Deep learning for classifying the stages of periodontitis on dental images: a systematic review and meta-analysis.

BACKGROUND: The development of deep learning (DL) algorithms for use in dentistry is an emerging trend. Periodontitis is one of the most prevalent oral diseases, which has a notable impact on the life quality of patients. Therefore, it is crucial to classify periodontitis accurately and efficiently. This systematic review aimed to identify the application of DL for the classification of periodontitis and assess the accuracy of this approach. METHODS: A literature search up to November 2023 was implemented through EMBASE, PubMed, Web of Science, Scopus, and Google Scholar databases. Inclusion and exclusion criteria were used to screen eligible studies, and the quality of the studies was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. Random-effects inverse-variance model was used to perform the meta-analysis of a diagnostic test, with which pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) were calculated, and a summary receiver operating characteristic (SROC) plot was constructed. RESULTS: Thirteen studies were included in the meta-analysis. After excluding an outlier, the pooled sensitivity, specificity, positive LR, negative LR and DOR were 0.88 (95%CI 0.82-0.92), 0.82 (95%CI 0.72-0.89), 4.9 (95%CI 3.2-7.5), 0.15 (95%CI 0.10-0.22) and 33 (95%CI 19-59), respectively. The area under the SROC was 0.92 (95%CI 0.89-0.94). CONCLUSIONS: The accuracy of DL-based classification of periodontitis is high, and this approach could be employed in the future to reduce the workload of dental professionals and enhance the consistency of classification.

A20 Orchestrates Inflammatory Response in the Oral Mucosa through Restraining NF-κB Activity.

Deregulated immune response to a dysbiotic resident microflora within the oral cavity leads to chronic periodontal disease, local tissue destruction, and various systemic complications. To preserve tissue homeostasis, inflammatory signaling pathways involved in the progression of periodontitis must be tightly regulated. A20 (TNFAIP3), a ubiquitin-editing enzyme, has emerged as one of the key regulators of inflammation. Yet, the function of A20 in the oral mucosa and the biological pathways in which A20 mitigates periodontal inflammation remain elusive. Using a combination of in vivo and ex vivo disease models, we report in this study that A20 regulates inflammatory responses to a keystone oral bacterium, Porphyromonas gingivalis, and restrains periodontal inflammation through its effect on NF-κB signaling and cytokine production. Depletion of A20 using gene editing in human macrophage-like cells (THP-1) significantly increased cytokine secretion, whereas A20 overexpression using lentivirus infection dampened the cytokine production following bacterial challenge through modulating NF-κB activity. Similar to human cells, bone marrow-derived macrophages from A20-deficient mice infected with P. gingivalis displayed increased NF-κB activity and cytokine production compared with the cells isolated from A20-competent mice. Subsequent experiments using a murine ligature-induced periodontitis model showed that even a partial loss of A20 promotes an increased inflammatory phenotype and more severe bone loss, further verifying the critical function of A20 in the oral mucosa. Collectively, to our knowledge, these findings reveal the first systematic evidence of a physiological role for A20 in the maintenance of oral tissue homeostasis as a negative regulator of inflammation.

An integrated microfludic device for culturing and screening of Giardia lamblia.

In vitro culturing of trophozoites was important for research of Giardia lamblia (G. lamblia), especially in discovery of anti-Giardia agents. The current culture methods mainly suffer from lab-intension or the obstacle in standardizing the gas condition. Thus, it could benefit from a more streamlined and integrated approach. Microfluidics offers a way to accomplish this goal. Here we presented an integrated microfluidic device for culturing and screening of G. lamblia. The device consisted of a polydimethylsiloxane (PDMS) microchip with an aerobic culture system. In the microchip, the functionality of integrated concentration gradient generator (CGG) with micro-scale cell culture enables dose-response experiment to be performed in a simple and reagent-saving way. The diffusion-based culture chambers allowed growing G. lamblia at the in vivo like environment. It notable that the highly air permeable material of parallel chambers maintain uniform anaerobic environment in different chambers easily. Using this device, G. lamblia were successfully cultured and stressed on-chip. In all cases, a dose-related inhibitory response was detected. The application of this device for these purposes represents the first step in developing a completely integrated microfluidic platform for high-throughput screening and might be expanded to other assays based on in vitro culture of G. lamblia with further tests.

Clinical application of robots in dentistry: A scoping review.

PURPOSE: The surge in digitalization and artificial intelligence has led to the wide application of robots in various fields, but their application in dentistry started relatively late. This scoping review aimed to comprehensively explore and map the current status of the clinical application of robots in dentistry. STUDY SELECTION: An iterative approach was used to gather as much evidence as possible from four online databases, including PubMed, the China National Knowledge Infrastructure, the Japan Science and Technology Information Aggregator, Electronic, and the Institute of Electrical and Electronics Engineers, from January 1980 to December 2022. RESULTS: A total of 113 eligible articles were selected from the search results, and it was found that most of the robots were developed and applied in the United States (n = 56; 50%). Robots were clinically applied in oral and maxillofacial surgery, oral implantology, prosthodontics, orthodontics, endodontics, and oral medicine. The development of robots in oral and maxillofacial surgery and oral implantology is relatively fast and comprehensive. About 51% (n = 58) of the systems had reached clinical application, while 49% (n = 55) were at the pre-clinical stage. Most of these are hard robots (90%; n = 103), and their invention and development were mainly focused on university research groups with long research periods and diverse components. CONCLUSIONS: There are still limitations and gaps between research and application in dental robots. While robotics is threatening to replace clinical decision-making, combining it with dentistry to gain maximum benefit remains a challenge for the future.

Cell-Membrane Coated Self-Immolative Poly(thiourethane) for Cysteine/Homocysteine-Triggered Intracellular H2S Delivery.

Hydrogen sulfide (H2S) is an important gaseous signaling molecule with unique pleiotropic pharmacological effects, but may be limited for clinical translation due to the lack of a reliable delivery form that delivers exogenous H2S to cells at action site with precisely controlled dosage. Herein, we report the design of a poly(thiourethane) (PTU) self-immolative polymer terminally caged with an acrylate moiety to trigger release of H2S in response to cysteine (Cys) and homocysteine (Hcy), the most used and independent indicators of neurodegenerative diseases. The synthesized PTU polymer was then coated with the red-blood-cell (RBC) membrane in the presence of solubilizing agent to self-assemble into nanoparticles with enhanced stability and cytocompatibility. The Hcy/Cys mediated addition/cyclization chemistry actuated the biomimetic polymeric nanoparticles to disintegrate into carbonyl sulfide (COS), and finally convert into H2S via the ubiquitous carbonic anhydrase (CA). H2S released in a controlled manner exhibited a strong antioxidant ability to resist Alzheimer's disease (AD)-related oxidative stress factors in BV-2 cells, a neurodegenerative disease model in vitro. Thus, this work may provide an effective strategy to construct H2S donors that can degrade in response to a specific pathological microenvironment for the treatment of neurodegenerative diseases.

Quercetin Preserves Oral Cavity Health by Mitigating Inflammation and Microbial Dysbiosis.

Failure to attenuate inflammation coupled with consequent microbiota changes drives the development of bone-destructive periodontitis. Quercetin, a plant-derived polyphenolic flavonoid, has been linked with health benefits in both humans and animals. Using a systematic approach, we investigated the effect of orally delivered Quercetin on host inflammatory response, oral microbial composition and periodontal disease phenotype. In vivo, quercetin supplementation diminished gingival cytokine expression, inflammatory cell infiltrate and alveolar bone loss. Microbiome analyses revealed a healthier oral microbial composition in Quercetin-treated versus vehicle-treated group characterized by reduction in the number of pathogenic species including Enterococcus, Neisseria and Pseudomonas and increase in the number of non-pathogenic Streptococcus sp. and bacterial diversity. In vitro, Quercetin diminished inflammatory cytokine production through modulating NF-κB:A20 axis in human macrophages following challenge with oral bacteria and TLR agonists. Collectively, our findings reveal that Quercetin supplement instigates a balanced periodontal tissue homeostasis through limiting inflammation and fostering an oral cavity microenvironment conducive of symbiotic microbiota associated with health. This proof of concept study provides key evidence for translational studies to improve overall health.

An Efficient Carbon-Based Drug Delivery System for Cancer Therapy through the Nucleus Targeting and Mitochondria Mediated Apoptotic Pathway.

The emergence of nanocarriers solves the problems of antitumor drugs such as non-targeting, huge side effects, etc., and has been widely used in tumor therapy. Some kinds of antitumor drugs such as doxorubicin (DOX) mainly act on the nucleic acid causing DNA damage, interfering with transcription, and thereby disrupting or blocking the process of cancer cell replication. Herein, a new nanodrug delivery system, the carbon-based nanomaterials (CBNs)-Pluronic F127-DOX (CPD), is designed by using CBNs as a nanocarrier for DOX. As a result, the tumor growth inhibition rate of CPD group is as high as 79.42 ± 2.83%, and greatly reduces the side effects. The targeting rate of the CPD group of DOX in the tumor nucleus is 36.78%, and the %ID/g in tumor tissue is 30.09%. The CPD regulates the expression levels of Caspase-3, p53, and Bcl-2 genes by increasing intracellular reactive oxygen species (ROS) levels and reducing mitochondrial membrane potential, which indicates that mitochondrial-mediated pathways are involved in apoptosis. The CPD nanodrug delivery system increases the effective accumulation of DOX in tumor cell nuclei and tumor tissues, and generates massive ROS, thereby inhibiting tumor growth in vivo, representing a promising agent for anticancer applications.

A20 Restricts Inflammatory Response and Desensitizes Gingival Keratinocytes to Apoptosis.

The pathophysiology of periodontal disease involves a perturbed immune system to a dysbiotic microflora leading to unrestrained inflammation, collateral tissue damage, and various systemic complications. Gingival epithelial cells function as an important part of immunity to restrict microbial invasion and orchestrate the subsequent innate responses. A20 (TNFAIP3), an ubiquitin-editing enzyme, is one of the key regulators of inflammation and cell death in numerous tissues including gastrointestinal tract, skin, and lungs. Emerging evidence indicates A20 as an essential molecule in the oral mucosa as well. In this study, we characterized the role of A20 in human telomerase immortalized gingival keratinocytes (TIGKs) through loss and gain of function assays in preclinical models of periodontitis. Depletion of A20 through gene editing in TIGKs significantly increased IL-6 and IL-8 secretion in response to Porphyromonas gingivalis infection while A20 over-expression dampened the cytokine production compared to A20 competent cells through modulating NF-κB signaling pathway. In the subsequent experiments which assessed apoptosis, A20 depleted TIGKs displayed increased levels of cleaved caspase 3 and DNA fragmentation following P. gingivalis infection and TNF/CHX challenge compared to A20 competent cells. Consistently, there was reduced apoptosis in the cells overexpressing A20 compared to the control cells expressing GFP further substantiating the role of A20 in regulating gingival epithelial cell fate in response to exogenous insult. Collectively, our findings reveal first systematic evidence and demonstrate that A20 acts as a regulator of inflammatory response in gingival keratinocytes through its effect on NF-κB signaling and desensitizes cells to bacteria and cytokine induced apoptosis in the oral mucosa. As altered A20 levels can have profound effect on different cellular responses, future studies will determine whether A20-targeted therapies can be exploited to restrain periodontal inflammation and maintain oral mucosa tissue homeostasis.

[Diabetic constipation treated with acupoint embedding therapy and forlax: a randomized controlled trial].

OBJECTIVE: To compare the difference among the combined method of oral administration of forlaxand acupoint embedding therapy, the simple acupoint embedding therapy and the simple oral administration of for-lax in the clinical efficacy on diabetic constipation. METHODS: One hundred and fifty patients were randomized intoa comprehensive group, an acupoint embedding group and a forlax group, 50 cases in each one. In the acupointembedding group, the embedding therapy was applied to bilateral Tianshu (ST 25), Daheng (SP 15), Shangjuxu(ST 37) and Dachangshu (BL 25), once a week. In the forlax group, forlax (polyethylene glycol) was prescribedfor oral administration, once a day, 10 g each time. In the comprehensive group, the acupoint embedding therapyand forlax were combined and the methods were the same as the first two groups. The treatment for 4 weeks wasas one session, and 2 sessions were required in the three groups. Separately, in 4 weeks, 8 weeks of treatment and2 months after treatment, the constipation symptom scores were compared among the three groups. At the end of2 sessions of treatment, the clinical efficacy and adverse reactions were compared among the three groups. In2 months after treatment, the recurrence rate was compared among the three groups. RESULTS: The total effectiverate was 98. 0% (49/50) in the comprehensive group, better than 86. 0% (43/50) in the acupoint embeddinggroup and 78. 0% (11/50) in the forlax group (both P<0. 01). In the 4 weeks and 8 weeks of treatment, the con-stipation symptom scores were reduced significantly as compared with those before treatment in the three groups(all P<0. 05). The results in the comprehensive group were lower than those in the other two groups (all P<0. 05). In the 4 weeks of treatment, the scores were not different significantly between the acupoint embedding group and the forlax group (P>0.05). In 8 weeks of treatment and 2 months after treatment, the scores in the acupoint embedding group were better tan those in the forlax group (all p<0.05). There were 2 cases of drug adverse reaction in the comprehensive group, 6 cases in the forlax group and 0 case in the acupoint embedding group. The recurrence rate was 8.1% (4/49) in the comprehensive group, lower than 32.6% (14/43) in the acupoint embedding group and 59.0% (23/39) in the forlax group (both P<0.01). CONCLUSION: the combined therapy of acupoint embedding and forlax achieves the better clinical efficacy on diabetic constipation and constipation symptom scores as compared with the simple acupoint embedding therapy and the oral administration of forlax the short-term efficacy of the simple acupoint embedding therapy is not different significantly from the simple forlax medication, but the long-term efficacy and safety are better than those of simple forlax medicaiton.

Stable aerobic granules in continuous-flow bioreactor with self-forming dynamic membrane.

A novel continuous-flow bioreactor with aerobic granular sludge and self-forming dynamic membrane (CGSFDMBR) was developed for efficient wastewater treatment. Under continuous-flow operation, aerobic granular sludge was successfully cultivated and characterized with small particle size of about 0.1-1.0mm, low settling velocity of about 15-25 m/h, loose structure and high water content of about 96-98%. To maintain the stability of aerobic granular sludge, strategies based on the differences of settling velocity and particle-size between granular and flocculent sludge were implemented. Moreover, in CGSFDMBR, membrane fouling was greatly relieved. Dynamic membrane was just cleaned once in more than 45 days' operation. CGSFDMBR presented good performance in treating septic tank wastewater, obtaining average COD, NH(4)(+)-N, TN and TP removal rates of 83.3%, 73.3%, 67.3% and 60%, respectively, which was more efficient than conventional bioreactors since that carbon, nitrogen and phosphorus were simultaneously removed in a single aerobic reactor.