A comprehensive analysis of nucleotide excision repair characteristics defines a novel prognostic signature for acute myeloid leukemia.

OBJECTIVE: Nucleotide excision repair (NER) has been associated with various types of malignant tumors. However, the precise roles of nucleotide excision repair-related genes (NERGs) in acute myeloid leukemia (AML) remain incompletely understood. Hence, this study aimed to develop a prognostic signature incorporating NERGs in AML, which could potentially predict patient outcomes. MATERIALS AND METHODS: By querying the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases, we acquired RNA-seq data and clinical information pertaining to AML. To identify differentially expressed NERGs (DE-NERGs), we employed the Wilcoxon rank-sum test. Based on the expression patterns of DE-NERGs with prognostic significance, patients were categorized into two subgroups. A prognostic signature was developed through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to compare the differentially expressed genes (DEGs) between these two groups. Additionally, a nomogram was constructed using multivariate analysis. The biological pathways involved were elucidated through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA). RESULTS: We developed a prognostic model based on an 11-gene signature. Furthermore, the risk score derived from this model was demonstrated to independently serve as a prognostic marker for patients diagnosed with AML. CONCLUSIONS: Our prognostic model, based on NERGs, was developed and validated to provide insights into the onset and progression of AML and establish a foundation for more effective treatment. Our findings not only contribute to clinical decision-making but also underscore the significance of nucleotide excision repair. Furthermore, they may pave the way for the development of targeted therapeutic strategies specifically focused on this process.

[Disease spectrum analysis of children with inherited metabolic diseases detected by gas chromatography-mass spectrometry of urinary organic acids].

Objective: To investigate the spectrum of amino acid, organic acid, and fatty acid oxidative metabolic diseases in children diagnosed by detecting urinary organic acid levels using gas chromatography-mass spectrometry. Methods: From January 2005 to December 2021, clinical data of 2 461 children diagnosed with inherited metabolic diseases (IMD) by gas chromatography-mass spectrometry, in combination with tandem mass spectrometry and genetic testing in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. Results: Among 2 461 children, 1 446 were male and 1 051 were female. A total of 32 types of IMD were detected among 2 461 patients, which included 10 amino acid disorders in 662 cases (26.9%), 6 common diseases were hyperphenylalaninemia, citrin deficiency, ornithine carbamoyltransferase deficiency, maple syrup urine disease, alkaptonuria, and tyrosinemia-I, 17 types of organic acidemias in 1 683 cases (68.4%), 6 common diseases were methylmalonic acidemia, propionic acidemia, valeric acidemia-type Ⅰ, isovaleric acidemia, 3-methylcrotonyl-CoA carboxylase deficiency and multiple carboxylase deficiency and 5 fatty acid ß oxidative defects in 116 cases (4.7%), 2 common diseases were multiple acyl-CoA dehydrogenase deficiency and short-chain acyl-CoA dehydrogenase deficiency). Conclusion: Among the diseases diagnosed by analyzing urinary organic acid profiling with gas chromatography-mass spectrometry, the most common are organic acidemias, followed by amino acid disorders and fatty acid oxidation defects.

[The value of soluble thrombomodulin in evaluating endothelial injury in patients with kidney disease].

Objective: To evaluate the value of soluble thrombomodulin (sTM) in evaluating endothelial injury in patients with kidney disease. Methods: One hundred and thirty-three patients who first visited the Department of Nephrology of Beijing hospital for various reasons from September 2020 to January 2021 and 130 healthy people were collected and divided into groups according to age, gender, primary disease, complications and so on. The differences of sTM and serum creatinine in patients with different diseases and renal disease stages were analyzed. Results: For patients with chronic kidney disease (CKD), sTM increased significantly with the decrease of renal function. The level of sTM in patients with CKD stage 1-5 was (0.013±0.007), (0.019±0.010), (0.022±0.008), (0.027±0.008), (0.033±0.006)TU/L, respectively (F=21.005,P<0.05). There was no significant difference in the level of sTM between patients with non-CKD urinary tract infection (0.013±0.009) TU/L and patients with stage 1 CKD (t=1.023, P>0.05). No matter whether the patients were complicated with infection or cardiovascular disease, there was no significant difference in sTM level under the condition of serum creatinine matching (all P>0.05). In 4 patients with acute renal injury, serum creatinine returned to normal after active treatment, but sTM did not decrease significantly. Correlation analysis showed that there was a positive correlation between sTM and serum creatinine (r=0.697, P<0.01). Conclusion: sTM can evaluate the renal function damage of patients with CKD more early, and the level of sTM in patients with renal disease is more related to the degree of endothelial damage.

[Serum status and their changes of some vitamin substances and homocysteine in healthy subjects in Beijing].

Objective: To investigate serum status of folate, vitamin B(12), homocysteine (Hcy) and hydroxyvitamin D (25OHD) and their trends in different gender and age groups. Methods: This was a cross-sectional study. The enrolled subjects were those received medical examination in Beijing Hospital from September to November 2018 and were identified as appeared healthy persons. 1220 subjects were recruited and were divided into groups of young and middle age group (30-49 years, 50-59 years) and the elderly group (60-69 years, 70-79 years and ≥80 years). We measured folate, vitamin B(12), and 25OHD using electrochemiluminescence by chemiluminescence immunoassay. Hcy was measured by autobiochemical analyzer. Results: Total folate levels in male and female subjects were 7.16 (4.74-10.75) and 9.17 (6.49-13.55) µg/L respectively. Total vitamin B(12) levels in the male and female were 505.60 (386.80-700.90) and 582.60 (430.70-846.98) ng/L respectively. Hcy levels were 14.68 (12.25-18.58) and 11.29 (9.65-13.58) µmol/L. 25OHD levels were 21.60 (16.40-28.70) and 16.80 (12.30-24.15) µg/L respectively. Total folate and vitamin B(12) levels in female were higher than that in male subjects (Z=-7.796, -4.772, P<0.001). However, total Hcy and 25OHD levels in male were higher than that in female subjects (Z=-15.230, -8.447, P<0.001). Comparing with the substances in the above age groups, folate level in the elderly was lower than that in the younger age and middle age groups.However, vitamin B(12), 25OHD and Hcy levels were higher in the elderly groups. Furthermore, the levels of folate, vitamin B(12) and 25OHD were getting higher in the group of ≥80 years female compared with the rest of the age groups, but it turned lower in the male group of ≥80 years. Conclusions: There are some differences in the serum values of folate, vitamin B(12), Hcy and 25OHD among various age groups as well as between males and females. These should be considered in the development of national reference ranges.

Research on ketamine in mediating autophagy and inhibiting apoptosis of astrocytes in cerebral cortex of rats through NF-κB pathway.

OBJECTIVE: To investigate the effects of ketamine on autophagy and apoptosis of astrocytes in the cerebral cortex of rats, and determine whether nuclear factor-κB (NF-κB) pathway is involved in the regulation of autophagy and apoptosis of astrocytes. MATERIALS AND METHODS: A total of 36 male Sprague-Dawley (SD) rats were randomly divided into 3 groups: control group (Group C: intraperitoneal injection of equal amount of normal saline), glutamic acid group (Group G: intraperitoneal injection of 1 mg/kg glutamic acid) and glutamic acid + ketamine group (Group GK: intraperitoneal injection of 1 mg/kg glutamic acid and then injection of 5 mg/kg ketamine after 30 min). The cerebral cortex of rats in each group was taken after successive administration for 5 d. The number of glial fibrillary acidic protein (GFAP)-positive cells in the cerebral cortex of rats in each group was detected via immunofluorescence. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells (apoptotic cells) in the cerebral cortex was detected via TUNEL staining. The levels of inflammatory factors were detected using the enzyme-linked immunosorbent assay (ELISA) kit. Moreover, the expressions of autophagy-related proteins and apoptosis-related proteins in the cerebral cortex were detected via Western blotting, and the expressions of IκB-a and NF-κBp65 were also detected. RESULTS: The results of immunofluorescence showed that the number of GFAP-positive cells in the cerebral cortex of rats in Group G was significantly increased compared with that in Group C (p<0.01), and it was significantly decreased in Group GK compared with that in Group G (p<0.01). The results of TUNEL staining revealed that the number of TUNEL-positive cells in the cerebral cortex in Group G was significantly larger than that in Group C, and it was significantly smaller in Group GK than that in Group G (p<0.01). Results of ELISA demonstrated that compared with those in Group C, the contents of interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in Group G were significantly increased (p<0.01), but the content of IL-10 was significantly decreased (p<0.01). Compared with those in Group G, the contents of IL-6 and TNF-a in Group GK were significantly decreased (p<0.01), but the level of IL-10 was statistically elevated (p<0.01). Compared with those in Group C, the levels of LC3 II/I and cleaved caspase-3 in the cerebral cortex in Group G were significantly increased (p<0.01), but the p62 level and B-cell lymphoma-2/Bcl-2 associated X protein (Bcl-2/Bax) ratio were significantly decreased (p<0.01). In Group GK, the levels of LC3 II/I and cleaved caspase-3 were reduced, but the p62 level and Bcl-2/Bax ratio were increased. The expressions of IκB-α and NF-κBp65 in Group G were significantly decreased compared with those in Group C (p<0.01), and they were significantly higher in Group GK than those in Group G (p<0.01). CONCLUSIONS: Ketamine can reduce the glutamic acid-induced activation of astrocytes in the cerebral cortex, inhibit the autophagy and alleviate the apoptosis of astrocytes, the process of which is mediated by the NF-κB pathway, which provides the new molecular basis of ketamine in protecting astrocytes.

[Serum bone turnover markers and vitamin D level in diabetes patients with and without tuberculosis].

Objective: To investigate the levels of bone turnover marks and vitamin D(25OHD(3))in diabetes patients with and without tuberculosis. Methods: A total of 163 patients were recruited from Beijing Hospital and Jilin Provincial Academy of Tuberculosis Control and Prevention. including 80 diabetes patients without tuberculosis [39 males and 41 females, mean age (59±10) years], and 83 diabetes patients with tuberculosis [34 males and 49 females, mean age (56±12) years]. In the meantime, 80 healthy subjects were recruited as the normal control [39 males and 41 females, mean age (50±8) years]. The blood samples of all participants were taken after 10 hours fasting and before anti-tuberculosis treatment, and the levels of 25OHD(3), ß-crossLaps, Osteocalcin(OCN), and total procollagen type 1 amino-terminal propeptide(tP(1)NP) were meausured. One-way ANOVA and chis-square test were used for comparisons among the 3 groups and between groups respectively. Results: The concentration of 25OHD(3) was higher in diabetes patients without tuberculosis (16 µg/L) than in those with tuberculosis (14 µg/L), P<0.05, but significantly lower than that in the healthy subjects(21 µg/L) (P<0.01). The rate of 25OHD(3) deficiency was 79.8% (130/163) in diabetes patients (with and without tuberculosis), and significantly higher than that in healthy subjects 41.3% (33/80), P<0.01. The rate of serious deficiency of 25OHD(3) was 24.1% (20/83) in diabetes patients with tuberculosis. The level of tP(1)NP in diabetes patients (36 µg/L) was significantly lower than that in diabetes patients with tuberculosis 57 µg/L(P<0.01). Conclusions: 25OHD(3) deficiency was common in diabetes patients with and without tuberculosis. The level of tP(1)NP was significantly lower in diabetes patients without tuberculosis than those with tuberculosis, for which further studies were needed .