Objective To evaluate the clinical efficacy and safety of hydrotalcite chewable tablets in treatment of patients with functional dyspepsia epigastric pain syndrome(EPS), and to investigate the onset time of hydrotalcite after the first dosage and whether use of hydrotalcite in EPS is a costeffective strategy. Methods A multicenter, randomized, open, positive controlled clinical trial was carried out in 240 patients with EPS. The subjects randomly received eigher hydrotalcite or omeprazole for 2 weeks. The improvemcnt and the disappear time of symptoms were evaluated before and after treatment and cost-effective was analyzed between two groups. Results It was demonstrated that both hydrotalcite and omeprazole could relief symptoms after treatment. After treatment for 2 weeks, the total effective rate was 85. 71% in hydrotalcite group and 90. 43% in omeprazole group with no significant difference (P＞0.05). The median onset time of hydrotalcite after first dosage was 0.417 h. The overall direct cost per patient was RMB ￥122. 29 for hydrotalcite treatment and RMB ￥242.95 for omeprazole treatment. The main adverse events included diarrhea, thirst, bloating,headache and belching. No severe adverse event was found in two groups. Conclusions Hydrotalcite has fast effect on relief of EPS symptoms. Use of hydrotalcite is a cost-effective strategy in the management of EPS. It is a safe and effective medicine in treatment of EPS.

Objective To investigate the possibility and mechanism of Dangguibuxue Decoction in early prevention of the development of atherosclerosis (AS) based on the study of the effect of Dangguibuxue Decoction on the signal transduction iter of nuclear transcription factor-kappa Bp65 (NF-κBp65) in monocyte activated by oxidized low-density lipoprotein (ox-LDL) in RAW264.7 cells. Methods The rabbits were randomly divided into the control group and medicated serum group and then given respectively normal saline and Dangguibuxue Decoction orally for preparing the medicated serum. The suspension of RAW264.7 cells was vaccinated into culture flask and cultured for 24 hours, and then divided into the blank control group, ox-LDL group, inhibitor group and medicated serum group. Except the blank control group all other groups were given 100 mg/L ox-LDL to activate RAW264.7 cells. After incubation the cells were collected. The expression of NF-κBp65 was detected by using immunohistochemistry assay, and the quantity of activated protein in RAW264.7 cells was detected by using immunoblotting technique. Results In ox-LDL group there were a lot of brown-yellow positive granules observed in the cytochylema and nucleus of RAW264.7 cells, and less in the medicated serum group. The ratio of protein band gray scale was 1.288 3±0.013 9 in the ox-LDL group and 0.918 9±0.015 3 in the medicated serum group. There was a significant difference statistically between two groups (P<0.05). Conclusion Dangguibuxue Decoction can down-regulate the protein expression and activation of NF-κBp65 in RAW264.7 cells stimulated by ox-LDL. It may be one of the mechanisms of Dangguibuxue Decoction for antagonizing AS that the signal transduction iter of NF-κBp65 was blocked.

The aim of present study is to investigate the cardioprotective effect of a new compound acetyl ferulaic isosorbide (AFI), composed of ferulaic acid (FA) and isosorbide mononitrate (ISMN) by esterification in myocardial ischemia/reperfusion (MI/R). Male Sprague-Dawley rats, subjected to 30 minutes of myocardial ischemia and 3 hours of reperfusion, randomly received one of the following treatments separately: SHAM, I/R (MI/R + solvent), SF (MI/R+SF, 40 mg x kg(-1), ig), ISMN (MI/R + ISMN, 30 mg x kg(-1), ig), SF + ISMN (MI/R + SF + ISMN, 40 mg x kg(-1) + 30 mg x kg(-1), ig) and AFI (MI/R + AFI, 10 mg x kg(-1), ig). Left ventricle developed pressures (LVDP) and the maximal first derivative of developed pressure ( +/-dP / dtmax) were monitored throughout the experiments. Myocardial infarction size, serum creatine kinase (CK) activity, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, hydrogen peroxide (H2O2), malondialdehyde (MDA) and nitric oxide (NO) production were determined at the end of reperfusion. Compared with SF, ISMN or SF + ISMN treatment groups, AFI treatment decreased infarction size (n=8, P < 0.01), improved cardiac function as evidenced by increased LVDP and +/- dP/dtmax (n=8, P < 0.05), increased serum SOD activity, reduced serum CK and LDH activities, H2O2 and MDA production (n=8, P < 0.05). The new compound AFI showed a stronger cardioprotective effect against MI/R injury than SF, ISMN or their combined administration did.
Animals ; Cardiotonic Agents ; chemical synthesis ; chemistry ; pharmacology ; Creatine Kinase ; blood ; Electrocardiography ; Hydrogen Peroxide ; blood ; Isosorbide Dinitrate ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; L-Lactate Dehydrogenase ; blood ; Male ; Malondialdehyde ; blood ; Myocardial Reperfusion Injury ; blood ; pathology ; physiopathology ; prevention & control ; Myocardium ; pathology ; Nitric Oxide ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood

Biomacromolecules participate in various kinds of vital processes. Observing and analyzing their structural dynamic and the dynamic processes of intermolecular interaction at molecular level is important for understanding the action mechanism. Since its advent, single molecular fluorescence resonance energy transfer (SM-FRET) has demonstrated its great potential in studying the conformational change and interaction process of biomacromolecules, and a series of new mechanisms have been revealed. This review summarized recent progresses of SM-FRET in studying protein structural dynamic, nucleic acid structural dynamic, protein-protein and protein-nucleic acid interactions.

OBJECTIVETo explore the role of monitoring sex chromosome chimeric status by fluorescence in situ hybridization (FISH) in the identification of leukemic extramedullary relapse and post-transplant lymphoproliferative disease (PTLD) in acute lymphocytic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSSix ALL patients who received sex-mismatched allo-HSCT and manifested extravisceral lymphadenectasis or local lump were investigated. The sex chromosome chimeric status in tumor tissues and bone marrows (BM) were monitored by FISH, and EBV-RNA in the tumor tissues were detected by in situ hybridization (ISH).

RESULTSThe sex chromosomes in BM of all 6 patients were 100% donor-derived. Among the sex chromosome chimeric status of tumor tissues, three patients were mainly recipient-derived, and the percentage of sex chromosomes derived from recipients were 100%, 100% and 98.0%, respectively, and then they were diagnosed leukemic extramedullary relapse. The other 3 patients were donor-derived, the percentage was 98.5%, 96.0% and 91.5%, respectively, and were diagnosed PTLD. EBV-RNA and latent membrane protein (LMP-1) were positive in 2 patients with PTLD and negative in the other 4 patients. One patient with extramedullary relapse obtained partial remission, one with PTLD gained complete remission, and the others died eventually after therapy.

CONCLUSIONMonitoring the sex chromosome chimeric status by FISH is an effective method to distinguish leukemic extramedullary relapse from PTLD in ALL received sex-mismatched donor HSCT.

Adolescent ; Adult ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Lymphoproliferative Disorders ; pathology ; surgery ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; physiopathology ; surgery ; Recurrence ; Sex Chromosomes ; genetics ; physiology ; Transplantation Conditioning ; Young Adult

The aim of the present study is to explore the mechanism of estrogen on regulating cardiac function disorder by adjusting the stimulating adenylate cyclase G α protein (Gαs)-cycle adenosine monophosphate (cAMP) signal pathway. Adult female rats were randomly divided into five groups: sham group, ovariectomized group (OVX), OVX and 17β-estradiol given group (OVX+E₂), OVX and isoprenaline injected group (OVX+ISO), OVX and 17β-estradiol, isoprenaline injected group (OVX+E₂+ISO). Rats were ovariectomized, and two weeks later, OVX+E₂group was injected with E₂, OVX+ISO group was injected with ISO, OVX+E₂+ISO group was injected with E₂and ISO. Another four weeks later, the hemodynamic parameters were monitored by carotid artery intubation: left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal differentials of left ventricular developed pressure (+dp/dt(max)), and minimal differentials of left ventricular developed pressure (-dp/dt(max)). Brain natriuretic peptide (BNP) and cAMP concentration in plasma were determined; Gα(s) protein expression in myocardium was determined. The results showed that the hemodynamic parameters, the concentration of BNP and cAMP in plasma had no significant changes after ovariectomy compared with sham group. But after isoprenaline injection in ovariectomized rats, LVSP and +dp/dt(max) declined (P < 0.01), LVEDP and -dp/dt(max) elevated (P < 0.01); plasma BNP concentration increased (P < 0.01); plasma cAMP concentration decreased (P < 0.01), compared with OVX group. Further estrogen supplements improved the heart function treated by isoprenaline: LVSP and +dp/dt(max) elevated (P < 0.01), LVEDP and -dp/dtmax declined (P < 0.05, P < 0.01); the plasma BNP concentration decreased (P < 0.01); the plasma cAMP concentration increased (P < 0.01). Estrogen had no significant influence on Gαs protein expression. The results suggest that estrogen can alleviate myocardial injury and regulate cardiac function disorder by increasing cAMP level, finally improved the excessive suppression of myocardium.
Animals ; Cyclic AMP ; blood ; Estradiol ; pharmacology ; Estrogens ; pharmacology ; Female ; GTP-Binding Protein alpha Subunits, Gs ; metabolism ; Hemodynamics ; Isoproterenol ; adverse effects ; Myocardium ; pathology ; Natriuretic Peptide, Brain ; blood ; Ovariectomy ; Rats ; Signal Transduction

BACKGROUNDPrevious studies have suggested that interrupted clearance of nuclear DNA-protein complexes after cell death might initiate and propagate systemic lupus erythematosus (SLE). Deoxyribonuclease I (DNaseI) may be responsible for the removal of DNA from nuclear antigens at sites of high cell turnover, thus preventing the onset of SLE. The purpose of this study was to genotype the single nucleotide polymorphisms (SNPs) of DNase1 and characterize its gene expression and alternatively spliced transcripts in Chinese patients with SLE in order to understand the pathogenic role of DNase1 in human SLE.

METHODSFour SNPs located at the 3' end of the DNase1 gene, as listed on the SNP website, were selected for analysis. Those SNPs with relatively high heterozygosity were chosen for genotyping in 312 Chinese SLE families using the Taqman minor groove binder (MGB) allelic discrimination method. Haplotypes were constructed and linkage disequilibrium tests were performed using GeneHunter. DNase1 mRNA expression was detected using real-time polymerase chain reaction (PCR), and alternatively spliced transcripts were isolated using capillary electrophoresis. Any effects the specific SNP haplotypes had on DNase1 gene expression and the alternatively spliced transcripts were also assessed.

RESULTSrs179982 and rs1053874 had high heterozygosity, about 0.5 in this Chinese cohort, while rs1059857 was also found to be heterozygous. Analysis of the haplotype combining rs179982-rs1030874 (C-G) and rs179982-rs1030874-rs1059857 (C-G-G) revealed a skewed transmission in favor of affected offspring. DNase1 gene expression was higher in SLE patients than in normal controls (P < 0.001), but this was not related to disease activity or SNP haplotype. Capillary electrophoresis revealed that the pattern of alternatively spliced transcripts in patients differed from that of normal controls. Furthermore, different SNP haplotype combinations generated different transcript patterns in SLE patients.

CONCLUSIONSThe SNP haplotypes are in linkage disequilibrium in Chinese SLE patients and may induce the disease through a modification of DNase1 mRNA splicing rather than at the level of mRNA expression. There is a relatively unique transcript band in SLE patients independent of special haplotype, which suggests that other unknown factors might be involved in adjusting gene expression.

Adolescent ; Adult ; Alternative Splicing ; Deoxyribonuclease I ; genetics ; Female ; Haplotypes ; Humans ; Linkage Disequilibrium ; Lupus Erythematosus, Systemic ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

This study was aimed to investigate the correlation between HLA gene distribution and allele frequency of the patients with leukemia. PCR-SSP technique was used to detect the HLA genotype of 2994 umbilical cord blood units from healthy newborns (as control), the detecting result of which was compared with HLA genotypes of 1246 patients with leukemia searched in our cord blood bank. The differences between two groups were compared and analyzed. The results indicated that as compared with the control group, the allele frequencies of HLA-B*56 (0.56%), B*70 (0.24%) obviously increased (RR = 2.2546, 6.2598, χ(2) = 5, 5.98, P < 0.05), while the allele frequencies of HLA-A*03 (3.45%), A*30 (4.86%), B*13 (8.75%), B44* (3.25%), B61* (5.70%), DRB1*07 (8.23%), DRB1*15 (14.21%) obviously decreased in patients with leukemia (RR = 0.5889, 0.7187, 0.7359, 0.5713, 0.7127, 0.6242, 0.7976, χ(2) = 19.23, 9.82, 14.33, 20.48, 11.99, 33.21, 11.56, P < 0.01). It is concluded that HLA-B*56, B*70 alleles seem to be characterized by the genetic susceptibility to leukemia and may be served as risk markers for leukemia occurrence, while the HLA-A*03, A*30, B*13, B*44, B*61, DRB1*07, DRB1*15 can be considered as genetic indicators for resistance of leukemia.
Adolescent ; Adult ; Alleles ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Fetal Blood ; Gene Frequency ; Genotype ; HLA-A Antigens ; genetics ; HLA-B Antigens ; genetics ; HLA-DRB1 Chains ; genetics ; Humans ; Infant, Newborn ; Leukemia ; genetics ; Middle Aged ; Young Adult

Objective:The aim of the current study is to understand the sleep disorders in children with autism and related factors.Methods:A case-control study method was conducted in this study which included 198 children autism who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition (DSM-Ⅳ) and 233 cases of gender-and age-matched normal children.Their general demographic and sleep data were collected and the children with autism were assessed with Autism Behavior Checklist,Child Behavior Checklist and Autism Spectrum Screening Questionnaire.Correlation analysis and regression analysis were performed to compare sleep quality,sleep problems and the related factors of the two groups.Results:The scores of difficulty falling asleep,sleep restlessness,taking hold or shaking,restless sleep,interrupted sleep,nightmares,sleepwalking,night terrors,sleep snoring,nocturnal enuresis,sleep apnea,mouth breathing,sweating and sleep scores were higher in the autism group compared to the normal control group before falling asleep (P ＜ 0.05),while the proportion of daytime sleep time in the autism group was lower than the normal control group (P ＜0.05).With sleep status as dependent variable,linear regression analysis was conducted with children's birth weight,walking month age,speaking month age,father age,and autism spectrum as independent variables.The multiple linear regression analysis showed the scores of,sensory behaviors,body and object use behaviors,and self-help behaviors in Autism Behavior Checklist for autistic children were positively associated with their sleep (β =0.21,0.21,0.29,P ＜ 0.05).However,paternal age at birth in the autism group had negative associatin with the sleep of autistic children (β =-0.16,P ＜0.05).In the autism group,their total scores of Autism Behavior Checklist and the scores of language and social behavior in Autism Behavior Checklist were not associated with their sleep status score (P ＞ 0.05).Conclusion:It suggests that children with autism may have more sleep problems,and their sleep problems are related to autism symptoms including the scores of,sensory behaviors,body and object use behaviors,and self-help behaviors in Autism Behavior Checklist for autistic and their paternal age at birth.

Objective: To determine the in vitro and in vivo absorption properties of active ingredients of the Chinese medicine, baicalein, to enrich mechanistic understanding of oral drug absorption. Methods: The Biopharmaceutic Classification System (BCS) category was determined using equilibrium solubility, intrinsic dissolution rate, and intestinal permeability to evaluate intestinal absorption mech-anisms of baicalein in rats in vitro. Physiologically based pharmacokinetic (PBPK) model commercial software GastroPlus?was used to predict oral absorption of baicalein in vivo. Results: Based on equilibrium solubility, intrinsic dissolution rate, and permeability values of main absorptive segments in the duodenum, jejunum, and ileum, baicalein was classified as a drug with low solubility and high permeability. Intestinal perfusion with venous sampling (IPVS) revealed that baicalein was extensively metabolized in the body, which corresponded to the low bioavailability predicted by the PBPK model. Further, the PBPK model predicted the key indicators of BCS, leading to reclassification as BCS-II. Predicted values of peak plasma concentration of the drug (Cmax) and area under the curve (AUC) fell within two times of the error of the measured results, highlighting the superior prediction of ab-sorption of baicalein in rats, beagles, and humans. The PBPK model supported in vitro and in vivo evi-dence and provided excellent prediction for this BCS class Ⅱ drug. Conclusion: BCS and PBPK are complementary methods that enable comprehensive research of BCS parameters, intestinal absorption rate, metabolism, prediction of human absorption fraction and bioavailability, simulation of PK, and drug absorption in various intestinal segments across species. This combined approach may facilitate a more comprehensive and accurate analysis of the absorption characteristics of active ingredients of Chinese medicine from in vitro and in vivo perspectives.