Human brucellosis and fever of unknown origin.

BACKGROUND: Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted. METHODS: We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records. RESULTS: The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05). CONCLUSION: Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis.

Biodegradation of 5-chloro-2-picolinic acid by novel identified co-metabolizing degrader Achromobacter sp. f1.

Several bacteria have been isolated to degrade 4-chloronitrobenzene. Degradation of 4-chloronitrobenzene by Cupriavidus sp. D4 produces 5-chloro-2-picolinic acid as a dead-end by-product, a potential pollutant. To date, no bacterium that degrades 5-chloro-2-picolinic acid has been reported. Strain f1, isolated from a soil polluted by 4-chloronitrobenzene, was able to co-metabolize 5-chloro-2-picolinic acid in the presence of ethanol or other appropriate carbon sources. The strain was identified as Achromobacter sp. based on its physiological, biochemical characteristics, and 16S rRNA gene sequence analysis. The organism completely degraded 50, 100 and 200 mg L-1 of 5-chloro-2-picolinic acid within 48, 60, and 72 h, respectively. During the degradation of 5-chloro-2-picolinic acid, Cl- was released. The initial metabolic product of 5-chloro-2-picolinic acid was identified as 6-hydroxy-5-chloro-2-picolinic acid by LC-MS and NMR. Using a mixed culture of Achromobacter sp. f1 and Cupriavidus sp. D4 for degradation of 4-chloronitrobenzen, 5-chloro-2-picolinic acid did not accumulate. Results infer that Achromobacter sp. f1 can be used for complete biodegradation of 4-chloronitrobenzene in remedial applications.

Complement factor H and susceptibility to major depressive disorder in Han Chinese.

BACKGROUND: Accumulating evidence suggests that altered immunity contributes to the development of major depressive disorder (MDD). AIMS: To examine whether complement factor H (CFH), a regulator of activation of the alternative pathway of the complement cascade, confers susceptibility to MDD. METHOD: Expression analyses were tested in 53 unmedicated people with MDD and 55 healthy controls. A two-stage genetic association analysis was performed in 3323 Han Chinese with or without MDD. Potential associations between CFH single nucleotide polymorphisms and age at MDD onset were evaluated. RESULTS: CFH levels were significantly lower in the MDD group at both protein and mRNA levels (P = 0.009 and P = 0.014 respectively). A regulatory variant in the CFH gene, rs1061170, showed statistically significant genotypic and allelic differences between the MDD and control groups (genotypic P = 0.0005, allelic P = 0.0001). Kaplan-Meier survival analysis showed that age at onset of MDD was significantly associated with the C allele of rs1061170 (log rank statistic χ(2) = 6.82, P = 0.009). The C-allele carriers had a younger age at onset of MDD (22.2 years, s.d. = 4.0) than those without the C allele (23.6 years, s.d. = 4.3). CONCLUSIONS: CFH is likely to play an important role in the development of MDD. rs1061170 has an important effect on age at onset of MDD in Han Chinese and may therefore be related to early pathogenesis of MDD, although further study is needed.

Contribution of long duration of undiagnosed bipolar disorder to high frequency of relapse: A naturalistic study in China.

BACKGROUND: With attention to misdiagnosis of bipolar disorder (BP), long duration of undiagnosed bipolar disorder (DUBP) had been reported recently in years. This study aims to investigate the contributions of long DUBP to the frequency of relapse in bipolar patients, and explore affect factors of DUBP. METHOD: From 26 hospitals throughout China, 3896 participants diagnosed with BP according to International Classification of Diseases 10th criteria were enrolled in this study. Socio-demographic and clinical data were collected from medical records and specific questionnaires through clinical interviews with patients and their relatives. RESULTS: (1) Our results showed that the mean of DUBP was 40.52months. In total, 779 patients (19.995%) reported DUBP greater than 5years, and 1931 patients (49.564%) reported their DUBP greater than 2years. The number of mood episodes was averaged 5.44, and the frequency ratio of (hypo) mania to depressive episodes was 1.49 (3.27/2.19). (2) Multiple linear regression analysis revealed that DUBP was significantly contributed to the number of relapse (Beta=0.072, p<0.001) after considering the confounding including gender, age at study entry, age of onset, age of first (hypo) manic episodes, age of first depressive episodes, type of first episodes and family history of mental illness. (3) Factors including age at the study entry (Beta=0.526, p<0.001), age of onset (Beta=-1.654, p<0.001), age of first (hypo) manic episode (Beta=0.348, p<0.001), age of first depressive episode (Beta=0.983, p<0.001), depression as the type of first episode (Beta=0.058, p<0.001) and family history of mental illness (Beta=0.029, p<0.05) were significantly contributed to long DUBP. CONCLUSION: It was concluded that long DUBP might lead to high frequent relapse in bipolar patients. The factors correlated with long DUBP include older age, early age of onset, depression as the type of first episode and family history of mental illness. The findings of our study suggest emergency task to early reorganization of bipolar disorder, and improving clinicians' recognition of bipolar disorder from patients with depressive episodes, especially in children and adolescents.

Aquamicrobium terrae sp. nov., isolated from the polluted soil near a chemical factory.

A Gram-negative, aerobic, non-motile bacterial strain hun6(T) isolated from the polluted soil near a chemical factory in northern Nanjing, China was investigated to clarify its taxonomic position. Growth of strain hun6(T) occurred between 10 and 45 °C (optimum, 30 °C) and between pH 6.0 and 8.0 (optimum, pH 7.0). No growth occurred at NaCl concentrations greater than 5 % (w/v). The 16S rRNA gene sequence analysis indicated that strain hun6(T) belongs to the genus Aquamicrobium. The sequence similarities of strain hun6(T) to other type strains of Aquamicrobium genus were all below 98.5 %. The presence of ubiquinone-10, the predominant fatty acid summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) and C19:0 cyclo ω8c, a polar lipid pattern with phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, phosphatidylethanolamine and phophatidylmonomethylethanoamine were in accord with the characteristics of the genus Aquamicrobium. The G+C content of the genomic DNA was determined to be 63.5 mol%. The results of DNA-DNA hybridization, physiological and biochemical tests and chemotaxonomic properties allowed genotypic and phenotypic differentiation of strain hun6(T) from all known Aquamicrobium species. Therefore, strain hun6(T) can be assigned to a new species of this genus for which the name Aquamicrobium terrae sp. nov. is proposed. The type strain is hun6(T) (= CICC 10733(T) = DSM 27865(T)).

Global research status and trends of enteric glia: a bibliometric analysis.

Background: Enteric glia are essential components of the enteric nervous system. Previously believed to have a passive structural function, mounting evidence now suggests that these cells are indispensable for maintaining gastrointestinal homeostasis and exert pivotal influences on both wellbeing and pathological conditions. This study aimed to investigate the global status, research hotspots, and future directions of enteric glia. Methods: The literature on enteric glia research was acquired from the Web of Science Core Collection. VOSviewer software (v1.6.19) was employed to visually represent co-operation networks among countries, institutions, and authors. The co-occurrence analysis of keywords and co-citation analysis of references were conducted using CiteSpace (v6.1.R6). Simultaneously, cluster analysis and burst detection of keywords and references were performed. Results: A total of 514 publications from 36 countries were reviewed. The United States was identified as the most influential country. The top-ranked institutions were University of Nantes and Michigan State University. Michel Neunlist was the most cited author. "Purinergic signaling" was the largest co-cited reference cluster, while "enteric glial cells (EGCs)" was the cluster with the highest number of co-occurring keywords. As the keyword with the highest burst strength, Crohns disease was a hot topic in the early research on enteric glia. The burst detection of keywords revealed that inflammation, intestinal motility, and gut microbiota may be the research frontiers. Conclusion: This study provides a comprehensive bibliometric analysis of enteric glia research. EGCs have emerged as a crucial link between neurons and immune cells, attracting significant research attention in neurogastroenterology. Their fundamental and translational studies on inflammation, intestinal motility, and gut microbiota may promote the treatment of some gastrointestinal and parenteral disorders.

Paracoccus zhejiangensis sp. nov., isolated from activated sludge in wastewater-treatment system.

A bacterial strain, designated J6(T), was isolated from activated sludge, collected from a chemical wastewater treatment system in Zhejiang Province of China. The cells stained Gram-negative, were aerobic, pale-yellow, and non-motile short rods. Phylogenetic analysis of the 16S rRNA gene sequence indicated that the closest relative of this organism was Paracoccus aminophilus KACC 12262(T) = JCM 7686(T) (97.4 % sequence similarity). Strain J6(T) grew at 10-37 °C (optimum 30 °C), at pH 6.0-8.0 (optimum pH 7.0) and with 0-5 % NaCl (optimum 3 %, w/v). The predominant cellular fatty acid found was summed feature 8(C18:1 ω7c and/or C18:1 ω6c; 82.8 %). The major respiratory quinone-detected was Q-10 and the DNA G+C content was 61.9 mol %. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and several unknown polar lipids. Strain J6(T) showed low DNA-DNA relatedness values with P. aminophilus KACC 12262(T) (28 ± 3 %). The phylogenetic analysis, DNA-DNA hybridization, whole-cell fatty acid composition as well as biochemical characteristics allowed clear differentiation of the isolate from the other type strains of already described Paracoccus species. It is evident from the genotypic, phenotypic and chemotaxonomic analyses that strain J6(T) should be classified as a novel species of the genus Paracoccus, for which the name P. zhejiangensis sp. nov. is proposed. The type strain is J6(T) (KACC 16703(T) = CCTCC AB 2012031(T)).

Effect of acupuncture on neuroinflammation in animal models of Alzheimer's disease: A preclinical systematic review and meta-analysis.

Background: Despite neuroinflammation being an important component of the pathology of Alzheimer's disease (AD), effective therapies to alleviate neuroinflammation are still lacking. Many animal experiments in AD have found that acupuncture may ameliorate cognition by decreasing neuroinflammation and modulating cytokines, but its effects have not been systematically examined. We aimed to assess its efficacy on neuroinflammation in AD and to investigate the potential mechanisms. Materials and methods: The following databases were searched from inception until 24 August 2022: Web of Science, EMBASE, PubMed, the Cochrane Library, and China National Knowledge Infrastructure. Animal studies that reported the efficacy of acupuncture on neuroinflammation in AD were included. The SYRCLE Robt was utilized to evaluate methodological quality. Stata 17 was utilized to conduct a meta-analysis of cytokine levels and the results of the Morris water maze. Results: 23 studies were included, with a total of 417 rats/mice. The overall quality of all included reports was medium. The results indicated that acupuncture significantly reduced the expressions of pro-inflammatory cytokines which included IL-1ß [SMD = -3.50, 95% CI (-4.31, -2.69); I 2 = 78.6%] (P < 0.05), TNF-α [SMD = -3.05, 95% CI (-3.86, -2.24); I 2 = 69.6%] (P < 0.05), IL-6 [SMD = -3.22, 95% CI (-4.62, -1.81); I 2 = 77.6%] and enhanced the expressions of anti-inflammatory cytokines including IL-4 [SMD = 2.77, 95% CI (1.95, 3.59); I 2 = 33.9%] (P < 0.05), IL-10 [SMD = 1.84, 95% CI (1.20, 2.49); I 2 = 41.0%] (P < 0.05) in an animal model of AD. Regarding the Morris water maze, compared to the control group, the acupuncture group showed a shorter escape latency [SMD = -2.23, 95% CI (-2.89, -1.57); I 2 = 79.2%] (P < 0.05), longer duration in platform quadrant [SMD = 2.34, 95% CI (1.44, 3.23); I 2 = 81.7%] (P < 0.05), and increased platform crossing number [SMD = 2.79, 95% CI (2.06, 3.53); I 2 = 71.9%] (P < 0.05). Conclusion: Acupuncture may reduce neuroinflammation in AD by modulating cytokine expression. This modulation significantly improved cognitive function in animal models of AD. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354878.

[Neuronal synaptic reconstruction in hippocampus in chronic phase of pilocarpine-treated rats].

OBJECTIVE: To explore the aberrant formation of excitatory and inhibitory circuit rearrangements of hippocampus in temporal lobe epilepsy. METHODS: Pilocarpine-induced animal model was established. At around Day 60 post-modeling, retrograde tracer fluorogold (FG) was injected in vivo into CA1 and CA3 areas of hippocampus by stereotaxic apparatus. Immunohistochemistry of FG was used to observe the aberrant excitatory circuit rearrangements. Double immunofluorescence with NPY (neuropeptide Y) and FG was performed to observe the aberrant inhibitory circuit rearrangements. RESULTS: After an injection of FG into CA1 area, the FG-labeled pyramidal cells could be observed distantly from the zone of dye spread in CA1 area, CA3 area and subiculm. And the FG-labeled non-principal neurons could be seen in stratum oriens of CA1 and hilus in experimental group. Double immunofluorescence revealed that the FG-labeled NPY interneurons were located distantly from the zone of dye spread in CA1 area, CA3 area and hilus in experimental rats. When injection was administered in CA3 area, the FG-labeled pyramidal cells were visible in the whole CA3 area and hilus in both groups. Some pyramidal cells were present in CA1 in experimental group. Also some FG-labeled non-principle cells were found in hilus and distantly from the zone of dye spread in CA1 area. And the FG-labeled NPY neurons could be seen in hilus in experimental rats. CONCLUSION: Aberrant excitatory and inhibitory synaptic reconstruction exist in hippocampus in chronic phase of temporal lobe epilepsy, including excitatory synaptic connections among pyramidal cells in CA1 area, pyramidal cells between CA1 and subiculum and pyramidal cells between CA1 and CA3, inhibitory synaptic connections among dendritic interneurons in CA1 area, CA3 to CA1, hilus to CA1 and hilus to CA3 area. These circuit arrangements may play an important role in the pathogenesis of epilepsy.

[Association analysis between dopamine D1 receptor gene and symptom quantitative trait of schizophrenia].

OBJECTIVE: To explore the relationship between dopamine D1 receptor gene (DRD1) and symptom quantitative trait of schizophrenia. METHODS: Peripheral blood samples were collected from 211 schizophrenics and 247 healthy controls at our center. Five tag SNPs (single nucleotide polymorphisms) (rs4532, rs5326, rs2168631, rs6882300 & rs267418) within DRD1 gene were genotyped by TaqMan SNP genotyping assay. The positive and negative syndrome scale (PANSS) was used to quantify the phenotypes of schizophrenia. RESULTS: No significant differences existed in the frequencies of genotypes and alleles of DRD1 gene between the schizophrenics and normal controls (Ps > 0.05); strong linkage disequilibrium was observed between rs4532 and rs5326 (D' = 0.84); no significant difference of haplotypic distribution was identified between the patients and controls (Ps > 0.05); the patients with rs4532G allele had a higher negative subscale score than those without G allele (20.3 ± 3.3 vs 18.2 ± 3.9, P < 0.01). CONCLUSION: The rs4532 within DRD1 gene may be associated with negative symptom quantitative trait in schizophrenia.

NEAT1 knockdown suppresses endothelial cell proliferation and induces apoptosis by regulating miR­638/AKT/mTOR signaling in atherosclerosis.

Long non­coding RNAs (lncRNAs) have been validated to mediate the development of atherosclerosis (AS). In the present study, the molecular mechanisms and functions of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in the advancement of human aortic endothelial cells (HAECs) were investigated. The levels of lncRNA­NEAT1 and miR­638 expression in clinical samples and cells were explored via quantitative reverse transcription polymerase chain reaction. Colony formation and CCK­8 assays were performed to determine the proliferative capacity of cells, and the apoptotic capacity of cells was analyzed on the basis of apoptotic cell proportion and caspase­3 activity. Then, the proportion of cells and correlations among phosphoglycerate kinase 1 (PGK1), NEAT1, and miR­638 were determined through RNA immunoprecipitation and luciferase assays and bioinformatics analysis. Moreover, the expression levels of Ki­67, proliferating cell nuclear antigen, PGK1, Bax, Bcl­2, (p)­mTOR, (p)­AKT, and ß­catenin were analyzed via western blot analysis. In the serum of patients with AS and HAECs induced by oxidized low­density lipoprotein (ox­LDL), the expression level of miR­638 was decreased, whereas that of NEAT1 was increased. After ox­LDL therapy, NEAT1 knockdown suppressed HAEC proliferation and stimulated HAEC apoptosis, which could be reversed by the miR­638 inhibitor. NEAT1 inhibited miR­638 expression through direct mutual action. The following mechanical investigations revealed that PGK1 was a miR­638 target, whose expression was increased by NEAT1, a competing endogenous RNA of miR­638. Additionally, the miR­638 inhibitor contributed to proliferation and suppressed apoptosis through the activation of the AKT/mTOR signaling pathway in ox­LDL­induced HAECs. NEAT1 adjusted the AKT/mTOR signaling pathway via miR­638 in ox­LDL­induced HAECs to accelerate their proliferation and impede their apoptosis. This result revealed that NEAT1 may be valuable in the treatment of AS.

Altered resting-state fMRI signals and network topological properties of bipolar depression patients with anxiety symptoms.

BACKGROUND: This study aims to explore the changes in functional neuroimaging in bipolar depression patients with anxiety symptoms (BDP-A). METHODS: Forty-five BDP-A patients, 22 bipolar depression patients without anxiety symptoms (BDP-NA), and 48 healthy controls (HC) were finally involved. The low-frequency oscillation characteristics, functional connectivity (FC), and network properties among the three groups of participants were analyzed. RESULTS: Compared with the BDP-NA group, BDP-A patients exhibited significantly decreased amplitude of low-frequency fluctuation (ALFF) in the left middle frontal gyrus (MFG), superior occipital gyrus, and inferior parietal, but supramarginal and angular gyri (IPL). Enhanced FC from left IPL to middle temporal gyrus, from left precentral gyrus (PreCG) to bilateral angular gyri, medial superior frontal gyrus, and left superior frontal gyrus (SFG)/MFG were also revealed. Compared with HC, the BDP-A group showed remarkably increased ALFF in the left MFG/PreCG, right superior parietal gyrus, while decreased ALFF in the left inferior frontal gyrus, opercular part, and SFG. In addition, higher regional homogeneity in the left MFG/PreCG was found. LIMITATIONS: The limitations are as follows: (1) relatively small sample size; (2) not all the patients were drug-naive; (3) lack of pure anxiety disorder patients as a controlled group; (4) mental health conditions of HC were not systemic evaluated. CONCLUSIONS: BDP-A patients showed significant differences in resting-state fMRI properties when compared with BDP-NA or HC group. These results may infer the dysfunction of the dorsal attention network, the default network, and the fronto-limbic system as well as disrupted brain network efficiency in BDP-A patients.

[Fine mapping of a pure paroxysmal kinesigenic dyskinesia family].

OBJECTIVE: To fine map the gene responsible for pure paroxysmal kinesigenic dyskinesia in a Chinese family. METHODS: Six additional markers flanking the tightly linked markers were chosen in the candidate region resulting from a whole genome-wide scanning and tested by parameter and nonparameter analysis using Linkage and Genehunter softwares to fine map the candidate region. RESULTS: Evidence for linkage of the pure paroxysmal kinesigenic dyskinesia to chromosome 3 was further confirmed. A maximum two-lod score of 2.82 at theta=0 was obtained with D3S3669. Critical recombinants place the PKD gene between D3S1314 and D3S1265. CONCLUSION: A new locus of pure paroxysmal kinesigenic dyskinesia (PKD) is localized within a 10.2 cM interval on 3q28-29, between markers D3S1314 and D3S1265.

Clinical characteristics associated with therapeutic nonadherence of the patients with major depressive disorder: A report on the National Survey on Symptomatology of Depression in China.

AIMS: Nonadherence is one of the leading challenges to treatment of the major depressive disorder (MDD). Few studies have systematically analyzed the relationship between clinical characteristics, especially symptoms of depressive patients and their therapeutic nonadherence over a relatively large sample. This study aimed to investigate factors of nonadherence in a nationwide survey in China. METHODS: Participants with MDD who met the criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) were recruited from 32 sites throughout China. Patients were all over 16 years old. A doctor-rating questionnaire with 64 symptoms based on DSM-IV was constructed to evaluate depression-related feeling and behavior. Single-factor logistic regression was utilized to screen variables, and multifactor logistic regressive analysis was used to identify which factors were risk or protective for nonadherence. We included 882 patients of poor adherence and 857 patients of good adherence. RESULTS: Recurrence, untreated first episode, tricyclic antidepressant (TCA)-treated first episode, antidepressant-only-treated current episode, decrease or loss of interest, more somatic symptoms, and "atypical" symptoms were risk factors for nonadherence, whereas selective noradrenaline reuptake inhibitor (SNRI)-treated first episode was a protecting factor. CONCLUSION: Clinical characteristics may play an important role in predicting nonadherence. Doctors may have to pay much attention on patients with these factors and should keep on discussing them with patients.

Expression and localization of Fas-associated proteins following focal cerebral ischemia in rats.

The aim of this study was to investigate the changes of expression of Fas-associated proteins and its cellular localization in the peri-infarct region following transient focal cerebral ischemia. Adult male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAo) for 2 h and reperfusion for 1, 3, 6, 12 and 24 h. The expression of Fas-associated death domain protein (FADD), Fas-associated phosphatase-1 (FAP-1) caspase-8 and death-associated protein (Daxx), the pro-apoptotic genes, were examined by methods of RT-PCR, immunohistochemistry and Western blot. The results showed that the expression levels of mRNA and protein for FADD and caspase-8 increased significantly at 1-3 h after reperfusion, peaked at 12 h, then declined markedly at 24 h. The time course change of FAP-1 was consistent with that of FADD. The expression level of mRNA and protein for death-associated protein (Daxx) increased significantly at 3 h after reperfusion and persisted for 24 h at a high level. Immunofluorescence double-staining laser scanning showed that the immunoreactivity of FADD was localized in cytoplasm, and Daxx immunoreactivity was translocated from nucleus to cytoplasm at 3 h after reperfusion. The TUNEL-positive cells could be found in peri-infarct region at 3 h and increased with time after reperfusion. Our findings suggest a possible association between expression of FADD, caspase-8, Daxx and FAP-1 genes and apoptosis following ischemia.

[A preparative method of chronic experiment autoimmune encephalomyelitis].

OBJECTIVE: To explore the model of chronic experimental autoimmune encephalomyelitis (EAE)for the further study of multiple sclerosis. METHODS: A total of 72 female SPF C57BL/6J mice (inbred strain, aged 8 approximately 10 weeks), were randomly divided into an EAE group, a blank group and an adjuvant group, and each group was divided into 3 subgroups: an onset group, a peak group and a chronic phase group. The EAE group was immunized with mMOG35-55. RESULTS: At the end of the study, and 83.3% of the mice in EAE group suffered the onset, and 8.3% of the mice died. The highest clinical score reached grade 5, namely paralysis of the whole body and then death. In the EAE group, after being immunized first, the mice were all anosis during the first 13 days. They got ill on the third week, and in about 20 approximately 24 days the clinical symptom reached the peak, and in 28 approximately 32 days the chronic phase arrived,when parts of the clinical symptoms got relieved. On the contrary, both the adjuvant group and the blank group were healthy all the time. Characteristic appearance was detected in the EAE group. CONCLUSION: Antigen emulsion, mixture of artificially synthesized mMOG35-55 and complete Freundos adjuvant can successfully induce chronic EAE in the mice. The model of EAE duplicated in our study has the characteristics of high incidence, low death rate and stability, which can be used to carry out further research on multiple sclerosis.

A highly conserved G-rich consensus sequence in hepatitis C virus core gene represents a new anti-hepatitis C target.

G-quadruplex (G4) is one of the most important secondary structures in nucleic acids. Until recently, G4 RNAs have not been reported in any ribovirus, such as the hepatitis C virus. Our bioinformatics analysis reveals highly conserved guanine-rich consensus sequences within the core gene of hepatitis C despite the high genetic variability of this ribovirus; we further show using various methods that such consensus sequences can fold into unimolecular G4 RNA structures, both in vitro and under physiological conditions. Furthermore, we provide direct evidences that small molecules specifically targeting G4 can stabilize this structure to reduce RNA replication and inhibit protein translation of intracellular hepatitis C. Ultimately, the stabilization of G4 RNA in the genome of hepatitis C represents a promising new strategy for anti-hepatitis C drug development.

[Advance in researches on survival of motor neurons protein and its interaction proteins].

Survival of motor neurons(SMN) protein is the product of spinal muscular atrophy(SMA) gene. Now the function researching of SMN protein has become hotspot field to discuss the pathogenic mechanism of SMA. The construction, distribution and function of SMN protein are reviewed in this paper.

[Quantitative analysis of SMN gene copies in spinal muscular atrophy].

OBJECTIVE: To study the genetic basis in the patients with clinical diagnosis of spinal muscular atrophy(SMA) but without survival motor neuron telomeric copy (SMN-T) deletion; the relationship between the SMN-C (centromeric) copies and the phenotype; and the distribution of SMN-C and SMN-T copies in the SMA patients, the carriers and the controls. METHODS: Quantitative PCR analysis of SMN-T and SMN-C copies were carried out in 45 patients, 25 consanguineous and 33 control individuals. The patients were identified by clinical manifestation and muscular pathology. Two internal standards of SMN-T and cystic fibrosis transmembrane conductance regulator (CFTR) were constructed. Nonradioactive and nonfluorescence-labelling competitive PCR were used. The numbers of SMN-T and SMN-C copies were determined by calculating the ratios of SMN-T/CFTR and SMN-C/CFTR. RESULTS: Quantitation of SMN-T gene copies in SMA patients revealed that nine cases of type I-III were homozygously deleted. Two cases of type III had only one copy and four cases of type III had two copies. SMA IV and other type cases had two copies. Nine cases of consanguineous individuals had one copy, but other 16 had two copies. All of the normal individuals had two copies. Analysis of SMN-C copies showed that SMA I had < or = 2 copies, II-III had < or = 3 copies, SMA IV and others had 0-3 copies, the consanguineous individuals and normal individuals had 0-3 copies. CONCLUSION: The number of copies determined by PCR quantitative assay of SMN-T is in accordance with the result of PCR qualitative assay of homozygous deletion. Quantitative assay of the number of copies can find out the cases and the carriers of heterozygous deletion. The SMA phenotype is related to the number of copies of SMN-C; the smaller the number of copies the patient has, the severer the patient's phenotype will be. The pathogenesis of SMA IV and other types of SMA may not relate to SMN gene.