Development of Injectable Thermosensitive Nanocomposite Hydrogel for Ratiometric Drug Delivery to Treat Drug Resistant Chondrosarcoma In Vivo.

Chondrosarcoma(CS), a prevalent primary malignant bone tumor, frequently exhibits chemotherapy resistance attributed to upregulated anti-apoptosis pathways such as the Bcl-2 family. In this manuscript, a new strategy is presented to augment chemosensitivity and mitigate systemic toxicity by harnessing a nano-enabled drug delivery hydrogel platform. The platform utilizes "PLGA-PEG-PLGA", an amphiphilic triblock copolymer combining hydrophilic polyethylene glycol (PEG) and hydrophobic polylactide glycolide (PLGA) blocks, renowned for its properties conducive to crafting a biodegradable, temperature-sensitive hydrogel. This platform is tailored to encapsulate a ratiometrically designed dual-loaded liposomes containing a first-line chemo option for CS, Doxorubicin (Dox), plus a calculated amount of small molecule inhibitor for anti-apoptotic Bcl-2 pathway, ABT-737. In vitro and in vivo evaluations demonstrate successful Bcl-2 suppression, resulting in the restoration of Dox sensitivity, evident through impeded tumor growth and amplified necrosis rates at the tumor site. This delivery system showcases remarkable thermal responsiveness, injectability, and biodegradability, all finely aligned with the clinical demands of CS treatment. Collectively, this study introduces a transformative avenue for tackling drug resistance in CS chemotherapy, offering significant clinical potential.

Clinical performance of non-surgical periodontal therapy in a large Chinese population with generalized aggressive periodontitis.

AIM: This study aimed to evaluate clinical performance of non-surgical periodontal treatment (NSPT) and its influential factors in a large Chinese population with generalized aggressive periodontitis (GAgP). MATERIAL AND METHODS: Longitudinal periodontal examination data of 1,004 GAgP patients (numbers of patients with observation periods 6 weeks~, 3 months~, 6 months~, 1 year~, 3 years~ and >5 years were 203, 310, 193, 205, 70 and 23, respectively) were extracted from a hospital-based electronic periodontal charting record system and analysed by multilevel analysis. RESULTS: Mean probing depth (PD) and attachment loss (AL) reductions at patient level were 1.17 mm and 1.07 mm, respectively. Multilevel analysis demonstrated PD reductions after maintenance were mainly influenced by frequency of supportive periodontal treatment (FSPT), gender, adjunctive systemic use of antibiotics, baseline mobility, tooth type and baseline PD and bleeding index reductions were mainly influenced by FSPT, adjunctive systemic use of antibiotics, baseline AL, baseline mobility, tooth type and baseline PD. CONCLUSION: The clinical performance of NSPT on patients with GAgP was proved in the large Chinese population. Outcomes of NSPT were mainly influenced by FSPT, adjunctive systemic use of antibiotics, baseline mobility, tooth type and baseline PD.

Restoring masticatory function in a patient with severe microstomia using rapid prototyped mesh and a custom-made hinge and swing-lock prosthesis.

This clinical report describes the use of rapid prototyped mesh in a complete swing-lock prosthesis to restore masticatory function in an edentulous patient with severe microstomia and perioral scar tissue after an industrial hot tar accident.

Effectiveness of non-surgical periodontal therapy in a large Chinese population with chronic periodontitis.

AIM: The aim of this study was to evaluate the effectiveness of non-surgical periodontal treatment (NSPT) and its influential factors in a large Chinese population with chronic periodontitis. METHODS: Periodontal examination data of 10,789 patients with at least one periodontal re-evaluation record were extracted from a hospital-based electronic periodontal charting record system. Probing depth (PD) and bleeding index (BI) reductions after NSPT and their influential factors were analysed by multilevel analysis. RESULTS: Mean PD reductions at patient level and site level were 0.62 and 0.65 mm respectively. Mean reductions of percentage of tooth with BI > 1 and BI > 2 were 14.9% and 25.21%. Multilevel analysis demonstrated that PD and BI reductions were mainly influenced by baseline PD, baseline attachment loss (AL), baseline mobility, tooth type and frequency of periodontal maintenance (FPM). Besides, PD reduction was associated with baseline BI for all sites and was associated with gender and smoking status for sites with baseline PD ≥ 5 mm. CONCLUSION: The effectiveness of NSPT on patients with chronic periodontitis was proved in a large Chinese population. Outcomes of NSPT were mainly influenced by baseline PD, baseline AL, baseline mobility, tooth type and FPM.

Perception of Non-surgical Periodontal Treatment in Individuals Receiving or Not Receiving Local Anaesthesia.

PURPOSE: Patients might refuse the offer of local anaesthesia (LA) administration prior to dental treatment. This study investigates subjective discomfort perception during non-surgical mechanical periodontal therapy delivered with or without LA. MATERIALS AND METHODS: Sixty patients with mild to moderate chronic periodontitis and prior periodontal debridement experience were randomly enrolled in nonsurgical therapy of a quadrant with or without LA administration. Patients were free to comply or not with the allocated LA arrangement. Visual analogue scales (VAS) of discomfort perception at various stages of the treatment as well as overall satisfaction were recorded. Demographic, psychosocial and periodontal parameters were recorded. RESULTS: Thirty-one patients undergoing nonsurgical periodontal therapy not receiving (LA-) and 29 participants receiving LA (LA+) were studied. Compared to LA- patients, LA+ individuals perceived less discomfort during treatment and reported less dental anxiety (p<0.05). Lower overall treatment satisfaction was associated with prior unpleasant periodontal experience (p=0.047). Overall, debridement discomfort was associated with not receiving LA, noncompliance with the pain control regimen allocated, longer treatment duration, greater gingival inflammation and a higher percentage sites with probing pocket depths≥5 mm (p<0.05). CONCLUSION: Clinicians should be aware that patients who refuse LA can experience higher dental anxiety and therefore may require various pain control strategies for comfort during nonsurgical periodontal therapy, which, if not employed, can lead to less periodontal treatment satisfaction.

[Association between FADS1 rs174537 polymorphism and serum proteins in patients with aggressive periodontitis].

OBJECTIVE: To investigate the potential association between FADS1 rs174537 polymorphism and serum proteins in patients with aggressive periodontitis, which may provide benefits for diagnosis and treatment of aggressive periodontitis. METHODS: A total of 353 patients with aggressive periodontitis (group AgP) and 125 matched controls (group HP) were recruited in the study. Genotyping of FADS1 rs174537 and serum biochemical indexes were tested at the study's start. The relationships between the levels of TP, GLB, ALB, A/G and genotyping were analyzed. RESULTS: (1) The detection rate of allele G in group AgP was higher than that in group HP(68.1% vs. 61.2%, P=0.046,OR=1.35,95% CI 1.00-1.83); the detection rate of genotype GG in group AgP was higher than in group HP(45.5% vs. 34.4%,P=0.029, OR=1.60, 95% CI 1.05-2.44). (2) In group AgP, the patients with GG genotype exhibited significantly lower TP, GLB than the patients with GT+TT genotype [(77.08 ± 7.88) g/L vs. (79.00 ± 4.66) g/L, P=0.007; (28.17 ± 7.63) g/L vs.(29.88 ± 3.49) g/L,P=0.007) and the higher A/G(1.72 ± 0.22 vs.1.67 ± 0.22, P=0.040), but there was no significant difference in ALB between the patients with GG genotype and the patients with GT+TT genotype. In group HP, there were no significant differences in TP, GLB, A/G and ALB between individuals with genotype GT+TT and with genotype GG. (3)Compared with individuals with genotype GT+TT in group HP, the AgP patients with genotype GT+TT exhibited significantly higher TP, GLB [(79.00 ± 4.66) g/L vs. (75.20 ± 4.53) g/L, P<0.01; (29.88 ± 3.49) g/L vs.(26.55 ± 2.94) g/L, P<0.01) and the lower A/G(1.67 ± 0.22 vs. 1.88 ± 0.30, P<0.01), but there was no significant difference in ALB. There were no significant differences in TP, GLB, A/G and ALB the between the AgP patients with genotype GG and the healthy subjects with the same genotype either. CONCLUSION: FADS1 rs174537 polymorphism is associated with aggressive periodontitis. The patients with genotype GG in group AgP had relatively lower TP,GLB and higher A/G. Genotype GG might be a risk indicator for aggressive periodontitis by reducing host defense capability and contributing to inflammatory response in the occurrence and development of aggressive periodontitis.

[Determination of bone metabolic marker levels in perio-implant crevicular fluid and analysis of dental implants stability by resonance frequency in the early stage of healing].

OBJECTIVE: To investigate the changes of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) level in perio-implant crevicular fluid (PICF) and to monitor the development of the stability of Straumann® tissue-level implants by resonance frequency analysis (RFA) during the early phases of healing. METHODS: A total of 35 implants (length 10 mm) were placed. PICF samples were collected with filter paper strips at baseline, 1, 2, 3, 4, 6, 8, and 12 weeks post-surgery, respectively. The OPG, RANKL levels were determined by ELISA method. At the same time points, the implant stability quotient (ISQ) values were determined with Osstell™ mentor. RESULTS: During healing, PICF-OPG levels increased significantly 2 weeks after surgery when compared with the 4(th) -, 6(th) -, 8(th) - and 12(th) -week reevaluation (P<0.05). The OPG/RANKL ratio in PICF was significantly higher (P<0.05) than that in gingival crevicular fluid at 1 week post-surgery. ISQ slightly fluctuated within the first 4 weeks after installation. Following this, the ISQ values increased steadily for all the implants and up to 12 weeks. Significant differences were noted between the mean ISQ values at the 12th-week and other observation time points. CONCLUSION: The PICF-OPG levels may be effective in monitoring the process of osseointegration. All the ISQ values indicated the stability of Straumann® implants over a 12-week healing period. RFA is a reliable and effective assistant to monitor implant stability.

[Relationship between vitamin D receptor gene polymorphisms and chronic periodontitis].

OBJECTIVE: To investigate the relationship between vitamin D receptor (VDR) gene polymorphisms and chronic periodontitis(CP). METHODS: Buccal swabs from 105 patients with mild/mode-rate CP and 85 severe CP were collected, DNA was extracted from these buccal swabs using the TIANamp Swab DNA Kit [TIANGEN Biotech (Beijing) CO.Ltd]. The VDR rs1544410 and rs731236 were genotyped by the Sequenom MassARRAY system (Shanghai Benegene Biotechnology Co. Ltd), which was based on MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) technology. The distribution of the genotypes and allele frequencies were analyzed. RESULTS: The frequencies of the rs1544410 A allele and AA+AG genotype were significantly higher in severe CP than in mild/moderate CP of all the patients and the female patients respectively (all the patients: P=0.006, 0.007; the female patients: P=0.001, 0.001). The frequencies of the rs731236 C allele and CC+CT genotype were significantly higher in severe CP than in mild/moderate CP of all the patients and the female patients respectively (all the patients: P=0.003, 0.004; the female patients: P<0.001, <0.001). CONCLUSION: Gene polymorphisms of VDR rs731236 and rs1544410 may be associated with severe CP in Chinese Han population.

[Clinical and putative periodontal pathogens' features of different sites with probing depth reduction after non-surgical periodontal treatment of patients with aggressive periodontitis].

OBJECTIVE: To evaluate the differences of clinical parameters and putative periodontal pathogens in sites of different probing depth (PD) reduction after non-surgical periodontal treatment in patients with aggressive periodontitis (AgP). METHODS: Clinical examinations including plaque index, probing depth (PD), attachment level (AL) and bleeding index (BI), and full-mouth periapical photographs were collected from 20 patients with AgP. All the patients received non-surgical periodontal treatment, including oral hygiene instruction, supra-gingival scaling, subgingival scaling and root planing (SRP) and were followed up for 6 months post-therapy. Gingival crevicular fluids (GCF) were collected at 1 site in each quadrant before and at the end of 6 months post-therapy. Six kinds of putative periodontal pathogens and 6 kinds of short chain fatty acids (SCFAs) were detected in the GCF samples. RESULTS: The baseline clinical parameters of PD, AL and BI, the baseline concentration of succinic acid, acetic acid, propionic acid and butyric acid, and the prevalence of Treponema denticola were significantly higher in sites with PD reduction more than 2 mm sites compared with PD reduction no more than 2 mm sites [(7.7 ± 1.2) mm vs. (5.1 ± 1.8) mm, (6.3 ± 1.9) mm vs. (4.5 ± 2.2) mm, 3.8 ± 0.4 vs. 3.3 ± 0.8, 1.66 mmol/L vs. 1.10 mmol/L, 31.67 mmol/L vs.17.78 mmol/L, 3.31 mmol/L vs.1.95 mmol/L, 84.6% vs. 56.1%, P<0.05]. However, there were no significant differences in the clinical parameters, the 6 kinds of putative periodontal pathogen detection and SCFAs concentration between the 2 groups at the end of 6 months post-treatment. In sites with PD>5 mm at the end of 6 months post-therapy, all were found with red complex bacteria infection. CONCLUSION: The baseline clinical parameters are important factors in predicting PD reduction after non-surgical periodontal treatment in patients with AgP. In sites with deep pockets after non-surgical periodontal treatment, the active control of red complex bacteria is recommended.

[Analysis of serum IgG titers to Aggregatibacter actinomycetemcomitans serotype c in aggressive periodontitis patients].

OBJECTIVE: To analyze the serum IgG titers to Aggregatibacter actinomycetemcomitans(Aa) and associated factors in patients with aggressive periodontitis (AgP). METHODS: Venous blood samples were collected from 62 AgP patients and 45 periodontal healthy controls, unstimulated whole saliva and pooled subgingival plaque samples of AgP patients were also collected for the detection of Aa (PCR method). Serum IgG titers to Aa serotype c were measured by enzyme-linked immunosorbnent assay (ELISA). RESULTS: The detection rates of serum IgG to Aa serotype c in the AgP patients and the healthy controls were both 100%. The AgP patients exhibited significantly higher IgG titers to Aa serotype c than the healthy controls (11.1±1.9 vs. 9.1±1.8, P<0.01). There was no significant difference in serum IgG levels to Aa serotype c and in the prevalence of high-responding patients to Aa serotype c between the incisor-first molar type AgP patients and generalized AgP patients. Serum IgG titers to Aa serotype c in the Aa-positive AgP patients (the patients who were Aa-positive in subgingival plaque or saliva) were significantly higher than those of the Aa-negative patients (11.9±1.3 vs. 10.7±2.1, P<0.05). CONCLUSION: Serotype c was the main serotype of Aa in Chinese patients with AgP. Serum IgG responses in generalized AgP patients were comparable to those in incisor-first molar type AgP patients.

[Clinical effect of different sequences of debridement-antibiotic therapy in treatment of severe chronic periodontitis].

OBJECTIVE: To evaluate the feasibility of full-mouth debridement (subgingival scaling and root planning, SRP) by 2 times within 1 week and compare the clinical effects of different sequences of debridement-antibiotic usage in patients with severe chronic periodontitis (CP). METHODS: A double-blinded, placebo-controlled, randomized clinical trial was conducted in 30 severe CP patients (14 males and 16 females, 40.5 ± 8.4 years old on average from 35 to 60) receiving 3 different sequences of debridement-antibiotictherapy: Group A, antibiotic usage (metronidazole, MTZ, 0.2 g, tid, 7 d; amoxicillin, AMX 0.5 g, tid, 7 d) was started together with SRP (completed by 2 times in 7 d); Group B, antibiotic usage (MTZ 0.2 g, tid, 7 d; AMX 0.5 g, tid, 7 d) was started 1 d after SRP(completed by 2 times in 7 d); Group C, SRP alone[probing depth (PD), bleeding index (BI) and tooth mobility] was examined. The average full-mouth probing depth, the average full-mouth proximal probing depth (pPD), the percentage of sites with PD>5 mm (PD>5 mm%), the percentage of sites with proximal PD>5 mm (pPD>5 mm%), the average bleeding index (BI) and the percentage of sites with bleeding on probing (BOP%) were calculated. Clinical examinations were performed at baseline and 2 months post therapy. RESULTS: (1) Compared with baseline conditions, all the subjects showed clinical improvements in all the parameters evaluated 2 months post therapy, P<0.05. (2) Significant difference were observed in the average PD changes between Group A [(2.15 ± 0.42) mm], Group B [(1.76 ± 0.29) mm] and Group C [(1.57 ± 0.33) mm], P<0.05. No significant difference was observed in the average PD changes between Group B and Group C, P=0.354. Significant differences were observed in the average pPD changes between Group A [(2.45 ± 0.43)mm] and Group C[(1.90 ± 0.48) mm], P<0.05. No significant difference was observed in BI and BOP% changes between Group A,Group B and Group C. CONCLUSION: For patients with severe chronic periodontitis, it is safe and feasible to receive full-mouth SRP by 2 times within 1 week. The short-term (2 months) advantages in PD changes are observed in patients receiving SRP and antibiotic usage at the same time comparing with patients using antibiotics after SRP or SRP alone.

The emerging nexus of active DNA demethylation and mitochondrial oxidative metabolism in post-mitotic neurons.

The variable patterns of DNA methylation in mammals have been linked to a number of physiological processes, including normal embryonic development and disease pathogenesis. Active removal of DNA methylation, which potentially regulates neuronal gene expression both globally and gene specifically, has been recently implicated in neuronal plasticity, learning and memory processes. Model pathways of active DNA demethylation involve ten-eleven translocation (TET) methylcytosine dioxygenases that are dependent on oxidative metabolites. In addition, reactive oxygen species (ROS) and oxidizing agents generate oxidative modifications of DNA bases that can be removed by base excision repair proteins. These potentially link the two processes of active DNA demethylation and mitochondrial oxidative metabolism in post-mitotic neurons. We review the current biochemical understanding of the DNA demethylation process and discuss its potential interaction with oxidative metabolism. We then summarise the emerging roles of both processes and their interaction in neural plasticity and memory formation and the pathophysiology of neurodegeneration. Finally, possible therapeutic approaches for neurodegenerative diseases are proposed, including reprogramming therapy by global DNA demethylation and mitohormesis therapy for locus-specific DNA demethylation in post-mitotic neurons.

Synergistic Chemoimmunotherapy Augmentation via Sequential Nanocomposite Hydrogel-Mediated Reprogramming of Cancer-Associated Fibroblasts in Osteosarcoma.

In osteosarcoma, immunotherapy often faces hurdles posed by cancer-associated fibroblasts (CAFs) that secrete dense extracellular matrix components and cytokines. Directly removing CAFs may prove ineffective and even promote tumor metastasis. To address this challenge, a sequential nanocomposite hydrogel that reshapes CAF behavior is developed, enhancing tumor-infiltrating T-cells in osteosarcoma. The approach utilizes an injectable blend of carboxymethyl chitosan and tetrabasic polyethylene glycol, forming a hydrogel for controlled release of a potent CAF suppressor (Nox4 inhibitor, Nox4i) and liposomal Doxorubicin (L-Dox) to induce immunogenic cell death (ICD) upon in situ administration. Nox4i effectively counters CAF activation, overcoming T-cell exclusion mechanisms, followed by programmed L-Dox release for ICD induction in stroma-rich osteosarcoma models. Combining the co-delivery gel with αPD-1 checkpoint inhibitor further enhances its effectiveness in an orthotopic osteosarcoma model. Immunophenotyping data underscore a significant boost in tumor T-cell infiltration and favorable anti-tumor immunity at the whole-animal level.

Pluronic F108 coating decreases the lung fibrosis potential of multiwall carbon nanotubes by reducing lysosomal injury.

We compared the use of bovine serum albumin (BSA) and pluronic F108 (PF108) as dispersants for multiwalled carbon nanotubes (MWCNTs) in terms of tube stability as well as profibrogenic effects in vitro and in vivo. While BSA-dispersed tubes were a potent inducer of pulmonary fibrosis, PF108 coating protected the tubes from damaging the lysosomal membrane and initiating a sequence of cooperative cellular events that play a role in the pathogenesis of pulmonary fibrosis. Our results suggest that PF108 coating could serve as a safer design approach for MWCNTs.

[Relationship between volatile fatty acids and Porphyromonas gingivalis and Treponema denticola in gingival crevicular fluids of patients with aggressive periodontitis].

OBJECTIVE: Short chain fatty acids (SCFAs), such as succinic acid, acetic acid, propionic acid, butyric acid, etc. are metabolic product of putative periodontal pathogens, which play significant roles in periodontitis. The aim of this study was to analyze the relationship between Porphyromonas gingivalis (P. gingivalis), Treponema denticola (T. denticola), and the concentration of SCFAs in gingival crevicular fluid (GCF) of patients with aggressive periodontitis (AgP). METHODS: GCF was sampled from 4 sites per individual in 20 patients with AgP and 14 healthy controls. Concentrations of SCFAs, including succinic acid, acetic acid, propionic acid, butyric acid, and isovaleric acid in the supernant of GCF were analyzed by high performance capillary electrophoresis (HPCE), P. gingivalis and T. denticola in the deposit of the same GCF were detected by PCR with their electrophoretic band quantified. RESULTS: The concentrations of succinic acid, acetic acid, propionic acid, butyric acid, and isovaleric acid, the prevalence and PCR band quantity of P. gingivalis and T. denticola in GCF were all significantly higher in patients with AgP than that of healthy controls. In patients with AgP, butyric acid concentration was significantly higher in P. gingivalis positive sites than negative sites [2.87 (0.99, 4.36) mmol/L vs. 0.33 (0.00, 1.44) mmol/L, P<0.05], the concentrations of succinic acid, acetic acid, propionic acid, butyric acid, and isovaleric acid were positively correlated with PCR band quantity of P. gingivalis (r value was 0.334, 0.548, 0.411, 0.493, 0.273, respectively, P<0.05); the concentrations of SCFAs were significantly higher in T. denticola positive sites than negative sites: succinic acid, 1.67 (1.15, 2.11) mmol/L vs. 0.80 (0.48, 1.06) mmol/L; acetic acid, 31.95 (23.77, 43.13) mmol/L vs.12.51 (7.57, 15.69) mmol/L; propionic acid, 11.86 (6.55, 14.98) mmol/L vs. 2.82 (1.71, 7.03) mmol/L; butyric acid, 3.45 (2.41, 4.78) mmol/L vs. 0.54 (0.00, 1.56) mmol/L; isovaleric acid, 2.23 (1.05, 3.85) mmol/L vs. 0.62 (0.00, 2.33) mmol/L. The concentrations of succinic acid, acetic acid, propionic acid, butyric acid were positively correlated with PCR band quantity of T. denticola (r value was 0.443, 0.702, 0.625, 0.557, respectively, P<0.05). CONCLUSION: SCFAs concentrations reflect the quantity of P. gingivalis and T. denticola in patients with AgP, and may be an indicator to the disease progression in patients with AgP.

[Effect of periodontal therapy on metabolic control and serum biochemical markers in subjects with type 2 diabetes and chronic periodontitis].

OBJECTIVE: To investigate the effect of periodontal therapy on periodontal clinical index, metabolic control and serum biochemical markers in subjects with type 2 diabetes and chronic periodontitis comprehensively. METHODS: Forty patients with type 2 diabetes and chronic periodontitis were enrolled, and periodontal clinical parameters, HbA1c, fasting blood glucose (FBG) and serum biochemical markers were tested at baseline and 3 months after initial periodontal therapy. RESULTS: The periodontal clinical parameters (PLI, BI,PD,CAL and BOP) improved significantly 3 months after initial periodontal therapy (P<0.001). The HbA1c also decreased statistically (P=0.014), while there was no change in venous fasting blood glucose. Other serum biochemical markers changed significantly including serum phosphor increased, calcium-phosphorus ratio decreased, triglyceride decreased, Apo A1 increased, lipoprotein a decreased, and serum total bilirubin increased. CONCLUSION: The initial periodontal therapy can significantly improve periodontal clinical parameters and HbA1c control, but the effect on venous fasting blood glucose was not revealed yet. In addition, initial periodontal therapy can also intervene serum phosphorus,calcium-phosphorus ratio, and the metabolism of lipid.

[Predictive model for post-treatment tooth loss of patients with aggressive periodontitis].

OBJECTIVE: To establish a predictive model for long-term tooth loss of patients with aggressive periodontitis (AgP) after periodontal treatment. METHODS: Patients diagnosed as AgP in Department of Periodontology, Peking University School and Hospital of Stomatology, who were re-evaluated 3 to 11 years after periodontal treatment were enrolled (n=85). Logistic regression was performed to select background, periodontal and radiographic factors which were related to long-term post-treatment tooth loss. A predictive model was built and analyzed by receiver operator characteristic (ROC) curve. RESULTS: After periodontal treatment, 55 teeth from 22 patients lost further. High prevalence of baseline bone loss, root abnormality, and residual severe bleeding sites, as well as poor compliance to maintenance were detected as risk factors in the predictive model. ROC analysis found the sensitivity and specificity of the model could reach up to 80% simultaneously. CONCLUSION: Predictive model for post-treatment tooth loss of patients with AgP is an important adjunct in clinical practice.

Comparison of the inflammatory states of serum and gingival crevicular fluid in periodontitis patients with or without type 2 diabetes mellitus.

Background/purpose:There is a two-way relationship between periodontitis and type 2 diabetes mellitus. This study aimed to compare the inflammatory states in serum and gingival crevicular fluid (GCF) in periodontitis patients with or without type 2 diabetes mellitus (T2DM) and healthy subjects. Materials and methods: 20 subjects were systematic and periodontal healthy (H group), 40 subjects were with periodontitis (CP group), and other 40 were with periodontitis and type 2 diabetes mellitus (DC group). Fasting blood glucose (FBG) and HbA1c was tested. GCF and serum level of interleukin (IL) -17, visfatin, receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL)/osteoprotegerin (OPG) ratio were measured. Results: The GCF volume, total amount of IL-17, vastatin, RANKL/OPG ratio in GCF and their concentrations in serum were higher (P < 0.05) in CP and DC groups than in H group, which were also higher (P < 0.05) in DC group than in CP group except for visfatin in GCF and IL-17 in serum. At sample sites of PD ≤ 3 mm, GCF volume, IL-17, visfatin and RANKL/OPG ratio in DC and CP groups were higher (P < 0.05) than that in H group, which were also higher in DC group than in CP group either with PD ≤ 3 mm or PD > 3 mm. Inflammatory state in GCF was positively correlated to systemic inflammation, and both of them were positively correlated to FBG. Conclusion: Moderate and severe periodontitis aggravated systemic inflammation. T2DM together with periodontitis resulted in more severe systemic inflammation. The positive correlation between the periodontal and systemic inflammation and their association with FBG indicated an inflammatory link between periodontitis and T2DM.

Targeted intracellular delivery of antituberculosis drugs to Mycobacterium tuberculosis-infected macrophages via functionalized mesoporous silica nanoparticles.

Delivery of antituberculosis drugs by nanoparticles offers potential advantages over free drug, including the potential to target specifically the tissues and cells that are infected by Mycobacterium tuberculosis, thereby simultaneously increasing therapeutic efficacy and decreasing systemic toxicity, and the capacity for prolonged release of drug, thereby allowing less-frequent dosing. We have employed mesoporous silica nanoparticle (MSNP) drug delivery systems either equipped with a polyethyleneimine (PEI) coating to release rifampin or equipped with cyclodextrin-based pH-operated valves that open only at acidic pH to release isoniazid (INH) into M. tuberculosis-infected macrophages. The MSNP are internalized efficiently by human macrophages, traffic to acidified endosomes, and release high concentrations of antituberculosis drugs intracellularly. PEI-coated MSNP show much greater loading of rifampin than uncoated MSNP and much greater efficacy against M. tuberculosis-infected macrophages. MSNP were devoid of cytotoxicity at the particle doses employed for drug delivery. Similarly, we have demonstrated that the isoniazid delivered by MSNP equipped with pH-operated nanovalves kill M. tuberculosis within macrophages significantly more effectively than an equivalent amount of free drug. These data demonstrate that MSNP provide a versatile platform that can be functionalized to optimize the loading and intracellular release of specific drugs for the treatment of tuberculosis.

[Clinical evaluation of periodontal intrabony defects treated with a reconstituted bovine porous bone mineral containing bone morphogenetic proteins].

OBJECTIVE: To compare the outcomes of bovine porous bone mineral (BPBM) containing bone morphogenetic proteins (BMP) and BPBM alone in periodontal intra-bony defects. METHODS: In the study, 22 intrabony defects of 9 patients with periodontitis were recruited. All the patients had at least one pair of intrabony defects of ≥3 mm. The split-mouth and single blind methods were used. The defects were randomly assigned to BPBM containing BMP (test) or BPBM alone (control). After debridement, the intrabony defects were treated by bone graft. Assessments at baseline and after 6 months included plaque index, attachment level, probing pocket depth, bleeding indexes on probing and gingival recession. The early wound-healing, adverse effects and patients' perceptions were also recorded. RESULTS: The gain in clinical attachment was (3.0±1.2) mm in the test group and (3.2±1.1) mm in the control group. The pocket reduction was (3.4±1.5) mm in the test group and (2.8±1.0) mm in the control group. The reduction of bleeding index was 1.9±1.3 in the test group and 2.3±0.8 in the control group. There was no statistical difference between the test group and control group (P>0.05). CONCLUSION: Both treatment modalities led to similar significant clinical improvements.