ObjectiveTo screen key genes associated with neuroblastoma （NB） diagnosis and prognosis using the Gene Expression Omnibus （GEO） database， and to investigate the expression and clinical significance of nucleoporin 93 （NUP93） in NB tissues. MethodsNB gene chip data （GSE73517， GSE49710， GSE19274） were retrieved from the GEO database. Differentially expressed genes （DEGs） commonly upregulated in high-risk groups were screened. The R2 database was then used to assess the prognostic value of DEGs that were commonly upregulated in the MYCN amplification group. Finally， NUP93 expression levels in the tissues from 60 NB， 25 ganglioneuroblastoma （GNB）， and 26 ganglioneuroma （GN） cases were measured by immunohistochemistry . ResultsTwenty-five DEGs were identified as commonly upregulated in high-risk groups. Among these， 10 genes （SIVA1， NUP93， STIP1， LSM4， RAI14， MYOZ3， KNTC1， TNFRSF10B， TACC3 and CEP152） showed significantly higher expression in MYCN-amplified subgroups （P＜0.05）. Survival analysis revealed that high NUP93 expression was associated with shorter overall survival （HR = 4.0， 95% CI： 3.0，5.3， P = 1.80 × 10⁻³⁴）. Immunohistochemistry results revealed that NUP93 expression in NB tissues was significantly higher than in GNB and GN tissues （P＜0.001）. NUP93 expression was positively correlated with high mitosis-karyorrhexis index （MKI； P=0.040）， poor differentiation （P＜0.001）， and MYCN expression （r_s = 0.793， P ＜0.001）. ConclusionsHigh expression of NUP93 is associated with high MKI and poor differentiation， and predicts unfavorable prognosis in patients with NB， suggesting it may promote tumor progression by regulating MYCN. NUP93 has the potential to be a novel diagnostic biomarker and therapeutic target for NB.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

A 14-year girl was admitted with akinesia and difficulty walking due to gait instability after two oral doses of compound diphenoxylate (lomotil). When she was 18-month old, drowsiness and inability to walk were observed after taking lomotil, the symptoms were relieved by taking B vitamins for treatment. The laboratory tests showed the increased blood branched chain amino acid levels; gene detection indicated that the child had compound heterozygous variations of c.745G>A(p.G249S) and c.485-1G>C in the BCKDHA gene. The girl was finally diagnosed as maple syrup urine disease. The domestic and foreign literature was searched, and 11 child cases of maple syrup urine disease with onset of unsteadiness and ataxia were reported, none of whom was associated with oral administration of compound diphenoxylate.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is considered a serious global threat. However, little is known regarding the multidrug resistance (MDR) mechanisms of CRKP. This study investigated the phenotypes and MDR mechanisms of CRKP and identified their clonal characteristics. METHODS: PCR and sequencing were utilized to identify antibiotic resistance determinants. Integron gene cassette arrays were determined by restriction fragment length polymorphism (RFLP) analysis. Multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were used for epidemiological analysis. Plasmids were typed by using a PCR-based replicon typing and analyzed by conjugation and transformation assays. RESULTS: Seventy-eight strains were identified as resistant to at least one carbapenem; these CRKP strains had a high prevalence rate (38.5%, 30/78) of carbapenemase producers. Additionally, most isolates harbored MDR genes, including Extended spectrum β-lactamases (ESBLs), AmpC, and quinolone and aminoglycoside resistance genes. Loss of porin genes was observed, and Class 1 integron was detected in 66.7% of the investigated isolates. PFGE and MLST results excluded the occurrence of clonal dissemination among these isolates. CONCLUSIONS: A high prevalence of NDM-1 genes encoding carbapenem resistance determinants was demonstrated among the K. pneumoniae isolates. Importantly, this is the first report of bla(NDM-1) carriage in a K. pneumoniae ST1383 clone in China and of a MDR CRKP isolate co-harboring bla(NDM-1), bla(KPC-2), bla(CTX-M), bla(SHV), acc(6′)-Ib, rmtB, qnrB, and acc(6′)-Ib-cr.
China* ; Clone Cells ; Drug Resistance, Bacterial ; Drug Resistance, Microbial ; Drug Resistance, Multiple* ; Electrophoresis, Gel, Pulsed-Field ; Genes, MDR ; Integrons ; Klebsiella pneumoniae* ; Klebsiella* ; Molecular Epidemiology ; Phenotype ; Plasmids ; Pneumonia ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Prevalence ; Replicon

ObjectiveTo analyze the problems in the catheter related bloodstream infection (CRBSI) control for critically ill patients to reduce the incidence of CRBSI in emergency nursing practice.Methods An action research was performed to identify the problems causing high occurrence rate of CRBSI in emergency intensive care unit (EICU). According to the process of "plan-action-observation-reflection",doctors and nurses were surveyed on the knowledge-attitude-action successively. The preventive measures were determined in accordance with advices of emergency medical care specialist to improve the clinical practice of CRBSI control and control the incidence of CRBSI.Results An action group containing 19 EICU medical workers was built up. After the first round from June to July 2015,the incidence rate of CRBSI was 12.12‰. After the second round from August to September 2015,the incidence rate of CRBSI decreased to 8.90‰. Logistic regression analysis showed that the ductal indwelling time and gender of patients affected the occurrence of CRBSI.Conclusions In the study of decreasing the incidence of CRBSI,action research can improve the clinical nursing practice of CRBSI in EICU and is worth trying in the field of intensive care.

There was a 1 1 -year -old school -aged girl complaining of abdomen intumescing and declining physical fitness for 1 6 months,and hydropericardium for 5 months.The child had a intumescent abdomen and strength diminished strength suddenly.After the strenuous exercise she was more tired than before and lost her appetite.The girl was found cardiac enlargement and calcification of pericardium during security check at the airport.The thoracoabdomi-nal computed tomography(CT)suggested hydropericardium,hydrothorax effusion in the right,and seroperitoneum,pel-vic effusion.The girl had no response to pericardiocentesises,anti -inflammation and antituberculosis therapies.The in-flammatory markers and the findings of autoimmunity were normal after her admission.The purified protein derivatives (PPD)test was (++),but the antituberculosis therapy was invalid,so the diagnosis was unclear.The she had peri-cardiectomy.The pericardium visceral and parietale′s pathology showed hyperplasia,hyalinosis and organization of fi-brous connective tissue,congestion of the blood capillaries,infiltration of inflammatory cells.Terminally,she was diag-nosed as constrictive pericarditis.Symptoms disappeared after treatments with cardiotonic,diuretic and potassium sup-ply.The comprehensive analysis is important clinically,the possible causes should be removed gradually,and pathologi-cal examination must be emphasized during the diagnosis of constrictive pericarditis.

Aedes ; virology ; Animals ; China ; epidemiology ; Genetic Variation ; Genome, Viral ; Humans ; Multigene Family ; Viral Proteins ; genetics ; Zika Virus ; classification ; genetics ; isolation & purification ; Zika Virus Infection ; epidemiology ; virology

Objective To report clinical manifestations, electroencephalogram (EEG), and the genotypes of two siblings with type Ⅲ Gaucher disease.Methods Two patients with different features were siblings. Their clinical data, signs, peripheral leukocytes acid β-glucosidase activity, andGBA gene were analyzed.Results (1) The proband was a boy. He visited us at the age of nine years old because of hepatosplenomegaly, thrombocytopenia and growth retardation without any neurologic symp-toms. He had normal intelligence but abnormal EEG ifndings. The activity of acid β-glucosidase in his leucocytes decreased to 1.5 nmol h-1·mg-1 Pr (normal range 6.0-16.7 nmol h-1·mg-1 Pr), supporting the diagnosis of type Ⅲ Gaucher disease. (2) The elder sister of the proband was 12 years old. She had tonic-clonic seizure and myoclonus seizure from the age of seven years old. Mild hepatomegaly, abnormal EEG, poor effect for antiepileptics, and progressive deterioration of psychomotor abilities were found. Her blood leucocytes acid β-glucosidase activity decreased to 1.8 nmol h-1·mg-1 Pr (normal range 6.0-16.7 nmol h-1·mg-1 Pr). Two heterozygous missense mutations, c.680A>G, (p.N188S) and c.1342G>C (p.D409H) were detected from the two siblings, respec-tively.Conclusions Patients with type Ⅲ Gaucher disease usually have the onset in childhood with typical features of Gaucher disease without neurologic involvement. Abnormal EEG may be helpful to the differential diagnosis of type I or type Ⅲ. On the other hand, neurologic manifestations could be presented as the ifrst symptom in some patients without viscera enlargement. The patients of type Ⅲ Gaucher disease with the same genotype could have different phenotypes, even between the siblings.

Objective To investigate the molecular epidemiology and infectious risk factors of linezolid-resistant Enterococci (LRE) isolates in the First Affiliated Hospital of Chongqing Medical University.Methods Thirteen LRE isolates were collected from 2011 to 2013 and confirmed by broth dilution susceptibility testing.The minimum inhibitory concentrations (MIC) of twelve antimicrobial agents were analyzed using Vitek 2 compact.The molecular epidemiology of LRE isolates was determined by multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and the Diversilab.A casecontrol study was conducted for the analysis of risk factors, and Logistic regression was performed to evaluate the independent risk factors.Results All thirteen LRE isolates showed low-level resistance to linezolid, and most of these isolates were resistant to tetracycline, erythromycin and ciprofloxacin.However, they had high sensitivity to penicillin, ampicillin and tigecycline.Sequence type 480 was predominant in the hospital, and three isolates (isolates 3, 4, and 5) from July to September 2013 were found to have the same ST, PFGE pattern and rep-PCR group, indicating the same resistance clone.Admission to intensive care unit (ICU), peripheral vascular disease, males, hypoalbuminaemia, enema and linezolid therapy were identified as significant risk factors for LRE infections.Among these factors, admission to ICU, enema and linezolid therapy were independent risk factors for the acquisition of LRE.Conclusions Thirteen LRE isolates collected in the hospital showed a multidrug-resistant phenotype, and a small-scale prevalence was detected from 2011 to 2013.Therefore, attention should be paid to monitor the LRE in the hospital to decrease the prevalence of LRE infections.

Olfactory neuroblastoma is a rare malignant tumor. Although multiple therapeutic modalities including surgery, radio-therapy, or chemotherapy could be used in patients with olfactory neuroblastoma, no standardized treatment has been achieved. This re-view introduces a case of adult olfactory neuroblastoma treated by a multiple disciplinary team in Tianjin Medical University Cancer In-stitute and Hospital. This review also aims to explore a complete set of diagnostic and treatment practices for the benefit of future pa-tients.