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BACKGROUND@#Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca 2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo .@*METHODS@#Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo . Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively.@*RESULTS@#The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators.@*CONCLUSION@#I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.
Subject(s)
Animals , Mice , Calcium/metabolism , Cysteine Endopeptidases/metabolism , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Proteins/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/geneticsABSTRACT
Objective Based on the three years' peer review data of a project fund,the results of fund peer review were analyzed and evaluated,to provide references for further improvement of the peer review and management.Methods Based on the fund's peer review results of 2145 projects in three years,descriptive statistics,single-item identification index were adopted,as well as RJ normality test,t-test and other statistical methods,to analyze and assess the overall data of fund,project categories,individual scores,etc.Results The score distribution of the three year peer review project of the fund is almost normal distribution,and the overall consistency of peer review shows a better trend.The analysis shows that the peer review experts of the fund have better consistency in terms of project innovation,rationality and characteristics.While there were differences in the peer review of applicability.Conclusions The three year peer review data of the fund show that three years' evaluation results are reliable,reasonable,and the quality of evaluation is good,showing a better development trend in both project quality and expert consistency.
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Objective To study the dynamic changes of scientific research efficiency of 51 departments in a top three hospitals in Beijing from 2014 to 2016,and to provide reference information for improving the efficiency of scientific research in hospital departments.Methods The CCC model of DEA,BCC model were used for lateral analysis,and then Malmquist index was used for longitudinal analysis.Results There were 12 (23.53％) departments in 2014,11 (21.57％) departments in 2015,9 (17.65％) departments in 2016 data envelopment analysis was valid,from 2014 to 2016,41 (80.39％) departments of the hospital increased the total factor productivity.Conclusions The total factor productivity of the 51 departments in the hospital increased from 2014 to 2016,and technological progress was the main reason for its growth.
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Objective Discussion on the methods of retrospectively selecting peer review experts based on the results of review.Methods Based on the review data of peer reviewers,peer review experts are retrospectively selected based on the voting,rating and comprehensive evaluations,as well as their variations and errors during the review.Results Through the retrospective selection of peer reviewers,there is a better convergence of reviews,which assures the quality of future peer reviews.This method is superior to the prospective selection of peer reviewers.Conclusions Based on the results of the review,retrospective selection of peer review experts is feasible and helpful for the selection of high-level peer review experts,which can improve the quality of peer review and standardize peer review.
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Objective Based on the data of scientific research output in a top three hospital in Beijing from 2015 and 2016,stochastic frontier analysis is conducted to estimate the efficiency of scientific research performance in different departments of this hospital,so as to draw the impetus for the growth of departments.Methods According to the results of the stochastic frontier model,comprehensive analysis and evaluation are conducted for the research performance of various departments.Results The overall average technical efficiency of the hospital is 0.44,and improvement space for the technical efficiency of scientific research performance is still 0.56.There are significant differences in the technical efficiency of each department.Among the four major categories,the D section is higher than the technical efficiency of class A,B and C departments.Conclusions The overall technical efficiency of the hospital is not high,the level of scientific research output of the four types of departments is not balanced,which should be emphasized in the improvement of scientific research performance level.
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Circular RNAs(circRNAs)are a novel type of RNA that function as microRNA(miRNA)sponges,RNA-binding proteins,and regulators of nuclear transcription.CircRNAs play a dual role in cancer,wherein their function as miRNA sponges could lead to either an oncogenic stimulus or tumor suppression.CircRNAs can also serve as novel diagnostic and prognostic biomarkers,as well as thera-peutic targets for cancer;both these functions have great potential for clinical application in cancer diagnosis and therapy.Here,we re-view the mechanisms of action and potential clinical applications of circRNAs in tumors.
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Objective Evaluate the efficiency of scientific research output of the 54 departments in a hospital,to put forward improvement suggestions based on the evaluation results.Methods Select appropriate indicators of scientific input and output,use the Data Envelopment Analysis method to evaluate and analyze the efficiency.Results According to the analysis of DEA,calculate the values of overall efficiency,technical efficiency,scale efficiency and scale income.Then compare and analyze the relative efficiency of different units scientific output,to identify the relatively superior department a mong the various categories.Conclusions According to the evaluation results,to find out the input surplus and insufficient output of each decision units.Then we will put forward suggestions on hospital resource allocation to optimize the scientific input and output,to improve the competitiveness of the hospital,and to activate the potential of each department's scientific research.
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Objective To analyze CYP17A1 gene mutation in a patient with 46,XY disordered sex development and to explore the possible influence on the phenotype of the patient.Methods Eight exons of CYP17AI gene in the patient and her parents were amplified and directly sequenced.In order to construct Mini-gene system,PCR fragments containing wildtype and mutant splicing sites were inserted in expression vector,and then transfected into cells.RT-PCR was used to observe the influence of splicing site mutation.Wildtype and aberrant splicing CYP17A1 cDNA expression plasmids were constructed and transfected into cells respectively,and CYP17A1 enzyme activity was tested in vitro.Results Mutation analysis revealed compound heterozygous CYP17A1 mutations,with Y329fs in one allele and a synonymous substitution( c.1263G＞A:GCG＞GCA) in another allele.In vitro analysis showed that the synonymous substitution induced a novel splicing site,which resulted in aberrant splicing of CYP17A1 mRNA and lacked six or seven amino acids after 415 in splicing product.In vitro transfection and enzyme activity experiment showed that the aberrant splicing product abolished the enzyme activity completely.However,this mutation did not completely influence splicing.The patient also had a part of normal splicing product,which was a coincidence to the phenotype of the patient.Conclusion This is the first description of an exonic splicing mutation in CYP17A1 relevant to the 17ot-hydroxylase deficiency phenotype.The functional study of the aberrant splicing variant has been initiated.
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To investigate the clinical features, genetic diagnosis, and treatment of a patient with Prader-Willi syndrome(PWS). For a case with clinically suspected PWS, methylation specific PCR(MSPCR)amplification was applied to CpG islands of SNRPN(exon α)gene locus in the 15q11-q13. Furthermore, the diagnosis was comfirmed by the method of bisulfite sequencing PCR(BSPCR). Metabolic status before and after the operation of sleeve gastrectomy were compared. Absence of amplification of paternal allele on chromosome 15q11-q13 was detected in the case by MSPCR, different from the normal control. Results of BSPCR further proved a full methylation of CpG islands in the SNRPN gene locus. Four months after sleeve gastrectomy, systemic metabolic status and ventricular function were improved. MSPCR and BSPCR were both consistent with genetic diagnosis of PWS. Weight loss surgery is expected to be a major therapy of this disease.
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Objective To evaluate the effects of metformin on thyrotropin(TSH)levels. Methods From the patients with type 2 diabetes mellitus or metabolic syndrome, 48 patients with primary hypothyroidism were enrolled and grouped. 17 patients were treated only with metformin(group A), 19 patients with metformin and stable L-T4substitution(group B), and the remaining 12 patients with antidiabetic drugs(other than metformin)and L-T4(group C). Meanwhile, 20 euthyroid patients with other thyroid abnormalities(group D)and 30 patients without thyroid diseases(group E)served as control. TSH, FT3, FT4, TT3, TT4, and blood glucose were determined regularly in all these subjects. Results After administration of metformin for 12 months, serum TSH were decreased in group A [(5.05±1.07 vs 2.61±0.91)mU/L, P＜0.01] and group B [(2.67±1.03 vs 1.35±0.74)mU/L, P＜0.01]. No difference was found in FT3and FT4in both groups. TSH levels were raised from(1.30±0.71)to(2.58±1.02)mU/L(P＜0.01)within 8～12 weeks in 13 out of 15 patients after metformin withdrawal. Serum TSH and thyroid hormones in the other 3 groups were not significantly changed. Conclusion Administration of metformin may lead to reduction of serum TSH level.
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Objective To investigate a Chinese pedigree suffering from Leydig cell hypoplasia ( LCH) based on clinical data and genetic diagnosis. Methods The patient was diagnosed by means of clinical data, hormone profiles, and human chorionic gonadotropin ( hCC) test. The luteinizing hormone/chorionic gonadotropin receptor(LHCGR) gene of the patient and family members was amplified and sequenced. Results The patient presented with male pseudohermaphroditism, low level of testosterone, which did not respond to hCG. Genetic analysis of the LHCGR revealed two novel mutations: a missense mutation located in exon 5, resulting in Ile replaced by Thr in the extracellular domain; and a splice site mutation in the 3' terminal of intron 6( IVS6-3 C→A). Proband's sister (46, XX) who lacked clinical manifestations showed the identical genotype with the patient. Conclusions A mutation in the consensus sequence of 3' splice site, in addition to a missense mutation (Ile 152Thr)in the extracellular ligand-binding domain is the cause of inactivation of the LHCGR gene in patient with Leydig cell hypoplasia.
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Objective To investigate the adrenal steroidogenic function in genotype-proven heterozygotes carrying mutations in CYP17A1 gene in vivo. Methods Eight patients and 14 family members from 5 families with 17-hydroxylase/17,20-lyase deficiency (17OHD) were recruited. The mutations of the CYP17A1 gene in these individuals were screened by direct sequencing of PCR products. The hormonal response to ACTH was evaluated in the 14 genotype-proven carriers and 45 age- and sex-matched normal subjects. Results Three mutations were found in 5 unrelated families. 14 carriers with CYP17A1 mutation were identified, including 7 heterozygotes with D487_F489del, 6 with Y329fs, and 1 for H373L. Compared to the normal subjects, the carriers exhibited lower basal and ACTH-stimulated cortisol levels, but higher ACTH-stimulated corticosterone level. The ratios of corticosterone to cortisol in the genotype-proven heterozygotes were higher than those of normal individuals at baseline and following ACTH-stimulation. Similarly, progesterone level and ratios of progesterone to 17-hydroxyprogesterone in the male heterozygotes were also higher than that of normal individuals before and after stimulation. No significant differences were observed in the hormone levels between two genotypes (D487_F489del vs Y329fs). Conclusions Genotype-proven carriers of 17OHD without apparent clinical symptoms exhibit decreased enzyme activity,analogous to mildly impaired adrenal 21-hydroxylase activity in the carriers of CYP21 A2 gene mutation.
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ed in vitro and in vivo,which was inhibited by aspirin treatment.
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ObjectiveTo investigate the correlation of dysphagia and malnutrition of patients with acute stroke and to establish intervention countermeasures.MethodsThe Swallow Water Test was performed by professional rehabilitation nurses in 100 cases of acute stroke patients without food and water within 24 hours after admission and two weeks later to confirm the existence of dysphagia.Rehabilitation exercises of swallow function were performed pertinently.At the same time,we evaluate the state of nutrition of these patients and followed up for two weeks,and to determine the state of malnutrition.ResultsThere was 23.0%(23/100) acute stroke patients didn't pass the initial Swallow Water Test,19 patients (82.5%) with dysphagia could swallow normally before discharge,13% patients needed indwelling nasal-gastric tube.The rate of malnutrition in dysphagia group (34.8%) was higher than patients without dysphagia (11.7%),the difference was statistically significant (P<0.05).In addition,the activity ability of daily living was poorer,the disability degree was higher and the average day of hospitalization was longer in dysphagia group in the fourth week.ConclusionsTo estimate the dysphagia timely in acute stroke patients can make the medical staff think highly of this status to formulate the scientific project of nutrition and provide the scientific rehabilitation exercises to the patients.It can decrease the incidence rate of malnutrition,complications and the disability degree of the acute stroke patients and to promote early rehabilitation.
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Expression of platelet-derived growth factor (PDGF)-B mRNA was measured by semi-quantitative RT-PCR in renal cortex of diabetic and control Wistar rats. The expression of PDGF-B mRNA in renal cortex of diabetic rats was 2.5-fold of normal rats, suggesting that PDGF-B seems to play a role in diabetic nephro-pathy.
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Changes in IL-2/IL-2R system in 25 patients with thyrotoxic Graves disease and 20 eu-thyroids were investigated and compared with those of 15 normal controls. The thyrotoxic patients showed a high concentration of serum sIL-2R and a large amount of circulating IL-2R-?- cells but a decreased production of IL-2 by PBMC. However, these abnormalities had a tendency to become normal with improvement of the disease. The IL-2 was correlated with the percentage of IL-2R-?- cells and sIL-2R. This study may provide clues to the im-munopathogenesis in Graves Disease.