Novel 7-formyl-naphthyridyl-ureas derivatives as potential selective FGFR4 inhibitors: Design, synthesis, and biological activity studies.

Total twenty-five 7-formyl-naphthyridyl-urea derivatives were designed, synthesized and evaluated for their inhibition of FGFR4 kinase and antitumor activity. The pharmacological data indicated that most of the tested compounds showed high selectivity towards FGFR4 kinase and could significantly inhibit FGFR4 and the tumor cells lines with the high expression of FGFR4. In particular, compounds 6f, 6g, 6h, 6l, 6m and 6s showed a good performance in pharmacokinetic tests. When tested in mice, the representative compound 6f was found to have good pharmacokinetic parameters, low toxicity, and better tumor inhibiting activity in vivo.

Interleukin-18 promoter polymorphisms and plasma levels are associated with increased risk of periodontitis: a meta-analysis.

OBJECTIVE: Emerging evidence has showed that interleukin-18 (IL-8) promoter polymorphisms and plasma IL-18 levels may be associated with increased risk of periodontitis, but individually published results are inconclusive. The aim of this meta-analysis was to derive a more precise estimation of these associations. METHODS: A literature search of PubMed, Cochrane Library, Embase, Web of Science, SpringerLink, China BioMedicine and China National Knowledge Infrastructure databases was conducted on articles published before April 1st, 2013. Crude odds ratio (OR) or standardized mean difference (SMD) with 95 % confidence intervals (CI) were calculated. RESULTS: Nine case-control studies were included with a total of 576 periodontitis patients and 458 healthy controls. Two common polymorphisms (-607A > C and -137G>C) in the IL-18 gene were addressed. Our meta-analysis results indicated that the C variant of IL-18 -607A>C polymorphism was associated with increased periodontitis risk (C allele vs. A allele: OR = 1.86, 95 % CI: 1.30-2.65, P = 0.001; AC+CC vs. AA: OR = 2.64, 95 % CI: 1.34-5.21, P = 0.005). There was also a significant association between the C variant of IL-18 -137G>C polymorphism and an increased periodontitis risk (C allele vs. G allele: OR = 1.47, 95 % CI: 1.13-1.91, P = 0.004; GC+CC vs. GG: OR = 1.66, 95 % CI: 1.21-2.29, P = 0.002). Furthermore, the mean levels of plasma IL-18 of periodontitis patients were also higher than those of healthy controls (SMD = 1.18, 95 % CI: 0.51-1.85, P = 0.001). CONCLUSION: The current meta-analysis suggests that IL-18 promoter polymorphisms and plasma IL-18 levels are associated with increased risk of periodontitis. IL-18 promoter polymorphisms and elevated plasma IL-18 levels may be useful biomarkers for predicting the development of periodontitis.

96-Week Treatment of Tenofovir Amibufenamide and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients.

Background and Aims: Tenofovir amibufenamide (TMF) is a novel phosphoramidated prodrug of tenofovir with noninferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate (TDF) in 48 weeks of treatment. Here, we update 96-week comparison results. Methods: Patients with chronic hepatitis B were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks. The virological suppression was defined as HBV DNA levels <20 IU/mL at week 96. Safety was evaluated thoroughly with focusing on bone, renal, and metabolic parameters. Results: Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations. Noninferior efficacy was maintained in the pooled population, while it was first achieved in patients with HBV DNA ≥7 or 8 log10 IU/mL at baseline. Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted, while a smaller decline of which was seen in the TMF group than in the TDF group (p=0.01). For bone mineral density, patients receiving TMF displayed significantly lower reduction levels in the densities of spine, hip, and femur neck at week 96 than those receiving TDF. In addition, the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend. Conclusions: TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles (NCT03903796).

Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B.

BACKGROUND: Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF). AIM: To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). METHODS: We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. RESULTS: We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg-negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. CONCLUSION: TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).

[Evaluation of the effect of concentrated growth factor in oral rehabilitation].

PURPOSE: To investigate the clinical effect of concentrated growth factor (CGF) in oral cavity repair. METHODS: From February 2013 to February 2016 in our hospital, 60 patients with insufficient bone underwent dental implantation. CGF was used alone in 27 patients (CGF group), CGF was used with autologous bone or bone material in 33 patients (CGF mixed group). Bone repair was observed and evaluated. SPSS19.0 software package was used for statistical analysis. RESULTS: Wound healing time in CGF group and CGF mixed group (8.43±0.72) d and (8.04±0.98) d, wound healing rate was 92.60% in CGF group and 90.91% in CGF group, the difference was not statistically significant (P>0.05); Implant success rate in CGF group and CGF mixed group was 92.31% and 96.36% , respectively. The difference was not statistically significant (P>0.05). CONCLUSIONS: CGF has good effect in repair of bone defect, and the long-term effect is stable. It is a simple and safe material for bone regeneration.