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.

Clinical value of combining serum tumor marker detection with fecal occult blood testing in diagnosing colorectal cancer.

This study aimed to investigate the value of combining the detection of serum tumor markers, namely, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 199, CA 242, and CA 50, with fecal occult blood (FOB) testing in the diagnosis of colorectal cancer (CRC). One hundred patients with CRC who were diagnosed and treated at the First Hospital of Jiaxing, Zhejiang Province, China, between January 2019 and April 2020 were enrolled as the case group, and 200 healthy people who underwent a physical examination at the hospital during the same period were recruited as the control group. The concentrations of CEA, CA199, CA242, and CA50 in serum were measured alongside FOB indicators. Compared with the control group, the concentrations of CEA, CA199, CA242, and CA50 in the case group were significantly higher, and they were related to age, tumor differentiation, tumor stage, and other clinicopathological features (P<0.05). The diagnostic performance of the combination of four tumor markers for CRC was significantly better than when using a single marker (four-combined test: AUC (area under the curve) AUC=0.80), and the diagnostic performance was further improved after adding the fecal occult blood test test (FOBT) results (five-combined test: AUC=0.90). The combined detection of the five indexes was found to be effective for the early diagnosis of CRC (AUC=0.87). We concluded that the detection of serum tumor markers CEA, CA199, CA242, and CA50 combined with an FOBT could significantly improve the sensitivity and accuracy of a CRC diagnosis and contributed to an early diagnosis and appropriate treatment.

[The impact of ambient PM(2.5) on daily outpatient visits due to chronic obstructive pulmonary disease, among the urban residents of Ningbo city].

Objective: To explore the short-term effects of ambient PM(2.5) on the outpatient visits of chronic obstructive pulmonary disease (COPD) in Ningbo city. Methods: Through the regional health information platform, number of daily COPD outpatients from the four general hospitals in Ningbo was gathered. Related data on meteorological and air pollution from 2014 to 2016 was also collected. Generalized additive model (GAM) of Possion regression was used to estimate the impact of PM(2.5) pollution on COPD outpatients and the lagging effects. Results: In cold (November- April) or warm seasons (May-October), an 10 µg/m(3) increase of PM(2.5) would result in the excessive number of COPD outpatients as 1.87% (95%CI: 0.98%-2.76%), 2.09% (95%CI: 1.11%-3.08%) and 2.56% (95%CI: 0.56%-4.59%), respectively. In terms of the short-term effects of PM(2.5) the strongest was seen in the days of warm season but without delay (P<0.05). The strongest effect appeared at day 4 in cold season and the effect was particularly significant seen in the over 65 year-old group or in the female population. After the introduction of PM(10), SO(2) and NO(2), the concentration of PM(2.5), did not show significant effect on the number of hospital visits due to COPD on the same day (P>0.05). The effect of COPD on the fourth day showed a slight change after the lagging, and the effect was statistically significant (P<0.05). Conclusion: The increase of PM(2.5) concentration in Ningbo was related to the increase of COPD outpatient numbers. Effective prevention measures should be taken to protect the vulnerable population and to reduce the risk of COPD.

Ipriflavone promotes osteogenesis of MSCs derived from osteoporotic rats.

OBJECTIVE: To explore whether Ipriflavone could prevent postmenopausal osteoporosis (PMOP) and improve bone quality via promoting osteogenesis of bone marrow-derived mesenchymal stem cell (MSCs). MATERIALS AND METHODS: MSCs were extracted from rats and identified using flow cytometry. Osteogenic specific genes and adipogenic specific genes in MSCs were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). The effect of Ipriflavone on osteogenesis was detected by CCK-8 (cell counting kit-8) assay, ALP activity detection, alizarin red staining and Western blot, respectively. Furthermore, ovariectomized PMOP rat model was constructed. The effects of Ipriflavone on osteogenesis, BMD and bone biomechanical properties of ovariectomized rats were detected. RESULTS: MSCs derived from ovariectomized rats exerted multiple differentiation potentials. CCK-8 assay indicated that 0.8 µM Ipriflavone were the maximal dose that did not affect MSCs proliferation, which was selected for the following experiments. In vitro researches demonstrated that Ipriflavone remarkably promoted MSCs osteogenesis. In vivo results indicated that BMD, BV/TV, Tb.N and Tb.Th were decreased in ovariectomized rats than those of rats in sham group. Ipriflavone treatment remarkably prevented osteoporosis via promoting MSCs osteogenesis in ovariectomized rats. CONCLUSIONS: Ipriflavone prevents postmenopausal osteoporosis, improves bone quality and protects bone tissue via promoting MSCs osteogenesis.

[Study on influence of air temperature on daily chronic obstructive pulmonary disease mortality in Ningbo].

Objective: To study the influence of daily air temperature on daily chronic obstructive pulmonary disease (COPD) mortality in residents in Ningbo. Methods: A time-series analysis using distributional lag non-linear model (DLNM) was conducted to estimate the attributable numbers and fraction of average air temperature on the daily COPD mortality in Ningbo from 2011 to 2016, by controlling the long-term time trend, day of week, air pollutants and other weather variables. Results: A reverse J-shape relationship was found between the average air temperature and COPD mortality, and the minimum-mortality temperature (MMT) was 25.5 ℃. The relative risks of extreme low and extreme high air temperature over lag 0-14 d were 2.767 (95%CI: 1.950-3.928) and 1.197 (95%CI: 1.021-1.404). In total, 31.62% (95%CI: 23.05%-38.89%) of COPD mortality (4 963 cases, 95%CI: 3 469-6 027) was attributable to non-MMT exposure, More attributable deaths were due to low air temperature, with a fraction of 30.41% corresponding to 4 772 deaths, compared with 1.22% and 192 deaths due to high air temperature. Low air temperature and high temperature were more likely to influence the mortality in females and those aged ≥65 years, but the influence was not significant in people aged <65 years. Conclusion: Both high and low air temperature were associated with an increased risk of COPD mortality in residents in Ningbo, especially during cold season, related measures on disease prevention should be taken to protect vulnerable population to reduce the risk of COPD mortality.

[Relationship between weather factors and heat stroke in Ningbo city].

OBJECTIVE: To explore the main effects of weather factors on heat stroke. METHODS: Data from case report on heat stroke was collected in Ningbo city during 2011 to 2014. Temperature threshold, lag effects and interaction of weather factors on heat stroke had been analyzed, using the piecewise regression model, distributed lag non-linear model, response surface model and other methods. RESULTS: RESULTS showed that temperature and humidity were more correlated with heat stroke than other weather-related factors. Through different models, daily average temperature always presented a better role in predicting the heat stroke, rather than maximum or minimum temperature. Positive association between daily average temperature and heat stroke was obvious, especially at lag 0-1 days, with its threshold as 29.1 (95% CI: 28.7-29.5) ℃ . The cumulative RR of heat stroke at 90(th) percentile of daily average temperature versus 10(th) percentile was 14.05 (95% CI: 7.23-27.31) in lag 0-1 days. The effects of daily relative humidity on heat stroke appeared nonlinear, with low humidity showing a negative effect on heat stroke and could lag for 1-4 days. However, the effect of high humidity was not significant, with the cumulative RR of low humidity and high humidity as 2.35 (95%CI: 1.27-4.33) and 0.86 (95%CI: 0.40-1.85) in lag of 0-4 days, respectively. We also noticed that there was an interactive effect of both temperature and humidity on heat stroke. Under high temperature and low humidity, the risk of heat stroke showed the highest. CONCLUSIONS: Temperature and humidity showed obvious relationship with heat stroke in Ningbo city, with the threshold temperature as 29.1 ℃. Under high temperature and low humidity, the risk of heat stroke became the highest.

Cryopreservation of gemmae of Marchantia polymorpha L. (Marchantiophyta, Marchantiaceae) without prior pretreatment.

BACKGROUND: Successful cryopreservation of gametophytic material of bryophytes requires pretreatment with sucrose or abscisic acid. Compared to gametophyte materials, spore and gemmae cryopreservation may be more efficient, simple and stable systems for storing large amounts of genetic diversity of bryophytes within a small space. However, there has still been no attempt at cryopreserving bryophyte gemmae. OBJECTIVE: The aim of this study is to determine whether bryophyte gemmae with differing levels of desiccation tolerance could survive and germinate after cryopreservation without prior encapsulation and pretreatment. MATERIALS AND METHODS: Gemmae of Marchantia polymorpha L. were dried with silica gel for different times and then rapidly cooled in liquid nitrogen. RESULTS: The germination level of fresh gemmae was 95 % After 3 h predrying and 1 d in LN, germination was 68 % and was still up to 59 % after storage for 75 days. CONCLUSION: We conclude that the natural desiccation tolerance of bryophyte gemmae permits cryopreservation without prior pretreatment other than drying.

EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition.

Recent evidence indicates that long noncoding RNAs (lncRNAs) have a critical role in the regulation of cellular processes such as differentiation, proliferation, and metastasis. These lncRNAs are dysregulated in a variety of cancers and many function as tumor suppressors; however, the regulatory factors involved in silencing lncRNA transcription are poorly understood. In this study, we showed that epigenetic silencing of lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) occurs in non-small-cell lung cancer (NSCLC) cells through direct transcriptional repression mediated by the Polycomb group protein enhancer of zeste homolog 2 (EZH2). SPRY4-IT1 is derived from an intron within SPRY4, and is upregulated in melanoma cells; knockdown of its expression leads to cell growth arrest, invasion inhibition, and elevated rates of apoptosis. Upon depletion of EZH2 by RNA interference, SPRY4-IT1 expression was restored, and transfection of SPRY4-IT1 into NSCLC cells resulted in a significant antitumoral effect, both in culture and in xenografted nude mice. Moreover, overexpression of SPRY4-IT1 was found to have a key role in the epithelial-mesenchymal transition through the regulation of E-cadherin and vimentin expression. In EZH2-knockdown cells, which characteristically showed impaired cell proliferation and metastasis, the induction of SPRY4-IT1 depletion partially rescued the oncogenic phenotype, suggesting that SPRY4-IT1 repression has an important role in EZH2 oncogenesis. Of most relevance, translation of these findings into human NSCLC tissue samples demonstrated that patients with low levels of SPRY4-IT1 expression had a shorter overall survival time, suggesting that SPRY4-IT1 could be a biomarker for poor prognosis of NSCLC.

AtMYB44 regulates resistance to the green peach aphid and diamondback moth by activating EIN2-affected defences in Arabidopsis.

Recently we showed that the transcription activator AtMYB44 regulates expression of EIN2, a gene essential for ethylene signalling and insect resistance, in Arabidopsis thaliana (Arabidopsis). To link the transactivation with insect resistance, we investigated the wild-type and atmyb44 mutant plants, genetically Complemented atmyb44 (Catmyb44) and AtMYB44-Overexpression Transgenic Arabidopsis (MYB44OTA). We found that AtMYB44 played a critical role in Arabidopsis resistance to the phloem-feeding generalist green peach aphid (Myzus persicae Sulzer) and leaf-chewing specialist caterpillar diamondback moth (Plutella xylostella L.). AtMYB44 was required not only for the development of constitutive resistance but also for the induction of resistance by both herbivorous insects. Levels of constitutive and herbivore-induced resistance were consistent with corresponding amounts of the AtMYB44 protein constitutively produced in MYB44OTA and induced by herbivory in Catmyb44. In both cases, AtMYB44 promoted EIN2 expression to a greater extent in MYB44OTA than in Catmyb44. However, AtMYB44-promoted EIN2 expression was arrested with reduced resistance levels in the EIN2-deficient Arabidopsis mutant ein2-1 and the MYB44OTA ein2-1 hybrid. In the different plant genotypes, only MYB44OTA constitutively displayed phloem-based defences, which are specific to phloem-feeding insects, and robust expression of genes involved in the biosynthesis of glucosinolates, which are the secondary plant metabolites known as deterrents to generalist herbivores. Phloem-based defences and glucosinolate-related gene expression were not detected in ein2-1 and MYB44OTA ein2-1. These results establish a genetic connection between the regulatory role of AtMYB44 in EIN2 expression and the development of Arabidopsis resistance to insects.

Association between ABO blood groups and osteoporosis severity in Chinese adults aged 50 years and over.

This study investigated whether the ABO blood groups contributed to the severity of osteoporosis in 1452 community-dwelling Chinese adults aged 50-85 years. Osteoporosis severity was scored as: F(0), no osteoporosis; F(1), osteopenia; F(2), osteoporosis; and F(3), severe osteoporosis. The proportions of adults with a non-O blood group were 55.0%, 62.0%, 70.8% and 72.6% for the groups with F(0), F(1), F(2) and F(3) osteoporosis scores, respectively. Having a non-O blood group was associated with an increased severity of osteoporosis, even after adjustment for gender, age and cigarette consumption (odds ratio 1.8; 95% confidence interval 1.0, 2.9). This study demonstrated that having a non-O blood group was an independent risk factor for the progression of osteoporosis in Chinese adults with osteoporosis aged ≥ 50 years.

Serum fructose concentration in rats after single dose oral administration of Si-Wu-Tang.

Our previous study showed that fructose is an important active constituent that is responsible for Si-Wu-Tang's (SWT) effects promoting hematopoiesis and immunity. In order to provide primary data for analysis of the mechanism of fructose's bioactivity, the concentration of serum fructose in rats after a single oral administration dose of Si-Wu-Tang was determined. The concentration of serum fructose in fasting rats was 0.34 ± 0.24 mg/dL. After oral administration of 7.2 mL per kg body weight of SWT extract (1 mL extract corresponds to 1 g SWT dried herbs), serum fructose levels reached a peak concentration of 1.03 ± 0.25 mg/dL within 60 min, and then declined to the baseline level within 180 min, a pattern which is similar to the one reported for oral administration of pure fructose. The peak concentration was only 2-3 times higher than the baseline serum fructose concentration. These results showed that the increase of blood fructose concentration after oral administration of SWT is small and transient, which is very probably due to the quick metabolism of fructose by the liver. We suggest, for future research, it is necessary to consider the probability that fructose's bioactivity on hematopoiesis and immunity is not exerted by fructose in its original form, but after it is metabolized by the liver.

Rehmanniae Radix provides most of the free fructose and glucose in Si-Wu-Tang decoction.

Our previous study showed that free fructose is an important active constituent responsible for Si-Wu-Tang's (SWT) effect promoting hematopoiesis and immunity. However, the contribution from SWT's four ingredient drugs to the free fructose content in the SWT decoction was not clear. To answer this question, in this study, the fructose, glucose and sucrose content in the SWT decoction, in the decoctions of each single ingredient drug, and in the decoctions of the four formulae lacking each single ingredient drug were determined by HPLC-ELSD. The results showed that the fructose and glucose content in the decoction of single Rehmanniae Radix were almost the same as those in the SWT decoction. In the single Rehmanniae Radix decoction concentrations were: 4.25 ± 0.53 mg/mL for fructose, and 3.43 ± 0.60 mg/mL for glucose; in the SWT decoction concentrations were: 4.10 ± 0.43 mg/mL for fructose, and 3.42 ± 0.32 mg/mL for glucose, while the content of fructose and glucose in the decoctions of single Angelica Radix, single Paeoniae Radix, single Chuanxiong Rhizoma and the formula lacking Rehmanniae Radix were either very small or undetectable. On the other hand, the fructose and glucose content in the decoctions of the formulae lacking Angelica Radix, lacking Paeoniae Radix and lacking Chuanxiong Rhizoma also were approximately the same as those in the SWT decoction. This indicated that Rehmanniae Radix provides most of the free fructose and glucose in the SWT decoction, and therefore plays an important role in SWT's effect promoting hematopoiesis and immunity. As for sucrose in the SWT decoction, Angelica Radix was shown to be a major donor.