial presentation are a reliable marker of ADHF. However, the prognostic significance of NT-proBNP levels measured on admission remains unknown. With a better understanding of how admitting NT-proBNP levels impacts readmission rates, length of stay and mortality, future prospective studies with specific interventions can be developed to reduce all-cause readmissions, shorten length of stay and reduce mortality. Methods: In this retrospective study, we evaluated heart failure with reduced ejection fraction (HFrEF) admissions from 2017-2018 with a focus on 30-, 60- and 90-day all-cause readmissions, length of stay (LOS) and in-hospital mortality rate that are predicted by NT-proBNP levels measured on admission. Using the HCA Healthcare Enterprise Data Warehouse, adult patients age 18 to 75 were selected using admission ICD-10 codes for HFrEF. Dialysis patients were excluded. Our search of 90 hospitals yielded 21,445 patients who were stratified into quartiles depending on their admission NT-proBNP levels: group 1 (<1669 pg/ml), group 2 (1670-4274 pg/ml), group 3 (4275-10,499 pg/ml) and group 4 (>10,500 pg/ml). Results: Readmission Rates: The 60-day all-cause readmission was significantly (p = 0.047) higher in group 4 compared to group 1 (adjusted odds ratio (OR) = 1.116, p = 0.013) and group 2 (adjusted OR = 1.111, p = 0.014). The 90-day all cause readmission for group 4 was also significantly higher when compared to group 1 (adjusted OR = 1.105, p = 0.021).Length of Stay: Elevated NT-proBNP concentrations were associated with a significantly longer LOS (p <0.0005). Pairwise, comparisons and estimates for adjusted LOS showed a positive linear association between higher NT-proBNP groups and longer LOS.Mortality: Higher inpatient mortality rates were associated with elevated NT-proBNP levels. The mortality rate was 0.9% in group 1 compared to a 4.7% mortality rate in group 4. Adjusted OR for mortality increased with increasing levels of NT-proBNP. Conclusions: Based on the analysis, higher admitting NT-proBNP levels were associated with significantly higher 60-day all-cause readmission, longer LOS and increased mortality. These findings suggest that measuring NT-proBNP levels at admission may provide an indication of patient outcomes. Prospective studies with targeted strategies can be developed to reduce readmissions, shorten LOS and reduce mortality based on admission NT-proBNP levels.

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INTRODUCTION: SLIT-ROBO is a ligand-receptor family of neuronal guidance cues that has been involved in pathological and physiological angiogenesis. SLIT-ROBO expression is altered in many tumours. However, no data exist about the role of the whole family in acute myelogenous myeloid leukemia (AML). PURPOSE: Herein, we assessed the expression of all SLIT-ROBO family in bone marrow (BM) biopsy of AML patients and control group on both protein and RNA levels. METHODS: The paraffin-embedded tissue blocks were subjected to immunohistochemistry for SLIT1, SLIT2, SLIT3, ROBO1, ROBO2, ROBO3, and ROBO4. Microvessel density (MVD) was evaluated by CD34 immunohistochemistry. An in silico analysis using The Cancer Genome Atlas data repository was conducted for assessment of RNA level. RESULTS: Acute myeloid leukemia patients were generally high expressers of ROBO1 and ROBO2 compared to the controls (p < 0.0001, p < 0.001, respectively). In contrast, low expression of SLIT1, SLIT2, and SLIT3 ligands has been noted more commonly in AML than in control BM samples (p < 0.0001, p = 0.003, and p = 0.001, respectively). ROBO4 expression correlated with MVD. The in silico analysis showed a poor prognostic value of high ROBO3 and low SLIT2 RNA levels (p = 0.0003 and p = 0.0008, respectively), as well as high ROBO3 and ROBO4 RNA levels in cytogenetic poor risk groups of patients (p = 0.0029 and p = 0.0003, respectively). CONCLUSIONS: These data indicate that SLIT-ROBO family members play a role in the biology of AML. Low expression of SLIT in BM of AML patients may suggest its expression alterations in AML. Increased expression of ROBO1 and ROBO2 in AML patients suggests their participation in AML pathogenesis.

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Objective To study the role of leucine rich repeat neuronal 3 (LRRN3) in the prolif-eration of non-small cell lung cancer and its possible mechanism of expression regulation. Methods The expression of LRRN3 in non-small cell lung cancer was detected by real-time quantitative polymerase chain reaction ( qPCR) , immunohistochemistry and bioinformatics retrieval;A lung cancer cell line A549-LRRN3 with stable over-expression of LRRN3 was established by lentivirus over-expression technology;The effect of LRRN3 on the proliferation of non-small cell lung cancer was detected by methyl thiazolyl tetrazolium ( MTT) assay;Bioinformatics search for changes in methylation of LRRN3 promoter region and treatment of lung cancer cells by methyltransferase inhibitors to detect the effect of methylation on the regulation of LR-RN3 expression; Finally, bioinformatics search analyzes the correlation between LRRN3 and lung cancer prognosis. Results The mRNA expression of LRRN3 in clinical tissues of non-small cell lung cancer (n=12) was significantly lower than that of adjacent normal tissues (n=12) (P=0. 0014). The results of immunohistochemistry showed that the protein expression level of LRRN3 in non-small cell lung adenocar-cinoma was lower than that in normal tissues (P=0. 001), and the expression in non-small cell lung squa-mous cell carcinoma was also lower than that in normal tissues (P=0. 003). Overexpression of LRRN3 in-hibited the proliferation of tumor cells (P<0. 01), and the hypermethylation of LRRN3 in the promoter re-gion inhibited its transcriptional expression. LRRN3 was positively correlated with the survival prognosis of lung adenocarcinoma (P=5. 2e-09;HR=0. 48). Conclusions Hypermethylation in the promoter region of LRRN3 inhibits its transcriptional expression, thereby promoting the proliferation of lung cancer cells.

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Massive peptide sharing between the Zika virus polyprotein and host tissue proteins could elicit significant host-pathogen interactions and cross-reactions leading to autoimmune diseases. This study found similarities in the Zika V proteins and human nerve tissue proteins. 63 human nerve proteins were screened for similarities with the Zika V of which Neuromodulin, Nestin, Galanin, Bombesin, Calcium-binding protein were found to have similarities to the Zika V poly protein C at different sequence regions. These sequence similarities could be significant in regulating pathogenic interactions/autoimmunity, as Polyprotein C is known to be a virulent factor.

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Objective: To investigate the protection effects of the activation of NMDAR1(NMDA receptor 1)/ERK1/2 signal pathway on visual cortex nerve cells induced by levodopa in amblyopia rats. Methods: SD rats of SPF grade, were randomly divided into for groups of 9, group A. Control, B. MD group, C. L-levodopa(20 mg·kg(-1))+MD group, D. H-levodopa (80 mg·kg(-1))+MD group, E. H-levodopa+MD+MK801 group, F. H-levodopa+MD+PD98059 group, G. MD+MK801 group, H. MD+PD98059 group, I. MD+DMSO group. Amblyopia rats were made by suture of the right eye. Levodopa was used to treatment amblyopia by gavage, and intervened by intracerebroventricular injection of MK801 and PD98059 respectively. The expression of NR1, p-ERK1/2, ERK1/2, NGF and c-FOS were detected by Western blotting. Nissl staining was used to detect morphological changes of neurons. Neuronal apoptosis was detected by TUNEL method, and detected the expression of Caspase-3, NGF and c-FOS by immunohistochemical staining. One/Two way Chi-square analysis was used for data analysis. LSD-t test was used as comparison between every two groups. Results: The morphology of Nissl bodies in neurons was complete and clear in A group, and the size of Nissl bodies got smaller, and caused karyopyknosis and loss of neurons in visual cortex of B group. Compared with A group, the apoptosis of visual cortical neurons(23.09±2.00 vs. 2.20±0.35, t=12.120, P=0.000) and the number of Caspase-3 postive cells (22.70±1.50 vs. 3.30±0.54, t=12.120, P=0.000)were significantly increased, the expression of NGF(0.31±0.04 vs. 0.74±0.09, t=7.674, P=0.000) and c-FOS(0.25±0.03 vs. 0.57±0.07, t=5.919, P=0.000) and the rats of NGF(8.30±0.82 vs. 35.18±2.01, t=12.37, P=0.0000) and c-FOS (10.84±1.02 vs. 35.68±2.55, t=9.056, P=0.0001) postive cell were decreased significantly in B group. After treatment with levodopa, the morphology of neurons recovered, the apoptosis of visual cortical neurons relieved, the expression of NR1(0.75±0.09 vs. 0.40±0.05, t=8.528, P=0.001) and p-ERK1/2(2.13±0.26 vs. 0.68±0.17, t=3.488, P=0.008) were increased significantly, and the rats of NGF (18.07±0.87 vs. 8.30±0.82, t=8.18, P=0.0000) and c-FOS (19.78±0.91 vs. 10.84±1.02, t=6.543, P=0.0001) postive cells were significantly increased. MK-801 or PD98059 intervention could effectively attenuate the effect of levodopa. It could effectively down-regulated the expression of NR1 (0.53±0.06 vs. 0.95±0.12, t=5.647, P=0.005) and p-ERK1/2(1.52±0.18 vs. 2.58±0.30, t=3.091, P=0.013) interference with MK801 or PD98059 in MD rats. MK-801 or PD98059 intervention further promote the Nissl body volume reduced, neurons karyopyknosis, the apoptosis of visual cortical neurons and Caspase-3 expression, and restrain the expression of NGF and c-FOS. Conclusion: Levodopa played a protective role in visual cortex nerve cells of amblyopia rats at least partially through activation of NMDA-ERK1/2 signal pathway. (Chin J Ophthalmol, 2017, 53: 931-940).

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Objective To investigate the effect of minocycline on the cognition and expressions of brain-derived neurotrophic factor (BDNF), apoptosis related factor Bcl-2 and Bax in hippocampus of rats with Alzheimer’s disease (AD). Methods The rat model was established by microinjection of Aβ25-35 into lateral ventricle. Thirty healthy male SD rats were randomly divided into three groups:control group, model group and minocycline treatment group. Normal saline 1 mL/(kg·d) was intraperitoneally injected in control group and model group. The minocycline treatment group was intraperitoneally injected with minocycline 50 mg/(kg · d) for 14 days. Morris water maze was used to detect the behaviors of animals. The expressions of BDNF, Bcl-2 and Bax in hippocampus were measured by Western blotting and enzyme linked immunosorbent assay (ELISA). The apoptosis of neurons was detected by TdT-mediated dUTP nick-end labeling (TUNEL). Results Minocycline greatly improved the behaviors of AD rats, up-regulated the expressions of BDNF and Bcl-2, and down-regulated the expression of Bax in hippocampus, and reduced cell apoptosis. Conclusion Minocycline plays a protective role in neural function by promoting the growth of neurons and inhibiting the neuronal apoptosis.

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Objective To evaluate the role of etomidate post-conditioning on mitochondrial permeability transition pore (mPTP) in the rat cortical neurons subjected to oxygen-glucose deprivation and restoration (OGD/R) and the relationship with Robo receptors.Methods The cortical neurons obtained from Sprague-Dawley rats (＜ 24 h after birth) were cultured in vitro and seeded in 6-well plates (2 ml/well).The neurons were divided into 4 groups (n=24 each) using a random number table:control group (group C),OGD/R group,etomidate post-conditioning group (group E),and etomidate post-conditioning + Robo receptor blocker group (group ER).The neurons were subjected to O2-glucose deprivation for 90 min followed by restoration of O2-glucose supply for 24 h.In E and ER groups,etomidate was added to the culture medium with the final concentration of 6 μmol/L immediately after onset of O2-glucose supply.In group ER,Robo blocker RoboN was added to the culture medium with the final concentration of 1 μg/ml at 6 h before O2-glucose deprivation.The neuronal apoptosis was detected using Hoechst/PI double staining,the viability of neurons was measured by MTT assay,and the amount of lactic dehydrogenase (LDH) released was measured using colorimetric method.The mitochondria were extracted,and mitochondrial permeability transition pore (mPTP) opening was detected.Results Compared with group C,the apoptosis rate,amount of LDH released,and mPTP opening were significantly increased,and the cell survival rate was decreased in OGD/R,E and ER groups (P＜0.05).Compared with group OGD/R,the apoptosis rate,amount of LDH released,and mPTP opening were significantly decreased,and the cell survival rate was increased in group E,and the apoptosis and amount of LDH released were significantly decreased,and the cell survival rate was increased in group ER (P＜0.05).Compared with group E,the apoptosis rate,amount of LDH released,and mPTP opening were significantly increased,and the cell survival rate was decreased in group ER (P＜0.05).Conclusion Etomidate post-conditioning mitigates OGD/R-induced damage to the cortical neurons through activating Robo receptors and inhibiting mPTP opening in rats.

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ObjectiveTo determine the optimal timing of antenatal taurine supplementation to improve neuron and neural stem cell proliferation in fetal rats with intrauterine growth restriction.Methods Twenty-five pregnant SD rats were randomly divided into five groups (five rats in each group): group A was the control group, group B to E were the fetal growth restriction (FGR) model groups with low-protein diet during the experiment, group C, D, and E were supplemented with taurine [300 mg/(kg·d)] at day 9, 11 and 15, respectively. The birth weight of newborn rats was measured after natural delivery. The rats with body weight two standard deviations lower than the average weight in group A were diagnosed as FGR. There were five litters of newborn rats in each group, and two were randomly selected from each litter, resulting in ten newborn rats in each group. Proliferating cell nuclear antigen (PCNA) and fatty acid binding protein 7 (FABP7) positive cell expression in newborn rat brain tissues were detected by immunohistochemistry. Single factor analysis of variance, LSD tests were used for statistical analysis.ResultsThe average birth weight of newborn rats in group A, B, C, D and E were (6.61±0.45), (4.65±0.23), (5.37±0.17), (5.74±0.21), and (5.00±0.24) g, respectively. Average birth weight was lower in group B than in group A (t=2.447), higher in group D and E than in group B (t=2.306 and 2.306), higher in group D than in group C and E (t=2.306 and 2.306), and the differences were statistically significant (allP0.05). The IOD in group D was higher than that in group E, and the difference was statistically significant (t=4.182,P<0.05).ConclusionsAntenatal taurine supplementation can promote neuron and neural stem cell proliferation in rats with FGR. The effect is most obvious on the 11th day of pregnancy, and may lead to the promotion of brain development.

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Nesfatin-1 is a peptide secreted by peripheral tissues, central and peripheral nervous system. It is involved in the regulation of energy homeostasis related with food regulation and water intake. Nesfatin-1 can pass through the blood-brain barrier in both directions. It suppresses feeding independently from the leptin pathway and increases insulin secretion from pancreatic beta islet cells. That is why nesfatin-1 has drawn attention as a new therapeutic agent, especially for the treatment of obesity and diabetes mellitus. Its effects on nutrition have been studied in more detail in literature. On the other hand, its effects on other physiological parameters and mechanisms of action still need to be clarified. Synthesizing the research on nesfatin-1 can help us better understand this field. Hippokratia 2015, 19 (1): 4-10.

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The purpose of this study was to investigate prognostic significance of Dopamine and cAMP-Regulated neuronal Phosphoprotein 32 (DARPP-32) expression in primary colorectal cancer. The study material consisted of clinical and histopathological data of 100 patients operated for colorectal cancer between 1994 and 1997. For immunohistochemical analysis, specific rabbit antibodies for DARPP-32 were used and the percentage of stained tumor cells was calculated under gross magnification (400 times) on a sample of 500 tumor cells. DARPP-32 expression in the primary tumor was significantly greater in patients with distant metastases compared to patients with no distant metastases (p=0.002). In multivariate regression analysis, DARPP-32 expression in the primary tumor was a significant predictor of distant metastases. With a cut-off point of 76.5%, DARPP-32 expression in the primary tumor significantly influenced both overall and disease free survival, especially for Dukes A and B patients (p=0.037). The results of this study indicate that DARPP-32 may be a potential marker of worse prognosis and a valuable tool for managing further adjuvant treatment in patients with stages Dukes A and B colorectal cancer.

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Objective To investigate the expressions of Slit2 and Nogo-A in the ipsilateral hippocampus after cerebral hemorrhage in rats.Methods A total of 64 adult Sprague-Dawley (SD) rats was randomly divided into control and model groups.Collagenase Ⅶ was used to induce cerebral hemorrhage model.Immunohistochemistry was used to detect the expressions of Slit2 and Nogo-A in hippocampus at the cerebral hemorrhage side at the time points (24 h,7 d,14 d,and 21 d).Results Compared to the control group,the expressions of Slit2 and Nogo-A were significantly enhanced in model group (P ＜0.01),with the highest level at the 7 d.Conclutions Cerebral hemorrhage can significantly enhance expressions of Slit2 and Nogo-A with a positive correlation of Slit2 and Nogo-A,which might have an important effect on the recovery of brain injury.

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Objective To investigate the potential therapeutic efficacy of lentivirus-mediated artemin (ARTN) gene modified bone marrow mesenchymal stem cells (MSCs) transplantation on the rat model of Parkinson' s disease (PD) and the effects on expression of brain-related proteins.Methods MSCs were isolated and cultured in vitro,transfected by recombinant lentiviral vectors carrying ARTN gene.The PD rat model established by 6-hydroxydopamine (6-OHDA) was randomly divided into 5 groups:Sham group,PD group,MSCs group,MSCs transfected with empty lentiviral vectors transplanted (LV-MSCs)group and MSCs transfected with recombinant lentiviral vectors carrying ARTN gene transplanted (LVARTN-MSCs) group.The MSCs,LV-MSCs and LV-ARTN-MSCs groups were transplanted into the left striatum of each rat model of PD and ethology tests in every group were made with intraperitoneal injection of apomorphine (APO) 2,4,6,8 weeks after transplantation.The expression of tyrosine hydroxylase (TH) protein in substantia nigra (SN) was measured by Western blotting and immunohistochemistry,and immunofluorescence showed ARTN gene modified MSCs expression in rat brain tissue.The levels of dopamine (DA),dihydroxy-phenylacetic acid and homovanillic acid in striatum of each group were detected by high performance liquid chromatography.Results After injection of APO,rotation frequency decreased in LV-ARTN-MSCs group,i.e.(179.33 ± 10.74) circles/30 min vs (235.83 ± 18.95),(203.67 ±11.50) and (206.33 ± 11.86) circles/30 min in PD,MSCs and LV-MSCs groups (q =8.828,P ＜ 0.01;q =3.802,P ＜ 0.05;q =4.219,P ＜ 0.05).The percentage of TH-positive cells in SN after cell transplantation was increased significantly in LV-ARTN-MSCs group (64.05％ ± 5.49％) when compared with PD group (34.18％ ±3.35％),MSCs group (52.59％ ±4.48％) and LV-MSCs group (50.57％ ± 4.41％),respectively (q =13.280,5.135,6.028,all P ＜0.01).At the same time,TH protein in SN after cell transplantation was also increased obviously in LV-ARTN-MSCs group.ARTN gene modified MSCs can survive for at least 6 weeks in the rat brain of PD,mainly concentrated in the transplantation side of striatum.Eight weeks later,the levels of DA in striatum after cell transplantation were elevated significantly in MSCs group (2.34 ± 0.54),LV-MSCs group (2.28 ± 0.45) and LV-ARTN-MSCs group (2.28 ± 0.45)when compared with PD group (0.87 ± 0.07) (q =5.233,P ＜ 0.05;q =5.020,P ＜ 0.01;q =20.190,P ＜ 0.01),and LV-ARTN-MSCs group showed the most significant improvement.Conclusion ARTN gene modified bone marrow MSCs transplanted into the striatum of brain may have therapeutic effects on rat models of PD.

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Objective To investigate the association between high-risk types of human papillomavirus (HR-HPV) load and the expression of nestin in different cervical lesions.Methods The hybridization capture Ⅱ (HC-Ⅱ) assay was used to test the HR-HPV load from 60 patients who were the first time to do the cervical cancer screening in Xiangya Hospital,and immunohistochemistry was used to detect the expression of nestin in those biopsy tissue samples.Results (1) The lgHPV level (logarithm of HR-HPV load) in the high level lesion group was higher than the low level one (P ＜0.05),and HR-HPV load was positively associated with the degree of cervical lesions (rs =0.269,P =0.037).(2) The expression of nestin in A group was weaker than groups B and C (H =7.271,22.843,P ＜0.01),and the expression of nestin in C group was stronger than B group (H =7.270,P ＜0.01),and the expression of nestin was positively associated with the degree of cervical lesion (rs =0.646,P =0.000).(3) The HR-HPV load was positively associated with the expression of nestin (P ＜ 0.05).Conclusions The HR-HPV load and the expression of nestin are closely related to the cervical lesions,and the joint detection has a referential value for early prevention of cervical lesions and prediction of progress of cervical precancerous lesion.It might guide the early prevention and treatment of cervical cancers.

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Neuroglobin (Ngb) is an oxygen-carrying globin that specifically expresses in brain tissue.It is involved in energy metabolism,mitochondrial function,as well as cell survival and proliferation of signaling pathway regulation.Under physiological conditions,Ngb presents as a form of ferrous deoxy hexacoordination,which has stronger oxygen affinity.During ischemia and hypoxia,the expression of Ngb is upregulated in brain tissue and interacts through a variety of proteins of its downstream,and plays a protective role for the damaged brain tissue.

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Objective To report the clinical and genetic characteristics of a dentatorubralpallidoluysian atrophy (DRPLA) pedigree with an onset of cognitive impairment.Methods Clinical data of this pedigree was collected.The numbers of CAG repeats in the exon 5 of atrophin-1 (ATN1) gene were analysed in the proband and the other 4 healthy family individuals.The polymerase chain reaction (PCR) products of the proband underwent cloning-sequencing using an original TA cloning kit.Results There were 5 patients in this family,4 with onset in adult and one in childhood.The proband had an onset manifestation of cognitive impairment,while the other 3 adult patients presented with ataxia.The two-year-old child in the pedigree had myoclonic epilepsy.The proband had 61 CAG repeats in the exon 5 of ATN1 gene.After TA cloning-sequencing of the proband ' s PCR products,there were 2 different numbers of CAG repeats,including 61 and 64.Conclusions The clinical manifestations of DRPLA can have obvious heterogeneity in one family.Some patients present with cognitive impairment.It is very important to test the numbers of CAG repeats of ATN1 gen for DRPLA diagnosis.Somatic mosaicism may be also observed in Chinese DRPLA patients.

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Objective To discuss clinical,electroencephalogram(EEG) and PRRT2 gene mutation by reporting a febrile seizure (FS) with paroxysmal kinesigenic dyskinesia (PKD) family.Methods Detailed clinical data of the family were collected.The proband (Ⅳ1) and another 4 patients (Ⅲ1,Ⅲ4,Ⅳ2,Ⅳ3)were studied through clinical examinations.Clinical symptoms of Ⅳ2 were not typical,who was diagnosed as a suspected case.Mutation analysis of PRRT2 gene was screened by polymerase chain reaction (PCR) and DNA direct sequencing in 5 patients (Ⅳ1,Ⅲ1,Ⅲ4,Ⅳ2,Ⅳ3) and 4 unaffected family members (Ⅱ2,Ⅲ2,Ⅲ5,Ⅳ4).Results PKD patients had brief involuntary movements in the limbs or trunk induced by sudden voluntary movement when patients were in the stationary state since the teenagers.Two cases (Ⅲ,Ⅲ4) were accompanied by FS.Three cases(Ⅳ1,Ⅲ1 and Ⅲ4)had abnormal EEG records.The PRRT2 gene mutation (c.649dupC mutation) was identified in a healthy member (Ⅳ4) and 4 patients (Ⅳ1,Ⅲ1,Ⅲ4,Ⅳ3).Conclusions FS with PKD family has a PRRT2 gene mutation.The diagnosis is mainly based on family history,typical clinical manifestations and genetic test.This kind of disease may have pre-symptomatic patients.

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OBJECTIVE: Given the ability of mood stabilizers and antipsychotics to promote cell proliferation, we wanted to determine the effects of these drugs on neuronal markers previously reported to be altered in subjects with psychiatric disorders. METHODS: Male Sprauge-Dawley rats were treated with vehicle (ethanol), lithium (25.5 mg per day), haloperidol (0.1 mg/kg), olanzapine (1.0 mg/kg) or a combination of lithium and either of the antipsychotic drugs for 28 days. Levels of cortical synaptic (synaptosomal associated protein-25, synaptophysin, vesicle associated protein and syntaxin) and structural (neural cell adhesion molecule and alpha-synuclein) proteins were determined in each treatment group using Western blots. RESULTS: Compared to the vehicle treated group; animals treated with haloperidol had greater levels of synaptosomal associated protein-25 (p<0.01) and neural cell adhesion molecule (p<0.05), those treated with olanzapine had greater levels of synaptophysin (p<0.01) and syntaxin (p<0.01). Treatment with lithium alone did not affect the levels of any of the proteins. Combining lithium and haloperidol resulted in greater levels of synaptophysin (p<0.01), synaptosomal associated protein-25 (p<0.01) and neural cell adhesion molecule (p<0.01). The combination of lithium and olanzapine produced greater levels of synaptophysin (p<0.01) and alpha-synuclein (p<0.05). CONCLUSION: Lithium alone had no effect on the neuronal markers. However, haloperidol and olanzapine affected different presynaptic markers. Combining lithium with olanzapine additionally increased alpha-synuclein. These drug effects need to be taken into account by future studies examining presynaptic and neuronal markers in tissue from subjects with psychiatric disorders.