Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment.

Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood-brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice.

Timing selection for loosened tooth fixation based on degree of alveolar bone resorption: a finite element analysis.

OBJECTIVE: This study aimed to evaluate timing of fixation to retard bone absorption using finite element analysis(FEA). METHODS: Volunteer CT images were used to construct four models of mandibles with varying degrees of alveolar bone resorption. By simulating occlusal force loading, biomechanical analysis was made on the periodontal membrane, tooth root and surrounding bone (both cancellous and cortical) of mandibular dentition. RESULTS: The von Mises stress value of the periodontal structures was positively related with the degree of alveolar bone resorption, and the von Mises stress at the interface between the periodontal membrane and tooth root was increased significantly in moderate to severe periodontitis models. The von Mises stress at the interface between the periodontal cortical bone and cancellous bone was increased significantly in the severe periodontitis model. And the von Mises stress value with oblique loading showed significantly higher than vertical loading. CONCLUSION: Teeth with moderate to severe periodontitis, loosened tooth fixation can be used to retard bone absorption.

Influence of bone anatomical morphology of mandibular molars on dental implant based on CBCT.

BACKGROUND: To apply CBCT to investigate the anatomical relationship between the mandibular molar and alveolar bone, aimed to provide clinical guidelines for the design of implant restoration. METHODS: 201 CBCT data were reevaluated to measure height of the alveolar process (EF), width of the alveolar process (GH), width of the basal bone (IJ), the angle between the long axis of the first molar and the alveolar bone (∠a) and the angle between the long axis of the alveolar bone and basal bone (∠b). The angle and width were measured to determine the implant-prosthodontic classification of the morphology in the left lower first molar (36) and right lower first molar (46). All measurements were performed on the improved cross-sectional images. RESULTS: EF, GH and IJ were measured as (10.83 ± 1.31) mm, (13.93 ± 2.00) mm and (12.68 ± 1.96) mm for 36, respectively; and (10.87 ± 1.24) mm, (13.86 ± 1.93) mm and (12.60 ± 1.90) mm for 46, respectively. No statistical significance was observed in EF, GH, IJ, ∠a and ∠b between 36 and 46 (all P > 0.05). The morphology was divided into three categories including the straight (68.7-69.2%), oblique (19.9-20.4%) and concave types (11%). Each type was consisted of two subcategories. CONCLUSIONS: The proposed classification could provide evidence for appropriate selection and direction design of the mandibular molar implant in clinical. The concave type was the most difficult to implant with the highest risk of lingual perforation. The implant length, width, direction required more attention.

The clinical accuracy of the implant digital surgical guide: A meta-analysis.

PURPOSE: To systematically evaluate the accuracy of clinical applications of digital guides. METHODS: First, PubMed and Embase databases were searched using the PICO standard. Eligible articles were included. Second, the eligible articles were classified according to the different types. Next, the NOS and ROB2 as evaluation indicators were used to evaluate the bias of those included articles. Finally, sensitive factors were excluded through the outcomes and data analyses were retrieved. RESULTS: More than 1,562 articles were retrieved, and 38 in vivo research documents were systematically analyzed after screening according to the inclusion criteria, which mainly listed three aspects of the coronal, apical, and angular implant data, and integrated the same type of articles in the study. To test its heterogeneity, the P-values of those articles included in the analysis were all less than 0.05. Finally, in the comparison between the guide group and the free-hand group after excluding sensitive factors, the standardized mean difference (Std.MD) of the angle was 1.26 (95% CI 1.06, 1.47), the Std.MD of the apical point was 1.38 (95% CI 1.12, 1.63), and the Std.MD of the coronal point was 0.98 (95% CI 0.66, 1.29). Comparing the maxillary and mandibular groups after excluding sensitive factors, the Std.MD of the coronal point was -0.31 (95% CI -0.52, -0.09), the Std.MD of the apical point was -0.15 (95% CI -0.34, 0.03), and the Std.MD of the angle is -0.23 (95% CI -0.46, 0.01). Comparison between the smoking group and the nonsmoking group, and between the flap group and the flapless group showed that there was not enough evidence to make a reliable assessment. CLINICAL SIGNIFICANCE: Compared with free-hand operation, a digital guide is more accurate in the apex, the coronal point and the angle, and the accuracy in the angle was very high. The difference in accuracy between the maxillary and mandibular groups was not statistically significant. Other factors such as smoking habit and flap need more clinical data.

The survival rate of transcrestal sinus floor elevation combined with short implants: a systematic review and meta-analysis of observational studies.

BACKGROUND: Currently, insufficient bone volume always occurs in the posterior maxilla which makes implantation difficult. Short implants combined with transcrestal sinus floor elevation (TSFE) may be an option to address insufficient bone volume. PURPOSE: The clinical performance of short implants combined with TSFE was compared with that of conventional implants combined with TSFE according to the survival rate. METHOD: In this systematic review and meta-analysis, we followed the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Articles were identified through PubMed, Embase, the Cochrane Library, and manual searching. Eligibility criteria included clinical human studies. The quality assessment was performed according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. The odds ratio (OR) with its confidence interval (CI) was considered the essential outcome for estimating the effect of short implants combined with TSFE. RESULTS: The registration number is INPLASY202050092. Eleven studies met the inclusion criteria, including 1 cohort study and 10 cross-sectional studies. With respect to the 1-year survival rate, no significant effect was observed between short implants (length ≤ 8 mm) and conventional implants combined with TSFE (I2=0%, OR=1.04, 95% CI: 0.55-1.96). Similarly, no difference was seen between the two groups regarding the survival rate during the healing period (I2=10%, OR=0.74, 95% CI: 0.28-1.97) and 3-year loading (OR=1.76, 95% CI: 0.65-4.74). CONCLUSION: There was no evidence that the survival rate of short implants combined with TSFE was lower or higher than that of conventional implants combined with TSFE when the residual bone height was poor and the implant protrusion length of short implants was less than or similar to conventional implants. Nevertheless, the results should be interpreted cautiously due to the lack of random controlled trials in our meta-analysis.

Simultaneous ammonia and nitrate removal in an airlift reactor using poly(butylene succinate) as carbon source and biofilm carrier.

In this study, an airlift inner-loop sequencing batch reactor using poly(butylene succinate) as the biofilm carrier and carbon source was operated under an alternant aerobic/anoxic strategy for nitrogen removal in recirculating aquaculture system. The average TAN and nitrate removal rates of 47.35±15.62gNH4-Nm(-3)d(-1) and 0.64±0.14kgNO3-Nm(-3)d(-1) were achieved with no obvious nitrite accumulation (0.70±0.76mg/L) and the dissolved organic carbon in effluents was maintained at 148.38±39.06mg/L. Besides, the activities of dissimilatory nitrate reduction to ammonium and sulfate reduction activities were successfully inhibited. The proteome KEGG analysis illustrated that ammonia might be removed through heterotrophic nitrification, while the activities of nitrate and nitrite reductases were enhanced through aeration treatment. The microbial community analysis revealed that denitrifiers of Azoarcus and Simplicispira occupied the dominate abundance which accounted for the high nitrate removal performance. Overall, this study broadened our understanding of simultaneous nitrification and denitrification using biodegradable material as biofilm carrier.

Peginterferon alfa-2b in the treatment of Chinese patients with HBeAg-positive chronic hepatitis B: a randomized trial.

BACKGROUND: In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0µg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B. OBJECTIVE: This multicenter, randomized trial evaluated the safety and efficacy of regimens utilizing increased dose or treatment duration in treatment-naive Chinese patients with chronic hepatitis B. STUDY DESIGN: 670 HBeAg-positive patients from China, Malaysia, Taiwan area, Singapore, and Thailand were enrolled. Patients received PEG-IFN alfa-2b 1.0µg/kg/wk (arm A) or 1.5µg/kg/wk (arm B) for 24 weeks, or 1.5µg/kg/wk for 48 weeks (arm C). The primary end point was loss of HBeAg 24 weeks after end of treatment. RESULTS: At the end of follow-up, HBeAg loss was significantly greater in arm C compared with arm A (31.3% vs. 17.3%; P=0.001) and arm B (31.3% vs. 18.1%; P=0.001). No significant difference in the rate of HBeAg loss was observed between arms A and B. The proportions of patients with HBe seroconversion, HBV DNA levels <20,000IU/mL, and ALT normalization at the end of follow-up were significantly higher in arm C compared with arm A and arm B. In arms A, B, and C, rates of early treatment discontinuation were 6.3%, 4.9%, and 8.9%; of discontinuation due to an AE, 2%, 3%, and 3%; and of AEs requiring dose modification, 3%, 6%, and 10%, respectively. CONCLUSIONS: In Chinese patients with HBeAg-positive chronic hepatitis B, PEG-IFN alfa-2b 1.5µg/kg/wk for 48 weeks is more efficacious compared with 1.0 and 1.5µg/kg/wk for 24 weeks.