Background
Tripartite motif 47 (TRIM47), a member of the TRIM family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). We found that levels of TRIM47 mRNA and protein were increased significantly in colorectal tumors compared with nontumor tissues and the increased levels were associated with advanced tumor stage and poor outcome.
Methods
We used quantitative polymerase chain reaction and western blot to measure levels of TRIM47 mRNA and protein in human colorectal cancer and paired normal tissues. TRIM47 was knocked down and overexpressed in colorectal cancer cells, and the effects on cell proliferation, migration and growth of xenograft tumors in nude mice were assessed. The signaling pathways were examined by western blot and immunoprecipitation assays.
Results
TRIM47 promoted CRC proliferation and metastasis in vitro and in vivo as an oncogene. Mechanistically, TRIM47 interacted physically with SMAD4, increasing its ubiquitination and degradation. Loss of SMAD4 leaded to up-regulation of CCL15 expression and caused growth and invasion in human CRC cells through the CCL15-CCR1 signaling. Moreover, TRIM47 overexpression played a role in CRC chemoresistance in response to 5-FU therapy.
Conclusions
Our study demonstrated a functional role of the TRIM47-SMAD4-CCL15 axis in CRC progression and suggested a potential target for CRC therapy.
Electronic supplementary material
The online version of this article (10.1186/s13046-019-1143-x) contains supplementary material, which is available to authorized users.
BackgroundRespiratory tract infections (RTIs) are the most common illness in children, and rapid diagnosis is required for the optimal management of RTIs, especially severe infections.MethodsNasopharyngeal swab or sputum specimens were collected from children aged 19 days to 15 years who were admitted to a hospital in Shanghai and diagnosed with RTIs. The specimens were tested with the FilmArray Respiratory Panel, a multiplex PCR assay that detects 16 viruses, Mycoplasma pneumoniae (M. pneumoniae), Bordetella pertussis (B. pertussis) and Chlamydophila pneumoniae (C. pneumoniae).ResultsAmong the 775 children studied, 626 (80.8%, 626/775) tested positive for at least one organism, and multiple organisms were detected in 198 (25.5%). Rhinoviruses/enteroviruses (25.5%, 198/775) were detected most often, followed by respiratory syncytial virus (19.5%, 151/775), parainfluenza virus 3 (14.8%, 115/775), influenza A or B (10.9%), adenovirus (10.8%), M. pneumoniae (10.6%) and B. pertussis (6.3%). The prevalence of organisms differed by age, and most of the viruses were more common in winter. Of the 140 children suspected of having pertussis, 35.0% (49/140) tested positive for B. pertussis.ConclusionsFilmArray RP allows the rapid simultaneous detection of a wide number of respiratory organisms, with limited hands-on time, in Chinese pediatric patients with RTIs.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3429-6) contains supplementary material, which is available to authorized users.
BackgroundCurrent methods of lymph node (LN) staging are controversial in predicting the survival of SBA. We aimed to develop an alternative LN-classification-based nomogram to individualize SBA prognosis.MethodsBased on the data from the Surveillance, Epidemiology, and End Results (SEER) database of patients diagnosed with SBA between 2004 and 2014, we identified the cut-off points for the number of LNs examined and the number found to be metastatic using the K-adaptive partitioning (KAPS) algorithm. Using metastatic LNs, a nomogram predicting the survival of SBA was derived, internally and externally validated, and measured by calibration curve, C-index, and decision curve analysis (DCA), and compared to the 8th TNM stage.ResultsA total of 1516 patients were included. The cut-off of 17 was the optimal examined LN number. For metastatic LN numbers, the cut-off points were 0, 2, and 8. The C-index for the nomogram was higher than the 8th TNM staging (internal: 0.734; 95% CI, 0.693 to 0.775 vs. 0.677; 95% CI, 0.652 to 0.702, P < 0.001; external: 0.715; 95% CI, 0.674 to 0.756 vs. 0.648; 95% CI, 0.602 to 0.693, P < 0.001). Also, the nomogram showed good calibration in internal and external validation and larger net benefit than TNM staging.ConclusionWe modified current N staging into a 4-level staging system based on the number of metastatic LNs: N0, no LN metastasis; N1, 1–2 metastatic LNs; N2, 3–8 metastatic LNs, and N3, >8 metastatic LNs and set the least examined LN number to 17. A nomogram based on this staging showed great clinical usability than TNM staging for predicting the survival of SBA patients.
We found that age, sex, sleep, and some dietary habits impacted weight, and suggests that specific cultural and economic factors may impact risk of a child being overweight or obese.
Background
Due to the lack of a sensitive, specific and rapid detection method, aetiological diagnosis of pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae, MP) is a constantly challenging issue. This retrospective study aimed to compare the diagnostic methods for Mycoplasma pneumoniae in children and evaluate their values.
Methods
From November 2018 to June 2019, 830 children with community-acquired pneumonia were selected from the Department of Respiratory Medicine, Shanghai Children’s Medical Center. On the first day of hospitalization, sputum, throat swab and venous blood samples were collected to analyse MP-IgM (particle agglutination, PA), MP-IgM (immune colloidal gold technique, GICT), MP-DNA, MP-RNA (simultaneous amplification and testing, SAT) and MP-DNA (real-time polymerase chain reaction, RT-PCR).
Results
Among these 830 children, RT-PCR showed that the positive rate was 36.6% (304/830), in which the positive rate of macrolide resistance (A2063G mutation) accounted for 86.2% of cases (262/304). Using RT-PCR as the standard, MP-RNA (SAT) had the highest specificity (97.5%), and MP-IgM (PA) had the highest sensitivity (74.0%) and Youden index (53.7%). If MP-RNA (SAT) was combined with MP-IgM (PA), its Kappa value (0.602), sensitivity (84.2%), specificity (78.7%) and Youden index (62.9%) were higher than those of single M. pneumoniae detection.
Conclusions
Our research indicated that a combination of MP-RNA (SAT) plus MP-IgM (PA) might lead to reliable results as an early diagnostic method for children with clinical manifestations of Mycoplasma pneumoniae pneumonia.
Background Small bowel vascular malformation disease (SBVM) is the most common cause of obscure gastrointestinal bleeding (OGIB). Several studies suggested that EGFL6 was able to promote the growth of tumor endothelial cells by forming tumor vessels. To date, it remains unclear how EGFL6 promotes pathological angiogenesis in SBVM and whether EGFL6 is a target of thalidomide. Methods We took advantage of SBVM plasma and tissue samples and compared the expression of EGFL6 between SBVM patients and healthy people via ELISA and Immunohistochemistry. We elucidated the underlying function of EGFL6 in SBVM in vitro and by generating a zebrafish model that overexpresses EGFL6, The cycloheximide (CHX)-chase experiment and CoIP assays were conducted to demonstrate that thalidomide can promote the degradation of EGFL6 by targeting CRBN. Results The analysis of SBVM plasma and tissue samples revealed that EGFL6 was overexpressed in the patients compared to healthy people. Using in vitro and in vivo assays, we demonstrated that an EMT pathway triggered by the EGFL6/PAX6 axis is involved in the pathogenesis of SBVM. Furthermore, through in vitro and in vivo assays, we elucidated that thalidomide can function as anti-angiogenesis medicine through the regulation of EGFL6 in a proteasome-dependent manner. Finally, we found that CRBN can mediate the effect of thalidomide on EGFL6 expression and that the CRBN protein interacts with EGFL6 via a Lon N-terminal peptide. Conclusion Our findings revealed a key role for EGFL6 in SBVM pathogenesis and provided a mechanism explaining why thalidomide can cure small bowel bleeding resulting from SBVM.
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