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Ribosomes are abundant,large RNA-protein complexes that are the sites of all protein synthesis in cells.Defects in ribosomal proteins(RPs),including proteoforms arising from genetic variations,alternative splicing of RNA transcripts,post-translational modifications and alterations of protein expression level,have been linked to a diverse range of diseases,including cancer and aging.Comprehensive character-ization of ribosomal proteoforms is challenging but important for the discovery of potential disease biomarkers or protein targets.In the present work,using E.coli 70S RPs as an example,we first developed a top-down proteomics approach on a Waters Synapt G2 Si mass spectrometry(MS)system,and then applied it to the HeLa 80S ribosome.The results were complemented by a bottom-up approach.In total,50 out of 55 RPs were identified using the top-down approach.Among these,more than 30 RPs were found to have their N-terminal methionine removed.Additional modifications such as methylation,acetylation,and hydroxylation were also observed,and the modification sites were identified by bottom-up MS.In a HeLa 80S ribosomal sample,we identified 98 ribosomal proteoforms,among which multiple truncated 80S ribosomal proteoforms were observed,the type of information which is often overlooked by bottom-up experiments.Although their relevance to diseases is not yet known,the integration of top-down and bottom-up proteomics approaches paves the way for the discovery of proteoform-specific disease biomarkers or targets.
ABSTRACT
Objective:To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS).Methods:This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration.Results:(1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant ( P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups ( P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant ( P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion:The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.
ABSTRACT
Objective To investigate the relationship between single nucleotide polymorphism (SNP) of transcription factor 7-like 2 (TCF7L2) at locus rs7903146,rs290487,rsl1196205,rs 12255372 and genetic susceptibility in women with gestational diabetes mellitus (GDM).Methods As a case-control study,100 pregnant women with GDM and 100 healthy pregnant women in the Maternal and Children Health Hospital of Jiangxi Province were recruited from January 2010 to July 2013.Clinical parameters,including body mass index (BMI),fasting insulin (FINS),fasting plasma glucose (FPG) and homeostatic model assessment-insulin resistance index (HOMA-IR) were measured after admission to hospital.Allelespecific PCR was used to analyze the SNP of TCF7L2 at locus rs7903146,rs290487,rs11196205,rs12255372.Results (1)The BMI,FPG,FINS and HOMA-IR in GDM group were(27.4±3.0) kg/m2,(5.6±1.0) mmol/L,(6.2±3.4) mU/L and 1.8± 1.0,and were (24.2±2.9) kg/m2,(5.3±0.8) mmol/L,(4.5±2.8) mU/L,1.2± 0.8 in the control group,respectively.The differences had statistically significance (P＜0.05).(2)The SNP of TCF7L2 gene,locus rs7903146 were CC,CT and TT genotype; the SNP of locus rs290487 were CC,CT and TT genotype; and the SNP of locus rs1 1196205 were GG and CC genotype; while the SNP of locus rs12255372 was GG genotype.(3)The distribution frequencies of genotype CC,CT and TT at locus rs7903146 in the GDM group were 40％ (40/100),36％ (36/100) and 24％ (24/100),respectively.While in the control group,they were 55％ (55/100),38％ (38/100) and 7％ (7/100),respectively.The frequencies of C and T allele of rs7903146 were 58％and 42％ in the GDM group,and in the control group they were 74％ (148/200) and 26％ (52/200).The differences of genotype distribution and C/T allele frequency of rs7903146 between the two groups were statistically significant (P＜0.05).(4)The distribution frequencies of genotype CC,CT and TT at locus rs290487 in the GDM group were 12 ％ (12/100),36 ％ (36/100) and 52％ (52/100),and were 16％ (16/100),34％ (34/100) and 50％ (50/100) in the control group.The frequencies of C and T allele of rs290487 were 30％ (60/200) and 70％ (140/200) in the GDM group,and were 33％ (66/200) and 67％ (134/200) in the control group.There was no difference of genotype distribution and C/T allele frequency of rs290487 between the two groups (P＞0.05).(5)The distribution frequencies of genotype GG and CC at locus rs1 1196205 in the GDM group were 99％ (99/100) and 1％ (1/ 100),while those in the control group were 100％(100/100) and 0％.The frequency of G and C allele of rs1 1196205 were 99％(198/200) and 1％(2/200) in the GDM group,while in the control group were 100％ (200/200) and 0.There was no difference of genotype distribution and G/C allele frequency of rs11196205 between the two groups (P＞0.05).(6)The distribution frequencies of genotype GG at locus rs12255372 were 100％(100/100) in both the GDM group and the control group.The frequencies of G allele of rs12255372 were 100％ (200/200) in both the GDM group and the control group.There was no difference of genotype distribution and G allele frequency of rs12255372 between the two groups (P＞0.05).(7)After adjusting for age,gestational age,BMI,FPG and FINS,pregnant women with TT genotype at locus rs7903146 were more likely to have hyperglycemia compared with the C allele carriers (OR=2.77,95％ CI:1.03-7.57,P＜0.05).Conclusions The polymorphism of locus rs7903146 in TCF7L2 gene may be associated with genetic susceptibility in women with GDM.TT genotype is likely to be risk factor in the pathogenesis of GDM.