Environmental Exposure ; adverse effects ; Hearing Loss ; etiology ; Humans ; Noise, Occupational ; adverse effects ; Occupational Diseases ; etiology ; Occupational Exposure ; adverse effects ; Risk Factors ; Smoking ; adverse effects ; Vibration ; adverse effects

Alternative splicing of pre-messenger RNA (pre-mRNA) is a crucial mechanism for the diversity of the human transcriptome and proteome. Alternative splicing is a complex gene regulation process. Whole-transcriptome analysis shows that 95% of human exonic genes are alternatively spliced, involving various cis-acting elements and trans-acting factors. Any changes in any component or step may cause erroneous splicing events and lead to the occurrence of various related diseases. In addition to gene replacement therapy that directly changes the splicing results, RNA splicing modification is expected to become a new therapeutic strategy to alleviate or treat diseases by targeting and correcting abnormal pre-mRNA splicing. Splicing modification tools currently developed including RNA trans-splicing, antisense oligonucleotides, small interfering RNA, and small molecule drugs can correct abnormal splicing through different ways. This article reviews the resent progress of epigenetic regulation of pre-mRNA alternative splicing in recent years, and discusses the occurrence and regulation of alternative splicing, the types of diseases caused by related splicing defects, and the current-used tools for targeting and altering splicing. The importance of splicing modification strategies in the future treatment of human diseases is envisioned.

In order to obtain the bifunctional chimeric molecule of single-chain urokinase-type plasminogen activator (scu-PA) which can inhibit platelet aggregation, PRGDWR peptide was inserted into the site between Gly 118 and Leu119 (called insertion mutant B, InB). The recombinant gene of InB was expressed by Pichia pastoris. The secreted protein was purified by metal chelate affinity and strong cation exchange chromatography. The amidolytic ability of mutant InB is 5 900 IU/mg, the kinetic constants is: KInB m,plg=56.8 μmol*L-1，kInBcat,plg=0.33 s- 1. The kinetic constants of plasminogen activation reaction is: KInB m,plg=0.397 μmol*L-1，kInBcat,plg=0.0164 s-1. Fibrin inhibit the catalytiv ability of InB during plasminogen activatio n, the influence factor is 0.463(means InB remain 46.3% of the catalytic abili ty when fibrin was involved in the reaction system). The mutant not only has alm ost the same catalytic ability as wild type scu-PA, but also has strong ability of anti-platelet aggregation(compared with scu-PA), IC50 of InB is 12.7 μmol*L-1.

Because the influence of fibrin on the reaction of plasm inogen activation by various plasminogen activators is different, the kinetic co nstant of the reaction of plasminogen activation catalyzed by InB with and witho ut fibrin were detected. The result is: Kfibrinm＝4.2 μmol*L -1，greater than the normal Km=0.379 μmol*L-1; kfib rincat＝0.107 s-1，greater than the normal kcat=0.0165 s-1. The results suggest that existence of fibrin in the reaction system of plasminogen activation depress the affinity between InB and plasminog en, but accelerates the hydrolysis of plasminogen by InB. The count up effect is inhibition.

Objective To observe the effect of acupuncture combined with massage on vertebral artery cervical spondylosis.Methods 100 patients with vertebral artery cervical spondylosis were randomly divided into the treatment group and control group with 50 cases in each group.The cases of the treatment group were treated with acupuncture neck to Jiaji,Baihui,Wind Point acupoints and massage therapy.The cases of the control group only took sibelium orally.Results The cure rate and total effective rate of the treatment group were 70.0% and 98.0% respectively;those of the control group were 51.1% and 86.0%.There was a significant difference in cure rate and total effective rate between two groups(P<0.05～0.01).Conclusion Acupuncture combined with massage treatment is effect on vertebral artery cervical spondylosis.

Humans ; Noise, Occupational ; adverse effects ; Occupational Exposure ; standards

Flavonoids ; analysis ; Soybeans ; analysis

Objective To study the differential proteome of kidney between lupus nephritis mouse and normal mouse.Methods The proteins of kidney were separated by two-dimensional gel electrophoresis(2-DE).The gels stained by silver were scanned by ImageScanner and analyzed by PDQuest software.Results About 573?52 and 658?43 protein spots were found in the three maps of control group and LN group respectively;the match ratio was 83% and 87% respectively.One hundred and fourteen spots were found increased that showed a two fold increase as comparing to control group.Conclusion A significant difference in protein expression of LN mouse kidney was found and may be related to the pathogenesis of LN.

To determine the etiologic agent of an outbreak of influenza viruses from Changsha Foothill Mountain International School in 2009, and to analyze the HA Gene Characteristic of the H1N1 influenza viruses. Twenty-five nasopharyngeal swab specimens from the outbreak of influenza viruses were tested by conventional RT-PCR and influenza viruses isolated simultaneously. Virus isolated (A/Yuelu/314/2009) from the outbreak was sequenced by CEQTM 8000 Genetic Analysis System and the sequencing results submitted to GenBank (Accession No: FJ912843), then the sequencing data was analyzed by ClustalX and Mega4.1softwares. Results showed the influenza viruses A(H1N1) of positive were 18 cases by influenza viruses isolated tests and 21 cases by conventional RT-PCR, respectively. The nucleotide and amino acid sequence homology of the HA gene of A/Yuelu/314/2009 are 99% compare with the vaccine strain (A/Brisbane/59/2007) in 2008~2009 years. The HA sequence data also showed that had 6 amino acid mutations (V148A, S158N, G202A, I203D, A206T, W435R), and the S158N located at antigenic site B of HA protein. Nine potential glycosylation sites (27, 28, 40, 71, 151, 176, 303, 497, 536) in the HA sequence of A/Yuelu/314/2009 is the same with A/Brisbane/59/2007, and the sequences of potential glycosylation sites were conserved. In this study, laboratory evidence diagnosed seasonal influenza A virus (H1N1) as the etiologic agent of the outbreak. The virus isolated (A/Yuelu/314/2009) strain of H1N1 subtype is not a new variant in Changsha in 2009 compare with the vaccine strain (A/Brisbane/59/2007), the outbreak of influenza A virus (H1N1) from Changsha Foothill Mountain International School maybe are caused by the change in genetic characteristics between vaccine strains and the decreased of immunity to influenza A virus (H1N1) in the crowd.

Extracellular single-unit discharge recording technique was used to examine the effects of Ginkgolide B (BN52021) on the discharges of neurons in CAI area of hippocampal slices and to elucidate the mechanisms involved.The results showed that:(1) In response to the application of ginkgolide B (0.1,1,10 βμmol/L; n =43) into the perfusate for 2 rain,the spontaneous discharge rates (SDR) of 42/43 (97.67%) neurons were significantly decreased in a dose-dependent manner; (2) Pretreatment with L-glutamate (L-Glu,0.2mmol/L) led to a marked increase in the SDR of all 10 (100%) neurons in an epileptiform pattern.The increased discharges were suppressed significantly after ginkgolide B (1 μmol/L) was applied into the perfusate for 2 rain; (3) In 8 neurons,perfusion of the selective L-type calcium channel agonist,Bay K 8644 (0.1 μmol/L),induced a significant increase in the discharge rate of 8/8 (100%) neurons.Ginkgolide B (1 μmoL/L) applied into the perfusate inhibited the discharges of 7/8 (87.5%) slices; (4) In 8 neurons,the broad potassium channels blocker,tetraethylammonium (TEA,1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 μmol/L).These results suggest that ginkgolide B can inhibit the electrical activity of CAI neurons.The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and may be concerned with delayed rectifier potassium channel (KDR),which indicated that ginkgolide B play a protective role on the central neurons.