Context/objectives: The fight against Chronic Non-Communicable Diseases (NCDs) is a long-term undertaking, which requires available, motivated and well-managed human resources (HR). The administrative management of sk...Context/objectives: The fight against Chronic Non-Communicable Diseases (NCDs) is a long-term undertaking, which requires available, motivated and well-managed human resources (HR). The administrative management of skills on both qualitative and quantitative levels is one of the essential functions of a health system. To better implement policies of fight against High Blood Pressure (HBP) and other chronic diseases, it is important to establish strategies to retain health personnel. This loyalty requires favorable working conditions and consideration of the contribution-reward couple. Good working conditions are likely to reduce the phenomenon of medical nomadism;conversely, poor HR management can contribute to their exodus towards exotic “green pastures”, thus leading to an additional crisis in the Cameroonian health system. The fight against HBP is a complex, multifaceted and multifactorial reality that requires appropriate management model for all types of resources mainly HR. The main objective of this research is to show the impact of poor management of human resources in Cameroon health system on medical nomadism and the ineffectiveness of the fight against High Blood Pressure. Method: A cross-sectional descriptive survey among five hundred (500) health facilities in the center region of Cameroon has been conducted. A stratified probabilistic technique has been used, and the number of health facilities to be surveyed has been determined using the “sample size estimation table” of Depelteau. The physical questionnaires have been printed and then distributed to data collectors. After data collection, the latter were grouped during processing in Excel sheets. The Chi-square test was used for data with a qualitative value and that of Kolmogorov-Sminorf for data with a quantitative value to assess the normality and reliability of data. The Crochach’s Alpha reliability test allowed us to have a summary of the means and variances and then to search for intragroup correlations between variables. Descriptive analysis was possible with the XLSTAT 2016 software. Results: 43.60% of Health Facilities (HF) managers were unqualified. 82.20% of HF managers have staff in a situation of professional insecurity. They are mainly contractual (49.00), decision-making agents (24.40%), casual agents (08.80). The proportion of unstable personnel is average of 22.00% and very unstable, 12.00%.展开更多
Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBD- asso...Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBD- associated anemia are iron deficiency and anemia of chronic disease. An important prognostic parameter of the success or failure of therapy is the outcome of the underlying disease. Iron deficiency should be appropriately managed with iron supplementation. However, the use of oral iron therapy is limited by several problems, the most important being gastrointestinal side effects leading occasionally to disease relapse and poor iron absorption. Intravenous iron preparations are more reliable, with iron sucrose demonstrating the best efficacy and tolerability. Treatment with erythropoietin or darbepoetin has been proven to be effective in patients with anemia, who fail to respond to intravenous iron. Patients with ongoing inflammation have anemia of chronic disease and may require combination therapy comprising of intravenous iron sucrose and erythropoietin. After initiating treatment, careful monitoring of hemoglobin levels and iron parameters is needed in order to avoid recurrence of anemia. In conclusion, anemia in the setting of IBD should be aggressively diagnosed, investigated, and treated. Future studies should define the optimal dose and schedule of intravenous iron supplementation and appropriate erythropoietin therapy in these patients.展开更多
Most studies of erythropoiesis have been performed either with the virally transformed MEL cells or with the scarce erythroblasts within unhomogeneous cell populations.MEL cells are the Friend virus transformed mouse...Most studies of erythropoiesis have been performed either with the virally transformed MEL cells or with the scarce erythroblasts within unhomogeneous cell populations.MEL cells are the Friend virus transformed mouse erythroleukemia cells and have lost the capacity to respond to erythropoietin.Moreover,the research in the field of erythropoiesis has been severely hampered by the paucity of erythroblasts obtained from chick embryos,human,mouse,rat fetal liver,mouse spleen,or the bone marrow.In our paper,the fetal blood from newly slaughtered pregnant sheep meets the needs of studies as abundant staring biological materials at the nucleotide level and also reflects in vivo proliferative and differential status of erythroblasts.Appling the technique of mRNA differential display with minor modification,we directly compared cDNA fragmerts from the fetal blood erythroblasts and adult pregnant sheep leukocytes by PCR on DNA sequencing gels and revealed two differentially expressing bands.One is a novel gene fragment, which has homology with UV-sensitive cone opsin or rhodopsin by examinating the predicted amino acid sequence.Since the blood cells are sensitive to radiation,it can be safely inferred that this fragment participate in the process of cytocidal effect of the radiation.The other fragment is glucose induced gene /elongation factor 2 3′end noncoding region,which was first cloned from glucose induced bovine aortic smooth muscle cells.Using Northern blot hybridization method,authentic specific expression was confirmed.展开更多
Background: Erythropoiesis-stimulating agents (ESAs) are widely used in the management of anemia in cancer patients. Despite their apparent effectiveness, recent studies have suggested that ESAs could result in ser...Background: Erythropoiesis-stimulating agents (ESAs) are widely used in the management of anemia in cancer patients. Despite their apparent effectiveness, recent studies have suggested that ESAs could result in serious adverse events and even higher mortality. The aim of the current study was to evaluate the benefits and risks of ESAs in the management of cancer patients with anemia using a recta-analysis. Methods: The initial literature search covered Medline, PubMed, Embase, and the Cochrane Center Register of Controlled Trials, and identified 1,569 articles. The final meta-analysis included eight randomized controlled trials (n=2,387) in cancer patients with 〈11 g/dL hemoglobin (Hb) at the baseline and target Hb (for stopping ESA treatment) at no more than 13 g/dL. The assessment measures included Hb response, blood transfusion rate and adverse events that included venous thromboemblism (VTE), hypertension, and on-study mortality. The results are expressed as pooled odds ratio (OR). Publication bias was assessed using funnel plot analysis. Results: ESAs significantly increased the Hb concentration [OR 7.85, 95% confidence interval (CI): 5.85 to 10.53, P〈O.O01] and reduced the red blood cell (RBC) transfusion rate (OR 0.52, 95% CI: 0.42 to 0.65, P〈0.001). ESAs did not increase the accumulated adverse events (OR 0.95, P=0.82), or the on-study mortality (OR 1.09, P=0.47). Conclusions: ESAs are not associated with increased frequency of severe adverse events in anemic cancer patients when the target Hb value is no more than 13 g/dL.展开更多
Coexistence of chronic kidney disease (CKD) and chronic heart failure (CHF) define a recently recognized clinical entity known as cardio-renal syndrome. Sufficient evidence suggests that the two pathological condition...Coexistence of chronic kidney disease (CKD) and chronic heart failure (CHF) define a recently recognized clinical entity known as cardio-renal syndrome. Sufficient evidence suggests that the two pathological conditions share common pathogenic etiology which is not yet fully defined. Superimposed anaemia is a common finding among patients suffering from cardio-renal syndrome. The combination of CKD, CHF and anaemia increase the probability of death by 6 times compared to normal individuals. Early attempts to restore anaemia either by iron supplementation, erythropoiesis stimulating agents (ESAs) or combination of the two have reported to improve quality of life, morbidity and mortality especially among patients treated by cardiologists. Recent publications of well controlled epidemiological studies failed to prove convincing beneficial effect of the above mentioned therapy moreover skepticism has raised concerning the safety of restoring anaemia among patients with cardio-renal syndrome as well as used medications. There are still unresolved problems concerning the definition of anaemia, by means of hemoglobin level among these patients, the target hemoglobin level and the therapeutic regimen of ESAs administration and iron supplementation. We need much more evidence in order to define an effective and safe treatment strategy correcting anaemia among patients with cardio-renal syndrome.展开更多
Normally, cyclin interacts with cyclin-dependent kinase (CDK) to form a cyclin-CDK complex, which promotes cell cycle progression, whereas cyclin-dependent kinase inhibitor (CDKI) molecules inhibit the formation of cy...Normally, cyclin interacts with cyclin-dependent kinase (CDK) to form a cyclin-CDK complex, which promotes cell cycle progression, whereas cyclin-dependent kinase inhibitor (CDKI) molecules inhibit the formation of cyclin- CDK complex, arresting cell cycle. Terminal erythropoiesis is closely coordinated with cell cycle exit, which is regulated by cyclins, CDKs, and CDKIs [1]. In the global transcriptome of human terminal erythropoiesis [2], p19INK4d is expressed highly, and its expression is significantly up-regulated during human terminal erythropoiesis. However, the roles of p19INK4d in terminal erythropoiesis are still unknown.展开更多
The aim of this observational study was to biochemically characterize the anaemia in GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) patients. Values for mean corpuscular volume, mean corpuscular hemoglobi...The aim of this observational study was to biochemically characterize the anaemia in GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) patients. Values for mean corpuscular volume, mean corpuscular hemoglobin and soluble transferrin receptor were normal, whereas serum iron and total iron binding capacity (TIBC) were subnormal, and mean ferritin was above the upper reference limit. Iron-restricted erythropoiesis (IRE), defined as a bone marrow smear staining positive for iron in combination with transferrin saturation less than 20%, was present in all patients. All patients exhibited clinical and biochemical signs of active inflammation with elevated C-reactive protein and an increased erythrocyte sedimentation rate.展开更多
AIM: TO evaluate the association between IEM and gastropharyngeal reflux disease (GPRD) in patients who underwent ambulatory 24-h dual-probe pH monitoring for the evaluation of supraesophageal symptoms. METHODS: A...AIM: TO evaluate the association between IEM and gastropharyngeal reflux disease (GPRD) in patients who underwent ambulatory 24-h dual-probe pH monitoring for the evaluation of supraesophageal symptoms. METHODS: A total of 632 patients who underwent endoscopy, esophageal manometry and ambulatory 24-h dual-pH monitoring due to supraesophageal symptoms (e.g. globus, hoarseness, or cough) were enrolled. Of them, we selected the patients who had normal esophageal motility and IEM. The endoscopy and ambulatory pH monitoring findings were compared between the two groups. RESULTS;: A total of 264 patients with normal esophageal motility and 195 patients with the diagnosis of IEM were included in this study. There was no difference in the frequency of reflux esophagitis and hiatal hernia between the two groups. All the variables showing gastroesophageal reflux and gastropharyngeal reflux were not different between the two groups. The frequency of GERD and GPRD, as defined by ambulatory pH monitoring, was not different between the two groups. CONCLUSION: There was no association between IEM and GPRD as well as between IEM and GERD. IEM alone cannot be considered as a definitive marker for reflux disease.展开更多
AIM:To study non-cardiac chest pain(NCCP) in relation to ineffective esophageal motility(IEM) and rapid food intake.METHODS:NCCP patients with a self-reported habit of fast eating underwent esophageal manometry for th...AIM:To study non-cardiac chest pain(NCCP) in relation to ineffective esophageal motility(IEM) and rapid food intake.METHODS:NCCP patients with a self-reported habit of fast eating underwent esophageal manometry for the diagnosis of IEM.Telephone interviews identified eating habits of additional IEM patients.Comparison of manometric features was done among IEM patients with and without the habit of rapid food intake and healthy controls.A case study investigated the effect of 6-mo gum chewing on restoration of esophageal motility in an IEM patient.The Valsalva maneuver was performed in IEM patients and healthy controls to assess the compliance of the esophagus in response to abdominal pressureincrease.RESULTS:Although most patients diagnosed with NCCP do not exhibit IEM,remarkably,all 12 NCCP patients who were self-reporting fast eaters with a main complaint of chest pain(75.0%) had contraction amplitudes in the mid and distal esophagus that were significantly lower compared with healthy controls [(23.45 mmHg(95%CI:14.06-32.85)vs 58.80 mmHg(95%CI:42.56-75.04),P < 0.01 and 28.29 mmHg(95%CI:21.77-34.81) vs 50.75 mmHg(95%CI:38.44-63.05),P < 0.01,respectively)].In 7 normal-eating IEM patients with a main complaint of sensation of obstruction(42.9%),the mid amplitude was smaller than in the controls [30.09 mmHg(95%CI:19.48-40.70) vs 58.80 mmHg(95%CI:42.56-75.04),P < 0.05].There was no statistically significant difference in manometric features between the fast-eating and normal-eating groups.One NCCP patient who self-reported fast eating and was subsequently diagnosed with IEM did not improve with proton-pump inhibition but restored swallow-induced contractions upon 6-mo gum-chewing.The Valsalva maneuver caused a markedly reduced pressure rise in the mid and proximal esophagus in the IEM patients.CONCLUSION:Habitual rapid food intake may lead to IEM.A prospective study is needed to validate this hypothesis.Gum-chewing might strengthen weakened esophageal muscles.展开更多
Administrative department, as the focus of national political system reform, is associated with optimization and adjustment of state institutions and plays a macro-control role in socialist economic development. Admin...Administrative department, as the focus of national political system reform, is associated with optimization and adjustment of state institutions and plays a macro-control role in socialist economic development. Administrative departments, just the "government", conduct economic control function to promote the sustainable development of social economic causes. The thesis firstly introduces administrative departments' era effect and causes of administrative departments' economic policy ineffectiveness. And on the basis of these, the thesis comes up with some solutions to solve economic ineffectiveness, hoping that it would be helpful to relevant researches.展开更多
Erythropoiesis is a complex,precise,and lifelong process that is essential for maintaining normal body functions.Its strict regulation is necessary to prevent a variety of blood diseases.Normal erythropoiesis is preci...Erythropoiesis is a complex,precise,and lifelong process that is essential for maintaining normal body functions.Its strict regulation is necessary to prevent a variety of blood diseases.Normal erythropoiesis is precisely regulated by an intricate network that involves transcription levels,signal transduction,and various epigenetic modifications.In recent years,research on posttranscriptional levels in erythropoiesis has expanded significantly.The dynamic regulation of splicing transitions is responsible for changes in protein isoform expression that add new functions beneficial for erythropoiesis.RNA-binding proteins adapt the translation of transcripts to the protein requirements of the cell,yielding mRNA with dynamic translation efficiency.Noncoding RNAs,such as microRNAs and lncRNAs,are indispensable for changing the translational efficiency and/or stability of targeted mRNAs to maintain the normal expression of genes related to erythropoiesis.N6-methyladenosine-dependent regulation of mRNA translation plays an important role in maintaining the expression programs of erythroid-related genes and promoting erythroid lineage determination.This review aims to describe our current understanding of the role of post-transcriptional regulation in erythropoiesis and erythroid-associated diseases,and to shed light on the physiological and pathological implications of the post-transcriptional regulation machinery in erythropoiesis.These may help to further enrich our understanding of the regulatory network of erythropoiesis and provide new strategies for the diagnosis and treatment of erythroid-related diseases.展开更多
The fetal liver(FL)is the key erythropoietic organ during fetal development,but knowledge on human FL erythropoiesis is very limited.In this study,we sorted primary erythroblasts from FL cells and performed RNA sequen...The fetal liver(FL)is the key erythropoietic organ during fetal development,but knowledge on human FL erythropoiesis is very limited.In this study,we sorted primary erythroblasts from FL cells and performed RNA sequencing(RNA-seq)analyses.We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis.Notably,the expression of genes enriched in proteolysis and autophagy was up-regulated in orthochromatic erythroblasts(OrthoEs),suggesting the involvement of these pathways in enucleation.We also performed RNA-seq of in vitro cultured erythroblasts derived from FL CD34+cells.Comparison of transcriptomes between the primary and cultured erythroblasts revealed significant differences,indicating impacts of the culture system on gene expression.Notably,the expression of lipid metabolism-related genes was increased in cultured erythroblasts.We further immortalized erythroid cell lines from FL and cord blood(CB)CD34+cells(FL-iEry and CB-iEry,respectively).FL-iEry and CB-iEry were immortalized at the proerythroblast stage and can be induced to differentiate into OrthoEs,but their enucleation ability was very low.Comparison of the transcriptomes between OrthoEs with and without enucleation capability revealed the down-regulation of pathways involved in chromatin organization and mitophagy in OrthoEs without enucleation capacity,indicating that defects in chromatin organization and mitophagy contribute to the inability of OrthoEs to enucleate.Additionally,the expression of HBE1,HBZ,and HBG2 was up-regulated in FL-iEry compared with CB-iEry,and such up-regulation was accompanied by down-regulated expression of BCL11A and up-regulated expression of LIN28B and IGF2BP1.Our study provides new insights into human FL erythropoiesis and rich resources for future studies.展开更多
EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto active...EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto actively regulate a variety of biological processes,including leukemia and embryogenesis,but whether and how EAF1/2 function in hematopoietic system related hypoxia tolerance during embryogenesis remains unclear.Here,we unveiled that deletion of EAF1/2(eaf1^(-/-)and eaf2^(-/-))caused reduction in hypoxia tolerance in zebrafish,leading to reduced erythropoiesis during hematopoietic processes.Meanwhile,eaf1^(-/-)and eaf2^(-/-)mutants showed significant reduc-tion in the expression of key transcriptional regulators scl,lmo2,and gata1a in erythropoiesis at both 24 h post fertilization(hpf)and 72 hpf,with gata1a downregulated while scl and lmo2 upregulated at 14 hpf.Mechanistically,eaf1^(-/-)and eaf2^(-/-)mutants exhibited significant changes in the expression of epigenetic modified histones,with a significant increase in the binding enrichment of modified histone H3K27me3 in gata1a promoter rather than scl and lmo2 promoters.Additionally,eaf1^(-/-)and eaf2^(-/-)mutants exhibited a dynamic expression of canonical WNT/β-catenin signaling during erythropoiesis,with significant reduction in p-β-Catenin level and in the binding enrichment of both scl and lmo2 promoters with the WNT transcriptional factor TCF4 at 24 hpf.These findings demonstrate an important role of Eaf1/2 in erythropoiesis in zebrafish and may have shed some light on regeneration medicine for anemia and related diseases and on molecular basis for fish economic or productive traits,such as growth,disease resistance,hypoxia tolerance,and so on.展开更多
BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impe...BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.展开更多
A simple in vivo bioassay suitable for the routine quality control testing of a new erythropoiesis stimulating protein was developed.Subcutaneous administration of the new erythropoiesis stimulating protein to Balb/c ...A simple in vivo bioassay suitable for the routine quality control testing of a new erythropoiesis stimulating protein was developed.Subcutaneous administration of the new erythropoiesis stimulating protein to Balb/c mice in a single dose resulted in a dose-dependent increase in the number of circulating reticulocytes.Within the erythropoiesis stimulating protein dose range of 3.125 to 200 ng per mouse,there is a strong linear relationship between the dose and reticulocyte counts in the treated mice.This linear relationship allows us to determine the biological potency of the testing erythropoiesis stimulating protein preparation relative to a reference standard using parallel line assay.Accuracy,precision,dose variation and blood collection time of this method were analyzed in order to choose doses in the linear range that are suitable for setting up a useful,precise,and economical bioassay.展开更多
The setting values of thresholds for fault feature parameters are critical in all kinds of protection schemes.When the detected feature parameter value exceeds the setting value,the protection will trip.However,the se...The setting values of thresholds for fault feature parameters are critical in all kinds of protection schemes.When the detected feature parameter value exceeds the setting value,the protection will trip.However,the setting value based conventional protection schemes sometimes cannot satisfy the protection requirements of neutral ineffectively earthed power systems(NIEPS)due to wide variations in operating conditions and the complexities of fault cases.In this paper,a novel single phase grounding fault protection scheme without threshold setting is proposed.The fault detection is achieved based on operating states rather than setting values.A fuzzy c-means algorithm is used to divide the operating state of the protected feeder into non-fault states and fault states.The cluster center of each state is then obtained by classifying the historical feature samples of the protected feeder extracted under various operating conditions into their corresponding states in a constructed multi-dimensional fault feature space.The distances between the detected feature samples and the cluster centers of the non-fault and the fault states are calculated.If the distance to the fault state is shorter than that to the non-fault state,a fault is detected.Otherwise,the feeder is considered normal.A PSCAD/EMTDC simulator is used to simulate a 35 kV NIEPS under various operating conditions,non-linear loads,and complex fault cases.Results show that the proposed single phase grounding fault protection scheme without threshold setting can protect the system correctly under all kinds of faults.展开更多
文摘Context/objectives: The fight against Chronic Non-Communicable Diseases (NCDs) is a long-term undertaking, which requires available, motivated and well-managed human resources (HR). The administrative management of skills on both qualitative and quantitative levels is one of the essential functions of a health system. To better implement policies of fight against High Blood Pressure (HBP) and other chronic diseases, it is important to establish strategies to retain health personnel. This loyalty requires favorable working conditions and consideration of the contribution-reward couple. Good working conditions are likely to reduce the phenomenon of medical nomadism;conversely, poor HR management can contribute to their exodus towards exotic “green pastures”, thus leading to an additional crisis in the Cameroonian health system. The fight against HBP is a complex, multifaceted and multifactorial reality that requires appropriate management model for all types of resources mainly HR. The main objective of this research is to show the impact of poor management of human resources in Cameroon health system on medical nomadism and the ineffectiveness of the fight against High Blood Pressure. Method: A cross-sectional descriptive survey among five hundred (500) health facilities in the center region of Cameroon has been conducted. A stratified probabilistic technique has been used, and the number of health facilities to be surveyed has been determined using the “sample size estimation table” of Depelteau. The physical questionnaires have been printed and then distributed to data collectors. After data collection, the latter were grouped during processing in Excel sheets. The Chi-square test was used for data with a qualitative value and that of Kolmogorov-Sminorf for data with a quantitative value to assess the normality and reliability of data. The Crochach’s Alpha reliability test allowed us to have a summary of the means and variances and then to search for intragroup correlations between variables. Descriptive analysis was possible with the XLSTAT 2016 software. Results: 43.60% of Health Facilities (HF) managers were unqualified. 82.20% of HF managers have staff in a situation of professional insecurity. They are mainly contractual (49.00), decision-making agents (24.40%), casual agents (08.80). The proportion of unstable personnel is average of 22.00% and very unstable, 12.00%.
文摘Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBD- associated anemia are iron deficiency and anemia of chronic disease. An important prognostic parameter of the success or failure of therapy is the outcome of the underlying disease. Iron deficiency should be appropriately managed with iron supplementation. However, the use of oral iron therapy is limited by several problems, the most important being gastrointestinal side effects leading occasionally to disease relapse and poor iron absorption. Intravenous iron preparations are more reliable, with iron sucrose demonstrating the best efficacy and tolerability. Treatment with erythropoietin or darbepoetin has been proven to be effective in patients with anemia, who fail to respond to intravenous iron. Patients with ongoing inflammation have anemia of chronic disease and may require combination therapy comprising of intravenous iron sucrose and erythropoietin. After initiating treatment, careful monitoring of hemoglobin levels and iron parameters is needed in order to avoid recurrence of anemia. In conclusion, anemia in the setting of IBD should be aggressively diagnosed, investigated, and treated. Future studies should define the optimal dose and schedule of intravenous iron supplementation and appropriate erythropoietin therapy in these patients.
文摘Most studies of erythropoiesis have been performed either with the virally transformed MEL cells or with the scarce erythroblasts within unhomogeneous cell populations.MEL cells are the Friend virus transformed mouse erythroleukemia cells and have lost the capacity to respond to erythropoietin.Moreover,the research in the field of erythropoiesis has been severely hampered by the paucity of erythroblasts obtained from chick embryos,human,mouse,rat fetal liver,mouse spleen,or the bone marrow.In our paper,the fetal blood from newly slaughtered pregnant sheep meets the needs of studies as abundant staring biological materials at the nucleotide level and also reflects in vivo proliferative and differential status of erythroblasts.Appling the technique of mRNA differential display with minor modification,we directly compared cDNA fragmerts from the fetal blood erythroblasts and adult pregnant sheep leukocytes by PCR on DNA sequencing gels and revealed two differentially expressing bands.One is a novel gene fragment, which has homology with UV-sensitive cone opsin or rhodopsin by examinating the predicted amino acid sequence.Since the blood cells are sensitive to radiation,it can be safely inferred that this fragment participate in the process of cytocidal effect of the radiation.The other fragment is glucose induced gene /elongation factor 2 3′end noncoding region,which was first cloned from glucose induced bovine aortic smooth muscle cells.Using Northern blot hybridization method,authentic specific expression was confirmed.
基金supported by the Development Projects of Science and Technology of Shandong Province, China (2012GGE27073)
文摘Background: Erythropoiesis-stimulating agents (ESAs) are widely used in the management of anemia in cancer patients. Despite their apparent effectiveness, recent studies have suggested that ESAs could result in serious adverse events and even higher mortality. The aim of the current study was to evaluate the benefits and risks of ESAs in the management of cancer patients with anemia using a recta-analysis. Methods: The initial literature search covered Medline, PubMed, Embase, and the Cochrane Center Register of Controlled Trials, and identified 1,569 articles. The final meta-analysis included eight randomized controlled trials (n=2,387) in cancer patients with 〈11 g/dL hemoglobin (Hb) at the baseline and target Hb (for stopping ESA treatment) at no more than 13 g/dL. The assessment measures included Hb response, blood transfusion rate and adverse events that included venous thromboemblism (VTE), hypertension, and on-study mortality. The results are expressed as pooled odds ratio (OR). Publication bias was assessed using funnel plot analysis. Results: ESAs significantly increased the Hb concentration [OR 7.85, 95% confidence interval (CI): 5.85 to 10.53, P〈O.O01] and reduced the red blood cell (RBC) transfusion rate (OR 0.52, 95% CI: 0.42 to 0.65, P〈0.001). ESAs did not increase the accumulated adverse events (OR 0.95, P=0.82), or the on-study mortality (OR 1.09, P=0.47). Conclusions: ESAs are not associated with increased frequency of severe adverse events in anemic cancer patients when the target Hb value is no more than 13 g/dL.
文摘Coexistence of chronic kidney disease (CKD) and chronic heart failure (CHF) define a recently recognized clinical entity known as cardio-renal syndrome. Sufficient evidence suggests that the two pathological conditions share common pathogenic etiology which is not yet fully defined. Superimposed anaemia is a common finding among patients suffering from cardio-renal syndrome. The combination of CKD, CHF and anaemia increase the probability of death by 6 times compared to normal individuals. Early attempts to restore anaemia either by iron supplementation, erythropoiesis stimulating agents (ESAs) or combination of the two have reported to improve quality of life, morbidity and mortality especially among patients treated by cardiologists. Recent publications of well controlled epidemiological studies failed to prove convincing beneficial effect of the above mentioned therapy moreover skepticism has raised concerning the safety of restoring anaemia among patients with cardio-renal syndrome as well as used medications. There are still unresolved problems concerning the definition of anaemia, by means of hemoglobin level among these patients, the target hemoglobin level and the therapeutic regimen of ESAs administration and iron supplementation. We need much more evidence in order to define an effective and safe treatment strategy correcting anaemia among patients with cardio-renal syndrome.
基金supported in part by the National Natural Science Foundation of China(Grant Nos.81270576 and 81470362)
文摘Normally, cyclin interacts with cyclin-dependent kinase (CDK) to form a cyclin-CDK complex, which promotes cell cycle progression, whereas cyclin-dependent kinase inhibitor (CDKI) molecules inhibit the formation of cyclin- CDK complex, arresting cell cycle. Terminal erythropoiesis is closely coordinated with cell cycle exit, which is regulated by cyclins, CDKs, and CDKIs [1]. In the global transcriptome of human terminal erythropoiesis [2], p19INK4d is expressed highly, and its expression is significantly up-regulated during human terminal erythropoiesis. However, the roles of p19INK4d in terminal erythropoiesis are still unknown.
文摘The aim of this observational study was to biochemically characterize the anaemia in GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) patients. Values for mean corpuscular volume, mean corpuscular hemoglobin and soluble transferrin receptor were normal, whereas serum iron and total iron binding capacity (TIBC) were subnormal, and mean ferritin was above the upper reference limit. Iron-restricted erythropoiesis (IRE), defined as a bone marrow smear staining positive for iron in combination with transferrin saturation less than 20%, was present in all patients. All patients exhibited clinical and biochemical signs of active inflammation with elevated C-reactive protein and an increased erythrocyte sedimentation rate.
文摘AIM: TO evaluate the association between IEM and gastropharyngeal reflux disease (GPRD) in patients who underwent ambulatory 24-h dual-probe pH monitoring for the evaluation of supraesophageal symptoms. METHODS: A total of 632 patients who underwent endoscopy, esophageal manometry and ambulatory 24-h dual-pH monitoring due to supraesophageal symptoms (e.g. globus, hoarseness, or cough) were enrolled. Of them, we selected the patients who had normal esophageal motility and IEM. The endoscopy and ambulatory pH monitoring findings were compared between the two groups. RESULTS;: A total of 264 patients with normal esophageal motility and 195 patients with the diagnosis of IEM were included in this study. There was no difference in the frequency of reflux esophagitis and hiatal hernia between the two groups. All the variables showing gastroesophageal reflux and gastropharyngeal reflux were not different between the two groups. The frequency of GERD and GPRD, as defined by ambulatory pH monitoring, was not different between the two groups. CONCLUSION: There was no association between IEM and GPRD as well as between IEM and GERD. IEM alone cannot be considered as a definitive marker for reflux disease.
文摘AIM:To study non-cardiac chest pain(NCCP) in relation to ineffective esophageal motility(IEM) and rapid food intake.METHODS:NCCP patients with a self-reported habit of fast eating underwent esophageal manometry for the diagnosis of IEM.Telephone interviews identified eating habits of additional IEM patients.Comparison of manometric features was done among IEM patients with and without the habit of rapid food intake and healthy controls.A case study investigated the effect of 6-mo gum chewing on restoration of esophageal motility in an IEM patient.The Valsalva maneuver was performed in IEM patients and healthy controls to assess the compliance of the esophagus in response to abdominal pressureincrease.RESULTS:Although most patients diagnosed with NCCP do not exhibit IEM,remarkably,all 12 NCCP patients who were self-reporting fast eaters with a main complaint of chest pain(75.0%) had contraction amplitudes in the mid and distal esophagus that were significantly lower compared with healthy controls [(23.45 mmHg(95%CI:14.06-32.85)vs 58.80 mmHg(95%CI:42.56-75.04),P < 0.01 and 28.29 mmHg(95%CI:21.77-34.81) vs 50.75 mmHg(95%CI:38.44-63.05),P < 0.01,respectively)].In 7 normal-eating IEM patients with a main complaint of sensation of obstruction(42.9%),the mid amplitude was smaller than in the controls [30.09 mmHg(95%CI:19.48-40.70) vs 58.80 mmHg(95%CI:42.56-75.04),P < 0.05].There was no statistically significant difference in manometric features between the fast-eating and normal-eating groups.One NCCP patient who self-reported fast eating and was subsequently diagnosed with IEM did not improve with proton-pump inhibition but restored swallow-induced contractions upon 6-mo gum-chewing.The Valsalva maneuver caused a markedly reduced pressure rise in the mid and proximal esophagus in the IEM patients.CONCLUSION:Habitual rapid food intake may lead to IEM.A prospective study is needed to validate this hypothesis.Gum-chewing might strengthen weakened esophageal muscles.
文摘Administrative department, as the focus of national political system reform, is associated with optimization and adjustment of state institutions and plays a macro-control role in socialist economic development. Administrative departments, just the "government", conduct economic control function to promote the sustainable development of social economic causes. The thesis firstly introduces administrative departments' era effect and causes of administrative departments' economic policy ineffectiveness. And on the basis of these, the thesis comes up with some solutions to solve economic ineffectiveness, hoping that it would be helpful to relevant researches.
基金supported by grants from the National Natural Science Foundation of China(Grant numbers 81920108004 and 82270127)the Fundamental Research Funds of the Central Universities of Central South University(Grant number 2021zzts0562)the Fundamental Research Funds for the Scientific Research Innovation Project of Hunan Province(Grant number CX20210182).
文摘Erythropoiesis is a complex,precise,and lifelong process that is essential for maintaining normal body functions.Its strict regulation is necessary to prevent a variety of blood diseases.Normal erythropoiesis is precisely regulated by an intricate network that involves transcription levels,signal transduction,and various epigenetic modifications.In recent years,research on posttranscriptional levels in erythropoiesis has expanded significantly.The dynamic regulation of splicing transitions is responsible for changes in protein isoform expression that add new functions beneficial for erythropoiesis.RNA-binding proteins adapt the translation of transcripts to the protein requirements of the cell,yielding mRNA with dynamic translation efficiency.Noncoding RNAs,such as microRNAs and lncRNAs,are indispensable for changing the translational efficiency and/or stability of targeted mRNAs to maintain the normal expression of genes related to erythropoiesis.N6-methyladenosine-dependent regulation of mRNA translation plays an important role in maintaining the expression programs of erythroid-related genes and promoting erythroid lineage determination.This review aims to describe our current understanding of the role of post-transcriptional regulation in erythropoiesis and erythroid-associated diseases,and to shed light on the physiological and pathological implications of the post-transcriptional regulation machinery in erythropoiesis.These may help to further enrich our understanding of the regulatory network of erythropoiesis and provide new strategies for the diagnosis and treatment of erythroid-related diseases.
基金supported by the Science and Technology Research Project of Henan(Grant No.232102311003)the National Natural Science Foundation of China(Grant No.U1804282)。
文摘The fetal liver(FL)is the key erythropoietic organ during fetal development,but knowledge on human FL erythropoiesis is very limited.In this study,we sorted primary erythroblasts from FL cells and performed RNA sequencing(RNA-seq)analyses.We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis.Notably,the expression of genes enriched in proteolysis and autophagy was up-regulated in orthochromatic erythroblasts(OrthoEs),suggesting the involvement of these pathways in enucleation.We also performed RNA-seq of in vitro cultured erythroblasts derived from FL CD34+cells.Comparison of transcriptomes between the primary and cultured erythroblasts revealed significant differences,indicating impacts of the culture system on gene expression.Notably,the expression of lipid metabolism-related genes was increased in cultured erythroblasts.We further immortalized erythroid cell lines from FL and cord blood(CB)CD34+cells(FL-iEry and CB-iEry,respectively).FL-iEry and CB-iEry were immortalized at the proerythroblast stage and can be induced to differentiate into OrthoEs,but their enucleation ability was very low.Comparison of the transcriptomes between OrthoEs with and without enucleation capability revealed the down-regulation of pathways involved in chromatin organization and mitophagy in OrthoEs without enucleation capacity,indicating that defects in chromatin organization and mitophagy contribute to the inability of OrthoEs to enucleate.Additionally,the expression of HBE1,HBZ,and HBG2 was up-regulated in FL-iEry compared with CB-iEry,and such up-regulation was accompanied by down-regulated expression of BCL11A and up-regulated expression of LIN28B and IGF2BP1.Our study provides new insights into human FL erythropoiesis and rich resources for future studies.
基金supported by the Nation Natural Science Foundation of China(Program No.32070807)by the National Key R&D Program of China(2018YFD0900101)by the project 2020SKLBC-KF06 of State Key Laboratory of Biocontrol.
文摘EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto actively regulate a variety of biological processes,including leukemia and embryogenesis,but whether and how EAF1/2 function in hematopoietic system related hypoxia tolerance during embryogenesis remains unclear.Here,we unveiled that deletion of EAF1/2(eaf1^(-/-)and eaf2^(-/-))caused reduction in hypoxia tolerance in zebrafish,leading to reduced erythropoiesis during hematopoietic processes.Meanwhile,eaf1^(-/-)and eaf2^(-/-)mutants showed significant reduc-tion in the expression of key transcriptional regulators scl,lmo2,and gata1a in erythropoiesis at both 24 h post fertilization(hpf)and 72 hpf,with gata1a downregulated while scl and lmo2 upregulated at 14 hpf.Mechanistically,eaf1^(-/-)and eaf2^(-/-)mutants exhibited significant changes in the expression of epigenetic modified histones,with a significant increase in the binding enrichment of modified histone H3K27me3 in gata1a promoter rather than scl and lmo2 promoters.Additionally,eaf1^(-/-)and eaf2^(-/-)mutants exhibited a dynamic expression of canonical WNT/β-catenin signaling during erythropoiesis,with significant reduction in p-β-Catenin level and in the binding enrichment of both scl and lmo2 promoters with the WNT transcriptional factor TCF4 at 24 hpf.These findings demonstrate an important role of Eaf1/2 in erythropoiesis in zebrafish and may have shed some light on regeneration medicine for anemia and related diseases and on molecular basis for fish economic or productive traits,such as growth,disease resistance,hypoxia tolerance,and so on.
文摘BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.
文摘A simple in vivo bioassay suitable for the routine quality control testing of a new erythropoiesis stimulating protein was developed.Subcutaneous administration of the new erythropoiesis stimulating protein to Balb/c mice in a single dose resulted in a dose-dependent increase in the number of circulating reticulocytes.Within the erythropoiesis stimulating protein dose range of 3.125 to 200 ng per mouse,there is a strong linear relationship between the dose and reticulocyte counts in the treated mice.This linear relationship allows us to determine the biological potency of the testing erythropoiesis stimulating protein preparation relative to a reference standard using parallel line assay.Accuracy,precision,dose variation and blood collection time of this method were analyzed in order to choose doses in the linear range that are suitable for setting up a useful,precise,and economical bioassay.
基金supported in part by National Natural Science Foundation of China under Grant 61233008 and Grant 51277014.
文摘The setting values of thresholds for fault feature parameters are critical in all kinds of protection schemes.When the detected feature parameter value exceeds the setting value,the protection will trip.However,the setting value based conventional protection schemes sometimes cannot satisfy the protection requirements of neutral ineffectively earthed power systems(NIEPS)due to wide variations in operating conditions and the complexities of fault cases.In this paper,a novel single phase grounding fault protection scheme without threshold setting is proposed.The fault detection is achieved based on operating states rather than setting values.A fuzzy c-means algorithm is used to divide the operating state of the protected feeder into non-fault states and fault states.The cluster center of each state is then obtained by classifying the historical feature samples of the protected feeder extracted under various operating conditions into their corresponding states in a constructed multi-dimensional fault feature space.The distances between the detected feature samples and the cluster centers of the non-fault and the fault states are calculated.If the distance to the fault state is shorter than that to the non-fault state,a fault is detected.Otherwise,the feeder is considered normal.A PSCAD/EMTDC simulator is used to simulate a 35 kV NIEPS under various operating conditions,non-linear loads,and complex fault cases.Results show that the proposed single phase grounding fault protection scheme without threshold setting can protect the system correctly under all kinds of faults.