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Objective:To explore the combination of high risk screening and family screening for potential patients with Fabry disease in adult hemodialysis population, and to improve the diagnostic efficiency of the disease.Methods:It was a cross-sectional investigation study. High-risk screening for Fabry disease was performed on adult hemodialysis patients with end-stage kidney disease who were admitted to Yongkang First People's Hospital of Zhejiang Province between November 2022 and February 2023. Dry blood paper α-galactosidase A (α-Gal A) detection assay was performed in males, or glycosphingolipids (Lyso-GL-3) detection assay was performed in females. GLA genetic assay was performed for further diagnosis after abnormal screening results. Family screening was carried out on the family members of the confirmed Fabry disease patients, and α-Gal A activity and Lyso-GL-3 of peripheral blood were measured. Additionally, urine routine, blood biochemistry, eye examination, hearing test, cranial magnetic resonance imaging, and electrocardiogram were performed to assess organ damage. Results:Among 244 hemodialysis patients, 139 (56.97%) were males and 105 (43.03%) were females. The age ranged from 25 to 81 years (with median age of 61 years). One female patient with Fabry disease was identified GLA IVS4+919G>A mutation, resulting in a total prevalence of 0.41%. Pedigree screening was conducted on 41 family members of the patient, leading to the confirmation of 12 patients (including the proband), including 3 males and 9 females. Among them, 9 patients were abnormal in enzyme examination, 10 patients were abnormal in substrate, and 11 patients were abnormal in gene sequencing. None of the 12 patients exhibited limb pain, hypohidrosis, angiokeratoma, corneal opacity, and hearing impairment. Eight patients had heart abnormalities. Nine patients had abnormal urine routine (albuminuria or hematuria) and one patient had abnormal renal function. Four patients had abnormal cranial magnetic resonance imaging findings. Conclusions:One GLA IVS4+919G>A mutation family is successfully identified through the combination of high-risk screening and family screening in adult hemodialysis patients, with a total of 12 cases of Fabry disease. The combination of high-risk screening and family screening proves to be effective in detecting potential patients with Fabry disease, and improve the screening efficiency of Fabry disease.
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Objective:To identify the strengths and weaknesses of hospital development through the application of individual scientific research performance assessment, thereby providing a basis for the formulation of science and technology policies.Methods:We established a research performance assessment system and conducted research performance assessments across the hospital for three consecutive years. The assessment results were analyzed in-depth, utilizing the Kruskal-Wallis test to determine if there were differences in the overall level of assessment scores between years and series; the Mann-Whitney test to analyze differences between the promoted and non-promoted groups; the χ2 test to analyze whether age, degree, gender, and maternity situations affected assessment grades. Results:From 2020 to 2022, the individual scientific research performance assessment scores showed an overall upward trend, with the average per capita assessment score increasing significantly from 35.26 points in 2020 to 74.04 points in 2022. There were statistical differences in the assessment scores of different professional titles, indicating that the senior professionals > the associate senior professionals > the intermediates. There was no significant difference between the promoted and non-promoted groups. Additionally, age, degree, gender, and maternity factors affected assessment grades.Conclusions:It has been preliminarily established that the assessment of individual scientific research performance can effectively steer the scientific innovation activities of researchers, and play a positive role in enhancing the overall scientific research strength. The findings from the data analysis indicate that the hospital is expected to continuously enhance its scientific research performance by focusing on newly recruited doctoral personnel, establishing a system of support and guidance, and providing preferential support to female researchers. The assessment results serve as a " benchmark" for management departments and provide data-driven insights for the development of science and technology policies.
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By collecting 475 protocol violation reports of pediatric clinical trials accepted by the ethics committee of a grade A tertiary hospital from January 2016 to December 2022, and conducting classification statistics of the responsible body, types of violation, and natures of violation, this paper analyzed and discussed the specific reasons and response measures for protocol violation. The results showed that the most common types of protocol violation included missed medication and incorrect medication dosage for pediatric research participants, missed laboratory inspection, over-windowed follow-up, and non-compliance with inclusion/exclusion criteria. And the responsibility bodies were pediatric research participants and/or their guardians, followed by the researchers. Besides, the sponsor, clinical trial coordinator, and other factors also contributed to protocol violation. Establishing awareness of responsible body, emphasizing subject management, building sound quality control system, and strengthening ethical supervision are the main countermeasures to prevent and reduce protocol violation in pediatric clinical trials, which helps to protect the safety and rights of pediatric research participants and promote standardized research in pediatric clinical trials.
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IgA-dominant infection-related glomerulonephritis (IgA-IRGN) is a unique form of infection-associated glomerulonephritis. The main causative organism is staphylococcus. Although IgA-IRGN is rare in children, the prevalence is gradually increasing, and the prognosis is poor in children with immunodeficiency and mucocutaneous barrier dysfunction. The clinical manifestations are varying degrees of hematuria, proteinuria, acute kidney injury and hypocomplementemia. The renal pathology is similar to postinfectious glomerulonephritis, therefore differential diagnosis is challenging. The paper reviews the current research progress of IgA-IRGN to improve the pediatrician's understanding of IgA-IRGN in children and avoid misdiagnosis.
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Systemic lupus erythematosus (SLE) is a serious autoimmune disease that affects multiple systems and organs throughout the body. Thrombotic microangiopathy (TMA) is a rare clinical syndrome that can lead to multiple organ dysfunction and even threaten life. Clinically, SLE patients with TMA are relatively rare, especially in children, but the mortality of SLE patients with TMA is significantly increased. The article reports 2 cases of successful remission of SLE complicated with TMA after treatment with eculizumab, and discusses the diagnosis, clinical manifestations and treatment of SLE complicated with TMA in children, so as to provide clinical basis for the diagnosis and treatment of SLE complicated with TMA in children.
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Pediatric idiopathic nephrotic syndrome (INS) is characterized by massive albuminuria, hypoproteinemia, edema and hyperlipidemia, with a long course and high probability of relapse and prolongation. Long-term complications caused by long-term usage of hormones and immunosuppressants in children with INS seriously affect their physical and mental health and quality of life. Most children with steroid-sensitive nephrotic syndrome can be cured before adulthood, while some of them relapse in adulthood. Long-term prognosis of children with steroid-resistant nephrotic syndrome is poor. There have been few studies in China followed the long-term outcomes and its related factors of children with INS over 10 years. The paper reviewed the literatures on the long-term outcomes of children with INS, including renal survival, growth, mental health, learning and work, marriage and fertility, disease recurrence and long-term related complications, to explore the factors related to the poor long-term outcomes of children with INS and to assist in clinical decision-making and follow-up management.
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In recent years, it has been demonstrated in some studies that adrenocorticotropic hormone (ACTH) is effective in the treatment of certain steroid-resistant nephrotic syndrome, including membranous nephropathy, focal segmental glomerular sclerosis, minimal change nephropathy and so forth.ACTH can effectively relieve proteinuria and protect renal function, suggesting that there may be other mechanisms in addition to the adrenocorticotropic effect.This article mainly introduces the biological characteristics of ACTH, in combination with the clinical and basic studies on the treatment of nephrotic syndrome by ACTH, and clarifies several possible mechanisms, in an attempt to provide basis for clinical application.
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C3 glomerulopathy is a rare disease of glomeruli mediated by abnormal activation of alternative complement pathway secondary to congenital genetic defects and acquired autoantibodies.Renal biopsy is the gold standard for diagnosing C3 glomerulopathy.C3 glomerulopathy encompasses both dense deposit disease and C3 glomerulonephritis.The main glomerular immunofluorescence staining is C3, with few or without immunoglobulins deposition, which is the obvious pathological feature.The clinical manifestations of C3 glomerulopathy are usually various, with limited detection methods and therapies and poor prognosis.This article mainly reviews the progress of C3 glomerulopathy in recent years, in order to improve clinical understanding of C3 glomerulopathy, and choose individualized therapy.
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Hemolytic uremic syndrome (HUS) is one of the important causes of acute and chronic renal dysfunction in children, with microvascular hemolytic anemia, thrombocytopenia, and renal injury as its characteristic triad.In recent years, with new insights into the etiology and pathogenesis of HUS, the classification of HUS has become more detailed, the diagnosis and treatment are more accurate, and the emergence of complement C 5 monoclonal antibody has greatly improved the treatment rate of HUS.In this study, the diagnosis, and treatment of HUS are introduced.
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Infection is one of the most familiar complications in children with idiopathic nephrotic syndrome.Although vaccination is an effectual measure in prevention of secondary infections, it still faces many problems.On the one hand, children′s own immune status (immune system dysfunction, administration with immunosuppressants, etc.) lends additional uncertainties to whether the immune system can produce sufficient protective antibodies after vaccination.On the other hand, potential risks (recurrence of nephrotic syndrome and induction of vaccine related diseases) need to be comprehensively assessed at the time of vaccination.In this paper, the safety, effectiveness and timing of va-ccination in children with nephrotic syndrome in the post-COVID-19 period were summarized, and possible problems of vaccination against severe acute respiratory syndrome Coronavirus 2(SARS-CoV-2) were discussed.
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The arsenic compounds including arsenic trioxide and arsenic sulfide have played a crucial role in the clinical treatment of hematologic malignancies and solid tumors. Arsenic agents can induce tumor cells differentiation, apoptosis and autophagy, eliminate leukemia-initiating cells, and directly bind to the target proteins. This paper reviews the mechanism progress of arsenic agents in various tumors to further understand the intricate anti-tumor mechanisms of arsenic agents and to expand its therapeutic spectrum.
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Objective:To investigate the efficacy and safety of adrenocorticotropic hormone (ACTH) in treating primary nephrotic syndrome in children with dual resistance to glucocorticoids and calcineurin inhibitors (CNIs).Methods:Clinical data of 6 children with primary nephrotic syndrome treated with ACTH in the Children's Hospital of Zhejiang University School of Medicine from January 1, 2015 to December 31, 2019 were retrospectively collected. All the enrolled patients were children with primary nephrotic syndrome with dual resistance to glucocorticoids and CNIs. All the 6 children were given 0.4-1.0 IU·kg -1·d -1 ACTH (total ≤25 IU)+5% glucose 500 ml intravenous infusion for 8 h during the hormone reduction process, with a course of treatment for 5 days, once a month, and continuous treatment for 3-6 months. Clinical data such as 24 h urinary protein quantification, serum albumin, serum cholesterol, estimated glomerular filtration rate (eGFR) level and glucocorticoid dosage were collected at equal time points at 6 months before treatment, at the beginning of treatment, at the end of treatment and at 6 months of follow-up after treatment of ACTH to evaluate the efficacy and adverse reactions. Results:The onset age of 6 children was (4.89±1.77) years, and the age of the first treatment with ACTH was (9.49±3.06) years. All the 6 children completed 3 to 6 months of ACTH treatment, with 2 cases of complete remission, 2 cases of partial remission and 2 cases of no remission. At the end of ACTH treatment, 24 h urinary protein was significantly decreased ( P=0.026), serum albumin level was significantly increased ( P=0.003), and glucocorticoid dosage was significantly decreased ( P<0.001) than before treatment. At 6 months after the end of ACTH treatment, there was no statistical significance in 24 h urinary protein, serum albumin and hormone dosage compared with the end of ACTH treatment (all P>0.05), and the blood cholesterol level continued to decrease ( P=0.039). There was no significant change in eGFR during observation period ( P>0.05). In the process of ACTH infusion, all the 6 children showed transient decrease in urine output, rash in 2 cases, and elevated blood glucose in 1 case, which could be spontaneously relieved after drug withdrawal. There were no serious cardiovascular events, renal impairment, infection and other adverse reactions. Conclusions:ACTH has a good effect on children with primary nephrotic syndrome who are dual resistant to glucocorticoids and CNIs. ACTH can reduce proteinuria, decrease the dosage of glucocorticoids, improve the clinical remission rate, and has good security.
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Objective@#To evaluate the effects of adeno-associated virus (AAV) carrying hFⅧ by serotype 8 (AAV8/hFⅧ) on hemophilia A (HA) mice by gene therapy strategy.@*Methods@#pAAV-CB-EGFP, pH22 (serotype 2) and pfΔ6 (adenovirus helper) were used to package AAV into HEK-293 cells in different conditions (ratios of cells to plasmids). The efficiency of transfection and infection were evaluated using immunofluorescence microscope to seek an optimized package condition. pAAV-TTR-hFⅧ, pH 28 (serotype 8) and pfΔ6 were applied to package AAV8/hFⅧ in HEK-293 cells using the optimized package condition. The purified AAV8/hFⅧ were intravenously injected into HA mice and the effects of gene therapy were estimated.@*Results@#The efficiency of package was evaluated according to the amount and intensity of enhanced green fluorescent protein (EGFP) under immunofluorescence microscope. Four package conditions including 10 cm-dish to transfect 10 μg plasmids, 20 cm-dish to 20 μg, 30 μg and 40 μg plasmids were employed, and the condition of 20 cm-dish to transfect 20 μg plasmids reached the highest transfection efficiency at 24 h, 48 h and 72 h after transfection. The small scale AAV-EGFP was packaged using the optimized condition and an AAV crude extract was harvested by a freeze-thaw method. HEK-293 and 16095 cells were infected by the AAV crude extract, and the preferential infection efficiency was recognized in 16095 cells under immunofluorescence microscope. Then, AAV8/hFⅧ was packaged and purified based on the optimized transfection condition, and the high purity of AAV8/hFⅧ was detected by Western blot. Fractions of AAV8/hFⅧ at the dose of 8×1012 vg/kg were injected into HA mice through tail vein, an eye-bleeding was performed at every two weeks, and the activity of FⅧ was measured by aPTT assay. Results showed that the activity of FⅧ maintained at the therapeutic level and lasted up to 12 weeks after injection.@*Conclusion@#The purified AAV8/hFⅧ based on the optimized package condition could play a role in HA mice gene therapy, and the long-term therapeutic effects of AAV8/hFⅧ were observed in vivo.
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Coronavirus disease 2019 (COVID-19) is a grade B infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In pace with the spreading of the disease, biosafety risk of the biological specimen preservation in biobanks has been significantly increased and biosafety protection during biological specimen preservation become increasingly important. According to the related national rules and the corresponding guidelines of Chinese Medical Association, this paper introduced the etiology about SARS-CoV-2, epidemiology about COVID-19, and the biosafety protection principles of individuals and biological specimen storage places in the process of personal protection, protection of collection, transport, handling, preservation, detection, post-detection disposal and emergencies of biological specimen. Emphasized to carry out a strict biosafety-risk assessment on biological specimen basing on virus load information, infectivity, and sample type (possible contact transmission, aerosol transmission, and fecal oral transmission).
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Humains , Betacoronavirus , Confinement de risques biologiques , Normes de référence , Infections à coronavirus , Épidémiologie , Pandémies , Pneumopathie virale , Épidémiologie , Prévalence , Appréciation des risques , Manipulation d'échantillons , Normes de référenceRÉSUMÉ
OBJECTIVE@#To investigate genetic characteristics of Alport syndrome.@*METHODS@#High-throughput sequencing-based whole exome sequencing was performed in two patients with recurrent unexplained abnormal urinalysis. The pathogenicity of the genetic variations, type of Mendelian genetics, and clinical phenotypes were analysed, and the disease-cause mutations were confirmed in the family members using Sanger sequencing.@*RESULTS@#Two heterozygous splice site mutations of gene c.2147-2A > T (IVS27) and c.646-2A > G (IVS11) (NM_033380) were found in patients of the two families, which showed a co-segregation association with the affected members of the families.@*CONCLUSIONS@#Alport syndrome is mainly inherited from direct female patients, and prenatal genetic screening based on amniotic fluid testing can effectively prevent birth defects in patients with a family history of this characteristic phenotype.
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Femelle , Humains , Collagène de type IV , Génétique , Dépistage génétique , Mutation , Néphropathie familiale avec surdité , Génétique , Phénotype , Diagnostic prénatalRÉSUMÉ
Objective@#To establish comprehensive laboratory reference intervals for Chinese children.@*Methods@#This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex.@*Results@#In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old.@*Conclusion@#This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.
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Splenic lymphoma with villous lymphocytes (SLVL) or splenic marginal zone lymphoma with circulating villous lymphocytes is rare, and prolymphocytic transformation of SLVL is rarer. At present, only one case of SLVL with t(8;14)(q24;q32) translocation has been reported. In this study, we report a case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) chromosome translocation that we inclined to SLVL with a prolymphocytic transformation. A 73-year-old female showed marked hepatosplenomegaly and high lymphocytosis (lymphocytes > 200 × 10/L). The abnormal lymphocytes had short coarse villi and round nuclei with prominent nucleoli. The immunophenotypes showed CD19, CD20, HLA-DR, CD22, CD5, Kappa, CD25, CD71, Lambda, CD7, CD10, CD23, CD34, CD33, CD13, CD14, CD117, CD64, CD103, and CD11c. The karyotype showed complex abnormality: 46XX,+ 3,-10, t(8;14)(q24; q32)[11]/46XX[9]. The cytoplasmic projection, immunological characteristics, and trisomy 3 chromosome abnormality supported the diagnosis of SLVL. However, the presence of prominent nucleoli and high lymphocytosis suggested prolymphocytic transformation, probably as a result of t(8,14) chromosome translocation. In this report, we described an unusual case of B-lymphoproliferative disorder with villous lymphocytes harboring t(8;14)(q24;q32) translocation, which could provide help in the diagnosis and differential diagnosis of B-lymphocytic proliferative diseases.
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Sujet âgé , Femelle , Humains , Lymphocytes B , Anatomopathologie , Immunophénotypage , Syndromes lymphoprolifératifs , Génétique , Anatomopathologie , Translocation génétiqueRÉSUMÉ
Renal tubular acidosis (RTA) is a hyperchloremic metabolic acidosis characterized by a normal anion gap due to reduced urinary acidification.Multiple mechanisms act in the renal tubule to maintain balance in hydrogen ion secretions and bicarbonate absorption.In recent years,more and more proteins have been found to be associated with RTA,so hereditary RTA has attracted people's attention.Mutations in the gene SLC4A1,encoding C1-/HCO3-exchanger (kAE1);in the gene ATP6V1B1,encoding B1 subunit of H+-ATP ase;in the gene ATP6V0A4,encoding a4 subunit of H +-ATP ase;in the gene SLC4A4,encoding Na+/HCO3-cotransporter(kNBCe1);in the gene CA2,encoding carbonic anhydrase Ⅱ are identified in the pathogenesis of hereditary RTA.The search for pathogenetic genes for clinically suspected hereditary RTA patients can help us to make accurate genetic diagnosis and provide targeted treatment interventions.
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OBJECTIVES: Henoch-Schönlein purpura nephritis and immunoglobulin A nephropathy are two diseases with similar clinical presentations but very different prognoses. Transforming growth factor β1 and monocyte chemoattractant protein-1 have been associated with the development of tissue fibrosis. We examined the development of tubulointerstitial fibrosis and its relationship with Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in these patients. METHODS: Renal tissue samples were collected by renal biopsy from 50 children with Henoch-Schönlein purpura nephritis and 50 children with immunoglobulin A nephropathy. Hematoxylin and eosin and Masson's trichrome-stained tissues were examined using light microscopy. Tubulointerstitial fibrosis was graded using the method described by Bohle et al. (1). The immunohistochemical detection of Transforming growth factor β1 and monocyte chemoattractant protein-1 expression was correlated with the tubulointerstitial fibrosis grade. Clinical Trial registration number: ZJCH-2012-0105. RESULTS: Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in the renal tissues was significantly greater in the patients with immunoglobulin A nephropathy than in the patients with Henoch-Schönlein purpura nephritis (both p<0.001). The immunoglobulin A nephropathy patients had a higher tubulointerstitial fibrosis grade than the Henoch-Schönlein purpura nephritis patients (p<0.001). The tubulointerstitial fibrosis grade was in accordance with the Transforming growth factor β1 and monocyte chemoattractant protein-1 expression levels in both diseases (both p<0.001). CONCLUSION: Transforming growth factor β1 and monocyte chemoattractant protein-1 expression was associated with the development of immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis. Further studies are needed to better evaluate this association.
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Humains , Mâle , Femelle , Enfant d'âge préscolaire , Enfant , Adolescent , 12131/métabolisme , Chimiokine CCL2/métabolisme , Facteur de croissance transformant bêta-1/métabolisme , Glomérulonéphrite à dépôts d'IgA/métabolisme , Tubules rénaux/métabolisme , Pronostic , 12131/anatomopathologie , Fibrose , Glomérulonéphrite à dépôts d'IgA/anatomopathologie , Tubules rénaux/anatomopathologieRÉSUMÉ
Objective:To explore influence of hyperglycemia on hospitalization and follow‐up prognosis in patients with acute ST elevation myocardial infarction (STEMI ) undergoing direct percutaneous coronary intervention (PCI) .Methods :A total of 218 patients ,who were diagnosed as STEMI and received emergency PCI within 12h af‐ter onset from our hospital ,were enrolled .According to blood glucose level at hospitalization and OGTT results , they were divided into normal blood glucose (NBG) group (n= 108) ,hyperglycemia group (n= 60) and diabetes mellitus (DM) group (n=50) .Cardiac function indexes were evaluated ;Logistic regression analysis was used to an‐alyze influencing factors for mortality in these patients .Results:Compared with NBG group , the in‐hospital mortal‐ity was significant rise (1.9% vs .10.0% ) in DM group ;there were significant rise in percentages of ≥double‐vessel coronary disease (41.2% vs .68.8% vs .66.7% ) and ≥2 stents implanted (14.72% vs .50.0% vs .55.6% ) in women in hyperglycemia group and DM group (P<0.05 or <0.01);Multi‐factor Logistic regression analysis indi‐cated that Killip class ,NT‐proBNP ,number of diseased vessels and body mass index were independent risk factors of in‐hospital mortality of these patients (OR=1.012~5.923 ,P<0.05 all) ,and female was a strong independent risk factor for in‐hospital mortality and mortality within one‐year follow‐up (OR=20.376 ,7.227 ,P<0.01 both) .Con‐clusion:The mortality significantly rises in STEMI patients undergoing emergency PCI complicated with hyperglyce‐mia ,especially in female patients .