Potent antitumor efficacy of human dental pulp stem cells armed with YSCH-01 oncolytic adenovirus.

BACKGROUND: Systemic administration of oncolytic adenovirus for cancer therapy is still a challenge. Mesenchymal stem cells as cell carriers have gained increasing attention in drug delivery due to their excellent tumor tropism, immunosuppressive modulatory effects, and paracrine effects. However, the potential of human dental pulp stem cells (hDPSCs) loaded with oncolytic adenovirus for cancer biotherapy has not been investigated yet. METHODS: The stemness of hDPSCs was characterized by FACS analysis and Alizarin red staining, Oil Red O staining, and immunofluorescence assays. The biological fitness of hDPSCs loaded with oncolytic adenovirus YSCH-01 was confirmed by virus infection with different dosages and cell viability CCK-8 assays. Additionally, the expression of CAR receptor in hDPSCs was detected by qPCR assay. Tumor tropism of hDPSC loaded with YSCH-01 in vitro and in vivo was investigated by Transwell assays and living tumor-bearing mice imaging technology and immunohistochemistry, Panoramic scanning of frozen section slices assay analysis. Furthermore, the antitumor efficacy was observed through the different routes of YSCH-01/hPDSCs administration in SW780 and SCC152 xenograft models. The direct tumor cell-killing effect of YSCH-01/hDPSCs in the co-culture system was studied, and the supernatant of YSCH-01/hDPSCs inhibited cell growth was further analyzed by CCK-8 assays. RESULTS: hDPSCs were found to be susceptible to infection by a novel oncolytic adenovirus named YSCH-01 and were capable of transporting this virus to tumor sites at 1000 VP/cell infectious dosage in vitro and in vivo. Moreover, it was discovered that intraperitoneal injection of hDPSCs loaded with oncolytic adenovirus YSCH-01 exhibited potential anti-tumor effects in both SW780 and SCC152 xenograft models. The crucial role played by the supernatant secretome derived from hDPSCs loaded with YSCH-01 significantly exerted a specific anti-tumor effect without toxicity for normal cells, in both an active oncolytic virus and an exogenous protein-independent manner. Furthermore, the use of hDPSCs as a cell carrier significantly reduced the required dosage of virus delivery in vivo compared to other methods. CONCLUSIONS: These findings highlight the promising clinical potential of hDPSCs as a novel cell carrier in the field of oncolytic virus-based anti-cancer therapy.

Ag nanocomposite hydrogels with immune and regenerative microenvironment regulation promote scarless healing of infected wounds.

BACKGROUND: Bacterial infection, complex wound microenvironment and persistent inflammation cause delayed wound healing and scar formation, thereby disrupting the normal function and appearance of skin tissue, which is one of the most problematic clinical issues. Although Ag NPs have a strong antibacterial effect, they tend to oxidize and form aggregates in aqueous solution, which reduces their antibacterial efficacy and increases their toxicity to tissues and organs. Current research on scar treatment is limited and mainly relies on growth factors and drugs to reduce inflammation and scar tissue formation. Therefore, there is a need to develop methods that effectively combine drug delivery, antimicrobial and anti-inflammatory agents to modulate the wound microenvironment, promote wound healing, and prevent skin scarring. RESULTS: Herein, we developed an innovative Ag nanocomposite hydrogel (Ag NCH) by incorporating Ag nanoparticles (Ag NPs) into a matrix formed by linking catechol-modified hyaluronic acid (HA-CA) with 4-arm PEG-SH. The Ag NPs serve dual functions: they act as reservoirs for releasing Ag/Ag+ at the wound site to combat bacterial infections, and they also function as cross-linkers to ensure the sustained release of basic fibroblast growth factor (bFGF). The potent antibacterial effect of the Ag NPs embedded in the hydrogel against S.aureus was validated through comprehensive in vitro and in vivo analyses. The microstructural analysis of the hydrogels and the in vitro release studies confirmed that the Ag NCH possesses smaller pore sizes and facilitates a slower, more sustained release of bFGF. When applied to acute and infected wound sites, the Ag NCH demonstrated remarkable capabilities in reshaping the immune and regenerative microenvironment. It induced a shift from M1 to M2 macrophage polarization, down-regulated the expression of pro-inflammatory factors such as IL-6 and TNF-α, and up-regulated the expression of anti-inflammatory IL-10. Furthermore, the Ag NCH played a crucial role in regulating collagen deposition and alignment, promoting the formation of mature blood vessels, and significantly enhancing tissue reconstruction and scarless wound healing processes. CONCLUSIONS: We think the designed Ag NCH can provide a promising therapeutic strategy for clinical applications in scarless wound healing and antibacterial therapy.

A Superior Two-Dimensional Phosphorus Flame Retardant: Few-Layer Black Phosphorus.

The usage of flame retardants in flammable polymers has been an effective way to protect both lives and material goods from accidental fires. Phosphorus flame retardants have the potential to be follow-on flame retardants after halogenated variants, because of their low toxicity, high efficiency and compatibility. Recently, the emerging allotrope of phosphorus, two-dimensional black phosphorus, as a flame retardant has been developed. To further understand its performance in flame-retardant efficiency among phosphorus flame retardants, in this work, we built model materials to compare the flame-retardant performances of few-layer black phosphorus, red phosphorus nanoparticles, and triphenyl phosphate as flame-retardant additives in cellulose and polyacrylonitrile. Aside from the superior flame retardancy in polyacrylonitrile, few-layer black phosphorus in cellulose showed the superior flame-retardant efficiency in self-extinguishing, ~1.8 and ~4.4 times that of red phosphorus nanoparticles and triphenyl phosphate with similar lateral size and mass load (2.5~4.8 wt%), respectively. The char layer in cellulose coated with the few-layer black phosphorus after combustion was more continuous and smoother than that with red phosphorus nanoparticles, triphenyl phosphate and blank, and the amount of residues of cellulose coated with the few-layer black phosphorus in thermogravimetric analysis were 10 wt%, 14 wt% and 14 wt% more than that with red phosphorus nanoparticles, triphenyl phosphate and blank, respectively. In addition, although exothermic reactions, the combustion enthalpy changes in the few-layer black phosphorus (-127.1 kJ mol-1) are one third of that of red phosphorus nanoparticles (-381.3 kJ mol-1). Based on a joint thermodynamic, spectroscopic, and microscopic analysis, the superior flame retardancy of the few-layer black phosphorus was attributed to superior combustion reaction suppression from the two-dimensional structure and thermal nature of the few-layer black phosphorus.

Antagonist enamel wear of tooth-supported monolithic zirconia posterior crowns in vivo: A systematic review.

STATEMENT OF PROBLEM: An assessment of the evidence for the antagonist enamel wear of tooth-supported monolithic zirconia posterior crowns is lacking. PURPOSE: The purpose of this systematic review was to identify and summarize clinical studies related to the antagonist enamel wear of tooth-supported monolithic zirconia posterior crowns. MATERIAL AND METHODS: PubMed, Embase, and Cochrane library searches were performed and complemented by manual searches from database inception to December 25, 2017, for title and abstract analysis. RESULTS: Initially, 198 articles were obtained through database searches. Twenty-one articles were selected for full-text analysis, and 5 studies met the inclusion criteria. Because of the heterogeneity in design, surface treatment, measurement methods, and wear parameters, a meta-analysis was not possible. The selected studies were analyzed regarding the antagonist natural enamel wear of zirconia, measurement methods, and surface treatment. The results of the antagonist enamel wear varied widely, which made comparing them scientifically with absolute values difficult. CONCLUSIONS: This review indicated that the antagonist enamel wear of zirconia was similar to or more than that of natural teeth but less than that of metal-ceramics. Additional properly designed, longer follow-up clinical trials with larger sample sizes are needed to evaluate the antagonist enamel wear of monolithic zirconia crowns in vivo.

Impact of platelet-rich fibrin on mandibular third molar surgery recovery: a systematic review and meta-analysis.

BACKGROUND: The present study investigated and evaluated the efficacy and safety of platelet-rich fibrin (PRF) in patients during bilateral mandibular third molars extraction by systematic review and meta-analysis. METHODS: The PubMed, Embase, and Cochrane library databases were retrieved, and the effect of PRF on the healing process of the alveolar socket after surgical extraction of the mandibular third molars was evaluated by meta-analysis. The postoperative pain, swelling, trismus, osteoblastic activity, and soft tissue healing were assessed, and the incidence of alveolar osteitis, weighted mean difference (WMD)/standard mean difference (SMD), the risk ratio (RR), and the 95% confidence interval (CI) were calculated. RESULTS: The current results showed that the local application of PRF during lower third molar extraction prevented postoperative complications. Subsequently, the pain (SMD = - 0.53, 95% CI: - 1.02--0.05, Pheterogeneity = 0.001, I2 = 75.7%) and swelling (WMD = - 0.55, 95% CI: - 1.08--0.01, Pheterogeneity = 0.573, I2 = 0) were relieved and the incidence of alveolar osteitis was reduced (RR = 0.35, 95% CI: 0.16-0.75, Pheterogeneity = 0.597, I2 = 0%). However, no significant difference was observed in trismus, osteoblastic activity, and soft tissue healing between the PRF and non-PRF groups. CONCLUSION: The current study confirms that PRF only reduces some of the postoperative complications but does not prevent all the postoperative complications. PRF significantly relieved the pain and swelling and reduced the incidence of alveolar osteitis after the extraction of an impacted lower third molar.

[Effects of GBR and Delayed Loading on Bone Ring Grafting with Simultaneous Implant Insertion: an Experimental Study on Beagle Dogs].

OBJECTIVE: To determine the effects of guided bone regeneration (GBR) and delayed loading on autogenous bone ring grafting. METHODS: Autogenous bone ring augmentation with simultaneous implant insertion was performed in the mandibular premolars region of six Beagle dogs. The Bone quality of four mandibular premolars [second premolar (P2) and fourth premolar (P4)] were detected using cone beam CT (CBCT). The P2s and P4s of bilateral mandible were extracted, with three extracting sites being randomly selected to create buccal defects and the remaining one serving as control. GBR and bone ring grafting with simultaneous implant insertion was performed on two of the three experimental sites with buccal defects 3 months later, while the other one was treated with bone ring grafting with simultaneous implant insertion. Routine implant placement was performed in the control group. Vertical bone resorption and sulcus deep around the implants were measured three months after occlusal loading with abutment. RESULTS: Three months after operations, 83.3% of bone rings grafts were successful and 100% of implants survived. Delayed healing appeared more in the dogs with GBR compared those treated with bone ring grafting with simultaneous implant insertion, resulting in an increase in vertical bone resorption. Compared with the control group, delayed loading had no effects on vertical bone resorption and the health of gingiva tissues after autogenous bone ring transplant. CONCLUSION: GBR is not a preferred procedure for bone ring grafts, which may increase the risk of delayed healing and site infections, leading to failure of implants. Healed bone ring grafts can resist loadings as normal.

The association between chronic periodontitis and vasculogenic erectile dysfunction: a systematic review and meta-analysis.

AIM: The purpose of this systematic review and meta-analysis was to explore the association between erectile dysfunction (ED) and chronic periodontitis (CP) in observational studies. MATERIALS AND METHODS: A literature search of PubMed, EMBASE and Cochrane up to and including May 22, 2015, was conducted by two independent reviewers. Statistical analysis was performed using Review Manager 5.3, and the results are expressed as odds ratios (ORs) together with 95% confidence intervals (CIs), as determined using a random effects model. Subgroup analysis was performed by age. RESULTS: Of the 250 potentially eligible articles, four studies, involving 38,111 cases and 174,807 controls, were included. Based on random effects meta-analysis, a significant association between CP and ED was identified (OR = 3.07, 95% CI: 1.87-5.05, p < 0.001). Sensitivity analysis was performed due to the presence of statistically extensive heterogeneity (I(2) = 98%). CONCLUSIONS: The results of this systematic review revealed a positive association between CP and ED; however, because the presence and extent of statistical heterogeneity limits the conclusiveness of our findings, larger and better-controlled studies of socially homogeneous populations as well as pathophysiological studies are required to confirm the relationship between CP and ED and to explore the biological mechanisms involved.

Microsurgery for root coverage: A systematic review.

OBJECTIVE: To evaluate whether microsurgery gains better result in root coverage compared to conventional surgical techniques. METHODS: A number of databases were searched to identify eligible studies from January 1992 to January 2015. THE FOLLOWING OUTCOMES WERE EVALUATED: number of sites exhibiting complete root coverage and patients' esthetic satisfaction. RESULTS: Four Randomized Clinical Trials (RCTs) fulfilled the inclusion criteria. A pooled estimate from the two RCTs regarding sub-epithelial connective tissue grafts (SCTG) showed significant achievement in complete root coverage in the microsurgical group [relative risk (RR):1.63; 95% confidence interval (CI): 1.12 to 2.36; P=0.01] with acceptable heterogeneity. The other two studies were about coronal advanced flap (CAF) with enamel matrix derivative or free rotated papilla autograft and did not qualify for meta-analysis. Patients' esthetic satisfaction was analyzed only by one study. CONCLUSIONS: Using microsurgical technique for treating gingival recessions may be effective in achieving complete root coverage for SCTG.

Reality check: the cost-effectiveness of removing body checking from youth ice hockey.

BACKGROUND/AIM: The risk of injury among Pee Wee (ages 11-12 years) ice hockey players in leagues that allow body checking is threefold greater than in leagues that do not allow body checking. We estimated the cost-effectiveness of a no body checking policy versus a policy that allows body checking in Pee Wee ice hockey. METHODS: Cost-effectiveness analysis alongside a prospective cohort study during the 2007-2008 season, including players in Quebec (n=1046), where policy did not allow body checking, and in Alberta (n=1108), where body checking was allowed. Injury incidence rates (injuries/1000 player-hours) and incidence proportions (injuries/100 players), adjusted for cluster using Poisson regression, allowed for standardised comparisons and meaningful translation to community stakeholders. Based on Alberta fee schedules, direct healthcare costs (physician visits, imaging, procedures) were adjusted for cluster using bootstrapping. We examined uncertainty in our estimates using cost-effectiveness planes. RESULTS: Associated with significantly higher injury rates, healthcare costs where policy allowed body checking were over 2.5 times higher than where policy disallowed body checking ($C473/1000 player-hours (95% CI $C358 to $C603) vs $C184/1000 player-hours (95% CI $C120 to $C257)). The difference in costs between provinces was $C289/1000 player-hours (95% CI $C153 to $C432). Projecting results onto Alberta Pee Wee players registered in the 2011-2012 season, an estimated 1273 injuries and $C213 280 in healthcare costs would be avoided during just one season with the policy change. CONCLUSION: Our study suggests that a policy disallowing body checking in Pee Wee ice hockey is cost-saving (associated with fewer injuries and lower costs) compared to a policy allowing body checking. As we did not account for long-term outcomes, our results underestimate the economic impact of these injuries.

Effects of sodium lauryl sulfate and postbiotic toothpaste on oral microecology.

The diversity and delicate balance of the oral microbiome contribute to oral health, with its disruption leading to oral and systemic diseases. Toothpaste includes elements like traditional additives such as sodium lauryl sulfate (SLS) as well as novel postbiotics derived from probiotics, which are commonly employed for maintaining oral hygiene and a healthy oral cavity. However, the response of the oral microbiota to these treatments remains poorly understood. In this study, we systematically investigated the impact of SLS, and toothpaste containing postbiotics (hereafter, postbiotic toothpaste) across three systems: biofilms, animal models, and clinical populations. SLS was found to kill bacteria in both preformed biofilms (mature biofilms) and developing biofilms (immature biofilms), and disturbed the microbial community structure by increasing the number of pathogenic bacteria. SLS also destroyed periodontal tissue, promoted alveolar bone resorption, and enhanced the extent of inflammatory response level. The postbiotic toothpaste favored bacterial homeostasis and the normal development of the two types of biofilms in vitro, and attenuated periodontitis and gingivitis in vivo via modulation of oral microecology. Importantly, the postbiotic toothpaste mitigated the adverse effects of SLS when used in combination, both in vitro and in vivo. Overall, the findings of this study describe the impact of toothpaste components on oral microflora and stress the necessity for obtaining a comprehensive understanding of oral microbial ecology by considering multiple aspects.

[Oral health and hygiene behavior in chronic renal failure patients].

PURPOSE: To investigate the oral health and hygiene behavior of chronic renal failure(CRF) patients in Shenzhen, so as to provide basis for formulating education for them. METHODS: The history of renal failure, oral health status and oral health care behavior of 336 patients with chronic renal failure(CRF) in the hemodialysis center of Shenzhen Second People's Hospital were investigated by questionnaire and oral examinations. RESULTS: At an average, dialysis was required for 3.2 years. The main cause of renal failure was glomerulonephritis in 49.11% of patients, hypertensive kidney lesion in 19.35% and diabetic nephropathy in 15.77% of patients; 77.8% of them kept brushing teeth two or more than two times every day; 72.9% patients suffered from oral problems such as toothache in recent 12 months. The rate of visiting a dentist when having complaints was 21.7%. CONCLUSIONS: The state of oral health of CRF is worse than the general population of comparable age in China, while their hygiene behavior is better than the corresponding reference general population. However, their consciousness of dental treatment is poor. Therefore, health education for CRF patients should include knowledge about oral diseases complicated with CRF and correct medical philosophy.

Spatiotemporal distribution and control measure evaluation of droplets and aerosol clouds in dental procedures.

We evaluated the distributions of dental splatters and the corresponding control measure effects with high-speed videography and laser diffraction. Most of the dental splatters were small droplets (<50 µm). High-volume evacuation combined with a suction air purifier could clear away most of the droplets and aerosols.

Subgroup detection-based dental caries status and inequalities trend exploration: A nationwide, 10-year-repeated cross-sectional study.

Background: The goal of this study was to identify potentially important factors for the dental health though heterogeneous effects of risk factors within Chinese adolescent populations with different characteristics by analyzing the repeated cross-sectional data collected in the 3rd (2005) and 4th (2015) National Oral Health Survey. Methods: We studied the relationships between the decayed, missing and filled permanent teeth (DMFT) score, which was a discrete value, with the caries risk factors (region, census type, gender, only child or not, parents' education level, tooth bushing, dentist visit history, knowledge score, sugar intake, and pit-and-fissure sealants status), though the Poisson mixture regression model, which could identify subgroups among the full population and estimate the heterogeneous effects of risk factors simultaneously. We performed a series of tests and trend analysis based on the model fitting results to explore the primary causes for the dental caries issue clearly and intuitively. Results: A total of 39,049 teenagers aged 12 years were involved in the analysis. The Poisson mixture regression model clustered all individuals into three subgroups, where the mean values (standard deviations) of DMFT were 0.18 (0.56), 1.31 (1.49), and 2.91 (1.89), respectively. Model fitting results indicated that the heterogeneous effects of the involved risk factors were significant. In addition, we also found significant differences in the distributions and trends of DMFT within different categories of selected risk factors (region, census type, gender and dentist visiting history) from the projection analysis results. The estimated and projected proportions showed that the proportion of high caries risk population in the southwestern region increased by 31.8%, and will become even more severe as it will be the major component of high caries risk population in 2025. Conclusions: We found that the trends for the developments and changes of dental caries within populations with different characteristics were inequality. The regional difference is the primary factor for diversified changes in DMFT. The findings in this study provide support for intervention and prevention policies for the deterioration of dental caries risk within different adolescent populations.

Novel multifunctional papers based on chemical modified cellulose fibers derived from waste bagasse.

Most technologies to produce multifunctional paper involved the defect of poor uniformity and stability. Herein, a high stability multi-functional cellulose-based paper was developed via a multiple chemical modification derived from waste bagasse. Firstly, the acetoacetyl groups was anchored on the surface of bagasse cellulose fibers by a heterogeneous transesterification. Then, paper was made based on these modified fibers. The fluorophore and gentamicin sulfate (Gen) were bonded in-situ to the paper through Hantzsch reaction and the form of enamine bond, respectively. The resulting paper exhibited excellent multifunctional properties, such as fluorescence property, antibacterial property and hydrophobic property. These properties are very stable to external environments. In addition, relatively mild surface modification has no obvious effect on fibers and shows similar whiteness and stiffness properties as that of the CAA paper. Thus, these novel functional papers held great potential for many fields such as food packaging, anti-counterfeiting, and other specialty papers.

Effect of microplastics on nasal and gut microbiota of high-exposure population: Protocol for an observational cross-sectional study.

Microplastics have the characteristics of small size, high specific area, strong ability to adsorb pollutants, and difficult to degrade. They have become a major global environmental problem that humans urgently need to address. A balanced microecosystem is essential to human health. Animal studies have shown that long-term exposure to microplastics can change the characteristics of the microbiota in organisms, leading to respiratory, digestive, immune, and other system diseases. However, the current research on microplastics is still dominated by animal experiments, and the impact of microplastics on human health is still in its infancy, so relevant research is urgently needed. Twenty participants with high exposure to microplastics will come from a plastic factory in Chengdu, China. We will perform 16S rDNA sequencing on participants' nasal secretions, and stool samples. Additionally, we will perform 8700 LDIR laser infrared imaging of environmental soil and air filter membrane samples. For comparison, we will also collect samples from 20 volunteers from an area with good environmental quality in Chengdu. To find out the potential predictors and to access the difference between the groups, statistical analysis will be performed in the end. The study will be the first observational cross-sectional study focusing on the effects of microplastics on nasal and gut microbiota of high-exposure population. The study is expected to provide reliable evidence to fill the gaps in the impact of microplastics on human health.

Effect of microplastics on nasal and intestinal microbiota of the high-exposure population.

Background: Microplastic has become a growing environmental problem. A balanced microbial environment is an important factor in human health. This study is the first observational cross-sectional study focusing on the effects of microplastics on the nasal and gut microbiota in a highly exposed population. Methods: We recruited 20 subjects from a Plastic Factory (microplastics high-exposure area) and the other 20 from Huanhuaxi Park (microplastics low-exposure area) in Chengdu, China. We performed the microplastic analysis of soil, air, and intestinal secretions by laser infrared imaging, and microbiological analysis of nasal and intestinal secretions by 16S rDNA sequencing. Results: The result shows that the detected points of microplastics in the environment of the high-exposure area were significantly more than in the low-exposure area. Polyurethane was the main microplastic component detected. The microplastic content of intestinal secretions in the high-exposure group was significantly higher than in the low-exposure group. Specifically, the contents of polyurethane, silicone resin, ethylene-vinyl acetate copolymer, and polyethylene in the high-exposure group were significantly higher than in the low-exposure group. Moreover, high exposure may increase the abundance of nasal microbiotas, which are positively associated with respiratory tract diseases, such as Klebsiella and Helicobacter, and reduce the abundance of those beneficial ones, such as Bacteroides. Simultaneously, it may increase the abundance of intestinal microbiotas, which are positively associated with digestive tract diseases, such as Bifidobacterium, Streptococcus, and Sphingomonas, and reduce the abundance of intestinal microbiotas, which are beneficial for health, such as Ruminococcus Torquesgroup, Dorea, Fusobacterium, and Coprococcus. A combined analysis revealed that high exposure to microplastics may not only lead to alterations in dominant intestinal and nasal microbiotas but also change the symbiotic relationship between intestinal and nasal microbiotas. Conclusion: The results innovatively revealed how microplastics can affect the intestinal and nasal microecosystems. Clinical trial registration: ChiCTR2100049480 on August 2, 2021.

A novel signal amplification strategy electrochemical immunosensor for ultra-sensitive determination of p53 protein.

In this work, we fabricated a novel sandwich-type electrochemical immunosensor for quantitative and ultra-sensitive determination of tumor suppressor protein p53 by signal amplification strategy. Conductive polymers poly (3, 4-ethylenedioxythiophene): polystyrenesulfonate (PEDOT:PSS) has significantly effect on enhancing charge transfer and markedly increases the sensitivity of electrochemical immunosensing. Gold nanoparticles (AuNPs) as high conductivity nanocarriers were also used to capture monoclonal antibodies (Ab1) due to their large specific surface areas. In addition, pH responsive zeolitic imidazolate framework (ZIF-8) was used to load the redox probe 2, 3-diaminophenazine (DAP) and the secondary antibodies (Ab2) to form a sensitive-type ZIF-8-DAP-Ab2 immunoprobe. After the sandwich-type immunoassay with the free p53 protein, with the release of probe DAP after the electrochemical signal amplificated by PEDOT:PSS and AuNPs, the ultra-sensitive and quantitative determination of p53 protein was realized with working range of 1-120 ng mL-1 and low detection limit of 0.09 ng mL-1. Besides, the fabricated electrochemical immunosensor exhibited good recovery, high sensitivity, reliability, and selectivity.

Identifying heterogeneity in the risk factors of dental caries status in Chinese adolescents using Poisson mixture regression.

OBJECTIVE: The purpose of this study was to cluster individuals into groups with different dental health characteristics and make statistical inferences on the effect differences among different groups simultaneously to identify the heterogeneity of risk factors in Chinese adolescents by analysing the data from the 4th Chinese National Oral Health Survey. METHODS: For decayed, missing and filled permanent teeth (DMFT), mean values were statistically analysed for their relationships with different categories of all involved variables. As DMFT scores only have discrete values, Poisson mixture regression was adopted to model the heterogeneity and complex patterns in the association and to detect the subgroup. The Bayesian information criterion (BIC) was used to determine the optimal number of subgroups. A series of Wald tests were used to explore the relationship between risk factors including the interaction effects and the number of DMFT. RESULTS: A total of 100 986 individuals aged 12-15 years old were analysed. The model clustered different individuals into three subgroups and built three submodels for detailed statistical inference simultaneously. The number of individuals in the three subgroups were 52 576 (52.1%), 41 969 (41.5%) and 6441 (6.4%), respectively. The mean (SD) of DMFT of the three subgroups was 0.50 (1.05), 0.99 (1.21), 5.59 (2.50). The model fitting results indicated that the effects of all risk factors on DMFT appear to be different in three subgroups. Controlling the confounding effects, our analysis implied that the regional inequality was the main contributing factor to dental caries among adolescents in Chinese mainland. CONCLUSIONS: The risk factors of dental caries exhibited heterogeneity in groups with different characteristics. The Poisson mixture regression model could cluster individuals into groups and identify the heterogeneous effects of risk factors among different groups. The findings support the need for different targeted interventions and prevention measures in groups with different dental health characteristics.

Efficacy-shaping nanomedicine by loading Calcium Peroxide into Tumor Microenvironment-responsive Nanoparticles for the Antitumor Therapy of Prostate Cancer.

Rationale: Prostate cancer has become one of the most threatening malignant tumors in men, leading to an imperative need to develop effective and safe therapies. Because of the unique metabolism of tumor cells, the tumor microenvironment (TME) exhibits distinctive properties compared with normal tissues, among which the pH difference has been utilized as an ideal antitumor strategy. Herein, we introduce a reactive oxygen species (ROS)-controlled-release nanosystem with TME-responsiveness by applying hollow mesoporous silica nanoparticles (HMSNs) as carriers loaded with calcium peroxide (CaO2) and coated with polyacrylic acid (PAA) to construct the functional material CaO2@HMSNs-PAA. The differences in pH values and exogenous ROS scavenging abilities between the tumor tissue and normal tissues and the dual pH-responsiveness from CaO2 and PAA lay a scientific foundation for the application of CaO2@HMSNs-PAA in the tumor-selective therapy for prostate cancer. Methods: The morphology and the structure of the nanosystem were characterized by the transmission electron microscope, scanning electron microscope, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, zeta potential, dynamic light scattering measurement, low-angle X-ray diffraction patterns and nitrogen adsorption/desorption isotherm. The CaO2 loading capacity and release profiles in different buffer solutions were determined by inductively coupled plasma-mass spectrometry. The in vitro intracellular uptake of CaO2@HMSNs-PAA was explored on the PC-3 prostate cancer cell line via confocal laser scanning microscopy. The CCK-8 cell proliferation assay was conducted to evaluate the cytotoxicity of CaO2@HMSNs-PAA against PC-3 cells. ROS produced by CaO2@HMSNs-PAA was observed by a fluorescence microscope. The flow cytometry was utilized to analyze the apoptosis of PC-3 cells induced by CaO2@HMSNs-PAA. The Western blot analysis was performed to detect expressions of critical mitochondria-mediated apoptosis markers in PC-3 cells after incubation with CaO2@HMSNs-PAA. The in vivo biosafety and antitumor efficacy were evaluated out on BALB/c mice and BALB/c nude mice subcutaneously transplanted with PC-3 cells, respectively. Results: Comprehensive characterizations indicated the successful synthesis of CaO2@HMSNs-PAA with significant TME-responsiveness. The experimental results demonstrated that the well-developed nanocarrier could efficiently deliver CaO2 to the tumor site and release ROS in response to the decreased pH value of TME, exerting ideal antitumor effects both in vitro and in vivo by activating the mitochondria-mediated apoptosis pathway. Simultaneously, this nanoplatform caused no detectable damage to normal tissues. Conclusions: After loading into the above nanocomposite, the free CaO2 without a significant antitumor effect can exert excellent antitumor efficacy by responsively releasing ROS under the acidic TME to induce the mitochondria-mediated apoptosis via remarkable oxidative stress and simultaneously minimize damages to normal tissues. The current study presents a new concept of "efficacy-shaping nanomedicine" for the tumor-selective treatment of prostate cancer.

The effect of the heights and thicknesses of the remaining root segments on buccal bone resorption in the socket-shield technique: An experimental study in dogs.

BACKGROUND: To date only a few studies have been done on the use of the socket-shield technique for preserving the resorption of the buccal bone in aesthetically sensitive sites. Besides, there have been no further studies on the effect of the heights and thicknesses of the remaining root segments on buccal bone resorption when using this method. PURPOSE: The aim of this study was to evaluate the effect of different heights and thicknesses of the remaining root segments on bone resorption in the socket-shield technique. MATERIALS AND METHODS: Four healthy female beagle dogs were used in this study. The third premolar (P3) and the fourth premolar (P4) on both sides of the mandible were hemisected in the buccal-lingual direction, and the clinical crown of the distal root was beheaded. In the experimental groups, the roots were worn down in the apical direction until they were located at the buccal crestal level (Group A) or 1 mm higher than that level (Group B). In the control group, the distal root segments were extracted. Then, implant placement was performed into the distal root. After 3 months of healing, the specimens were prepared for histological diagnosis. RESULTS: There was no difference between Group A and Group B when using the socket-shield technique, but the results of both groups were better than those of the control group. CONCLUSIONS: The height of the root segments has little effect on the bone absorption of alveolar bone, while the bone absorption was strongly influenced by the thickness of the root segments. More precisely, the absorption may decrease if the thickness of the root fragment increases, when the thickness of the root plate is in the 0.5-1.5 mm range.