A novel mutation in the ABCD1 gene causes adrenomyeloneuropathy by impairing autophagy level / 中华神经科杂志

Objective:To report a Chinese family with a novel ABCD1 gene mutation at c.332T>G (p.V111G) site and discuss its clinical characteristics and molecular mechanism.Methods:The clinical data, laboratory examination, and imaging examination results were analyzed to make the clinical diagnosis of a middle-aged onset patient from the First Affiliated Hospital of Zhengzhou University in May 2017. High-throughput sequencing was used to discover a novel ABCD1 gene mutation. Sanger sequencing was used to find out whether other family members contain the same ABCD1 gene mutation. The pathogenicity of this mutation was explored by protein structure prediction and pathogenicity analysis. Adrenoleukodystrophy protein-green fluorescent protein (ALDP-GFP) and ALDP-GFP (V111G) plasmids were constructed and human embryonic kidney 293 cells were transfected, then immunofluorescence and Western blotting were used to explore the molecular mechanism of this mutation (completed in Henan Provincial People′s Hospital).Results:The proband (a 39-year-old male) was diagnosed as adrenomyeloneuropathy, a subset of X-linked adrenoleukodystrophy, with a novel heterozygous missense mutation in the ABCD1 gene at c.332T>G (p.V111G) site, and his mother and two daughters were all carriers. Protein structure prediction and pathogenicity results suggested that this mutation is pathogenic. Overexpression of ALDP-GFP (V111G) in the human embryonic kidney 293 cells resulted in a significant decrease in the expression levels of ALDP and the abnormal localization from the peroxisomal membrane to the cytoplasm, accompanied by significant down-regulation of LC3-Ⅱ/LC3-Ⅰ and beclin-1.Conclusion:c.332T>G (p.V111G) is a novel pathogenic mutation in the ABCD1 gene, which causes adrenomyeloneuropathy by impairing autophagy.

Expression and clinical significance of plasma miR-124 in acute ischemic stroke / 实用医学杂志

Objective To investigate the expression and clinical significance of plasma miR-124 in acute ischemic stroke (AIS). Methods Forty patients with AIS were collected and 40 volunteers without history of AIS were set as control. Infarction volume was detected by MRI; plasma miR-124 expression level was measured by RTPCR technique and neural function was evaluated by NIHSS scores. Results Compared with that in the control group, plasma miR-124 level in AIS group was significantly reduced (P < 0.05). Plasma miR-124 level in AIS patients with infarction volume greater than 3 cm3 was significantly lower than that of AIS patients with infarction volume less than 3 cm3 (P < 0.05). Correlation analysis showed a negative correlation between miR-124 and infarction volume (r =-0.473, P < 0.05). Plasma miR-124 level in AIS with NIHSS score higher than 5 was significantly lower than that of AIS patients with NIHSS lower than 5 (P< 0.05). NIHSS score negatively correlated with the miR-124 level of AIS patients (r =-0.567, P < 0.05). Conclusion The plasma miR-124 is significantly reduced in patients with AIS, and negatively correlated with the cerebral infarction volume and NIHSS score.

G-CSF is a key modulator of MDSC and could be a potential therapeutic target in colitis-associated colorectal cancers

Granulocyte colony-stimulating factor (G-CSF) is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells (MDSCs) promote neoplastic progression through multiple mechanisms by immune suppression. Despite the findings of G-CSF function in colon cancer progression, the precise mechanism of G-CSF on MDSCs regulation and its blockade effects on tumor growth remains a worthy area of investigation. In this study we observed an overexpression of G-CSF in a mouse colitis-associated cancer (CAC) model, which was consistent with the accumulation of MDSCs in mouse colon tissues. Further in vitro studies demonstrated that G-CSF could promote MDSCs survival and activation through signal transducer and activator of transcription 3 (STAT3) signaling pathway. Moreover, compared with isotype control, anti-G-CSF mAb treatment demonstrated reduced MDSC accumulation, which led to a marked decrease in neoplasm size and number in mice. Our results indicated that G-CSF is a critical regulating molecule in the migration, proliferation and function maintenance of MDSCs, which could be a potential therapeutic target for colitis-associated cancer.

Nosocomial Infection in Multiple Sites: Clinical Analysis of 123 Cases / 中华医院感染学杂志

OBJECTIVE To analyze the cause,clinical characteristic and preventive measures in nosocomial infection of multiple sites. METHODS A total of 123 cases of nosocomial infection in multiple sites in our hospital in 2004 were prospectively monitored and analyzed retrospectively. RESULTS Among 1645 cases of nosocomial infection,123 cases suffered from nosocomial infection in multiple sites.The main infection sites were lower respiratory tract and urinary tract.The main risk factors were over usage of broad-spectrum antibiotics and invasive operation.The serious result was prolongation of duration in hospital,increase in mortality and expensiveness. CONCLUSIONS The nosocomial infection in multiple sites is a main object to be monitored.To prevent,discover and control nosocomial infection in time is an effective measure to reduce the risk of nosocomial infection.

Nosocomial Systemic Fungus Infection: A Clinical Analysis of 496 Cases / 中华医院感染学杂志

OBJECTIVE To analyze the condition of nosocomical systemic fungus infection and make preventive and control measures against nosocomial systemic fungus infection.METHODS The 496 fungus-cultured positive cases with average age of 61.04 years old among the discharged patients from Jan 2003 to Dec 2005 were reviewed and analyzed.RESULTS The rate of nosocomical systemic fungus infection was 0.53%,from which the over 60 age senile patients accounted for 63.1%.Lower respiratory tract and urinary tract were the most frequent infection sites.The Candida albicans was accounted for 70.71%.The death rate of patients with nosocomial systemic fungus infection was 27.82%.The major correlated factors of nosocomial systemic fungus infection were the widespread use of broad-spectrum antibiotics and not be standardized and the iatrojenic injury of respiratory and urological tracts.CONCLUSIONS The causes of nosocomial systemic fungus infection are closely related to medical treatment;the death rate of patients with nosocomial systemic fungus infection is obvious higher than that without it;to prevent and control nosocomial systemic fungus infection is the key point of nosocomial treatment.

Detection of p53 and K-ras gene mutation in portal venous blood of gastric carcinoma patients / 中国普通外科杂志

Objective To investigate the relations between p53 and K-ras gene mutation in portal venous blood of gastric carcinoma patients and cancer metastasis. Methods p53 and K-ras gene mutation was detected with PCR-SSCP technology in 62 cases of gastric carcinoma. Results p53 and K-ras mutation rate were 39% and 34% in portal venous blood, but only 8% and 4. 8% in peripheral blood; The rate of gene mutation in p53 and K-ras were 24% and 22% in patient without liver metastasis, 92% and 77% in patient with liver metastasis; The rate of gene mutation in p53 and K-ras in portal venous were 39% and 34% before surgical exploration, but 56% and 63% after exploration. The rate of positive detection of the mutation was significantly (P