Potential of neuroimaging as a biomarker in amyotrophic lateral sclerosis: from structure to metabolism.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration. The development of ALS involves metabolite alterations leading to tissue lesions in the nervous system. Recent advances in neuroimaging have significantly improved our understanding of the underlying pathophysiology of ALS, with findings supporting the corticoefferent axonal disease progression theory. Current studies on neuroimaging in ALS have demonstrated inconsistencies, which may be due to small sample sizes, insufficient statistical power, overinterpretation of findings, and the inherent heterogeneity of ALS. Deriving meaningful conclusions solely from individual imaging metrics in ALS studies remains challenging, and integrating multimodal imaging techniques shows promise for detecting valuable ALS biomarkers. In addition to giving an overview of the principles and techniques of different neuroimaging modalities, this review describes the potential of neuroimaging biomarkers in the diagnosis and prognostication of ALS. We provide an insight into the underlying pathology, highlighting the need for standardized protocols and multicenter collaborations to advance ALS research.

Block-based teaching method based on cybernetics: a trial with 115 Chinese undergraduate medical students.

BACKGROUND: Class attendance is important for academic performance. Personal interactions between teachers and students are difficult in large classes; the number of medical undergraduate students in China ranges from dozens to over 100. It is important for teachers to control the teaching process to improve student attendance and participation. METHODS: Two classes of fourth-year undergraduate medical students, with each class comprising 115 students, participated in the study. One class, the trial group, was taught by the block-based teaching method based on cybernetics. This study was conducted with three of the courses in the Introduction to Oncology subject, and the trial group's courses included several blocks. Each block had a test paper that the students responded to immediately in class using the Internet. The teacher obtained feedback from the students when the rate of correct responses to block-test questions was less than 90%. The teacher adjusted the teaching in the following blocks according to the feedback information. The other class, the control group, was taught using the traditional lecture-based teaching method. RESULTS: The average attendance in the trial group was 104/115 (90.43%), and that in the control group was 83/115 (72.17%) (p = 0.0003). The teacher adjusted the teaching three times in the radiotherapy course owing to the complex ideas. After feedback, information on chemotherapy for the upper body was adjusted once, as was that on chemotherapy for the lower body, owing to students' attitudes. The average total score of the trial group was 86.06 ± 17.46 and that of the control group was 80.38 ± 6.97 (p = 0.041). Questionnaire I showed that the trial group students' attendance and participation were better than in the control group. Questionnaire II showed that the block-based teaching method based on cybernetics was approved by the students. CONCLUSIONS: The block-based teaching method based on cybernetics used in medical classes with large numbers of Chinese undergraduate students had positive effects.

[Characteristics and Source Apportionment of Black Carbon Over the Eastern Tibetan Plateau].

As the most important absorbing aerosol, black carbon (BC) can affect radiation, clouds, and surface snow cover over the Tibetan Plateau. In this study, the BC mass concentrations were measured using a seven-channel aethalometer (AE-33) in Litang County over the eastern Tibetan Plateau from July 5 to September 5, 2017. The aethalometer model, potential source contribution function (PSCF), and concentration-weighted trajectory (CWT) models were used to analyze the variation characteristics, potential sources, and affecting areas of BC. The results showed that the mass concentration of ρ(BC) in Litang ranged from 0.4 to 4699.8 ng·m-3, with an average value of 816.4 ng·m-3, accounting for 5.96% of PM2.5. The average mass concentrations of ρ(BCliquid) and ρ(BCsolid) in Litang were 486.1 ng·m-3 and 398.5 ng·m-3, respectively, with a C of 0.51. The ρ(BC) mass concentration was mainly distributed from 0-2000 ng·m-3, which accounted for 92.5% of the total observation period. The diurnal variation in BC, BCliquid, and BCsolid showed a bimodal distribution, with the peaks appearing at 08:00 and 20:00, respectively. The first peak was mainly related to traffic sources and incomplete combustion of carbonaceous materials, whereas the second peak was mainly related to incomplete combustion of carbonaceous materials. The potential sources and affecting areas of PM2.5 and BC were different. Imports from abroad had a greater impact on the concentrations of PM2.5 and BC in Litang, and the affecting areas were mainly transmitted to the northeast in China. The high-value centers were mainly concentrated in the surrounding areas of Litang.

[Emission Characteristics of Organic Carbon and Elemental Carbon in PM10 and PM2.5 from Vehicle Exhaust and Civil Combustion Fuels].

To study the emission characteristics of carbonaceous aerosol in particulate matter emitted from vehicle exhaust and main civil combustion fuels, organic carbon (OC) and elemental carbon (EC) in PM10 and PM2.5 samples from vehicle sources (gasoline vehicles, light duty diesel vehicles, and heavy duty diesel vehicles), civil coal (chunk coal and briquette coal), and biomass fuels (wheat straw, wood plank, and grape branches) were collected and analyzed by using a multifunctional portable dilution channel sampler and the Model 5L-NDIR OC/EC analyzer. The results showed that there were significant differences in the proportion of carbonaceous aerosols in PM10 and PM2.5from different emission sources. The proportions of total carbon (TC) in PM10 and PM2.5 of different emission sources were 40.8%-68.5% and 30.5%-70.9%, respectively, and the OC/EC were 1.49-31.56 and 1.90-87.57, respectively. The carbon components produced by different emission sources were dominated by OC, and the OC/TC values in PM10 and PM2.5 were 56.3%-97.0% and 65.0%-98.7%, respectively. The proportions of OC in carbonaceous aerosols in PM10and PM2.5 were in the descending order of:briquette coal>chunk coal>gasoline vehicle>wood plank>wheat straw>light duty diesel vehicle>heavy duty diesel vehicle and briquette coal>gasoline car>grape branches>chunk coal>light duty diesel vehicle>heavy duty diesel vehicle, respectively. The main components of carbonaceous aerosols in PM10 and PM2.5 emitted from the various emission sources were different, and source apportionment of carbonaceous aerosols could be accurately distinguished by their ingredient composition profiles.

The obesity paradox in ST-segment elevation myocardial infarction patients: A meta-analysis.

OBJECTIVE: The aim of this study was to investigate whether there was a difference in survival after initial percutaneous coronary intervention (PCI) among ST-segment elevation myocardial infarction (STEMI) patients with different body mass index (BMI). METHODS: Literature retrieval was conducted on PubMed, Web of Science, Embase, CNKI, and Wanfang databases to obtain the published studies on the survival of STEMI patients with different BMI after initial PCI from the establishment of the database to 2022. All statistical analyses were performed using STATA16.0. RESULTS: Two hundred thirty-nine studies were retrieved, and 12 studies were eventually included. Meta-analysis showed that overweight patients [OR = 0.66, 95% CI (0.58, 0.76), p < .001] and obese patients [OR = 0.60, 95% CI (0.51, 0.72), p < .001] had lower in-hospital mortality than healthy-weight patients. Overweight patients [OR = 0.66, 95% CI (0.58, 0.74), p < .001] and obese patients [OR = 0.62, 95% CI (0.53, 0.72), p < .001] had lower short-term mortality than healthy-weight patients. In addition, overweight patients [OR = 0.63, 95% CI (0.58, 0.69), p < .001] and obese patients [OR = 0.59, 95% CI (0.52, 0.66), p < .001] also had lower long-term mortality than healthy-weight patients. There was no significant difference in in-hospital mortality [OR = 1.06, 95% CI (0.89, 1.27), p > .05], short-term mortality [OR = 1.04, 95% CI (0.89, 1.22), p > .05], and long-term mortality [OR = 1.07, 95% CI (0.95, 1.20), p > .05] between overweight and obese patients. CONCLUSION: This meta-analysis confirmed an obesity paradox in STEMI patients following PCI. The obesity paradox exists in in-hospital, short-term, and long-term conditions.

Identifying the hub gene and immune infiltration of Parkinson's disease using bioinformatical methods.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder that affects 1%-2% of the population over 60 years old. Immune response dysfunction in the brain contributes to the occurrence and development of PD. This study aimed to uncover the potential diagnostic genes for PD and characterize the immune cell infiltrates. METHODS: We downloaded the microarray data of patients with PD samples from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify the modules linked to PD in the GSE20163 dataset. Meanwhile, differentially expressed genes (DEGs) between the healthy control samples and PD samples were also identified. Then the PD-related genes were integrated based on the genes in the key module and DEGs. Functional enrichment analysis was used to explore the molecular mechanisms of these PD-related genes. Protein-protein interaction (PPI) network and least absolute shrinkage and selection operator (LASSO) analysis were used to further screen candidate genes for PD. Gene set enrichment analysis (GSEA) was applied to explore the biological functions of these candidate genes. The infiltration of immune cells was detected by single-sample gene set enrichment analysis (ssGSEA) algorithm in the GSE20163 dataset, and Pearson analysis was used to investigate the correlation of candidate genes with immune cells and immune checkpoint proteins. The expression of candidate genes in clinical samples was verified by qPCR. RESULTS: Altogether, we found a unique gene module related to PD, where 109 DEGs were identified in the GSE20163 dataset. Following these results, we screened 68 genes associated with PD. Gene Expression Omnibus (GEO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that these genes were markedly enriched in the pathway of synthesis and transport of neurons. Three candidate genes (SLC18A2, CALB1, and SYNGR3) were further identified in PD patients through PPI network and LASSO analysis. The receiver operating characteristic (ROC) curve indicated that the three candidate genes had a good performance in distinguishing the PD samples from healthy control samples. The proportions of the aDC, DC, NK CD56dim cells, and follicular helper T cells (TFH) were obviously different between the healthy control and PD samples. Moreover, CTLA4, LAG3, CEACAM1, and CD27 were highly expressed in the PD group. GSEA analysis for candidate genes revealed that they were all closely related to the neurogenic disease. Additionally, the three candidate genes were all strongly correlated with the above immune cells and immune checkpoint proteins. The qPCR results validated the expression differences of SLC18A2 and SYNGR3 in the clinical PD and control samples. CONCLUSION: The three candidate genes may be a useful tool for diagnosing PD patients. These findings provide a reference for exploring new therapeutic targets and strategies for PD treatment.

Combination Processing Method Reduced IgE-Binding Activity of Litopenaeus vannamei by Modifying Lysine, Arginine, and Cysteine on Multiple Allergen Epitopes.

Allergic reactions occur after the whole food is ingested, rather than the purified allergen. The present study explores the low-allergenic food processing for Litopenaeus vannamei by analysis of macrostructure, digestibility, and immunoreactivity. Furthermore, the presence of modified amino acids on the reported IgE epitopes was analyzed by mass spectrometry. Results showed that the combination processing of Maillard reaction (shrimp meat with galactose) with high temperature-pressure at 115 °C obviously changed the macrostructure and increased the digestibility for the shrimp meat. Meanwhile, the processing significantly reduced the IgG/IgE-binding activity of the shrimp meat. The hypo-IgE-binding activity in processed shrimp may be due to the modification of lysine, arginine, and cysteine residues in antigen epitopes. This is a comprehensive assessment of the specific amino acid residues modified by glycation of multiple allergens in processed L. vannamei, which provides a new research method to explore the hypo-IgE-binding activity in food.

[Distribution Characteristics and Source Analysis of Water-soluble Ions in Particulate Matter Under Different Weather Processes in Nanjing].

From November 16 to 28 2018, water-soluble ions in particulate matter and some trace gases in Nanjing City were observed using the online gas composition and aerosol monitoring system MARGA ADI 2080. Combined with meteorological elements and sounding data, the distribution characteristics and day-night differences of pollutants and water-soluble ions during haze, fog, clear, and precipitation processes were analyzed. The results show that the average concentration of PM2.5 varied from 26.9µg·m-3 (precipitation) to 96.4µg·m-3 (haze) while total water-soluble ions varied between 23.7µg·m-3 (precipitation) and 89.7µg·m-3 (haze). The ranked order of ion concentrations was NO3- > NH4+ > SO42- > Cl- > K+ > Ca2+ > Na+ > Mg2+ during haze and fog events, and NO3- > SO42- > NH4+ > Cl- > Ca2+ > K+ > Na+ > Mg2+ during clear weather and precipitation period. The diurnal distributions of water-soluble ions were quite different under the four conditions, although SO42-, NO3-, and NH4+(SNA) were ranked haze > fog > clear > precipitation for both day and night periods. According to the PMF source analysis, secondary sources were the main factors affecting haze; secondary sources, sea salt, and combustion sources were the main pollution sources to foggy conditions; and the removal effect of precipitation on coal-fired sources and secondary sources was more notable than during clear conditions.

Adding Concurrent Chemotherapy Significantly Improves the Survival of Stage II-IVb Nasopharyngeal Carcinoma Patients Treated With Concurrent Anti-EGFR Agents.

OBJECTIVE: Anti-EGFR Targeted agents were found to be capable of modulating the antitumor immunity in head and neck cancer and become more and more frequently used in the treatment of nasopharyngeal carcinoma(NPC). We aimed to explore whether adding concurrent chemotherapy influences the survival outcome of patients with stage II-IVb NPC treated with concurrent anti-EGFR agents and intensity-modulated radiation therapy (IMRT) and explore other prognostic factors for the patients. MATERIALS AND METHODS: A total of 656 stage II-IVb NPC patients treated with concurrent anti-EGFR agents plus IMRT between January 2011 and November 2015 were enrolled. Firstly, from these patients, a well-balanced cohort of 302 patients who received concurrent chemotherapy was created by matching potential prognostic factors. Furthermore, for all 656 stage II-IVb NPC patients, univariate and multivariate analyses of overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) were conducted to identify prognostic factors and to confirm the findings from the matching cohort. RESULTS: Compared with concurrent anti-EGFR agents alone, combining concurrent cisplatin and anti-EGFR agents significantly improved the OS (5-year 94.7% versus 84.3%, P=0.012) and PFS (5-year 82.0% versus 71.7%, P=0.039) of NPC patients with more severe hematologic toxicity and mucositis. The independent prognostic factors identified by multivariate analysis of OS and PFS included concurrent chemotherapy, epstein-barr virus(EBV) status and clinical stage. Patients treated without induction chemotherapy (IC) may achieve more benefits from the addition of concurrent chemotherapy to concurrent anti-EGFR agents. CONCLUSIONS: For stage II-IVb NPC patients treated with concurrent anti-EGFR agents, the addition of concurrent chemotherapy can significantly improve the survival outcome.

Effects of thermal processing on digestion stability and immunoreactivity of the Litopenaeus vannamei matrix.

Many types of shellfish, including shrimp, are sometimes cooked before ingestion. Hence, it is necessary to investigate how cooking (boiling, pressure treatment or none (raw)) affects the structure, digestibility and immunoreactivity of multi-component shrimp muscle. Protein extraction, simulated gastrointestinal digestion, immunoreactivity, immunoglobulin E (IgE)-mediated human mast cell degranulation, morphology, particle size and UV absorbance scanning were used to investigate changes in the shrimp muscle upon treatment. The extractability of proteins and allergens was highest with 0.5 mol L-1 NaCl. Pressure treatment increased the digestibility and reduced the immunoreactivity of shrimp edible portions. Thermal processing induced the production of regular fiber bundles, blue shifts of absorbance peaks and reduction of particle size in the complex food matrix. These changes in macro- and micro-structure can further affect gastrointestinal digestibility and immunoreactivity due to the interactions between multiple components in the whole food. In conclusion, the digestibility, immunoreactivity and structure were altered by thermal processing of the complex food matrix.

[Clinical Features and Laboratory Data Analysis of Glucose-6- Phosphate Dehydrogenase Deficiency].

OBJECTIVE: To explore clinical features and laboratory data of glucose-6-phosphate dehydrogenase（G6PD）deficiency and to investigate the relationship between them. METHODS: Clinical data of 43 patients with G6PD deficiency was analyzed, the statistical method was applied to investigate the relationship between clinical features and laboratory data. RESULTS: Among 43 patients，neonatal jaundice occurred as the first symptom in 10 cases，while acute hemolytic anemia occurred as the first symptom in 23 cases. The major clinical symptoms of G6PD deficiency included icteric skin and/or sclera，dark urine，fever，gastrointestinal symptoms，fatigue and lethargy. Symptoms of 26 patients were caused by obvious inducement，including fava beans（61.5%），infection（34.6%）and miocardial infarction（3.8%）. All of 43 patients showed decreased G6PD activity，while the level of their indirect serum bilirubin（IBIL）was positively correlated with reticulocyte percentage（Ret%，r=0.5881，P=0.013） and mean corpuscular volume（MCV，r=0.6854，P=0.0024）. Patients with neonatal jaundice as the first symptom，showed higher level of Ret%（P<0.01）and MCV（P<0.001）and low RBC count（P<0.01）and low Hb level（P<0.01）. as compard with patients with acute hemolytic anemia as first symptome. CONCLUSION: Neonatal jaundice and acute hemolytic anemia are common clinical features of G6PD deficiency. Laboratory results of IBIL，Ret% and MCV have auxiliary value to evaluate the severity of hemolysis induced by G6PD deficiency. Patients with neonatal jaundice as their first symptom show more severe hemolysis than those only suffered from acute hemolytic anemia.

Overexpression of CREPT confers colorectal cancer sensitivity to fluorouracil.

AIM: To investigate expression of cell cycle-related and expression-elevated protein in tumor (CREPT) in colorectal cancer (CRC) and determine its prognostic value in response to 5-fluorouracil (5-FU). METHODS: The relative expression of CREPT in CRC tumor samples was determined using immunohistochemistry. The protein content in cell lines was analyzed by immunoblotting. Cell viability was measured with the CCK-8 assay. Cell cycle and apoptosis analyses were performed with flow cytometry. RESULTS: CREPT was overexpressed in CRC tissues and correlated with histological grade. Clinicopathological analysis indicated that CREPT was positively related to tumor progression. Exogenous expression of CREPT stimulated cell proliferation and accelerated the cell cycle. More importantly, high expression of CREPT sensitized CRC cells to 5-FU treatment. Furthermore, we demonstrated that 5-FU elicited significant apoptosis in CREPT-positive cells. CONCLUSION: Aberrant overexpression of CREPT contributes to tumorigenesis of CRC by promoting cell proliferation and accelerating the cell cycle, and confers sensitivity to 5-FU. CREPT is a potential prognostic biomarker for 5-FU in CRC.