Correction to: Glycosylation of dentin matrix protein 1 is a novel key element for astrocyte maturation and BBB integrity

In the original publication, the label of Fig. 2C should be read as "GFAP/lectin/DAPI" not "DMP1/GFAP/lectin/DAPI".

Prognostic Analysis of EGFR-TKIs Combined with Gamma Knife in EGFR-mutant Lung Adenocarcinoma with Brain Metastasis / 中国肺癌杂志

BACKGROUND@#Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery.@*METHODS@#Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on.@*RESULTS@#A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS.@*CONCLUSIONS@#EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.

Single-cell transcriptomics reveals gene signatures and alterations associated with aging in distinct neural stem/progenitor cell subpopulations

Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSC/NPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive "big-data" processing, we report that NSC/NPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSC/NPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Interestingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSC/NPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSC/NPCs and their microenvironment in the context of the aging brain.

Glycosylation of dentin matrix protein 1 is a novel key element for astrocyte maturation and BBB integrity

The blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation. However, detailed molecular players involved in formation of BBB are not completely known. Dentin matrix protein 1 (DMP1)-proteoglycan (PG), which is known to be involved in mineralization of bones and dentin, is also expressed in soft tissues including brain with unknown functions. In the present study, we reported that DMP1-PG was expressed in brain astrocytes and enriched in BBB units. The only glycosylation site of DMP1 is serine89 (S89) in the N-terminal domain of the protein in mouse. Mutant mice with DMP1 point mutations changing S89 to glycine (S89G), which completely eradicated glycosylation of the protein, demonstrated severe BBB disruption. Another breed of DMP1 mutant mice, which lacked the C-terminal domain of DMP1, manifested normal BBB function. The polarity of S89G-DMP1 astrocytes was disrupted and cell-cell adhesion was loosened. Through a battery of analyses, we found that DMP1 glycosylation was critically required for astrocyte maturation both in vitro and in vivo. S89G-DMP1 mutant astrocytes failed to express aquaporin 4 and had reduced laminin and ZO1 expression, which resulted in disruption of BBB. Interestingly, overexpression of wild-type DMP1-PG in mouse brain driven by the nestin promoter elevated laminin and ZO1 expression beyond wild type levels and could effectively resisted intravenous mannitol-induced BBB reversible opening. Taken together, our study not only revealed a novel element, i.e., DMP1-PG, that regulated BBB formation, but also assigned a new function to DMP1-PG.

Research on relative factors of abnormal glycometabolism in chronic hepatitis C patients / 中华疾病控制杂志

Objective Hepatitis C virus patients are often accompanied by insulin resistance and diabetes.To probe the relative factors of abnormal glycometabolism in chronic HCV infections.Methods A total of 1 039 treatment-naive patients that were confirmed chronic HCV infected were enrolled in the study.The demographics,biochemical index parameters and other data about liver function and HCV viral load were got from infectious disease department of Jurong Pepole's Hospital in China.Results A total of 140 (13.5％) patients were diagnosed with some forms of abnormal glycometabolism.The body mass index (BMI) (x2 =9.231,P =0.010),waist circumference (x2 =7.984,P =0.018),systolic blood pressure (x2 =16.366,P ＜0.001),diastolic blood pressure (x2 =13.970,P =0.001),alanine aminotransferase(ALT) (x2 =4.809,P =0.028),HCV-RNA viral load (t =-3.818,P ＜0.001) were significantly different between non-diabetic HCV patients and abnormal glycometabolism patients.Multivariate logistic regression analysis showed that ALT(OR =2.986,95％ CI:1.171-7.615) and HCV-RNA viral load (OR =2.061,95％ CI:1.165-3.644) were found as risk factors in multivariate regression analysis for patients with chronic hepatitis C who had abnormal glucose metabolism.Conclusions Chronic hepatitis C patients with higher ALT and HCV-RNA level were more probably to suffer from abnormal glycometabolism.In order to find potentially novel risk factors of HCV with abnormal glucose metabolisn,further studies about genetic and other clinical factors need to be processed.

Related factors for severe liver fibrosis in chronic hepatitis C patients with remunerated blood donation history in Jurong of Jiangsu province / 中华流行病学杂志

Objective The incidence of liver fibrosis in patients with chronic hepatitis C is high.Without effective treatment,it would lead to liver cirrhosis.This study is to identify the related factors for the incidence of liver fibrosis in patients with chronic hepatitis C in order to make early intervention treatment and reduce the case fatality rate.Methods This cross-sectional survey was conducted in adults aged ≥50 years with local residence for more than 5 years in Jurong of Jiangsu province from March to May in 2015,the patients infected with hepatitis C virus through remunerated blood donation were screened and included in the analysis.Descriptive statistical analysis was done to compare the differences in the incidence of liver fibrosis among the patients with different age,sex and education level or co-infected with hepatitis B virus or not.The risk factors for severe liver fibrosis were identified with univariate and multivariate logistic regression analysis.Liver fibrosis was diagnosed by using FIB-4 index method.Results A total of 719 patients with chronic hepatitis C were surveyed.Severe liver fibrosis developed in 285 of the 719 patients,in whom 21.84％ was males.Multivariate logistic regression analysis showed that the patients with higher education level (OR=0.65,95％CI:0.47-0.90) and with access of antiviral therapy (OR=0.33,95％ CI:0.22-0.49) had lower risk for severe liver fibrosis,the patients with high fasting blood glucose level (OR=1.80,95％CI:1.19-2.77) and abnormal white blood cell count (OR=2.77,95％CI:1.95-3.90) had higher risk for severe liver fibrosis.Conclusions The incidence of severe liver fibrosis in patients with hepatitis C was affected by many factors.Higher education level and antiviral therapy were the protective factors,but high fasting blood glucose level and abnormal white blood cell count were the risk factors.

Related factors for severe liver fibrosis in chronic hepatitis C patients with remunerated blood donation history in Jurong of Jiangsu province / 中华流行病学杂志

Objective The incidence of liver fibrosis in patients with chronic hepatitis C is high.Without effective treatment,it would lead to liver cirrhosis.This study is to identify the related factors for the incidence of liver fibrosis in patients with chronic hepatitis C in order to make early intervention treatment and reduce the case fatality rate.Methods This cross-sectional survey was conducted in adults aged ≥50 years with local residence for more than 5 years in Jurong of Jiangsu province from March to May in 2015,the patients infected with hepatitis C virus through remunerated blood donation were screened and included in the analysis.Descriptive statistical analysis was done to compare the differences in the incidence of liver fibrosis among the patients with different age,sex and education level or co-infected with hepatitis B virus or not.The risk factors for severe liver fibrosis were identified with univariate and multivariate logistic regression analysis.Liver fibrosis was diagnosed by using FIB-4 index method.Results A total of 719 patients with chronic hepatitis C were surveyed.Severe liver fibrosis developed in 285 of the 719 patients,in whom 21.84％ was males.Multivariate logistic regression analysis showed that the patients with higher education level (OR=0.65,95％CI:0.47-0.90) and with access of antiviral therapy (OR=0.33,95％ CI:0.22-0.49) had lower risk for severe liver fibrosis,the patients with high fasting blood glucose level (OR=1.80,95％CI:1.19-2.77) and abnormal white blood cell count (OR=2.77,95％CI:1.95-3.90) had higher risk for severe liver fibrosis.Conclusions The incidence of severe liver fibrosis in patients with hepatitis C was affected by many factors.Higher education level and antiviral therapy were the protective factors,but high fasting blood glucose level and abnormal white blood cell count were the risk factors.

Coupled electrophysiological recording and single cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation

The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming various neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in performing both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses (WGCNA), we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neuronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions.

HCV infection status and risk factors in remunerated blood donors in Jiangsu province / 中华流行病学杂志

Objective To investigate the infection status of HCV in remunerated blood donors and risk factors in Jiangsu province.Methods A Cross-sectional study was conducted among people aged ＞50 years.Questionnaires were used to collect the information about their demographic characteristics and risk behaviors,and venous blood samples were collected from them to detect HCV anti-body,HCV-RNA and other biochemical indicators.EpiData and Stata were used for data entry and statistical analysis.Results The overall HCV sero-prevalence rates were 22.55％ and 61.05％ among remunerated blood donors.Data firom multiple stepwise regression analysis showed that alanine aminotransferase (ALT) (adjusted OR=1.38,95％CI:1.18-1.62) and aspartate aminotransferase (AST) (adjusted OR=l.30,95％CI:1.10-1.54) were associated with the outcomes of HCV infection,and fasting plasma glucose (adjusted OR=1.17,95％CI:1.01-1.35) were associated with HCV RNA viral loads.Conclusion The prevalence of HCV infection in remunerated blood donors was high,clinical ALT,AST and fasting plasma glucose levels were associated with the risk for HCV infection and HCV RNA viral load.

HCV infection status and risk factors in remunerated blood donors in Jiangsu province / 中华流行病学杂志

Objective To investigate the infection status of HCV in remunerated blood donors and risk factors in Jiangsu province.Methods A Cross-sectional study was conducted among people aged ＞50 years.Questionnaires were used to collect the information about their demographic characteristics and risk behaviors,and venous blood samples were collected from them to detect HCV anti-body,HCV-RNA and other biochemical indicators.EpiData and Stata were used for data entry and statistical analysis.Results The overall HCV sero-prevalence rates were 22.55％ and 61.05％ among remunerated blood donors.Data firom multiple stepwise regression analysis showed that alanine aminotransferase (ALT) (adjusted OR=1.38,95％CI:1.18-1.62) and aspartate aminotransferase (AST) (adjusted OR=l.30,95％CI:1.10-1.54) were associated with the outcomes of HCV infection,and fasting plasma glucose (adjusted OR=1.17,95％CI:1.01-1.35) were associated with HCV RNA viral loads.Conclusion The prevalence of HCV infection in remunerated blood donors was high,clinical ALT,AST and fasting plasma glucose levels were associated with the risk for HCV infection and HCV RNA viral load.

Lipogranuloma of the lung: a case report / 南方医科大学学报

Lipogranuloma is a rare benign disease accompanied by a reactive inflammatory process related to exogenous or endogenous lipids. We report a case of lipogranuloma of the lung mimicking pulmonary neoplastic disease in a 57-year-old woman, who presented with the symptom of coughing for a month. The diagnosis of lung cancer was considered for the CT finding of a mass in right lower lobe. The patient underwent subsequent operation, and pathological examination of the surgical specimen revealed a stromal lesion consisting of lipid vacuoles with foreign body type giant cells and scattered lymphocytes. The final diagnosis of lipogranuloma of the lung was established. Clinicians should be aware of lipogranuloma in the lung, which can be easily confused with lung tumors or other benign diseases. A careful differential diagnosis is necessary.