miR-5000-3p confers oxaliplatin resistance by targeting ubiquitin-specific peptidase 49 in colorectal cancer.

Colorectal cancer (CRC) is the most common form of gastrointestinal malignancies. A growing number of reports focusing on oxaliplatin (OXA) resistance in CRC treatment have revealed that drug resistance is an urgent issue in clinical applications, especially for finding effective therapeutic targets. Recently, microRNAs (miRNAs) are reported to play a critical role in tumor progressions and multi-drug resistance. The main aim of this study is to establish whether miR-5000-3p is an oncogene that is resistant to OXA and further confirm its underlying regulatory role in CRC. The OXA-associated gene expression dataset in CRC cells was downloaded from Gene Expression Omnibus (GEO) database. Statistical software R was used for significance analysis of differentially expressed genes (DEGs) between OXA-resistant (OR)-CRC cells and CRC cells, and results indicated ubiquitin-specific peptidase 49 (USP49) was upregulated in OR-CRC cells. Luciferase reporter assay showed that USP49 was verified to act as a downstream target gene of miR-5000-3p. From the results of TCGA database, miR-5000-3p expression was upregulated and USP49 was downregulated in patients with CRC. The function of miR-5000-3p was detected using MTT assay, wound healing, Transwell, and flow cytometry assays. Moreover, through in vitro and in vivo experiments, miR-5000-3p expression was confirmed to be upregulated in CRC cells or OR-CRC cells comparing to normal cell lines. Molecular mechanism assays revealed that USP49 binds to the miR-5000-3p promoter to increase the expression of miR-5000-3p, resulting in cancer cells sensitized to OXA. To sum up, these results suggest that miR-5000-3p may be a novel biomarker involved in drug-resistance progression of CRC. Moreover, the drug-resistance mechanism of miR-5000-3p/USP49 axis provides new treatment strategies for CRC in clinical trials.

[Prevalence of pediatric asthma in the rural areas of China: a Meta analysis].

OBJECTIVE: To systematically review the prevalence of pediatric asthma in the rural areas of China, and to provide data for the prevention and treatment of pediatric asthma. METHODS: PubMed, Cochrane, China National Knowledge Infrastructure, Wanfang Database, and Embase were searched for cross-sectional studies on the prevalence of pediatric asthma in the rural areas of China published up to August 31, 2019. Two researchers independently conducted preliminary screening and data extraction. Stata 14.0 and R software were used to perform a Meta analysis of prevalence rate. Subgroup analysis was also performed. RESULTS: A total of 24 articles were reviewed, with a sample size of 212 814 children, among whom there were 3 254 children with asthma, with an overall prevalence rate of 2.02% (95%CI: 1.67%-2.36%). Boys had a significantly higher prevalence rate than girls (3.64% vs 2.03%, P<0.001). The annual prevalence rate increased from 1.21% in 1990-1999 to 3.36% in 2011-2015. The prevalence rate of pediatric asthma was 3.15% in South China, which was higher than that in East China (2.31%), Southwest China (2.15%), North China (1.19%), and Central China (1.12%). Preschool children had the highest prevalence rate of 2.63%, followed by infants and young children (2.48%) and school-age children (1.41%). CONCLUSIONS: The prevalence rate of pediatric asthma is relatively low but tends to increase in the rural areas of China. Boys have a higher prevalence rate of asthma than girls, and the prevalence rate is higher in South China. Preschool children have the highest prevalence rate.

The development of the Japanese version of the compassionate engagement and action scales.

The last few years have seen increasing research on self-report measures of compassion. The Compassionate Engagement and Action Scale (CEAS) is rooted in an evolutionary approach to compassion, which focuses on the competencies of compassion those are engagement with distress or suffering, and taking action to alleviate and prevent it. This study sought to validate the CEAS in a Japanese population using a cross-sectional design. A total of 279 students (82 males, 191 females, 6 unknown) answered self-report questionnaires, including the Japanese version of CEAS. We found single-factor structures for compassion for others scales, compassion from others scales, and compassion for self scales. All scales were found to have acceptable internal consistency, test-retest reliability, content validity, and construct validity. Even though some limitations, these results indicate that the Japanese version of CEAS is an adequately constructed and useful measure to assess compassionate engagement and action toward others, from others, and for the self with Japanese population.

Down-regulated WDR35 contributes to fetal anomaly via regulation of osteogenic differentiation.

BACKGROUND: Autosomal recessive disorder is closely correlated with congenital fetal malformation. The mutation of WDR35 may lead to short rib-polydactyly syndrome (SRP), asphyxiating thoracic dystrophy (ATD, Jeune syndrome) and Ellis van Creveld syndrome. The purpose of this study is to investigate the role of WDR35 in fetal anomaly. RESULTS: The fetuses presented malformation with abnormal head shape, cardiac dilatation, pericardial effusion, and non-displayed left pulmonary artery and left lung. After the detection of genomic DNA (gDNA) in amniotic fluid cells (AFC), chromosomal rearrangement was found in arr[hg19] 2p25.3p23.3. It was revealed through multiple PCR-DHPLC that MYCN, WDR35, LPIN1, ODC1, KLF11 and NBAS contained duplicated copy numbers in 2p25.3p23.3. AF-MSCs were mostly positive for CD44, CD105, negative for CD34 and CD14. Western Blot test showed that WDR35-encoded protein was decreased in the patients' AFC compared to that in normal pregnant women. In the patients' amniotic fluid-derived mesenchymal stem cells (AF-MSCs), WDR35 overexpression could repair cilia formation, and the overexpression of WDR35 or Gli2 could significantly enhance ALP activity and expressions of osteogenic differentiation marker genes, including RUNXE2, OCN, BSP and ALP. However, WDR35 silencing in C3H10T1/2 cells could remarkably inhibit cilia formation and osteogenic differentiation. This inhibitory effect could be attenuated by Gli2 overexpression. CONCLUSIONS: The results demonstrated that copy number variation (CNV) of WDR35 may lead to skeletal dysplasia and fetal anomaly, and that down-regulated WDR35 may damage the cilia formation and sequentially indirectly regulate Gli signal, which would eventually result in negative regulation of osteogenic differentiation.

Biochemical, Physiological and Transcriptomic Comparison between Burley and Flue-Cured Tobacco Seedlings in Relation to Carbohydrates and Nitrate Content.

Burley tobacco is a genotype of chloroplast-deficient mutant with accumulates high levels of tobacco-specific nitrosamines (TSNAs) which would induce malignant tumors in animals. Nitrate is a principle precursor of tobacco-specific nitrosamines. Nitrate content in burley tobacco was significantly higher than that in flue-cured tobacco. The present study investigated differences between the two tobacco types to explore the mechanisms of nitrate accumulation in burley tobacco. transcripts (3079) related to the nitrogen and carbon metabolism were observed. Expression of genes involved in carbon fixation, glucose and starch biosynthesis, nitrate translocation and assimilation were significantly low in burley tobacco than flue-cured tobacco. Being relative to flue-cured tobacco, burley tobacco was significantly lower at total nitrogen and carbohydrate content, nitrate reductase and glutamine synthetase activities, chlorophyll content and photosynthetic rate (Pn), but higher nitrate content. Burley tobacco required six-fold more nitrogen fertilizers than flue-cured tobacco, but both tobaccos had a similar leaf biomass. Reduced chlorophyll content and photosynthetic rate (Pn) might result in low carbohydrate formation, and low capacity of nitrogen assimilation and translocation might lead to nitrate accumulation in burley tobacco.

The development of fears of compassion scale Japanese version.

OBJECTIVES: Cultivation of compassion is a useful way to treat mental problems, but some individuals show resistance. Fears of compassion can be an obstacle for clinicians when providing psychotherapy, and for clients when engaging in interpersonal relationships. Despite its importance, a Japanese version of fears of compassion scales (for others, from others, and for self) has not yet been developed. This study developed a Japanese version of the Fears of Compassion Scales and tested its reliability and validity. DESIGN: This study used a cross-sectional design, and a self-report procedure for collecting data. METHODS: A total of 485 students (121 males and 364 females) answered self-report questionnaires, including the draft Fears of Compassion Scales-Japanese version. RESULTS: There were distinctive factor structures for fear of compassion from others, and for self. The fear of compassion from others scale consisted of concern about compassion from others and avoidance of compassion from others. All scales had good internal consistency, test-retest reliability, face validity, and construct validity. Discrimination and difficulty were also calculated. CONCLUSIONS: These results indicate that the Fears of Compassion Scales-Japanese version is a well-constructed and useful measure to assess fears of compassion and the existence of cultural differences in fears of compassion.

[The relationship between the levels of HBV DNA loads and both the clinical characteristics and 48-week prognosis in patients with decompensated cirrhosis due to hepatitis B].

OBJECTIVE: To evaluate the relationship between the levels of HBV DNA loads and both the clinical characteristics and 48-week prognosis in patients with decompensated cirrhosis due to hepatitis B. METHODS: One hundred and forty-three patients with decompensated cirrhosis of hepatitis B virus infection were divided into low level HBV DNA group [HBV DNA < 10(5) copies/ml = (46 cases) and high-level HBV-DNA group (HBV DNA > or = 10(5) copies/ml) (97 cases)]. 21 cases in low-level group and 52 cases in high-level group treated with nucleoside analog. RESULTS: There was no significant difference between the two groups on the demography and the baseline in ALT, ALB, TBil, CHE before treatment, while in AST and HBeAg were statistically different. At 48-week, there was no significant difference between the two groups on the liver function. The mortality rate in low-level group was similar to that in high level group. In the low-level HBV DNA patients, hepatocellular carcinoma, spontaneous peritonitis and gastrointestinal hemorrhage were higer than that in the high-level HBV DNA patients. CONCLUSION: In patients with decompensated cirrhosis due to hepatitis B, those who were in low-level HBV DNA had not got better than that in high-level HBV DNA, which indicated that earlier treatment was also needed in low-level HBV DNA patients.