Nomogram to predict primary non-response to infliximab in patients with Crohn's disease: a multicenter study.

BACKGROUND: Infliximab (IFX) is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn's disease (CD); however, 9%-40% of patients do not respond to primary IFX treatment. This study aimed to construct and validate nomograms to predict IFX response in CD patients. METHODS: A total of 343 patients diagnosed with CD who had received IFX induction from four tertiary centers between September 2008 and September 2019 were enrolled in this study and randomly classified into a training cohort (n = 240) and a validation cohort (n = 103). The primary outcome was primary non-response (PNR) and the secondary outcome was mucosal healing (MH). Nomograms were constructed from the training cohort using multivariate logistic regression. Performance of nomograms was evaluated by area under the receiver-operating characteristic curve (AUC) and calibration curve. The clinical usefulness of nomograms was evaluated by decision-curve analysis. RESULTS: The nomogram for PNR was developed based on four independent predictors: age, C-reactive protein (CRP) at week 2, body mass index, and non-stricturing, non-penetrating behavior (B1). AUC was 0.77 in the training cohort and 0.76 in the validation cohort. The nomogram for MH included four independent factors: baseline Crohn's Disease Endoscopic Index of Severity, CRP at week 2, B1, and disease duration. AUC was 0.79 and 0.72 in the training and validation cohorts, respectively. The two nomograms showed good calibration in both cohorts and were superior to single factors and an existing matrix model. The decision curve indicated the clinical usefulness of the PNR nomogram. CONCLUSIONS: We established and validated nomograms for the prediction of PNR to IFX and MH in CD patients. This graphical tool is easy to use and will assist physicians in therapeutic decision-making.

SNHG16 knockdown inhibits tumorigenicity of neuroblastoma in children via miR-15b-5p/PRPS1 axis.

Neuroblastoma is an important problem in children. Long noncoding RNAs (lncRNAs) exhibit important roles in tumorigenicity of neuroblastoma. However, the role and mechanism of lncRNA small nucleolar RNA host gene 16 (SNHG16) in neuroblastoma tumorigenicity remain poorly understood. Forty-six neuroblastoma samples and 28 normal tissues were harvested. The levels of SNHG16, microRNA-15b-5p (miR-15b-5p), and phosphoribosyl pyrophosphate synthetase 1 (PRPS1) were detected via quantitative reverse transcription PCR or western blot. Cell proliferation as well as cycle distribution were measured via 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide or flow cytometry. Cell metastasis was investigated via epithelial-mesenchymal transition or transwell assay. The target relationship of miR-15b-5p and SNHG16 or PRPS1 was explored via starBase and dual-luciferase reporter assay. The role of SNHG16 in neuroblastoma in vivo was analyzed using a xenograft model. We found SNHG16 and PRPS1 levels were increased in neuroblastoma tissues and cells. SNHG16 knockdown inhibited cell proliferation, increased the cell cycle distribution at G0/G1 phase, and decreased the cells at S phase. SNHG16 overexpression caused an opposite effect. SNHG16 silence suppressed neuroblastoma cell metastasis. PRPS1 knockdown constrained cell proliferation and metastasis and regulated cell cycle distribution. miR-15b-5p was sponged by SNHG16 and directly targeted PRPS1. miR-15b-5p knockdown or PRPS1 overexpression mitigated the influence of SNHG16 silence on cell cycle, proliferation, and metastasis. SNHG16 knockdown reduced xenograft tumor growth. In conclusion, SNHG16 downregulation suppressed neuroblastoma tumorigenicity by regulating cell cycle, proliferation, and metastasis via miR-15b-5p/PRPS1 axis.

MDA19, a novel CB2 agonist, inhibits hepatocellular carcinoma partly through inactivation of AKT signaling pathway.

BACKGROUND: CB2 (cannabinoid receptor 2) agonists have been shown to exert anti-tumor activities in different tumor types. However, there is no study exploring the role of MDA19 (a novel CB2 agonist) in tumors. In this study we aimed to investigate the effects of MDA19 treatment on HCC cell lines, Hep3B and HepG2 and determine the relevant mechanisms. RESULTS: Cell proliferation analysis, including CCK8 and colony formation assays, indicated that MDA19 treatment inhibited HCC cell proliferation in a dose- and time-dependent manner. Flow cytometry suggested that MDA19 induced cell apoptosis and activation of mitochondrial apoptosis pathway. Transwell assay indicated that HCC cell migration and invasion were significantly inhibited by MDA19 treatment. Mechanism investigation suggested that MDA19 induced inactivation of AKT signaling pathway in HCC cells. In addition, we investigated the function of CB2receptor in HCC and its role in the anti-tumor activity of MDA19. By searching on Kaplan-Meier plotter ( http://kmplot.com/analysis/ ), we found that HCC patients with high CB2 expression had a better survival and CB2 expression was significantly associated with gender, clinical stages and race of HCC patients (P < 0.05). CB2 inhibited the progression of HCC cells and its knockdown could rescue the growth inhibition induced by MDA19 in HCC. Moreover, the inhibitory effect of MDA19 on AKT signaling pathway was also reversed by CB2 knockdown. CONCLUSION: Our data suggest that MDA-19 exerts an anti-tumor activity at least partly through inactivation of AKT signaling pathway in HCC. CB2 functions as a tumor suppressor gene in HCC, and MDA19-induced growth inhibition of HCC cells depends on its binding to CB2 to activate it. MDA-19 treatment may be a promising strategy for HCC therapy. REVIEWER: This article was reviewed by Tito Cali, Mohamed Naguib and Bo Chen.

The clinical effect of Prednisone in combination with Mycophenolate mofetil on idiopathic thrombocytopenic purpura (ITP) and its influence on the level of peripheral blood T lymphocytes and NK lymphocytes.

OBJECTIVE: To explore he curative effect and safety of Prednisone in combination with Mycophenolate in treating ITP and its influence on the level of peripheral blood T lymphocytes and NK lymphocytes. METHOD: 93 cases of ITP patients were divided into the observation group and the control group by the Random Number Table method, 48 cases for the observation group, 45 for another. Patients in the control group orally took 0.5 mg/kg Prednisone Acetate tablets daily, two times each in the morning and evening. And the observation group, based on the treatment of the control group, orally took Mycophenolate Mofetil Dispersible tablets twice a day, 1 g each time. According to patients' conditions, 3 to 5 courses were set for treatment with 3 weeks a course. Compared PLT amount and the changing situation of inflammatory factors, CD3+ and CD3+CD95L+ before and after the treatment, the level of CD3+Caspase-3+ and CD3+Caspase-8+, NK+, NK+ CD95L+, NK+Caspase-3+, NK+Caspase-8, the curative effect and adverse events. RESULT: After treatment, PLT amount in both groups increased, and the increase in the observation group was much higher than that of the control group, the difference had statistical significance (P < 0.05). The time needed for PLT amount in the control group to reach the normal and peak values was longer than that of the observation group, whose PLT peak value was higher than another group. The difference had statistical significance (P < 0.05). After the treatment, the levels of TNF-α and IL-6 were lowered, and the value of the observation group was lower than that of another. The difference between and within the group has statistical significance. After the treatment, the level of CD3+, CD3+CD95L+ and CD3+Caspase-8+ is much higher and CD3+Caspase-3+ level lower than that before the treatment. The difference has statistical significance (P < 0.05). After the treatment, the level of NK+ and NK+ CD95L+ is higher and the level of NK+Caspase-8+ lower than that before the treatment. The difference has statistical significance (P < 0.05). After the treatment, the total effective rate 91.67% of the observation group is much higher than that 75.56% of another. The difference has statistical significance (P < 0.05). After the treatment, the incidence rate of adverse events in the control group is 11.11% (5/45), while 4.17% (2/48) in the observation group. The difference between groups has statistical significance (χ2 = 3.890, P < 0.05). CONCLUSION: The curative effect of Prednisone in combination with Mycophenolate on ITP patients is better than orally taking Prednisone tablets. Moreover, when it comes to Prednisone in combination with Mycophenolate, both the PLT amount and immunocompetence are improved without much adverse reaction, and the molecules of peripheral blood T lymphocytes and NK lymphocytes can be effectively adjusted to relieve the symptoms. So the method is trustworthy to be popularized for clinical practices.

Production of Antigen-Binding Fragment against O,O-Diethyl Organophosphorus Pesticides and Molecular Dynamics Simulations of Antibody Recognition.

Immunoassay for pesticides is an emerging analytical method since it is rapid, efficient, sensitive, and inexpensive. In this study, a recombinant antigen-binding fragment (Fab) against a broad set of O,O-diethyl organophosphorus pesticides (DOPs) was produced and characterized. The κ chain and Fd fragment were amplified via PCR and inserted into the vector pComb3XSS and the soluble Fab on phagemid pComb3XSS was induced by isopropyl β-d-thiogalactoside in E. coli TOP 10F’. SDS-PAGE, Western blotting, and indirect competitive ELISA results indicated that Fab maintained the good characteristics of the parental mAb. To better understand antibody recognition, the three-dimensional (3D) model of Fab was built via homologous modeling and the interaction between Fab and DOPs was studied via molecular docking and dynamics simulations. The model clearly explained the interaction manner of Fab and DOPs, and showed that the Arg-L96 and Arg-H52 were mainly responsible for antibody binding. This work provided a foundation for further mutagenesis of Fab to improve its characteristics.

[Clinical observation of the lead discharging effect of paiqian chewing tablet].

OBJECTIVE: To observe the effect of paiqian chewing tablet (PQCT) on lead discharging and health in children. METHODS: Adopting self-control and inter-group control method, 94 children with blood lead level exceeding 100 microg/L were randomly divided into the observed group and the control group. The observation period for both groups was 30 days. RESULTS: At the 20th and 30th day of treatment, the urinary lead output in the observed group was significantly higher than that in the control group (P < 0.05, P < 0.01), and showed significant difference as compared with that before treatment (P < 0.05). Besides, the total amount of urinary lead discharging in the observed group was significantly more than that in the control group (P < 0.05). CONCLUSION: PQCT has markedly lead discharging improvement action with no influence on urinary calcium and zinc excretion. As all the routine indexes of blood and urine ranged within the normal extent, it demonstrated that PQCT was harmless to the health of observed individual.