Prognostic significance of serum cystatin C in acute brainstem infarctions patients.

OBJECTIVES: Some studies show that high circulating cystatin C (CysC) may predict cardiovascular events and death after ischemic stroke onset. However, the association between serum CysC and outcome in ischemic stroke patients remains contradictory. We sought to assess the association between a specific stroke subgroup, brainstem infarction (BSI) and serum CysC. MATERIALS AND METHODS: A total of 324 acute BSI patients were included in the study. Serum CysC was used to calculate estimated glomerular filtration rate (eGFRCysC) at baseline. Modified Rankin scale score ((mRS) ≥3) six months after acute BSI indicates poor functional outcome. Patients were categorized into two groups according to mRS and eGFRCysC. Logistic regression analyses were performed to determine independent risk factors. RESULTS: Lower eGFRCysC was associated with hemoglobin A1c (HbA1c). This risk remained statistically significant after controlling for age, hypertension, initial National Institutes of Health Stroke Scale (NIHSS) score, HbA1c, fibrinogen and homocysteine. The serum eGFRCysC levels were significantly lower in the poor functional outcome group than the good functional outcome group (P<0.001). Multivariate logistic regression analyses showed that eGFRCysC level was significantly lower in the poor outcome group after adjusting for age, previous infarctions, initial NIHSS score, and HbA1c. CONCLUSIONS: Lower eGFRCysC levels were strongly associated with poor functional outcome of acute BSI patients with a higher HbA1c level. Lower eGFRCysC may be a more helpful serologic biomarker for the prediction of prognosis in BSI.

[Resveratrol protects dopaminergic neurons in a mouse model of Parkinson's disease by regulating the gut-brain axis via inhibiting the TLR4 signaling pathway].

OBJECTIVE: To investigate the protective effect of resveratrol on intestinal barrier in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse models and its mechanism for regulating TLR4/MyD88/NF-κB signaling to protect dopaminergic neurons. METHODS: Fifty-two C57BL/6J mice were randomized into control group (n= 12), MPTP group (n=14), MPTP + resveratrol (30 mg/kg) group (n=13), and MPTP + resveratrol (90 mg/kg) group (n=13), and mouse models were established by intraperitoneal MPTP (30 mg/kg) injection for 7 days in the latter 3 groups. Behavioral tests were conducted to evaluate the effect of resveratrol on motor symptoms of the mice. Western blotting was used to detect the expression of TH, α-syn, ZO-1, Claudin-1, TLR4, MyD88, and NF-κB in the brain tissues of the mice. Immunohistochemistry, immunofluorescence, ELISA and transmission electron microscopy were used to verify the effect of resveratrol for suppressing inflammation and protecting the intestinal barrier. RESULTS: Compared with those in the normal control group, the mice in MPTP group showed significant changes in motor function, number of dopaminergic neurons, neuroinflammation, levels of LPS and LBP, and expressions of tight junction proteins in the intestinal barrier. Resveratrol treatment significantly improved motor function of the PD mice (P < 0.01), increased the number of neurons and TH protein expression (P < 0.05), down-regulated the expressions of GFAP, Iba-1, and TLR4, lowered fecal and plasma levels of LPS and LBP (P < 0.05), restored the expression levels of ZO-1 and Claudin-1 (P < 0.01), and down-regulated the expressions of TLR4, MyD88, and NF-κB in the colon tissue (P < 0.05). The mice with resveratrol treatment at 30 mg/kg showed normal morphology of the tight junction complex with neatly and tightly arranged intestinal villi. CONCLUSION: Resveratrol repairs the intestinal barrier by inhibiting TLR4/MyD88/NF-κB signaling pathway-mediated inflammatory response, thereby improving motor function and neuropathy in mouse models of MPTP-induced PD.

[Advances in the diagnosis, treatment, and prognosis of acute decompensatory cirrhosis].

Acute decompensatory cirrhosis is a common cause of hospital admission, readmission, and death, causing a heavy burden on patients, their families, and society. This article reviews the research advancement from the perspectives of concept evolution, pathogenesis, treatment, outcome, and prognosis models, providing new ideas for preventing and treating acute decompensatory cirrhosis.

[Parathyroid hormone-related protein aggravates nonalcoholic fatty liver disease induced by methionine choline-deficient diet in mice].

OBJECTIVE: To study the effect of parathyroid hormone-related protein (PTHrP) on nonalcoholic fatty liver disease (NAFLD) induced by methionine choline-deficient diet (MCD) in mice. METHODS: Twelve male C57BL/6J mice were randomized into blank control group, vehicle group and PTHrP group (n=4). The mice in vehicle group and PTHrP group received injections of a control adeno-associated virus (AAV) vector and an AVV vector carrying PTHrP (AAV-PTHrP) gene, respectively, followed one week later by MCD feeding for 3 weeks; the mice in the blank control were fed a normal diet for 4 weeks. Body weight changes of the mice were monitored during the experiment. At the end of the experiment, liver tissues were harvested from the mice for histological analysis using HE staining, oil red O staining, and Sirius red staining. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride, and free fatty acids (FFAs) in the liver and serum were detected to assess hepatic impairment and lipid metabolism of the mice. Cell models of NAFLD were established in mouse and human normal liver cells by treatment with 250 µmol/L FFAs for 24 h, and the effect of AAV-PTHrP on lipid deposition and viability of the cells were tested using Oil Red O and Nile red staining and CCK8 assay. RESULTS: Treatment with AAV-PTHrP, as compared with the control AVV vector, caused more rapid reduction of body weight in mice with MCD feeding and significantly increased the levels of AST (P < 0.05), ALT (P < 0.05), triglyceride (P < 0.01) and FFA (P < 0.05) in the liver and the scores of NAS (P < 0.01) and SAF (P < 0.05). HE and Oil red O staining of the liver tissue revealed obvious lipid deposition after MCD feeding, which was more serious in PTHrP group. In the cell experiment, FFAs induced steatosis in both mouse and human hepatocytes, and treatment with PTHrP increased the accumulation of lipid droplets and lowered the viability of the cell model of NAFLD (P < 0.01 or 0.05). CONCLUSION: PTHrP may aggravate MCD-induced NAFLD in mice by promoting the deposition of lipid droplets in the hepatocytes.

[Research progress of sodium butyrate in metabolic-associated fatty liver disease].

Metabolic-associated fatty liver disease (MAFLD) has become the most common chronic liver disease affecting global public health, and its incidence rate is increasing year by year. The molecular mechanism of its pathogenesis is not yet fully understood, and there is a shortage of effective clinical prevention and treatment methods. Studies have found that sodium butyrate can participate in gene regulation, immune regulation, intestinal barrier function regulation, oxidative stress and other in-vivo physiological activities. Furthermore, it also plays an important role in preventing and alleviating the MAFLD occurrence and development. This article reviews the related studies of sodium butyrate on gene expression regulation, fat metabolism improvement, intestinal flora regulation, and steatohepatitis improvement with MAFLD.

Growth differentiation factor 11 relieves acute lung injury in mice by inhibiting inflammation and apoptosis.

OBJECTIVE: Acute lung injury (ALI) is the most common organ damage in sepsis and sepsis-induced ALI is a clinically extremely dangerous disease. Therefore, it is essential to find an effective way to treat ALI. We hope to provide a new target for the treatment of clinical ALI by studying the effect of GDF11 on LPS-induced ALI. MATERIALS AND METHODS: C57BL/6 male mice and lipopolysaccharide (LPS) were used to induce mouse ALI. Recombinant GDF11 protein was used to treat mice to detect the effect of GDF11 on mouse ALI. In addition, BEAS-2B cells were used to further validate the effects of GDF11 on inflammation and apoptosis of alveolar epithelial cells. RESULTS: Recombinant GDF11 protein significantly reduced the expression of inflammatory factors and apoptosis-related pathways in mouse lung tissues. Overexpression of GDF11 in BEAS-2B cells also significantly attenuated the levels of inflammation and apoptosis in the cells. In addition, GDF11 can reduce the activity of TLR2/HMGB1/NF-κB signaling pathway, which is an important mechanism for GDF11 to play a role in lung protection. CONCLUSIONS: GDF11 can exert lung protection effects by inhibiting the TLR2/HMGB1/NF-κB signaling pathway and reduce the level of inflammation and apoptosis of the lung.

Voxel-wise meta-analysis of structural changes in gray matter of Parkinson's disease patients with mild cognitive impairment.

Evidence from previous voxel-based morphometry (VBM) studies indicates that widespread brain regions are involved in Parkinson's disease with mild cognitive impairment (PD-MCI). However, the spatial localization reported for gray matter (GM) abnormalities is heterogeneous. The aim of the present study was to quantitatively integrate studies on GM abnormalities observed in PD-MCI in order to determine whether a pattern exists. Eligible whole-brain VBM studies were identified by a systematic search of articles in PubMed and EMBASE databases spanning from 1995 to January 1, 2019. A meta-analysis was performed to investigate regional GM abnormalities in PD-MCI. The anisotropic effect size version of seed-based d mapping (AES-SDM) meta-analysis was conducted to explore the GMV differences of PD-MCI compared with PD patients with normal cognitive function (PD-NC). A total of 12 studies comprising 243 PD-MCI patients and 326 PD-NC were included in the meta-analysis. PD-MCI patients showed a robust GM decrease in the left insula and left superior temporal gyrus. Moreover, meta-regression analysis demonstrated that age, PD duration and stage, and Unified Parkinson's Disease Rating Scale III and Mini-Mental State Examination scores might be partly correlated with the GM abnormalities observed in PD-MCI patients. The convergent findings of this quantitative meta-analysis revealed a characteristic neuroanatomical pattern in PD-MCI. The findings provide some evidence that MCI in PD may result in the breakdown of the insula and temporal gyrus, which may serve as specific regions of interest for further investigations.

LncRNA AWPPH accelerates the progression of non-small cell lung cancer by sponging miRNA-204 to upregulate CDK6.

OBJECTIVE: This study aims to uncover the function of long non-coding RNA (lncRNA) AWPPH in the progression of non-small cell lung cancer (NSCLC) and the potential mechanism. PATIENTS AND METHODS: AWPPH and microRNA (miRNA-204) levels in NSCLC tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Kaplan-Meier curves were introduced for assessing overall survival in NSCLC patients expressing high or low level of AWPPH. Potential correlation between expression levels of AWPPH and miRNA-204 in NSCLC tissues was analyzed by Spearman correlation test. Through Dual-Luciferase reporter gene assay, the interaction among AWPPH, miRNA-204, and CDK6 was identified. Potential impacts of AWPPH/miRNA-204/CDK6 regulatory loop on mediating proliferative, migratory, and invasive capacities of A549 cells were evaluated through cell counting kit-8 (CCK-8) and transwell assay. RESULTS: Upregulated AWPPH and downregulated miRNA-204 were determined in NSCLC tissues. AWPPH level was negatively correlated to overall survival in NSCLC patients and miRNA-204 level in NSCLC tissues. Silence of AWPPH attenuated proliferative, migratory, and invasive capacities in A549 cells. MiRNA-204 was the downstream gene of AWPPH. Knockdown of miRNA-204 reversed the decreased viability, migratory, and invasive rates in A549 cells with AWPPH knockdown. In addition, CDK6 was the target gene of miRNA-204. Overexpression of miRNA-204 downregulated CDK6 level in A549 cells. The attenuated proliferative, migratory, and invasive capacities in A549 cells overexpressing miRNA-204 were reversed after CDK6 overexpression. CONCLUSIONS: LncRNA AWPPH serves as the miRNA-204 sponge to upregulate CDK6 level, thus aggravating the progression of NSCLC.

Voxel-wise meta-analysis of structural changes in gray matter of Parkinsons disease patients with mild cognitive impairment

Evidence from previous voxel-based morphometry (VBM) studies indicates that widespread brain regions are involved in Parkinson's disease with mild cognitive impairment (PD-MCI). However, the spatial localization reported for gray matter (GM) abnormalities is heterogeneous. The aim of the present study was to quantitatively integrate studies on GM abnormalities observed in PD-MCI in order to determine whether a pattern exists. Eligible whole-brain VBM studies were identified by a systematic search of articles in PubMed and EMBASE databases spanning from 1995 to January 1, 2019. A meta-analysis was performed to investigate regional GM abnormalities in PD-MCI. The anisotropic effect size version of seed-based d mapping (AES-SDM) meta-analysis was conducted to explore the GMV differences of PD-MCI compared with PD patients with normal cognitive function (PD-NC). A total of 12 studies comprising 243 PD-MCI patients and 326 PD-NC were included in the meta-analysis. PD-MCI patients showed a robust GM decrease in the left insula and left superior temporal gyrus. Moreover, meta-regression analysis demonstrated that age, PD duration and stage, and Unified Parkinson's Disease Rating Scale III and Mini-Mental State Examination scores might be partly correlated with the GM abnormalities observed in PD-MCI patients. The convergent findings of this quantitative meta-analysis revealed a characteristic neuroanatomical pattern in PD-MCI. The findings provide some evidence that MCI in PD may result in the breakdown of the insula and temporal gyrus, which may serve as specific regions of interest for further investigations.

Monomethyl fumarate protects cerebral hemorrhage injury in rats via activating microRNA-139/Nrf2 axis.

OBJECTIVE: Monomethyl fumarate (MF) exerts anti-inflammatory and antioxidant capacities. Whether microRNA-139 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) are involved in the pharmacological activity of MF remain unclear. We aim to elucidate the potential function of MF in intracerebral hemorrhage (ICH), and its possible mechanism. MATERIALS AND METHODS: Twenty-four Sprague Dawley (SD) rats were randomly assigned into sham group, ICH group and MF group, with 8 rats in each group. Rats in ICH and MF group were subjected to ICH procedures. Rat brain tissues were harvested at 48 h after ICH procedures. Evans blue extravasation was performed to evaluate ICH-induced rat brain damage. Content of cerebral edema and neurological deficit were examined to reflect the neuronal pathological lesions. Reactive oxygen species (ROS) content in rat brain was examined by immunofluorescence. Activities of oxidative stress indexes in rat brain homogenate were detected using relative commercial kits. MicroRNA-139 expression in rat brain was quantified by quantitative Real-time polymerase chain reaction (qRT-PCR). Finally, protein levels of Nrf2, HO-1, NQO1 and nuclear factor-kappa B (NF-κB) in rat brain tissues were examined by Western blot. RESULTS: Compared with rats in sham group, neurological deficit scores of rats in ICH group were lower. Disruption of blood-brain barrier and brain tissue edema of rats were pronounced in ICH group. However, MF pretreatment markedly alleviated the above mentioned cerebral lesions. In addition, MF pretreatment increased activities of SOD, GSH and CAT, but decreased MDA and ROS contents in rat brain homogenate relative to those in ICH group (p<0.05). Western blot analysis found that expression levels of Nrf2, HO-1 and NQO-1 were markedly upregulated after MF pretreatment, while the expression level of NF-κB was downregulated. At the cellular level, we altered microRNA-139 expression in SH-SY5Y cells by transfection of microRNA-139 mimics or inhibitor. Overexpression of microRNA-139 remarkably increased Nrf2 expression and decreased NF-κB expression. Treatment of high-dose MF upregulated Nrf2, downregulated NF-κB and decreased ROS content in SH-SY5Y cells. CONCLUSIONS: MF protects ICH in rats by inhibiting oxidative stress and inflammatory response through activating microRNA-139/Nrf2 axis.

The relationship between plasma homocysteine levels and MTHFR gene variation, age, and sex in Northeast China.

BACKGROUND: Hyperhomocysteinemia (HHcy) is the risk factor for cardiovascular disease and stroke. However, the impacts on the genetic variation of methylene tetrahydrofolate reductase (MTHFR) on plasma homocysteine levels in the Northeast Chinese population have not been studied. Therefore, this study was carried out to determine the relationship between HHcy and MTHFR gene variation, and whether it was influenced by age and sex of the population in Northeast China. MATERIALS AND METHODS: A total of 466 subjects were randomly enrolled in this study. According to the homocysteine levels (Hcy ≥ 15 µmol/L) of the subjects, they were divided into hyperhomocysteine (HHcy = 206) and normal homocysteine (Hcy = 260). Polymerase chain reaction/high-resolution dissolution curve and homocysteine determination kit methods were used for genotype testing and homocysteine detection, respectively. RESULTS: High plasma homocysteine levels are associated with MTHFR 677T and 1298A [P < 0.00, odds ratio (confidence interval) = 1.842 (1.418-2.394) >1], which is related to increasing age (Prange = 0.0005-0.0161), with the homocysteine levels of males higher than females (P < 0.0001). CONCLUSION: High plasma homocysteine levels were linked to the MTHFR gene mutation. In addition, plasma homocysteine levels increased significantly with age with male's homocysteine levels higher than that of females.

[The diagnostic framework for screening Alzheimer's disease in the Chinese population].

Criteria for diagnosis of Alzheimer's disease (AD) is not available in China. The international criteria is not a proper choice due to issues such as translation and lead to low diagnostic rate and high rate of missed diagnosis. The research group of Alzheimer's Disease Chinese (ADC) reviewed knowledge and techniques in neuropsychology, neuroimaging, molecular biology, and clinical neurology, and systematically studied the detection techniques such as memory, language, visuospatial, executive function, and medial temporal lobe visual scores on MRI, and their optimal threshold and diagnostic value for the diagnosis of AD. Through a systematic review and consensus meeting, a diagnostic framework for screening AD in the Chinese population was established. Among these methods, an operational standard for clinical pathology models increased the diagnostic sensitivity by 15%. The sensitivity and specificity of screening memory impairment increased by 18.1% and 11.6%, respectively. The sensitivity of screening medial temporal lobe atrophy increased by 24.5% and missed diagnosis was decreased by 34.5%. An operational standard for clinical biology models, incorporating the latest molecular imaging and molecular biology techniques, has enabled the early diagnosis of AD in China. The framework combines a principled diagnostic guideline with an operational screening protocol, which is applicable to all clinical settings and of great significance for the early detection, early diagnosis and early treatment of AD.

[Screening and diagnostic framework of vascular dementia in Chinese population].

For lack of cognitive screening standard system and controversy over the value of imaging for cerebrovascular diseases in China, the research group of Alzheimer's Disease Chinese (ADC) studied the knowledge of neuropsychology, neuroimaging and clinical neurology, systematically reviewed the diagnostic techniques such as memory, language, visuospatial, executive, function, and magnetic resonance imaging (MRI) of cerebrovascular diseases, and their optimal threshold and diagnostic value for vascular dementia. Via a consensus meeting, the diagnostic guidelines and practical screening process are combined to construct a framework in Chinese population, which is based on the objective evidence of medical history and clinical evaluation. The diagnosis of vascular dementia is supported by imaging evidence of cerebrovascular diseases and differentiates from other causes of dementia or comorbidities. This consensus is applicable to medical units in China, and is of great significance for early detection, early diagnosis and early treatment of vascular dementia.

Pressure-induced enhancement of thermoelectric power factor in pristine and hole-doped SnSe crystals.

We evaluate the influence of pressure on the thermoelectric power factors PF ≡ S 2 σ of pristine and Na-doped SnSe crystals by measuring their electrical conductivity σ(T) and Seebeck coefficient S(T) up to ∼22 kbar with a self-clamped piston-cylinder cell. For both cases, σ(T) is enhanced while S(T) reduced with increasing pressure as expected, but their imbalanced variations lead to a monotonic enhancement of PF under pressure. For pristine SnSe, σ(290 K) increases by ∼4 times from ∼10.1 to 38 S cm-1, while S(290 K) decreases by only ∼12% from 474 to 415 µV K-1, leading to about three-fold enhancement of PF from 2.24 to 6.61 µW cm-1 K-2, which is very close to the optimal value of SnSe above the structural transition at ∼800 K at ambient pressure. In comparison, the PF of Na-doped SnSe at 290 K is enhanced moderately by ∼30% up to 20 kbar. In contrast, the PF of isostructural black phosphorus with a simple band structure was found to decrease under pressure. The comparison with black phosphorus indicates that the multi-valley valence band structure of SnSe is beneficial for the enhancement of PF by retaining a large Seebeck coefficient under pressure. Our results also provide experimental confirmation on the previous theoretical prediction that high pressure can be used to optimize the thermoelectric efficiency of SnSe.

The aberrant activation of Wnt pathway caused by ß-catenin mutation and its prognostic significance in NK/T-cell lymphoma.

The aberrant activation of the Wnt/ß-catenin signal has an important role in the progression of cancers. Herein, we investigated ß-catenin mutation and the activation of the Wnt pathway in association with the clinical-pathological characteristics, chemo-resistance and prognosis of NK/T-cell lymphoma (NKTCL). Real-time quantitative PCR, immunocytochemistry and immunohistochemistry SP methods detected the levels of ß-catenin, c-myc and cyclin D1 in human NKTCL cell lines (SNK-6 and YTS) and NKTCL tissues. Mutation analysis was detected in exon 3 of ß-catenin gene; and we analyzed cell viability after histone deacetylase inhibitor (HDACi) treatment. As a result, 19 (38%) of NK/T-cell lymphoma displayed nuclear ß-catenin and 16 (32%) contained mutations in exon 3; while no mutations were detected in lymphomas negative for ß-catenin nuclear staining (p<0.05). Most mutations affecting ß-catenin were adjacent to regulatory phosphorylation sites. ß-catenin, c-myc and cyclin D1 were significantly elevated in SNK-6 and YTS cell lines compared to normal NK/T cells (p<0.05). Furthermore, the high expression of ß-catenin, c-myc and cyclin D1 significantly correlated with the III/IV Ann Arbor stage. Additionally, the expression of ß-catenin in the SNK-6 cell line decreased significantly after treatment with HDACi, and Kaplan-Meier survival analysis revealed that the elevated expression of ß-catenin correlated with poor prognosis in NKTCL patients (23.66±2.77 months vs 31.65±1.78 months, p=0.023). In conclusion: mutations in exon 3 of ß-catenin and the activated Wnt pathway are common in NK/T-cell lymphoma that has nuclear ß-catenin, and it is closely correlated with the Ann Arbor stage and prognosis in NKTCL patients.

Overexpression of miR-638 attenuated the effects of hypoxia/reoxygenation treatment on cell viability, cell apoptosis and autophagy by targeting ATG5 in the human cardiomyocytes.

OBJECTIVE: Myocardial ischemia/reperfusion (I/R) injury largely contributed to the damage of myocardial tissues in patients with coronary disease, which may subsequently lead to heart failure. MicroRNAs (miRNAs) are considered to be involved in the process of myocardial I/R injury. The present study aimed to investigate the in vitro functional role of miR-638 in the myocardial I/R injury in the human cardiomyocytes (HCMs). PATIENTS AND METHODS: MTT assay and flow cytometry assay were performed to determine cell viability and apoptosis of HCMs. Real Time-quantitative Polymerase Chain Reaction was used to determine miRNA and mRNA expression levels. The protein levels were determined by Western blot assay. RESULTS: Hypoxia/reoxygenation (H/R) treatment suppressed cell viability, increased cell apoptotic rate and suppressed miR-638 expression in the HCMs. The downregulation of miR-638 suppressed cell viability and induced cell apoptosis in the HCMs. The overexpression of miR-638 attenuated the effects of H/R treatment on the cell viability and cell apoptosis in the HCMs. In addition, miR-638 suppressed the expression of autophagy-related 5 (ATG5) by targeting the 3'untranslated region of ATG5. Enforced expression of ATG5 reversed the effects of miR-638 overexpression on cell viability and cell apoptosis in H/R-treated HCMs. More importantly, H/R treatment promoted autophagy in the HCMs, and this effect was significantly reversed by miR-638 mimic transfection. CONCLUSIONS: Our results suggested that the overexpression of miR-638 attenuated the effects of H/R treatment on cell viability, cell apoptosis and autophagy, at least partly by regulating the ATG5 expression in the HCMs.

[Dementia screening and diagnostic framework in Chinese population].

There are no standard diagnostic criteria for Alzheimer's disease (AD) in China. The copied international criteria has led to a high rate of missed diagnosis due to issues such as translation and cultural discrepancy. Under the principles of semantic equivalence, content equivalence and performance equivalence, the research group of Alzheimer's Disease Chinese (ADC) adopted several effective methods, such as two-way translation, content conversion, performance evaluation, etc. to systematically study the cognitive, behavioral, functional, and general assessment techniques in dementia screening and diagnosis, as well as their screening thresholds and diagnostic values. We also established a dementia screening and assessment framework in clinical practice through systematic reviews and group consensus. It has improved the early diagnosis rate of dementia in China, been accepted by home and abroad academic institutions, which is of great significance for early diagnosis and treatment of dementia.

Homoclinic-doubling and homoclinic-gluing bifurcations in the Takens-Bogdanov normal form with D 4 symmetry.

In this paper, we investigate the dynamics of a fourth-order normal form near a double Takens-Bogdanov bifurcation. The reduced system of this normal form possesses eight pairs of homoclinic orbits for certain parameter values. The nonlinear time transformation method is applied to obtain an analytical approximation of the homoclinic orbit in the perturbed system and to construct the homoclinic bifurcation curve as well. Using numerical continuation, period-doubling and homoclinic-doubling cascades emanating from a codimension-2 bifurcation point are found. A codimension-2 homoclinic-gluing bifurcation point at which several homoclinic orbits concerning the origin glue together to form a new homoclinic orbit is also obtained. It is shown that in the vicinity of these bifurcation points, the system may exhibit chaos and chaotic attractors.

Differential expression of HPG-axis genes in autotetraploids derived from red crucian carp Carassius auratus red var., ♀ × blunt snout bream Megalobrama amblycephala, ♂.

Autotetraploid fish (4n = 200, abbreviated as 4nRR), which reach sexual maturity at 1 year of age, were derived from the whole genome duplication of red crucian carp Carassius auratus red var. (RCC; 2n = 100) and possess four sets of chromosomes from RCC. The histological features of the gonads showed that the RCC and 4nRR both possessed normal gonadal structure and could arrive at maturation. To understand the expression characteristics of genes related to reproductive development in the autotetraploid fish, we analysed the nucleotide sequence and expression characteristics of the gnrh2, gthb and gthr genes, which are the pivotal genes of the hypothalamic-pituitary-gonadal (HPG) axis. We found that the gnrh2, gthb and gthr genes in 4nRR share remarkable homology with RCC, but there were obvious differences in expression levels between 4nRR and RCC. These results demonstrate that autotetraploidization can lead to gene expression changes. This study provides insights into the molecular mechanism underlying the reproductive development of autotetraploid fish and is expected to be of great significance for subsequent research on polyploidization.