[Clinical value of inflammatory biomarkers in predicting prognosis of patients with ureteral urothelial carcinoma].

OBJECTIVE: To evaluate the clinical value of inflammation-related markers in predicting the prognosis of patients with ureteral urothelial carcinoma. METHODS: 200 patients with ureteral urothelial carcinoma were randomly divided into two groups by split sample validation: modeling group and validation group. Paraffin embedded pathological specimens of the patients were reviewed. Immunohistochemical method was used to detect tumor-infiltrating neutrophil (TIN) (CD66b+), tumor-associated macrophage (TAM) (CD163+), lymphocyte (CD+, CD4+, CD8+) counts, peripheral blood neutrophil / lymphocyte ratio (NLR) and tumor tissue neutrophil/monocyte ratio (NMR). According to the results of pathological staging, the patients were divided into non-muscle-invasive and muscle-invasive ureteral urothelial carcinoma group. The resolution of the models was evaluated, and the prognostic nomogram models including only peripheral blood parameters and all parameters were established to compare the accuracy of the two models in predicting the prognosis of patients with urothelial carcinoma of the ureter. RESULTS: The median follow-up time was 36 months, the progression-free survival was 40 months, and 42 cases (21.0%) showed tumor progression within 3 years. Tumor size, pathological stage and pathological grade were all single-factor variables predicting the first recurrence of ureteral urothelial carcinoma three years after operation. Tumor size, pathological stage, pathological grade, TIN, TAM, NLR and NMR were multi-factor variables predicting the first recurrence three years after operation. Among 104 cases of non-muscle-invasive ureteral urothelial carcinoma, 10 cases (9.6%) recurred for the first time 3 years after operation, 96 cases (33.3%) of muscle invasive ureteral urothelial carcinoma, and the diffe-rence between the two groups was statistically significant (χ2=15.53, P < 0.05). The predictive nomogram model of progression free survival was established. The concordance index of progression free survi-val was 0.722 (95%CI: 0.70-0.78) in non-muscle-invasion group, and 0.725 (95%CI: 0.71-0.79) in muscle-invasion group, which was in good agreement with the observed 3-year survival rate. The results of discrimination test showed that the concordance index of the whole parameter prediction model of ureteral urothelial carcinoma was 0.726, which was higher than that of peripheral blood parameters (consistency index 0.672). The immune microenvironment of ureteral urothelial carcinoma improved the prediction accuracy of the model. CONCLUSION: The prognosis prediction model based on immune inflammation-related markers was established as a perfection and supplement for the existing pathological grading and staging system, providing a basis for accurate individualized treatment of patients with urete-ral urothelial carcinoma. The prognosis prediction model based on the relevant indicators of peripheral blood samples is established, which is easy to obtain specimens, and the detection method is simple and economical, which is more conducive to clinical application.

Randomized trial of oral versus enteral feeding for patients with postoperative pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Whether continued oral feeding may have a negative impact on healing of postoperative pancreatic fistula (POPF) is unclear. The aim was to test the hypothesis that oral feeding is non-inferior to enteral feeding in closure of POPF after pancreatoduodenectomy, and to clarify the effects of oral feeding on the duration and grade of POPF. METHODS: This multicentre, non-inferiority randomized trial of oral or enteral feeding of patients with POPF after pancreatoduodenectomy recruited patients between August 2013 and September 2016. The primary efficacy outcome was the 30-day fistula closure rate. The prespecified non-inferiority margin was 15 per cent. Other efficacy outcomes included grade of fistula, and hospital stay and costs. RESULTS: A total of 114 patients were included, and received oral (57) or enteral (57) feeding. The two groups were balanced in baseline characteristics and no patient was lost to follow-up. In intention-to-treat analysis, oral feeding was non-inferior to enteral feeding in terms of 30-day fistula closure rate (88 versus 89 per cent respectively; difference -1·8 per cent, lower limit of 95 per cent c.i. -14·4 per cent; P = 0·020 for non-inferiority). Compared with enteral feeding, oral feeding significantly reduced hospital costs and duration of stay. No significant differences were noted in the number of patients whose POPF evolved into grade B/C, or other outcomes. CONCLUSION: Oral feeding in patients with POPF after pancreatoduodenectomy did not increase the duration or grade of POPF, and was associated with reduced duration of stay and hospital costs. Registration number: NCT01755260 (http://www.clinicaltrials.gov).

miR-520h is crucial for DAPK2 regulation and breast cancer progression.

This corrects the article DOI: 10.1038/onc.2015.168.

miR-520h is crucial for DAPK2 regulation and breast cancer progression.

MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their interaction with 3'untranslated region of specific target mRNAs. Although the dysregulation of miRNAs has been identified in human cancer, only a few of these miRNAs have been functionally documented in breast cancer. Thus, defining the important miRNA and functional target involved in chemoresistance is an urgent need for human breast cancer treatment. In this study, we, for the first time, identified a key role of miRNA 520h (miR-520h) in drug resistance. Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. Furthermore, we observed that higher level of miR-520h is associated with poor prognosis and lymph node metastasis in human breast cancer patients. These results show that miR-520h is not only an independent prognostic factor, but is also a potential functional target for future applications in cancer therapeutics.

MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol.

Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.

The effect of etanercept on anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the changes in anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) following etanercept treatment in patients with rheumatoid arthritis. METHODS: The study included 90 patients with rheumatoid arthritis who failed treatment with disease modifying antirheumatic drugs (DMARDs). All patients were allowed to continue treatment with DMARDs; 52 of them received etanercept as a twice weekly 25 mg subcutaneous injection for three months, and the others did not. Serum samples were collected at baseline and one month intervals during the treatment course. The serum levels of anti-CCP and RF were tested by enzyme linked immunosorbent assay and nephelometry, respectively. RESULTS: At baseline, 45 of the 52 etanercept treated patients (86.5%) and 32 of the 38 controls (84.2%) were positive for anti-CCP. Tests for RF were positive in 78.9% and 84.2% of patients with or without etanercept treatment, respectively. The serum levels of anti-CCP and RF decreased significantly after a three month etanercept treatment (p = 0.007 and p = 0.006, respectively). The average decrease from baseline calculated for each individual patient in the etanercept treated group was 31.3% for anti-CCP and 36% for RF. The variation in anti-CCP was positively correlated with the variation in disease activity, swollen and tender joint counts, RF, and C reactive protein. CONCLUSIONS: Etanercept combined with DMARDs leads to a much greater decrease than DMARDs alone in the serum levels of anti-CCP and RF in rheumatoid arthritis, compatible with a reduction in clinical disease activity.

Orthodontic correction of a mandibular first molar deeply impacted by an odontoma: a case report.

Orthodontic correction was used to a 12-year-old boy with a mandibular first molar deeply impacted by an odontoma. Following surgical removal of the odontoma, the molar was exposed and brought to a proper position by orthodontic traction. The treatment time was 29 months. After a 20-month follow-up, the molar was still in a satisfactory position.

Verruciform xanthoma. Case report and literature review.

Verruciform xanthoma is a relatively uncommon lesion. Half of the reported cases occurred in the gingiva or alveolar ridge. In most cases, the clinical impressions are papilloma or verrucous carcinoma, which demonstrates the importance of the clinical and pathological recognition of this lesion. The cause of pathogenesis is still unknown since the first report in 1971. There are some cases reported in conjunction with leukoplakia, carcinoma in situ, pemphigus, and discoid lupus erythematosus (DLE), which merits close evaluation of this disease. This article reports two cases of verruciform xanthoma and reviews the evidence of its pathogenesis from the available literature.

Putative benzodiazepine partial agonists demonstrate receptor heterogeneity.

This study explored whether the behavioral heterogeneity of benzodiazepine receptor (BDZR) ligands is a consequence of multiple receptor subtypes or partial agonism. Putative partial agonists Ro16-6028, Ro23-1590, Ro23-0364, and abecarnil were compared with U78875, a mixed agonist-antagonist, and CGS8216, an inverse agonist, in five BDZR-mediated functions: hyperphagia, anxiolysis, sedation, hypothermia, and anticonvulsant activity. Only abecarnil was an agonist in all end points. Each of the other drugs exhibited qualitatively different responses at these end points. Specifically, Ro23-0364 produced no effect on body temperature, but was an agonist at other tests. Ro23-1590 had no effect on anxiolysis and hypothermia, but was an agonist at other tests. In contrast to other putative partial agonists, Ro16-6028 was found to be an antagonist in sedation and U78875 was an antagonist in hypothermia, but both were agonists at other end points. These qualitative differences in activity in the five behavioral end points studied cannot be explained by partial agonism at a single receptor and indicate that these ligands differentially activate multiple BDZR subtypes.