Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

Purpose/Significance To propose data governance and fusion technologies for different business application scenarios for the fusion of multi-source and multi-dimensional big data with complex sources and diverse standards.Method/Process Taking the practice of multi-source and multi-dimensional big data fusion in responding to major public health emergencies as an example,the pa-per focuses on the challenges faced by multi-source and multi-dimensional big data fusion,the design of the application architecture,technology integration,the implementation path,the application scenarios,etc.,and analyzes the application effect and the deficiencies that exist.Result/Conclusion Through the design of intelligent multi-source and multi-dimensional big data fusion technology,real-time monitoring,reading,governance,and interactive correlation of high-frequency updates at 100 billion levels are realized,and intel-ligent paths are explored for effectively responding to public emergencies.

Purpose/Significance To design a comprehensive data platform to meet the needs of collecting and sharing survey data on meteorological sensitive diseases,so as to enhance monitoring capabilities for meteorological sensitive diseases in China.Method/Process Through various methods such as data extraction,data exchange,data import and customized collection,disease data,meteoro-logical data,environmental data and diagnosis and treatment data are processed and integrated into the platform for unified management.Result/Conclusion This platform realizes the functions of data collection,aggregation,visualization display and data sharing,which can provide support for scientific researchers in various bases across the country to better manage and utilize meteorological sensitive disease survey data.

Objective: To develop the matrix-matched calibration curve correction-inductively coupled plasma mass spectrometry (ICP-MS) for the determination of lead in blood. Methods: Whole blood samples and blank whole blood were pretreated by direct dilution with a solution of 0.5% nitric acid and 0.01% TritonX-100 to obtain whole blood sample solutions and matrix-matched solvents at a 10-fold dilution. The mass concentration of lead was determined by using an ICP-MS instrument in He mode. 175Lu was added online as an internal standard. The standard working curve was calibrated with the matrix-matched solvent, and the mass concentration of lead in the whole blood samples was calculated based on the standard working curve. Recovery tests were performed on whole blood blind samples by spiking, and the relative standard deviation and average recovery rate were calculated. The accuracy and precision of this method were assessed by comparing it with the method recommended in the national standard in detection of lead in three types of bovine blood lead standard materials. Results: Good linearity was shown for lead at 0.5 to 100.0 μg/L, with a correlation coefficient of 1.000. The detection limit of lead was 0.4 μg/L, and the quantitation limit was 1.3 μg/L. The relative standard deviations were 0.65% and 1.10%. The average recovery ranged from 96.89% to 99.73%. The lead determination results were all within the normal reference ranges specified by the three certified reference materials for bovine blood samples. Conclusion The matrix-matched calibration curve correction-ICP-MS is suitable for high-throughput determination of blood lead.

Objective : To establish a microwave-assisted digestion-inductively coupled plasma mass spectrometry (ICP-MS) with an octopole reaction system for simultaneous determination of six heavy metals in peanuts, including Cr, Ni, As, Cd, Pb, Hg. Methods : Peanut samples were shelled and crushed evenly, and 0.350 0 g was accurately weighed and digested with 5 mL nitric acid and 1 mL hydrogen peroxide in a digestion tank. Following microwave-assisted digestion, pure water was used to quantify the samples, and internal standards and an octopole reaction system were used to remove the interference. Then, the contents of six heavy metals were determined in peanuts by ICP-MS. The accuracy and precision of ICP-MS were evaluated using national criteria ( GBW 10013 and GBW 10044 ) and spike-and-recovery testing. Results : The six heavy metals showed good linearity at the selected linear range ( r≥0.999 8 ). The detection limits of ICP-MS ranged from 0.001 4 to 0.023 8 ng/mL, and the spike-and-recovery rates ranged from 94.7% to 98.8%, with the relative standard deviations ranging from 0.7% to 3.6%. In addition, the determination results of the standard reference materials were all within the normal reference range. The detection of six heavy metals was 100.0% in 60 peanut samples, and the contents of six heavy metals were all low. Conclusion The established ICP-MS assay is feasible for simultaneous determination of multiple heavy metals in peanuts.

Ferroptosis is defined as an iron-dependent, non-apoptotic cell death pathway, with specific morphological phenotypes and biochemical changes. There is a growing realization that ferroptosis has significant implications for several neurodegenerative diseases. Even though ferroptosis is different from other forms of programmed death such as apoptosis and autophagic death, they involve a number of common protein molecules. This review focuses on current research on ferroptosis and summarizes the cross-talk among ferroptosis, apoptosis, and autophagy that are implicated in neurodegenerative diseases. We hope that this information provides new ideas for understanding the mechanisms and searching for potential therapeutic approaches and prevention of neurodegenerative diseases.
Apoptosis ; Autophagy ; Cell Death ; Ferroptosis ; Humans ; Neurodegenerative Diseases

Objective:To determine the prevalence of sarcopenia and explore related influencing factors of sarcopenia in maintenance hemodialysis (MHD) patients.Methods:MHD patients aged ≥18 years old and receiving therapies of ≥3 months from March 2019 to December 2019 in Blood Purification Centre of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively enrolled in this study. General data of the patients were collected. Grip strength was measured by the Jamar dynamometer and the chair stand was measured by a chair of standard height to assess skeletal muscle strength and appendicular skeletal muscle mass was measured by dual energy X-ray absorptiometry. Baseline data between MHD patients with and without myasthenia were compared. Logistic regression analysis method was used to analyze the influencing factors for sarcopenia in MHD patients.Results:A total of 125 MHD patients were enrolled, with 68 males (54.4%), age of (59.4±14.9) years and median dialysis age of 51.0(23.5, 101.0) months. Sarcopenia was diagnosed in 39 cases (31.2%). Compared with MHD patients without sarcopenia, age, tumor necrosis factor-α, von Willebrand factor (vWF) and proportion of using α ketones were higher, and serum carbondioxide combining power (CO 2CP), prealbumin, albumin and proportion of regular exercise were lower in MHD patients with sarcopenia (all P<0.05). Multivariable logistic regression analysis results showed that low CO 2CP ( OR=0.717, 95% CI 0.576-0.892, P=0.003), high vWF ( OR=1.037, 95% CI 1.016-1.058, P<0.001) and no regular exercise ( OR=0.309, 95% CI 0.118-0.810, P=0.017) were independent influencing factors of sarcopenia in MHD patients. Conclusions:The prevalence of sarcopenia in MHD patients is high. Low CO 2CP, high vWF and no regular exercise are independent influencing factors for sarcopenia in MHD patients.

Objective:To investigate the transcript factor Foxp1 mRNA expression in peripheral blood CD4 +T cells of patients with myasthenia gravis (MG), and the changes of Foxp1 mRNA expression before and after tacrolimus immunotherapy. Methods:A prospective study was performed. Twenty-six MG patients admitted to our hospital from January 2018 to January 2020 and 18 healthy controls accepted physical examination in our hospital from January 2018 to July 2019 were recruited. Quantitative myasthenia gravis score (QMGs) was used to assess MG severity. Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral venous blood of MG patients before treatment and 6 months after treatment, and healthy controls right after enrollment by density gradient centrifugation; CD4 +T cells were isolated from PBMCs by magnetic cell separation. The Foxp1 mRNA expression was detected by real-time fluorescent quantification PCR (RT-qPCR). Spearman's correlation coefficient was used to evaluate the correlations of Foxp1 mRNA expression with QMGs and serum acetylcholine receptor (AchR) antibody concentration in all subjects. Results:In the 26 MG patients, there were 10 with ocular MG and 16 with general MG; 7 patients were with thymoma, 2 were with thymic hyperplasia, and 17 were with normal thymus. The Foxp1 mRNA expression in CD4 +T cells of MG patients (0.692±0.257) was significantly decreased as compared with that in the heathy controls (1.051±0.364, P<0.05). Moreover, the Foxp1 mRNA expression in general MG patients was significantly lower than that in ocular MG patients ( P<0.05). The Foxp1 mRNA expression in MG patients 6 months after acrolimus monotherapy was significantly increased as compared with that before treatment ( P<0.05). There was a negative correlation between Foxp1 mRNA expression and QMGs ( r=-0.438, P=0.025). Conclusion:Transcript factor Foxp1 mRNA expression is downregulated in CD4 +T cells of MG patients, and its expression is negatively correlated with MG severity, which can reflect the effect of tacrolimus monotherapy on MG to some extent.

SOCS3, a feedback inhibitor of the JAK/STAT signal pathway, negatively regulates axonal regrowth and inflammation in the central nervous system (CNS). Here, we demonstrated a distinct role of SOCS3 in the injured spinal cord of the gecko following tail amputation. Severing the gecko spinal cord did not evoke an inflammatory cascade except for an injury-stimulated elevation of the granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-γ) cytokines. Simultaneously, the expression of SOCS3 was upregulated in microglia, and unexpectedly not in neurons. Enforced expression of SOCS3 was sufficient to suppress the GM-CSF/IFN-γ-driven inflammatory responses through its KIR domain by attenuating the activities of JAK1 and JAK2. SOCS3 was also linked to GM-CSF/IFN-γ-induced cross-tolerance. Transfection of adenovirus overexpressing SOCS3 in the injured cord resulted in a significant decrease of inflammatory cytokines. These results reveal a distinct role of SOCS3 in the regenerating spinal cord, and provide new hints for CNS repair in mammals.

The paper comprehensively understands the current construction situation of 30 provincial disease control websites through scientific evaluation methods and professional evaluation indexes,and finds and analyzes the major problems.The result shows that the website construction of disease control system is in the development phase generally,information publication and online service is provided with certain foundation,but the mutual communication and website design are relatively weak links which can be greatly improved.