Deep Tumor Penetration of CRISPR-Cas System for Photothermal-Sensitized Immunotherapy via Probiotics.

Since central cells are more malignant and aggressive in solid tumors, improving penetration of therapeutic agents and activating immunity in tumor centers exhibit great potential in cancer therapies. Here, polydopamine-coated Escherichia coli Nissle 1917 (EcN) bearing CRISPR-Cas9 plasmid-loaded liposomes (Lipo-P) are applied for enhanced immunotherapy in deep tumors through activation of innate and adaptive immunity simultaneously. After accumulation in the tumor center through hypoxia targeting, Lipo-P could be detached under the reduction of reactive oxygen species (ROS)-responsive linkers, lowering the thermal resistance of cancer cells via Hsp90α depletion. Owing to that, heating induced by polydopamine upon near-infrared irradiation could achieve effective tumor ablation. Furthermore, mild photothermal therapy induces immunogenic cell death, as bacterial infections in tumor tissues trigger innate immunity. This bacteria-assisted approach provides a promising photothermal-sensitized immunotherapy in deep tumors.

Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial.

BACKGROUND: Sjögren's syndrome is an autoimmune disease characterised by dry eyes and mouth, systemic features, and reduced quality of life. There are no disease-modifying treatments. A new biologic, ianalumab (VAY736), with two modes of suppressing B cells, has previously shown preliminary efficacy. This dose-finding trial aimed to assess the safety and efficacy of different subcutaneous doses of ianalumab in patients with moderate to severe primary Sjögren's syndrome. METHODS: VAY736A2201 was a randomised, parallel, double-blind, placebo-controlled, phase 2b dose-finding study done in 56 centres in 19 countries. Patients aged 18-75 years with primary Sjögren's syndrome with moderate to severe disease activity (European Alliance of Associations for Rheumatology [EULAR] Sjögren's Syndrome Disease Activity Index [ESSDAI] score ≥6) and symptom severity (EULAR Sjögren's Syndrome Patient Reported Index score ≥5) were eligible. Participants were randomly assigned (1:1:1:1) to receive subcutaneous placebo or ianalumab (5 mg, 50 mg, or 300 mg) every 4 weeks for 24 weeks using a secure, online randomisation system. Randomisation was stratified by the ESSDAI score at baseline (≥10 or <10). Study personnel and patients were masked to treatment assignment. The primary outcome was the change in ESSDAI score from baseline to 24 weeks in all randomly assigned patients. Dose-related change in disease activity (ESSDAI) from baseline at week 24 was assessed by multiple comparison procedure with modelling analysis. Safety was measured in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02962895. FINDINGS: Between June 27, 2017, and Dec 06, 2018, 293 patients were screened, 190 of whom were randomly assigned (placebo n=49, ianalumab 5 mg n=47, ianalumab 50 mg n=47, ianalumab 300 mg n=47). Statistically significant dose-responses were seen for overall disease activity (ESSDAI score) in four of the five dose-response models tested (p<0·025 in four models, p=0·060 in one model). The ESSDAI score decreased from baseline in all ianalumab groups, with the maximal ESSDAI score change from baseline observed in the ianalumab 300 mg group: placebo-adjusted least-squares mean change from baseline -1·92 points (95% CI -4·15 to 0·32; p=0·092). There were four serious adverse events in three patients considered treatment-related (pneumonia [n=1] and gastroenteritis [n=1] in the placebo group; appendicitis plus tubo-ovarian abscess in the same patient in the ianalumab 50 mg group). INTERPRETATION: The study met its primary objective, showing a dose-related decrease in disease activity as measured by ESSDAI at week 24. Overall, ianalumab was well tolerated and safe, with no increase in infections. To our knowledge, this is the first large, randomised, controlled trial in primary Sjögren's syndrome that met its primary endpoint, and its results mean there is potential for more studies of this mechanism in the future. FUNDING: Novartis.

The synthesis and functionalization of metal organic frameworks and their applications for the selective separation of proteins/peptides.

Recently, proteins separation has drawn great interest for the full investigation of a proteome because the proteins separation is the precondition when conducting clinical research or proteomics research. Metal organic frameworks (MOFs) are fabricated via covalent connection between organic ligands and metal ions/clusters units. MOFs have attracted much attention due to the ultra-high specific surface area, tunable structure, more metal site or unsaturated site, and chemical stability. Over the past decade, different functionalization types of MOFs have been reported in combination with amino acids, nucleic acids, proteins, polymers, and nanoparticles for various applications. In this review, the synthesis and functionalization of MOFs have been thoroughly discussed, and we introduced the existing problems and development trends in these fields. Furthermore, MOFs as advanced adsorbents for selective separation of proteins/peptides are summarized. Additionally, we present a comprehensive prospects and challenges in the preparation of robust functional MOFs-based adsorbents and make a final outlook on their future development prospects in selective separation of proteins/peptides.

Anti-biofilm effect of salivary histatin 5 on Porphyromonas gingivalis.

This study aimed to investigate the effects of salivary histatin 5 (Hst5) on Porphyromonas gingivalis (P. gingivalis) biofilms in vitro and in vivo and the possible mechanisms. In in vitro experiments, P. gingivalis biomass was determined by crystal violet staining. Polymerase chain reaction, scanning electron microscopy, and confocal laser scanning microscopy were used to determine the Hst5 concentration. A search for potential targets was performed using transcriptomic and proteomic analyses. In vivo experimental periodontitis was established in rats to evaluate the effects of Hst5 on periodontal tissues. Experimental results showed that 25 µg/mL Hst5 effectively inhibited biofilm formation, and increased concentrations of Hst5 increased the inhibitive effect. Hst5 might bind to the outer membrane protein RagAB. A combination of transcriptomic and proteomic analyses revealed that Hst5 could regulate membrane function and metabolic processes in P. gingivalis, in which RpoD and FeoB proteins were involved. In the rat periodontitis model, alveolar bone resorption and inflammation levels in periodontal tissues were reduced by 100 µg/mL Hst5. This study showed that 25 µg/mL Hst5 inhibited P. gingivalis biofilm formation in vitro by changing membrane function and metabolic process, and RpoD and FeoB proteins might play important roles in this process. Moreover, 100 µg/mL Hst5 inhibited periodontal inflammation and alveolar bone loss in rat periodontitis via its antibacterial and anti-inflammatory effects. KEY POINTS: • Anti-biofilm activity of histatin 5 on Porphyromonas gingivalis was investigated. • Histatin 5 inhibited Porphyromonas gingivalis biofilm formation. • Histatin 5 showed inhibitory effects on the occurrence of rat periodontitis.

Efficacy comparison of antibiotic bone cement-coated implants and external fixations for treating infected bone defects.

PURPOSE: This study aimed to investigate the clinical efficacy of antibiotic bone cement-coated implants compared with external fixations for treating infected bone defects. METHODS: We retrospectively enrolled 119 patients with infected bone defects in our hospital from January 2010 to June 2021, of which 56 were treated with antibiotic bone cement-coated implants and 63 were with external fixation. RESULTS: The pre-operative and post-operative haematological indexes were tested to assess the infection control; the post-operative CRP level in the internal fixation group was lower than that in the external fixation group. No statistical significance was found in the rate of infection recurrence, loosening and rupture of the fixation, and amputation between the two groups. Twelve patients in the external fixation group had pin tract infection. In the evaluation of the Paley score scale, bone healing aspect revealed no significant difference between the two groups, while in the limb function aspect, antibiotic cement-coated implant group showed a much better score than the external fixation group (P = 0.002). The anxiety evaluation scale result also showed lower score in the antibiotic cement implant group (P < 0.001). CONCLUSIONS: Compared with external fixation, antibiotic bone cement-coated implant had the same effect on controlling infection and was more effective in recovering limb function and mental health in the first-stage treatment of infected bone defects after debridement.

Stem cell-based therapy in periodontal regeneration: a systematic review and meta-analysis of clinical studies.

BACKGROUND: Periodontitis is a common and chronic inflammatory disease characterized by irreversible destruction of the tooth surrounding tissues, especially intrabony defects, which eventually lead to tooth loss. In recent years, stem cell-based therapy for periodontitis has been gradually applied to the clinic, but whether stem cell-based therapy plays a positive role in periodontal regeneration is unclear at present. METHODS: The clinical studies related to the evaluation of mesenchymal stem cells for periodontal regeneration in PubMed, Cochrane Central Register of Controlled trials (CENTRAL), Web of Science (WOS), Embase, Scopus, Wanfang and China national knowledge infrastructure (CNKI) databases were searched in June 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell free therapy for the treatment periodontitis, and to have a follow-up for at least six months. Two evaluators searched, screened, and assessed the quality and the risk of bias in the included studies independently. Review Manager 5.4 software was used to perform the meta-analysis, and GRADEpro GDT was used to evaluate the level of the evidence. RESULTS: Five randomized controlled trials (RCTs) including 118 patients were analyzed. The results of this meta-analysis demonstrated that stem cell-based therapy showed better therapeutic effects on clinical attachment level (CAL) (MD = - 1.18, 95% CI = - 1.55, - 0.80, P < 0.00001), pocket probing depth (PPD) (MD = - 0.75, 95% CI = - 1.35, - 0.14, P = 0.020), and linear distance from bone crest to bottom of defect (BC-BD)( MD = - 0.95, 95% CI = - 1.67, - 0.23, P = 0.010) compared with cell-free group. However, stem cell-based therapy presented insignificant effects on gingival recession (P = 0.14), linear distance from cementoenamel junction to bottom of defect (P = 0.05). CONCLUSION: The results demonstrate that stem cell-based therapy may be beneficial for CAL, PPD and BC-BD. Due to the limited number of studies included, the strength of the results in this analysis was affected to a certain extent. The high-quality RCTs with large sample size, multi-blind, multi-centric are still required, and the methodological and normative clinical study protocol should be established and executed in the future.

Application of vancomycin-impregnated calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan injectable hydrogels combined with BMSC sheets for the treatment of infected bone defects in a rabbit model.

BACKGROUND: The choice of bone substitutes for the treatment of infected bone defects (IBDs) has attracted the attention of surgeons for years. However, single-stage bioabsorbable materials that are used as carriers for antibiotic release, as well as scaffolds for BMSC sheets, need further exploration. Our study was designed to investigate the effect of vancomycin-loaded calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan (CSH/n-HA/CMCS) hydrogels combined with BMSC sheets as bone substitutes for the treatment of IBDs. METHODS: BMSCs were harvested and cultured into cell sheets. After the successful establishment of an animal model with chronic osteomyelitis, 48 New Zealand white rabbits were randomly divided into 4 groups. Animals in Group A were treated with thorough debridement as a control. Group B was treated with BMSC sheets. CSH/n-HA/CMCS hydrogels were implanted in the treatment of Group C, and Group D was treated with CSH/n-HA/CMCS+BMSC sheets. Gross observation and micro-CT 3D reconstruction were performed to assess the osteogenic and infection elimination abilities of the treatment materials. Histological staining (haematoxylin and eosin and Van Gieson) was used to observe inflammatory cell infiltration and the formation of collagen fibres at 4, 8, and 12 weeks after implantation. RESULTS: The bone defects of the control group were not repaired at 12 weeks, as chronic osteomyelitis was still observed. HE staining showed a large amount of inflammatory cell infiltration around the tissue, and VG staining showed no new collagen fibres formation. In the BMSC sheet group, although new bone formation was observed by gross observation and micro-CT scanning, infection was not effectively controlled due to unfilled cavities. Some neutrophils and only a small amount of collagen fibres could be observed. Both the hydrogel and hydrogel/BMSCs groups achieved satisfactory repair effects and infection control. Micro-CT 3D reconstruction at 4 weeks showed that the hydrogel/BMSC sheet group had higher reconstruction efficiency and better bone modelling with normal morphology. HE staining showed little aggregation of inflammatory cells, and VG staining showed a large number of new collagen fibres. CONCLUSIONS: Our preliminary results suggested that compared to a single material, the novel antibiotic-impregnated hydrogels acted as superior scaffolds for BMSC sheets and excellent antibiotic vectors against infection, which provided a basis for applying tissue engineering technology to the treatment of chronic osteomyelitis.

Investigation of hue effects in tooth whiteness perception.

OBJECTIVE: To identify the hue angles that provide the optimal perception of tooth whitening. METHODS: Thirty-three male/female adult observers with normal color vision were recruited to assess teeth images on a color calibrated display. Images of teeth were generated which simulated color changes in each of eight hue directions in the CIE a*b* plane, each equi-distant from a baseline tooth color. Using a paired comparison study design, observers were asked to indicate which of two images had whiter teeth. The data were converted into an interval scale using Thurstone's Law of Comparative Judgment. The relationship between the hue angles and the scores was modeled by curve fitting. RESULTS: The optimal hues were found in a region between green and blue in the CIE a*b chart. When the tooth color travels in an optimal hue direction, the same amount of color change will result in a greater change in whiteness perception than when traveling in other hue directions. CONCLUSIONS: The optimal hues for tooth whitening were identified from the visual perception study. The most effective tooth whitening direction is to change tooth color towards the greenish-blue hue direction. CLINICAL SIGNIFICANCE: This study gives clinicians and researchers a better understanding of tooth color hue effects in tooth whiteness perception.

Radiographic evaluation of a cross-shaped incision technique for thick-gingiva and thin-gingiva patients treated with implant-supported fixed prosthesis.

BACKGROUND: To evaluate a cross-shaped incision technique for thick-gingiva and thin-gingiva patients treated with implant-supported fixed prosthesis. METHODS: Total 55 patients receiving cross-shaped incision were assigned into thick-gingiva group (29 cases) and thin-gingiva group (26 cases). Follow-up was performed at 3 and 12-month after final restoration. RESULTS: Mesial and distal papilla height was significantly greater in thick-gingiva group than thin-gingiva group at 3 and 12 months, while periodontal depth and crestal marginal bone level around implant had no significant difference between the two groups during follow-up. No case of recession of buccal marginal gingiva was observed in thick-gingiva group. However, the recession of marginal gingiva of buccal aspect of the crown was found in 5 patients (19.2%) with thin-gingiva. CONCLUSIONS: The cross-shaped incision may be applied to reconstruct gingival papillae and avoid the gingival recession in patients with thick-gingiva phenotype. Trial registration This study was registered at ClinicalTrials.gov (registration number NCT04706078, date 12 January 2021, Retrospectively registered).

Water-Soluble Lanthanide-Titanium-Oxo Cluster, a Precursor for Biocompatible Nanomaterial.

Titanium-oxo clusters (TOCs) are attractive as a rapidly growing class of molecular materials due to their use as molecular models and precursors of nano-titanium-oxide. However, most TOCs can only be dissolved in nonaqueous solvents, which largely limits their potential applications in biological or environmental situations. Very few water-soluble TOCs were reported, which can be used directly in aqueous biomedical systems. However, until now, no research studies of such TOCs involved in biomedical fields have been documented. We report here a series of lanthanide-titanium-oxo clusters (LnTOCs) formulated as {H2@[Ln2Ti8(µ3-O)8(µ2-O)4(Ac)16]}3·24CH3CN·23H2O (Ln = Eu(III) 1, Tb(III) 2, and Yb(III) 3). The compounds are easily soluble in water and form a stable solution of the cluster aggregates (LnTOC-a). Therefore, nano-biocompatible TiO materals can be prepared from these LnTOCs just by dissolving them in water. The nanoscale aggregates in water solutions were characterized by SEI-MS, 1H NMR, XPS, IR, and EDS mapping. Using the EuTOC-a solution, excellent fluorescence sensor properties for biomolecule ascorbic acid were found. Furthermore, biocompatibility and fluorescent labeling properties of the EuTOC-a for HeLa cells were evaluated. The results indicated that water-soluble LnTOCs can be used to prepare biocompatible fluorescent Ln-Ti-O nanomaterials.

Pretreatment of corn cob in [EMIM][OAc] and [EMIM][OAc]/ethanol (water).

High cost and high viscosity of ionic liquid restricted its commercial application in pretreatment of lignocellulose. Water and ethanol were used as additive in [EMIM][OAc] to pretreat corn cob at moderate temperature (< 100 °C). It was found that enzyme hydrolysis (EH) sugar yield was increased with the increase of IL content. The largest EH sugar yield of 68.8% was obtained when pure IL was used. However, for [EMIM][OAc]/ethanol, the EH sugar yield as high as 66.9% was gained when the IL content was 80%, which was comparable to that for pure IL pretreatment. In addition, Kamlet-Taft parameter was calculated to characterize the polarity solvency of binary liquid phase, to illustrate the underlying reason for the increase of EH sugar and the lignin removal. Finally, to demonstrate the crystalline and microstructure change after pretreatment, XRD and SEM were performed for the raw materials and the pretreated samples.

Activation of Antigen-Specific CD8(+) T Cells by Poly-DL-Lactide/Glycolide (PLGA) Nanoparticle-Primed Gr-1(high) Cells.

PURPOSE: The aim of this study was to investigate the induction of antigen-specific T cell activation and cell cycle modulation by a poly-DL-lactide/glycolide (PLGA) nanoparticle (NP)-primed CD11b(+)Gr-1(high) subset isolated from mouse bone marrow. METHODS: PLGA NPs containing the ovalbumin (OVA) antigen were prepared using the double emulsion and solvent evaporation method, and protein release rate and cell viability were determined. The Lin2(¯)CD11b(+)Gr-1(high)Ly6c(low) (Gr-1(high)) subset was sorted from the bone marrow of C57BL/6 J mice by fluorescence-activated cell sorting (FACS) and co-cultured with OT-I CD8(+) splenic T cells. Proliferation of OT-I CD8(+) T cells was monitored, and cell cycles were determined by 5-bromo-2'-deoxyuridine (BrdU) labeling. RESULTS: Treatment of Gr-1(high) cells with PLGA/OVA NPs upregulated expression of the SIINFEKL-H2K(b) complex in the context of MHC I. Co-cultures of OT-I CD8(+) T cells with the PLGA/OVA NP-primed Gr-1(high) cells induced the proliferation of T cells in vitro and modulated cell division and morphology. Treatment of Gr-1(high) cells with PLGA/OVA NPs also induced cell apoptosis and necrosis. CONCLUSION: This study demonstrated the function of PLGA/OVA NPs in the activation of OT-I CD8(+) T cells and the capability of cross-presentation via the Gr-1(high) polymorphonuclear subset from mouse bone marrow.

Validation of 4ß-hydroxycholesterol and evaluation of other endogenous biomarkers for the assessment of CYP3A activity in healthy subjects.

AIMS: This study aimed to assess changes in the plasma concentrationss of 4ß-hydroxycholesterol (4ßHC) against intravenous (i.v.) and oral midazolam (MDZ) pharmacokinetics (PK) after administration of a potent CYP3A inhibitor [ketoconazole (KETO)] and inducer [rifampicin (RIF)]. METHODS: Thirty-two healthy subjects (HS) were allocated into three groups of 12 each in KETO and RIF and 10 in a placebo group (PLB). All HS were randomized to receive oral and i.v. MDZ on day 1 or 2 and on day 15 or 16 after receiving RIF (600 mg once daily), KETO (400 mg once daily) or PLB for 2 weeks. Subjects were followed until day 30. The effect of treatments on 4ßHC was assessed by analyzing % change from baseline using a linear spline mixed effects model. RESULTS: Compared with PLB, KETO decreased 4ßHC mean values up to 13% (P = 0.003) and RIF increased 4ßHC mean values up to 220% (P < 0.001). Within 14 days of stopping KETO and RIF, 4ßHC had either returned to baseline (KETO) or was still returning to baseline (RIF). Compared with baseline, mean oral MDZ AUC increased by 11-fold (90% CI ranging from 9-fold to 13-fold increase) and decreased by 92% (90% CI ranging from 90% to 95% decrease) after KETO and RIF, respectively. Similar trends were observed for 6ß-hydroxycortisol : cortisol (6ßHCL : CL) urinary ratios. CONCLUSIONS: Changes in plasma 4ßHC can be utilized as a surrogate for MDZ PK after multiple doses of potent CYP3A inducers. There is a more limited dynamic range for 4ßHC for assessment of potential CYP3A inhibitors. 4ßHC is a valuable tool for the assessment of potential CYP3A inducers in early drug development.

Diagnostic value associated with the combination of saliva pepsin and microorganisms in functional heartburn and gastroesophageal reflux disease.

Heartburn is a common symptom shared by both gastroesophageal reflux disease (GERD) and functional heartburn (FHB), which can make it challenging to differentiate between the two conditions. However, examining oral manifestations of GERD can be a cost-effective and readily available method to aid in this differentiation process. It may serve as a valuable tool in distinguishing GERD from FHB.

[Application of small intestinal submucosa absorbable biofilm in the repair of alveolar bone defects].

PURPOSE: To study the clinical efficacy of small intestinal submucosa (SIS) absorbable biological membrane in alveolar bone defect repair. METHODS: A total of 102 patients with alveolar bone defect who received guided bone regeneration (GBR) in our hospital from January 2020 to January 2022 were selected and divided into Bio-Gide group (51 cases using Bio-Gide absorbable biofilm) and SIS group (51 cases using SIS absorbable biofilm) by computer random number generator. The perioperative related indicators, blood calcium, blood phosphorus, biocompatibility, periodontal attachment loss (PAL) length, pulp sensitivity, tooth mobility, alveolar bone volume and adverse events of the two groups were compared. Statistical analysis was performed with SPSS 24.0 software package. RESULTS: There was no significant difference in operation time, intraoperative blood loss, visual analogue scale (VAS) score of pain on the first day after operation, VAS score on the fifth day after operation, wound healing time, blood calcium and phosphorus levels before operation, 1 d and 12 d after operation, PAL length before operation, 3 months, 6 months and 12 months after operation, pulp sensitivity and tooth looseness grade 1 and 2 percentage at 3, 6 and 12 months after operation, bone width increase, bone height increase at 12 months after operation and adverse event rate between the two groups (P＞0.05). Compared with Bio-Gide group, the wound healing time and biofilm absorption time were shortened in SIS group(P＜0.05), and the incidence of rejection was decreased 12 d after operation (P＜0.05). CONCLUSIONS: SIS absorbable biofilm and Bio-Gide absorbable biofilm have similar efficacy and safety in repairing GBR for alveolar bone defects, but the former is more biocompatible and the latter can provide longer barrier function.

Advances in autogenous dentin matrix graft as a promising biomaterial for guided bone regeneration in maxillofacial region: A review.

Autogenous dentin matrix (ADM), derived from a patient's extracted tooth, can be repurposed as an autologous grafting material in reconstructive dentistry. Extracted teeth provide a source for ADM, which distinguishes itself with its low rejection rate, osteoinductive capabilities and ease of preparation. Consequently, it presents a viable alternative to autogenous bone. Animal studies have substantiated its effective osteoinductive properties, while its clinical applications encompass post-extraction site preservation, maxillary sinus floor augmentation, and guided bone tissue regeneration. Nevertheless, the long-term efficacy of ADM applied in bone regeneration remains underexplored and there is a lack of standardization in the preparation processes. This paper comprehensively explores the composition, mechanisms underlying osteoinductivity, preparation methods, and clinical applications of ADM with the aim of establishing a fundamental reference for future studies on this subject.

Advances in the use of chlorhexidine for periodontitis treatment in diabetic patients: A review.

Periodontitis and diabetes mellitus exhibit a bidirectional relationship. This narrative review descriptively outlines the role of chlorhexidine in the periodontal treatment of diabetic patients, focusing on its antimicrobial mechanisms against microbial communities and its antiplaque effects. Although chlorhexidine is proven to be effective in combating microbial presence and improving gingivitis with substantial supporting evidence, its impact on glycemic control and insulin resistance in diabetic patients remains contentious. Additionally, the effectiveness of chlorhexidine as an adjunctive chemotherapeutic in the periodontal treatment of gestational diabetes has not yet been studied, highlighting a gap in research that necessitates further prospective studies and randomized controlled trials. Considering the interconnection between periodontal inflammation and glycemic levels, this article finally advocates for collaborative care between dental and medical professionals to manage periodontitis in diabetic patients effectively.

The application of drug behavior management methods in the treatment of dental fear and oral diseases in children: A review.

Oral behavior management methods include basic behavior management methods and drug behavior management methods. In many cases, dental treatment that cannot be done simply through basic behavior management is not possible. The uncooperative behavior of children with dental fear in oral treatment has increased the demand for medication based behavior management methods. Drug sedation can provide more effective analgesic and anti-anxiety effects, thereby helping to provide comfortable, efficient, and high-quality dental services. This article will review the drug sedation methods selected in clinical treatment of pediatric dental fear in recent years, as well as the safety and effectiveness of commonly used drugs, in order to provide guidance for dental professionals in clinical practice.

Clinical application prospects and transformation value of dental follicle stem cells in oral and neurological diseases.

Since dental pulp stem cells (DPSCs) were first reported, six types of dental SCs (DSCs) have been isolated and identified. DSCs originating from the craniofacial neural crest exhibit dental-like tissue differentiation potential and neuro-ectodermal features. As a member of DSCs, dental follicle SCs (DFSCs) are the only cell type obtained at the early developing stage of the tooth prior to eruption. Dental follicle tissue has the distinct advantage of large tissue volume compared with other dental tissues, which is a prerequisite for obtaining a sufficient number of cells to meet the needs of clinical applications. Furthermore, DFSCs exhibit a significantly higher cell proliferation rate, higher colony-formation capacity, and more primitive and better anti-inflammatory effects than other DSCs. In this respect, DFSCs have the potential to be of great clinical significance and translational value in oral and neurological diseases, with natural advantages based on their origin. Lastly, cryopreservation preserves the biological properties of DFSCs and enables them to be used as off-shelf products for clinical applications. This review summarizes and comments on the properties, application potential, and clinical transformation value of DFSCs, thereby inspiring novel perspectives in the future treatment of oral and neurological diseases.

Effectiveness of three auxiliary irrigation methods for cleaning the internal walls of root canals of curved isolated teeth.

OBJECTIVES: This study aimed to compare the effectiveness of ultrasound and acoustic and laser cleaning of curved root canals. METHODS: A total of 92 molars with independent root canals with a curvature of 20°-40° were prepared and standardized at 04 25# and stained with gentian violet solution for 72 h. Among them, 52 were randomly divi-ded into four groups for final rinsing (n=13): NI group, PUI group, EDDY group, and PIPS group. Ten samples in each group were cut horizontally along the long axis perpendicular to the root and divided into curved upper, curved, and apical segments. Images were taken with a stereomicroscope and Image J measurements were taken to calculate the depth of rinse penetration. The remaining three samples from each group were split along the long axis of the dentin, photographed by scanning electron microscope to record the dentin tubule exposure and staining layer, and scored for staining layer by double-blind method. SPSS 26.0 software was used to perform statistical analysis and select the best flushing method. An extra 40 samples were randomly divided into four groups for detection of flushing fluid penetration depth (n=10): 10, 20, 30, and 40 s. RESULTS: In the upper part, the mean depth of infiltration was not significantly different between the experimental and control groups (P>0.05). The PIPS group had a significantly lower smear layer score than the control group and the EDDY group (P<0.01). In the curved segment, the mean depth of infiltration was significantly greater in the PUI group than in the control group (P<0.05); the tarnish layer score was lower in each experimental group than in the control group. At the top, the mean depth of infiltration was greater in the PUI and PIPS groups than in the control group (P<0.05), and the smear layer score was lower in the PIPS group than in the other groups (P<0.05). After the time was changed, the depth of infiltration of PUI increased only in the apical segment as the flushing time increased. CONCLUSIONS: The PUI and PIPS methods facilitate the penetration of irrigation solution into the dentin canal in curved root canals, especially in the apical segment. The PIPS technique is effective in removing the smear layer in curved root canals.