To explore the regulation of eIF4E, we screened the protein interacting with eIF4E from human cDNA library by using yeast two-hybrid system. Several clones interacting with eIF4E were identified. One of them was homologous with HUWE1 (HECT, UBA and WWE domain containing 1, also named as ARF-BP1, HECTH9 or HUWE1). Cell co-immunoprecipitation showed that eIF4E could bind to HUWE1 in mammalian cells. We also found that HUWE1 bearing the HECT domain is necessary for its association with eIF4E.

Objective To investigate the expressions of high mobility group box-1(HMGB1) and high sensitivity C-re?active protein (hs-CRP) in patients with acute coronary syndrome (ACS) and the effects of atorvastatin on the two inflamma?tory cytokines. Methods A total of 90 patients with ACS and 90 cases of normal control subjects were selected in this study. The serum concentrations of HMGB1 and hs-CRP were measured before treatment in patients of ACS. Patients were randomly divided into two groups:control group (n=45) and atorvastatin group (n=45). Atorvastatin was given 20 mg/24 h and 40 mg/24 h. Blood samples were obtained from the patients for detection of HMGB1 and hs-CRP one week after treatment with atorvastatin. Results There were significantly higher serum levels of HMGB1 and hs-CRP in patients with ACS than those of control subjects (P<0.01). The level of HMGB1 was positively correlated with the level of hs-CRP in patients of ACS (r=0.389, P<0.01). Before treatment, there were no significant diffferences in level of HMGB1 and hs-CRP in patients with ACS between the two groups. After treatment with atorvastatin, the levels of HMGB1 and hs-CRP were decreased in the two groups of ACS, and those were significantly lower in the intensive group than the standard group (P<0.05). Conclu?sion HMGB1 could stimulate the secretion of hs-CRP and other inflammatory cytokines, playing an important role in the process of occurrence and development of atherosclerosis. High loading dose of atorvastatin may reduce the expression of HMGB1 and decrease the inflammation, and stabilize the plaques in patients with acute coronary syndrome.

Objective Through analysed the questionnaire about postpartum contraception knowledge-attitude-practice (KAP) among obstetricians,to understand the postpartum contraceptive knowledge,idea,attitude and related factors among obstetricians.Methods From October 2013 toDecember 2013,209 obstetricians of 10 different levels of the hospital of Tianjin area had been enrolled in this study,and KAP questionnaire was investigated.Results The knowledge of postpartum contraception among obstetricians was seriously lack,the total correct rate was 34.8％,the lowest score was 5 points,the highest was 80 points,the average score was 34.8± 13.5,more than 60 points accounted for only 2.9％ (6/209).86.6％ (181/209) obstetricians have thought it necessary to carry out postpartum contraceptive propaganda during pregnancy,and 97.6％ (204/209) obstetricians have thought it necessary to develop postpartum contraception training.92.8％ (194/209) and 94.2％ (197/209) obstetricians always informed that pay attention to contraception before discharge and postpartum visit,specific methods were not discussed.Obstetricians obtained relevant progress of contraceptive knowledge mainly through the daily medical work (92.8％,194/209),hoped that approach postpartum contraception related knowlege through continuing education courses (77.5％,162/209),special lectures in academic conference (72.2％,151/209) and special training (67.5％,141/209).Conclusions (1) The postpartum contraception knowledge among obstetricians is seriously lack.(2) The obstetricians hold positive attitude towards the propaganda for postpartum contraceptive knowledge.(3) Postpartum contraception related education only provided before discharging and postpartum visit,and the content was simply inform that pay attention to contraception,specific methods are not discussed.(4) To explore the reason why postpartum contraception situation is not ideal,that's because insufficient attention and propaganda,obstetricians don't update the contraception knowledge,and be lack of knowledge on the efficient,long-acting reversible contraception methods,exaggerated the side effects and complications.

Objective:To explore diagnostic value of nocturnal ST-T changes in 24h dynamic electrocardiogram (DCG)for coronary heart disease (CHD)and its clinical significance.Methods:A total of 103 cases,who showed ST-T changes in 24h DCG,received selective coronary angiography (CAG).Among them,the 56 patients with in-termittent nighttime significant ST-T changes were regarded as research group,while the other 47 patients with per-sistent ST-T changes were treated as control group.CAG results were compared and analyzed between two groups. Results:Compared with control group,there were significant rise in CAG positive rate (31.9% vs.67.9%),inci-dence rates of dyspnea and chest pain (27.7% vs.66.1%),hypertension (48.9% vs.71.4%),hyperlipidemia (31.9% vs.42.9%)and diabetes mellitus (17.0% vs.46.4%),percentages of lesions in left anterior descending artery (LAD,21.3% vs.57.1%),left circumflex coronary artery (LCX,14.8% vs.37.5%)and right coronary artery (RCA,12.8% vs.35.7%)in research group,P <0.05 or <0.01. Conclusion:Nocturnal ST-T signifieantly changes in 24h DCG,it possesses more diagnostic value for CHD,which can be regarded as a more sensitive index diagnosing myocardial ischemia.

BACKGROUND: Tissue engineering is increasingly viewed as a promising avenue for functional cartilage reconstruction.However, chondrocyte dedifferentiation during in vitro culture remains an obstacle for clinical translation of tissue engineered cartilage. Re-differentiated induction have been employed to induce dedifferentiated chondrocytes back to their original phenotype. Regrettably, these strategies have been proven to be only moderately effective. METHODS: To explore underlying mechanism, RNA transcriptome sequencing was conducted on primary chondrocytes (P0), dedifferentiated chondrocytes (P5), and redifferentiated chondrocytes (redifferentiation-induction of P5, P5.R). Based on multiple bioinformatics analysis, LGR5 was identified as a target gene. Subsequently, stable cell lines with LGR5 knocking-down and overexpression were established using P0 chondrocytes. The phenotypic changes in P1 and P5 chondrocytes with either LGR5 knockdown or overexpression were assessed to ascertain the potential influence of LGR5 dysregulation on chondrocyte phenotypes. Regulatory mechanism was then investigated using bioinformatic analysis, protein–protein docking, immunofluorescence co-localization and immunoprecipitation. RESULTS: The current study found that dysregulation of LGR5 can significantly impact the dedifferentiated phenotypes of chondrocytes (P5). Upregulation of LGR5 appears to activate the PI3K/AKT signal via increasing the phosphorylation levels of AKT (p-AKT1). Moreover, the increase of p-AKT1 may stabilize b-catenin and enhance the intensity of Wnt/b-catenin signal, and help to restore the dedifferentated phenotype of chondrocytes. CONCLUSION LGR5 can modulate the phenotypes of chondrocytes in P5 passage through PI3K/AKT signaling pathway.

OBJECTIVE: To determine the incidence and genotypes of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Dongguan region of Guangdong Province and assess the efficacy and feasibility of flow-through hybridization. METHODS: Peripheral blood samples were randomly selected and detected by modified G6PD/6PGD ratio method. Flow-through hybridization was used to detect 14 G6PD mutations among all samples. RESULTS: In total 1005 samples were collected, the detection rate for modified G6PD/6PGD ratio method and flow-through hybridization were 2.79% and 20.90%, respectively. The consistency of the two methods was poor(Kappa=0.187). When c.1311C>T mutation is excluded, the consistency of the two methods was good for males (Kappa=0.952) but still poor for females (Kappa=0.194). The most common mutations were c.1376G>T, c.1388G>A and c.95A>G. No G6PD deficiency was found among those only carrying the c.1311C>T mutation. CONCLUSION Flow-through hybridization can simultaneously detect 14 loci, covering over 90% of common mutations in Chinese population, and can be easily expanded. The routine method may miss many females carrying homozygous, compound heterozygous and heterozygous mutations, but the detection rate for male hemizygous mutation was much higher.
China ; DNA Mutational Analysis ; Female ; Genetic Testing ; Genotype ; Glucosephosphate Dehydrogenase ; genetics ; Glucosephosphate Dehydrogenase Deficiency ; diagnosis ; Humans ; Male ; Mutation

The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme(CYP),which plays a crucial role in the metabolism of neurosteroids.The antiepileptic drug phenytoin(PHT)has been observed to induce neuronal side effects in patients,which could be attributed to its induction of CYP expression and testosterone(TES)metabolism in the hip-pocampus.While pregnane X receptor(PXR)is widely known for its regulatory function of CYPs in the liver,we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile(PCN),a PXR agonist,has differential effects on CYP expression in the liver and hippocampus.Specifically,the PCN treatment resulted in the induction of cytochrome P450,family 3,subfamily a,polypeptide 11(CYP3A11),and CYP2B10 expression in the liver,while suppressing their expression in the hippocampus.Func-tionally,the PCN treatment protected mice from PHT-induced hippocampal nerve injury,which was accompanied by the inhibition of TES metabolism in the hippocampus.Mechanistically,we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent,rather than PXR independent,as demonstrated by genetic and pharmacological models.In conclusion,our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR.Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.

The seventh article of Measures for the Ethical Review of Biomedical Research Involving Humans (2016) stipulated that medical and health institutions without an ethics committee shall not carry out biomedical research involving Humans. The Opinions on Strengthening the Governance of Ethics in Science and Technology, issued in March 2022, clearly stated that the institutions that do not meet the conditions for establishing a scientific and technological ethics (review) committee should entrust other institutions to conduct the review. The fourteenth article of Measures for Ethical Review of Life Science and Medical Research Involving Humans (2023) proposes that if an institution, which carries out life science and medical research involving humans, has not established an ethics committee or its ethics committee is not competent for ethics review, it can entrust a competent ethics committee or regional ethics committee in writing to carry out ethical review. Most medical institutions at or above the second level in China have set up ethics committees. While most universities and colleges, scientific research institutions, enterprises and grass-roots medical and health institutions have not set up ethics committees, which lack a working system to protect the safety and interests of the participants, and is difficult to conduct life sciences and medical research involving humans. At present, there is a need for some research institutions that do not have the conditions to establish ethics committees to entrust their projects of life science and medical research involving humans to other institutions for ethical review. The entrusted review is still in the exploratory stage, and there is no relevant specification. The hasty implementation of entrusted review may not achieve the goal of effectively protecting the safety and interests of the participants, and even cause legal disputes. Based on the thematic discussion, with reference to the relevant laws and regulations, departmental rules, ethical standards, and the experience of the ethics committees of some domestic institutions in implementing the entrusted review, the guideline was formulated for the reference of the current entrusted review to ensure the safety and interests of the participants.

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.