?AIM: To study correcting effect and visual quality after laser - assisted in situ keratomileusis ( LASIK ) with femtosecond and posterior chamber intraocular lens ( ICL) implantation in high myopia patients.?METHODS: Fifty-five patients ( 106 eyes ) with high myopia from February 2012 to February 2015 in our hospital were analyzed. According to the different operation, patients were divided into the observation group( using ICL implantation, 27 cases with 53 eyes) and the control group (using LASIK, 28 cases with 53 eyes). Postoperative follow-up was 1a, to observe and analyze the visual quality, higher order aberration and complications of two groups.?RESULTS: Uncorrected visual acuity ( UCVA ) , the best corrected visual acuity ( BCVA ) , effectiveness index and security index at 1a postoperatively of observation group, were 1. 04±0. 86(LogMAR), 0. 97±0. 19(LogMAR), 104. 69± 18. 56, 108. 79 ± 17. 68, significantly higher than those of control group 0. 78 ± 0. 11 ( LogMAR ), 1. 04 ± 0. 09 (LogMAR), 93.78±15. 65, 100. 71±11. 68 (P<0. 05). And observation group in the two kinds of light and shade environment at various spatial frequency contrast sensitivity were higher than the control group. Those under the light environment at 1. 5, 3, 6, 12 c/d and under dark environment at 1. 5, 3, 6, 18 c/d compared were different between the two groups (P<0. 05). Spherical aberration and comatic aberration of observation group at 1a after operation were lower than those of control group (P<0. 05 ). The difference of trefoil between the two groups was not significant ( P > 0. 05 ). No severe complications were observed in both groups.?CONCLUSION: LASIK with femtosecond and ICL lens implantation can effectively improve the patient’s visual quality, but for patients with high myopia, ICL lens implantation effect is more significant, the safety index of ICL implantation, as well as the effectiveness index and the visual quality are better than those of LASIK.

OBJECTIVETo explore the prevalence of IDH gene (IDH1 and IDH2) mutations, types of mutations in patients with acute myeloid leukemia (AML), correlation with the internal tandem duplication(ITD) mutation of FLT3 gene, NPM1 gene mutation and some clinical characteristics.

METHODSThe mutations of IDH1 and IDH2 gene at exon 4, NPM1 gene at exon 12 and FLT3-ITD at exon 14 and 15 in 163 newly diagnosed AML patients were detected by PCR amplification followed by direct sequencing of genomic DNA.

RESULTS(1) IDH mutations were found in 25 patients (25/163), and all were heterozygous, of which IDH1 in 7 patients (4.29%) and IDH2 in 18 (11.04%). A total of 4 types of IDH1 mutations were identified (c.395G→A, p.R132H, n = 4; c.394C→A, p.R132S, n = 1; c.394C→G, p.R132G, n = 1; c.315C→T, n = 1). The IDH1 mutation caused substitutions of residue R132 except for one (c.315C→T). All IDH2 mutations caused changes of R140 (c.419G→A, p.R140Q, n = 18). The incidence of IDH2 mutation was significantly higher than that of IDH1 mutation (11.0% v 4.3%, P = 0.022). Both IDH1 and IDH2 mutation were detected in one patient, while IDH1 was synonymous substitution (c.315C→T). IDH-mutated cases showed a significantly higher frequency of concurrent FLT3-ITD mutation compared with wildtype cases (34.6% vs 11.9%, P = 0.003), so did IDH mutations concurrent NPM1 mutation vs NPM1 wildtype (28.1% vs 12.7%, P = 0.033), of which the frequency of concurrent NPM1 and FLT-ITD mutations cases with the IDH mutation was significantly higher than that of NPM1 and FLT-ITD negative (45.5% vs 11.7%, P = 0.002). IDH mutation incidence was significantly higher in normal karyotype cases than in abnormal ones (20.5% vs 5.8%, P = 0.020). Patients with IDH mutations were significantly older than wildtype patients(P < 0.001), whereas, there were no statistically significant differences in gender, peripheral blood (PB) count at diagnosis between two groups.

CONCLUSIONSThe incidence of IDH mutation is higher in patients with de novo AMLs, of which IDH2 mutation more frequently, and the patients associated with older age, normal karyotype at diagnosis. IDH mutation has a strong association with NPM1 and FLT3-ITD mutations, suggesting that IDH mutation has synergistic effect with the latter gene on leukemogenesis.

Adolescent ; Adult ; Aged ; DNA Mutational Analysis ; Female ; Genotype ; Humans ; Isocitrate Dehydrogenase ; genetics ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Young Adult

This study is to explore the possible mechanisms of the antidepressant-like effect of agmatine. By using two traditional "behavior despair" model, tail suspension test and forced swimming test, we examined the effects of some monoamine receptor antagonists (including beta-adrenergic receptor antagonist propranolol, beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol, alpha2-adrenergic receptor antagonists yohimbine and idazoxan and 5-HT3 receptor antagonist tropisetron) on the antidepressant-like action of agmatine in mice. Activity of adenylate cyclase (AC) in the synapse membrane from rat frontal cortex was determined by radioimmunoassay. Single dose of agmatine (5-40 mg x kg(-1), ig) dose-dependently decrease the immobility time in tail suspension test in mice, indicating an antidepressant-like effect. The effect of agmatine (40 mg x kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg x kg(-1), ip), alpha2-adrenergic receptor antagonists yohimbine (5-10 mg x kg(-1), ip) or idazoxan (4 mg x kg(-1), ip), but not beta-adrenergic receptor antagonist propranolol (5-20 mg x kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5-40 mg x kg(-1), ip). Agmatine (5-40 mg x kg(-1), ig) also dose-dependently decrease the immobility time in forced swimming test in mice. The effect of agmatine (40 mg x kg(-1), ig) was also antagonized by pindolol (20 mg x kg(-1), ip), yohimbine (5-10 mg x kg(-1), ip), or idazoxan (4 mg x kg(-1), ip). Incubation of agmatine (0.1-6.4 micromol x L(-1)) with the synaptic membrane extracted from rat frontal cortex activated the AC in a dose-dependent manner in vitro. While the effect of agmatine (6.4 micromol x L(-1)) was dose-dependently antagonized by pindolol (1 micromol x L(-1)) or yohimbine (0.25-1 micromol x L(-1)). Chronic treatment with agmatine (10 mg x kg(-1), ig, bid, 2 w) or fluoxetine (10 mg x kg(-1), ig, bid, 2 w) increased the basic activity, as well as the Gpp (NH)p (1-100 micromol x L(-1)) stimulated AC activity in rat prefrontal cortex. These results indicate that regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action.
Adenylyl Cyclases ; metabolism ; Adrenergic alpha-Antagonists ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Agmatine ; administration & dosage ; pharmacology ; Animals ; Antidepressive Agents ; administration & dosage ; pharmacology ; Behavior, Animal ; drug effects ; Depression ; metabolism ; physiopathology ; Dose-Response Relationship, Drug ; Fenclonine ; pharmacology ; Idazoxan ; pharmacology ; Male ; Mice ; Pindolol ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Biogenic Amine ; antagonists & inhibitors ; Serotonin 5-HT1 Receptor Antagonists ; Swimming ; Synapses ; enzymology ; Yohimbine ; pharmacology

This study was aimed to explore the effects of STI571 alone or with As₂O₃ on proliferation, apoptosis and caspase 3, bcl-xL mRNA expression of K562 cells, and the molecular mechanism of As₂O₃ enhancing the anti-leukemia effect of STI571 so as to provide the scientific basis for clinical treatment of chronic myeloid leukemia. The effect of drugs on proliferation of K562 cells was assayed by MTT method, the apoptosis rate of K562 cells was detected by flow cytometry with Annexin V/PI double staining, the caspase 3, bcl-xL mRNA expressions of K562 cells were determined by real time quantitative PCR. The results showed that STI571 alone or with As₂O₃ both could inhibit the proliferation of K562 cells. OD value in test groups reduced along with prolonging of action times, the OD values between different time points were significantly different (p < 0.05), furthermore the OD values at 72 hours in test groups were lowest, while as compared with control group, OD values at same time points in test groups all gradually decreased, among which decrease of OD value in test 5 group was most significant. The flow cytometric detection indicated that along with time prolonging, the apoptotic rate in control group not obviously changed, but the apoptotic rate in test groups gradually increased, the difference between time points was significant (p < 0.05), moreover apoptotic rate increased most obviously at 72 hours, while as compared with control group, apoptotic rate at same time points in test groups was gradually enhanced (p < 0.05), among which the apoptotic rate in test 5 group was highest. The real time qPCR assay revealed that as compared with control group, the bcl-xL mRNA expression in test groups reduced with decrease of 2-ΔΔCT value, furthermore the decrease of expression level in test 3 group was higher than that in test 2 group (p < 0.05), while the caspase 3 mRNA expression in test groups was enhanced with increase of 2-ΔΔCT value, moreover the increase of expression level in test 3 group was higher than that in test 2 group (p < 0.05). It is concluded that the STI571 can inhibit the proliferation of K562 cells, accelerate the apoptosis of K562 cells. The STI571 combined with As₂O₃ can enhance these two effects, increase the expression of caspase-3 mRNA and decrease the expression of bcl-xL mRNA. Therefore, the effect of STI571 combined with As₂O₃ on expression of caspase 3 and bcl-xL mRNA may be one of molecular mechanisms underlying their synergic antileukemia efficacy.
Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Benzamides ; Caspase 3 ; metabolism ; Cell Proliferation ; drug effects ; Gene Expression Regulation, Leukemic ; Humans ; Imatinib Mesylate ; K562 Cells ; Oxides ; pharmacology ; Piperazines ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Pyrimidines ; pharmacology ; bcl-X Protein ; metabolism

As an extension of the structure-based drug discovery, fragment-based drug discovery is matured increasingly, and plays an important role in drug development. Fragments in a small library, with lower molecular mass and high "ligand efficiency", are detected by SPR, MS, NMR, X-ray crystallography technologies and other biophysical methods. Then they are considered as starting points for chemical optimization with the guidance of structural biology methods to get good "drug-like" lead and candidate compounds. In this article, we reviewed the current progress of fragment-based drug discovery and detailed a number of examples to illustrate the novel strategies.
Computer-Aided Design ; Crystallography, X-Ray ; Drug Discovery ; methods ; Ligands ; Magnetic Resonance Spectroscopy ; Peptide Fragments ; chemical synthesis ; chemistry ; Protein Conformation ; Small Molecule Libraries ; Surface Plasmon Resonance

BACKGROUNDIn China, no multicenter double-blinded prospective randomized controlled study on labor induction has been conducted till now. This study is to evaluate the efficacy and safety of intravaginal accurate 25-μg misoprostol tablets for cervical ripening and labor induction in term pregnancy in nulliparous women.

METHODSThis was a double-blinded, prospective randomized controlled study including nulliparous women from 6 university hospitals across China. Subjects were randomized into misoprostol or placebo group with the sample size ratio set to 7:2. Intravaginal 25-μg misoprostol or placebo was applied at an interval of 4 h (repeated up to 3 times) for labor induction. Primary outcome measures were the incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h. Safety assessments included the incidences of maternal morbidity and adverse fetal/neonatal outcomes.

RESULTSA total of 173 women for misoprostol group and 49 women for placebo were analyzed. The incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h was higher in the misoprostol group than in the placebo (64.2% vs. 22.5%, relative risk [RR]: 2.9, 95% confidence interval [CI]: 1.4-6.0). The incidence of onset of labor within 24 h was significantly higher in the misoprostol group than in the placebo group (48.0% vs. 18.4%, RR: 2.6, 95% CI: 1.2-5.7); and the induction-onset of labor interval was significantly shorter in the misoprostol group (P = 0.0003). However, there were no significant differences in the median process time of vaginal labor (6.4 vs. 6.8 h; P = 0.695), incidence (39.3% vs. 49.0%, RR: 0.8, 95% CI: 0.4-1.5) and indications (P = 0.683) of cesarean section deliveries, and frequencies of maternal, fetal/neonatal adverse events between the groups.

CONCLUSIONIntravaginal misoprostol 25 μg every 4 h is efficacious and safe in labor induction and cervical ripening.

Administration, Intravaginal ; Adult ; Cervical Ripening ; drug effects ; Double-Blind Method ; Female ; Humans ; Labor, Induced ; methods ; Misoprostol ; administration & dosage ; therapeutic use ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, Third ; Young Adult

BACKGROUNDVolatile anesthetics (VAs) may affect varied and complex physiology processes by manipulating Ca(2+)-calmodulin (CaM). However, the detailed mechanism about the action of VAs on CaM has not been elucidated. This study was undertaken to examine the effects of VAs on the conformational change, hydrophobic site, and downstream signaling pathway of CaM, to explore the possible mechanism of anesthetic action of VAs.

METHODSReal-time second-harmonic generation (SHG) was performed to monitor the conformational change of CaM in the presence of VAs, each plus 100 µmol/L Ca(2+). A hydrophobic fluorescence indicator, 8-anilinonaphthalene-1-sulfonate (ANS), was utilized to define whether the VAs would interact with CaM at the hydrophobic site or not. High-performance liquid chromatography (HPLC) was carried out to analyze the activity of CaM-dependent phosphodiesterase (PDE1) in the presence of VAs. The VAs studied were ether, enflurane, isoflurane, and sevoflurane, with their aqueous concentrations 7.6, 9.5, 11.4 mmol/L; 0.42, 0.52, 0.62 mmol/L; 0.25, 0.31, 0.37 mmol/L and 0.47, 0.59, 0.71 mmol/L respectively, each were equivalent to their 0.8, 1.0 and 1.2 concentration for 50% of maximal effect (EC50) for general anesthesia.

RESULTSThe second-harmonic radiation of CaM in the presence of Ca(2+) was largely inhibited by the VAs. The fluorescence intensity of ANS, generated by binding of Ca(2+) to CaM, was reversed by the VAs. HPLC results also showed that AMP, the product of the hydrolysis of cAMP by CaM-dependent PDE1, was reduced by the VAs.

CONCLUSIONSOur findings demonstrate that the above VAs interact with the hydrophobic core of Ca(2+)-CaM and the interaction results in the inhibition of the conformational change and activity of CaM. This in vitro study may provide us insight into the possible mechanism of anesthetic action of VAs in vivo.

Adenosine Monophosphate ; analysis ; Anesthetics, Inhalation ; pharmacology ; Anilino Naphthalenesulfonates ; Calmodulin ; antagonists & inhibitors ; chemistry ; physiology ; Cyclic Nucleotide Phosphodiesterases, Type 1 ; analysis ; Fluorescence ; Humans ; Hydrophobic and Hydrophilic Interactions

57 rubella virus strains were isolated using Vero cell line or Vero/SLAM cell line from patients' throat swabs during rubella outbreaks and sporadics in 10 provinces of China from 2003 to 2007. Fragments of 1107 nucleotides of E1 genes of the isolates were amplified by RT-PCR, the PCR products were directly sequenced and analyzed. The phylogenetic analysis based on 739 nucleotides showed that out of 57 Chinese rubella virus strains, 55 belong to a distinguish branch of 1E genotype when comparing with 1E genotype rubella strains from other countries, and the other 2 Chinese rubella virus strains belong to 2B genotype. Most of the nucleotide mutations of 57 rubella viruses were silent mutations, and the amino acid sequences were highly conserved. Except one amino acid change (Thr212 --> Ser212) in two rubella viruses at the hemagglutination inhibition and neutralization epitopes, there had no change found at the important antigenic epitope sites of the other rubella viruses. 1E genotype rubella viruses isolated from 10 provinces of China from 2003 to 2007, and two imported 2B genotype rubella viruses from Vietnam suggested that 1E genotype was the predominant genotype in this period of time. The rubella virus genotypes circulated during 2003 to 2007 were different from that circulating during 1979 to 1984 and 1999 to 2002, the rubella prevailed in recent years was mainly caused by 1E genotype rubella viruses with multi-transmission routes.
Genotype ; Mutation ; Phylogeny ; Rubella virus ; classification ; genetics ; isolation & purification ; Time Factors

To study the epidemic characteristics of human rhinovirus (HRV) in children with acute respiratory infections in Gansu Province. 286 throat swabs were collected from children with acute respiratory in fections in Gansu Province during 2011. Multiplex reverse transcription-PCR (multiplex RT-PCR) assay was used to screen those specimens for detection of common respiratory tract pathogens. For HRV-positive samples, nested reverse transcription polymerase chain reaction (nested RT-PCR) was performed to amplify VP1 and VP4/VP2 gene fragments of HRV. The VP4/VP2 and VP1 regions of HRV-positive samples were sequenced and performed genotype analysis. Of 286 specimens fested, 27 were positive for HRV by multiplex RT-PCR and nested RT-PCR, of which 16 children were made (16/185), 8.64%) and 11 female (11/101,10.89%). The positive rate was 9.44% (27/286). The mean age of HRV-positive children was 3 years in this study, children less than one year old had the highest proportion 44.4% (12/ 27, 44.4%). The highest HRV positive rate fell on May, 2011 (6/27, 22.2%). Common cold accounted for the highest proportion, 12.24% (12/98) followed by pneumonia, 8.50% (13/153). The remaining 2 cases were bronchitis. Sequence analysis showed HRV A was the predominant genotype in Gansu Province in 2011, accounting for 84.62% (22/26) of positive cases, followed by HRV C (11.54%, 3/26) and only one HRV B was detected (3.85%, 1/26). HRV could be detected throughout the year in Gansu Province and primarily infected children under one year old. The group A was the epidemic genotype of HRV and move than one genotype existed in Gansu Province during 2011.
Adolescent ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Male ; Molecular Sequence Data ; Phylogeny ; Picornaviridae Infections ; epidemiology ; virology ; Respiratory Tract Infections ; epidemiology ; virology ; Rhinovirus ; classification ; genetics ; isolation & purification ; Seasons

OBJECTIVETo analyze the CARL gene mutation in the patients with chronic myeloproliferative neoplasm(MPN) and to explore the clinical significance of CALR mutation.

METHODSThe peripheral blood of patients was collected and the genomic DNA was exacted, the 9 exon of CALR gene and the fragment of human thrombopoetic receptor(MPL) gene were amplified by PCR, the mutation of CALR and MPL genes was detected by using the direct sequencing, the JAK2 V617F mutation was detected by using allele spicific PCR.

RESULTSThe CALR mutations were detected in 13 patients out of 55 MPN patients (23.6%). The frequency of CALR mutation was 22.7% (10/44) in 44 essential thrombocythemia(ET) patients. A total of 3 types of CALR mutation were identified (type I c.1092_1143del52bp, n=5; type II c.1154_1155insTTGTC, n=4; type III c.1094_1139del46bp, n=1). CALR mutations occurred at a frequency of 27.2% in primary myelofibrosis (PMF), including type I (n=2) and type II (n=1). The incidence of JAK2 V617F was 58.1%(32/55), that in ET and PMF was 59.1%(26/44) and 54.5% (6/11), respectively. The mutations of MPL W515 were not detectable in all cases, and the simultaneous mutation of CARL and MPL W515 was not detected. The median age of patients with CALR mutation was significantly younger than that of patients with JAK2 mutations (48 vs 64 years of old, P<0.05). The levels of hemoglobin and leukocytes in patients with CARL mutations were significantly lower (P<0.05) but the level of plateletes was higher than that in patients with JAK2 V617F mutations (P<0.05). Deep venous thrombosis occurred in 4 of 35 ET patients with the JAK2 V617F mutation (n=4), but did not occurr in the patients with CALR mutation. Karyotype abnormality was detected in only one case among 48 patients by chromosome karyotype analysis.

CONCLUSIONThe incidence of CALR mutation is high in ET and PMF patients without JAK2 V617F and MPL W515K mutations, which is associated with younger median age, lower leucocyte and hemoglobin levels, higher platelet counts, and rare thrombocytosis, compared with the patients with JAK2 V617F mutation.