DDB2 and MDM2 genes are promising markers for radiation diagnosis and estimation of radiation dose independent of trauma and burns.

In the field of biodosimetry, the current accepted method for evaluating radiation dose fails to meet the need of rapid, large-scale screening, and most RNA marker-related studies of biodosimetry are concentrating on a single type of ray, while some other potential factors, such as trauma and burns, have not been covered. Microarray datasets that contain the data of human peripheral blood samples exposed to X-ray, neutron, and γ-ray radiation were obtained from the GEO database. Totally, 33 multi-type ray co-induced genes were obtained at first from the differentially expressed genes (DEGs) and key genes identified by weighted gene co-expression network analysis (WGCNA), and these genes were mainly enriched in DNA damage, cellular apoptosis, and p53 signaling pathway. Following transcriptome sequencing of blood samples from 11 healthy volunteers, 13 patients with severe burns, and 37 patients with severe trauma, 6635 trauma-related DEGs and 7703 burn-related DEGs were obtained. Through the exclusion method, a total of 12 radiation-specific genes independent of trauma and burns were identified. ROC curve analysis revealed that the DDB2 gene performed the best in diagnosis of all three types of ray radiation, while correlation analysis showed that the MDM2 gene was the best in assessment of radiation dose. The results of multiple-linear regression analysis indicated that such analysis could improve the accuracy in assessment of radiation dose. Moreover, the DDB2 and MDM2 genes remained effective in radiation diagnosis and assessment of radiation dose in an external dataset. In general, the study brings new insights into radiation biodosimetry.

Molecular Hydrogen Reduces Electromagnetic Pulse-Induced Male Rat Reproductive System Damage in a Rodent Model.

Infertility has got to be a broadly concerned social issue these days, in which the malefactor cannot be overlooked. Numerous studies have shown that electromagnetic pulse (EMP) radiation may have seriously damaging effects on reproductive health, through nonthermal effects and oxidative stress. Molecular hydrogen, a selective hydroxyl radical scavenger, explains the protective effects against many diseases closely associated with oxidative damage, such as ionizing radiation (IR). We sought to characterize the beneficial effects of molecular hydrogen on the male reproductive system in a rodent EMP exposure model. The 8-week-old male Sprague-Dawley rats were exposed to EMP (peak intensity 1000 kV/m, pulse edge 20 ns, pulse width 200 ns, 1 Hz, and 200 pulses), with or without hydrogen-rich water. The pathological structure of the testis, the rate of apoptosis of the testis, the serum testosterone level, the sperm parameters, and the activity of the antioxidant enzymes of the testis were measured. Then, transcriptomic and untargeted metabolomic analyses were applied to uncover the underlying mechanism. Exposure to EMP increased testicular apoptosis rate and apoptosis protein level, decreased sperm viability and motility, decreased serum testosterone levels, and diminished testicular antioxidant capacity. Molecular hydrogen-alleviated damage decreased the testicular apoptosis rate and apoptosis protein level, increased sperm motility, increased serum testosterone levels, and improved antioxidative capacity. Omics results showed that molecular hydrogen has a strong influence on metabolic pathways, and EMP affects mainly oxidative phosphorylation, TNF signaling pathways, and cytokine-receptor interactions. The mechanism of molecular hydrogen's effect may be related to the reversal of some metabolite levels. These observations warrant molecular hydrogen as an innovative approach for potential protection against EMP.

Effects of different concentrations of intraluminal sodium chloride solution on intracavitary ECG used for arm infusion port implantation.

At present, there are few clinical studies on the application of high-concentration sodium chloride solutions in intracavitary ECG-guided catheter tip localization during the arm infusion port implantation. This study observed the effects of sodium chloride solutions with different concentrations on intracavitary ECG-guided arm infusion port implantation in the patients with cancer. The 657 patients receiving arm infusion port implantation in our hospital between January 2020 and August 2021 were randomly divided into 0.9% sodium chloride solution conduction group (group A), 5.45% sodium chloride solution conduction group (group B) and 10% sodium chloride solution conduction group (group C). The derived rate of stable intracavitary ECG, the occurrence rate of characteristic P wave, the time used for catheter tip localization and the optimal position rate of catheter tip were compared between the three groups. The derived rate of stable intracavitary ECG was significantly higher in the group B (97.78%) and group C (98.63%) than in the group A (93.90%) (all P < 0.05). The occurrence rate of characteristic P wave was also significantly higher in the group B (96.89%) and group C (97.72%) than in the group A (88.73%) (all P < 0.001). The time used for catheter tip localization was significantly shorter in the group B [(49.73 ± 8.15) s] and group C [(48.27 ± 8.61) s] than in the group A [(69.37 ± 19.99) s] (all P < 0.001). There was no significant difference in the optimal position rate of catheter tip among the three groups (P > 0.05). The 5.45% and 10% sodium chloride solutions are significantly superior comparing with 0.9% sodium chloride solution in the derived rate of stable intracavitary ECG, occurrence rate of characteristic P wave and time used for catheter tip localization, but there were no significant differences between 5.45 and 10% sodium chloride solutions. Moreover, the 5.45% sodium chloride solution is closer to physiological state comparing with 10% sodium chloride solution, so the 5.45% sodium chloride solution may be recommended for the intracavitary ECG-guided arm infusion port implantation.

First case report of complete paternal isodisomy of chromosome 10 harbouring a novel variant in COL17A1 that causes junctional epidermolysis bullosa intermediate.

BACKGROUND: Uniparental disomy (UPD) is a condition in which both chromosomes are inherited from the same parent, except for imprinting disorders. Uniparental isodisomy (UPiD) may result in a homozygous variant contributing to an autosomal recessive disorder in the offspring of a heterozygous carrier. Junctional epidermolysis bullosa intermediate (JEB intermediate) is an autosomal recessive inherited disease that is associated with a series of gene variants, including those of COL17A1. CASE PRESENTATION: We report the first case of complete paternal UPiD of chromosome 10 harbouring a novel homozygous variant in COL17A1: c.1880(exon23)delG (p.G627Afs*56). This variant led to the clinical phenotype of junctional epidermolysis bullosa intermediate in a 5-year-old child. Trio-whole exome sequencing (Trio-WES) and in silico data analysis were used for variant identification, Sanger sequencing was performed for variant validation, and pathological examination was performed as the gold standard for phenotype confirmation. CONCLUSIONS: We recommend the use of WES as a first-tier test for the diagnosis of epidermolysis bullosa, especially for paediatric patients. Moreover, UPD events should be detected and analysed routinely through WES data in the future.

Association Between Cholecystectomy and Gastric Cancer Risk: A Systematic Review and Meta-Analysis.

OBJECTIVES: Although several epidemiological studies have attempted to evaluate the relationship between cholecystectomy and gastric cancer risk, the findings have been controversial. This study aimed to carry out a systematic review and meta-analysis following the reporting guidelines to comprehensively analyze and quantify the evidence of the aforementioned association. METHODS: Studies were identified by searching the Medline (PubMed), Embase, and Web of Science from inception to November 30, 2020, with only studies published in English being considered. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects models. RESULTS: Eight studies (five cohort studies and three case-control studies) with a total of 26,063 gastric cancer patients and 848,081 participants were included. The summarized RR of the relationship between cholecystectomy and gastric cancer risk was 1.11 (95%CI: 1.03-1.20), with low heterogeneity (P = 0.117, I 2 = 37.8%). These positive findings were consistent in most subgroup analyses like region in Asia, number of cases ≥200, cohort study design, sex in male, low risk of bias, exposure collection by database, and adjustments made for age, gender, calendar year. Of note, we also observed positive association between cholecystectomy and non-cardia of gastric cancer risk (RR = 1.17, 95%CI: 1.04-1.33). No publication bias was present. CONCLUSIONS: The aforementioned evidence suggested that a history of cholecystectomy was associated with a slightly elevated risk of gastric cancer. Results of most subgroup analyses also supported the main findings. More prospective studies are warranted to further validate these findings.

[Dexmedetomidine alleviates LPS/D-Gal-induced acute liver injury via up-regulation of LC3-II expression in mice].

The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels were determined by ELISA. The protein expression levels of LC3-II and P62 in liver tissue were determined by Western blot. Liver histopathological changes were detected by HE staining. The results showed that, compared with control group, LPS/D-Gal enhanced ALT and AST activity, increased TNF-α and IL-6 levels, as well as MPO activity, up-regulated LC3-II and P62 protein expression levels, and significantly induced pathological damage in liver tissue. DEX reversed the above changes in the LPS/D-Gal group, whereas these protective effects of DEX were blocked by 3-MA. The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy.

[Inhibition effect of active fraction from clove on PI3K/Akt/mTOR signaling pathway to induce apoptosis of human colon cancer HCT116 cells].

To screen the sensitive cell lines of active fraction from clove(AFC) on human colon cancer cells, investigate the effects of AFC on the cells proliferation and apoptosis as well as PI3 K/Akt/mTOR(phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin) signaling pathways involved, and reveal the mechanism of AFC for inducing apoptosis of human colorectal carcinoma cells. Cell counting kit-8(CCK-8) assay was used to detect the cytotoxic effect of different concentrations of AFC. AFC-induced apoptosis was detected by Hoechst 33258 fluorescence staining and Annexin V-FITC/PI double staining. HCT116 cells were treated with AFC with or without pretreatment with insulin-like growth factor-Ⅰ(IGF-Ⅰ), and then the protein expression levels of caspase-3, caspase-9, poly ADP-ribose polymerase(PARP), PI3 K, p-PI3 K, Akt, p-Akt, mTOR and p-mTOR in PI3 K/Akt/mTOR signaling pathway were detected by Western blot. RESULTS:: showed that the most obvious inhibitory effect of AFC was on human colon cancer HCT116 cells, and the optimal AFC treatment time was 48 hours. After AFC treatment, typical apoptotic features such as nuclear chromatin concentration, nuclear fragmentation and apoptotic bodies appeared in a dose-dependent manner. Annexin V-FITC/PI double staining showed that as compared with the control group, 50 and 100 µg·mL~(-1) AFC groups increased the apoptosis rate of HCT116 cells significantly(P<0.001); AFC activated caspase-9, cleaved caspase-3 and cleaved PARP in a concentration-dependent manner. The protein expression levels of cleaved caspase-3/procaspase-3, cleaved PARP/PARP and caspase-9/ß-actin after treatment of AFC(100 µg·mL~(-1)) were significantly different from those in the control group(P<0.001). The relative protein expression of p-PI3 K, p-Akt and p-mTOR decreased in a concentration dependent manner, while Akt and mTOR showed no significant differences among groups. The ratios of p-PI3 K/PI3 K, p-Akt/Akt and p-mTOR/mTOR in the AFC groups(50 and 100 µg·mL~(-1)) were significantly lower than those in the control group(P<0.01). Its combination with IGF-Ⅰ weakened the effect of AFC in inhibiting PI3 K/Akt/mTOR signaling pathway. The ratios of p-Akt/Akt and p-mTOR/mTOR in the AFC+IGF-Ⅰ group were significantly enhanced as compared with the AFC group(P<0.05). Apoptosis-related protein expression levels(cleaved caspase-3 and cleaved PARP) in HCT116 cells treated with AFC+IGF-Ⅰ were also down regulated. As compared with the AFC group, the ratios of cleaved caspase-3/procaspase-3 and cleaved PARP/PARP in the AFC+IGF-Ⅰ group were significantly decreased(P<0.01). In summary, AFC activated caspase-mediated cascades and induced HCT116 cells apoptosis in a dose-dependent manner, which may be associated with the inhibition of the PI3 K/Akt/mTOR signaling pathway.

Procyanidin B2 inhibits lipopolysaccharide­induced apoptosis by suppressing the Bcl­2/Bax and NF­κB signalling pathways in human umbilical vein endothelial cells.

Human umbilical vein endothelial cells (HUVECs) serve a critical role in maintaining normal vascular function. Lipopolysaccharide (LPS), which is released from pathogenic bacteria in the blood, induces HUVEC apoptosis and injury to cause vascular dysfunction and infectious vascular diseases. Procyanidin B2 (PB2) possesses numerous functions, including antioxidant, antitumor, anti­inflammatory and antiapoptosis effects, but the molecular mechanism is not completely understood. The present study investigated the effects of PB2 on LPS­induced cytotoxicity and apoptosis in HUVECs, as well as the underlying mechanisms. The effects of PB2 on LPS­mediated alterations to cytotoxicity, mitochondrial membrane potential, apoptosis were assessed by performing Cell Counting Kit­8, JC­1 fluorescence, Hoechst 33258 staining assays, respectively. IL­1ß, IL­6 and TNF­α mRNA expression and protein levels were measured by performing reverse transcription­quantitative PCR and ELISAs, respectively. Bcl­2, Bax, cleaved caspase­3, cleaved caspase­7, cleaved caspase­9, phosphorylated (p)­IκB­α, p­IκB­ß, p­NF­κB­p65 and total NF­κB p65 protein expression levels were determined via western blotting. NF­κB p65 nuclear translocation was assessed via immunofluorescence. PB2 pretreatment markedly attenuated LPS­induced cytotoxicity and apoptosis in HUVECs. PB2 also significantly downregulated the expression levels of IL­1ß, IL­6, TNF­α, Bax, cleaved caspase­3, cleaved caspase­7, cleaved caspase­9 and p­NF­κB­p65, but upregulated the expression levels of Bcl­2, p­IκB­α and p­IκB­ß in LPS­induced HUVECs. Moreover, PB2 markedly inhibited LPS­induced NF­κB p65 nuclear translocation in HUVECs. The results suggested that the potential molecular mechanism underlying PB2 was associated with the Bax/Bcl­2 and NF­κB signalling pathways. Therefore, PB2 may serve as a useful therapeutic for infectious vascular diseases.