Immune checkpoint inhibitors (ICIs) present significant efficacy in the treatment of malignant tumors, and they have been approved as the first-line of treatment for various cancers. Pembrolizumab monotherapy or combined with chemotherapy has been recommended by domestic and foreign guidelines for the first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma. Although ICIs represent a milestone in the treatment of head and neck squamous cell carcinoma, potential problems still need to be addressed, such as the selection of the efficacy predictors for ICIs, the evaluation of the tumor response to ICIs, and the treatment of immune hyperprogression and immune-related adverse events. Therefore, to form a relatively unified understanding of ICIs treatment for head and neck squamous cell carcinoma, we integrated the clinical experience of multi-disciplinary experts of head and neck cancers on the basis of current clinical hot issues and finally developed this consensus.

External apical root resorption is among the most common risks of orthodontic treatment, and it cannot be completely avoided and predicted. Risk factors causing orthodontic root resorption can generally be divided into patient- and treatment-related factors. Root resorption that occurs during orthodontic treatment is usually detected by radiographical examination. Mild or moderate root absorption usually does no obvious harm, but close attention is required. When severe root resorption occurs, it is generally recommended to suspend the treatment for 3 months for the cementum to be restored. To unify the risk factors of orthodontic root resorption and its clinical suggestions, we summarized the theoretical knowledge and clinical experience of more than 20 authoritative experts in orthodontics and related fields in China. After discussion and summarization, this consensus was made to provide reference for orthodontic clinical practice.

Objective This study aimed to investigate whether the microglia in the spinal trigeminal nucleus caudal part (Sp5C) were activated in a rat model of trigeminal neuralgia and to explore whether the activation level of microglia is consistent with maxillofacial pain level. Methods Chronic constriction injury of trigeminal nerve (CCI) was induced by partial ligation of infraorbital nerve (IoN) in rats. The behavioral change of rats observed at D1, D5, D10, D15, and D30 days post-surgery and the change of pain threshold were detected with electronic Von Frey filaments served as an evaluation index of maxillofacial pain. Weight change was measured by weighing. Ionized calcium binding adaptor molecule-1 (Iba-1) expression level of Sp5C at each time point was detected, and three microglia morphological categories were analyzed by immunohistochemical staining. Results The changes of behavioral and pain threshold suggested the maxillofacial pain level first increased and then decreased post-surgery in the IoN-CCI group. Both the expressions of Iba-1 and proportion of ameboid morphology in ipsilateral Sp5C increased from D1 and reached their peaks in D10 and D5, respectively. Then, they recovered nearly to the same level with contralateral Sp5C on D30. This trend was consistent with the maxillofacial change. Conclusion The model of trigeminal neuralgia in rats constructed by partial ligation of infraorbital nerve can induce the activation of microglia in Sp5C, and the activation level is consistent with maxillofacial pain, which reached its peak at around D10 post-surgery.

Objective This study aimed to explore the specific mechanism, mediated by the reactive oxygen species (ROS) and PINK1/Parkin pathway, of the mitochondrial autophagy of human periodontal ligament cells (hPDLCs) under starvation conditions. Methods hPDLCs were isolated and cultured from normal periodontal tissues. Earle’s balanced salt solution (EBSS) was used to simulated a starvation environment and thus stimulate hPDLCs mitochondrial autophagy. N-Acetyl-L-cysteine (NAC) was used to inhibit ROS production to explore the role of ROS in hPDLC mitochondrial autophagy. Cyclosporin A was used to inhibit the PINK1/Parkin pathway to study the role of ROS and the PINK1/Parkin pathway in hPDLCs activation under starvation. The mitochondrial membrane potential was detected by flow cytometry with a JC-1 mitochondrial membrane potential detection kit. The morphological structure of mitochondria and the formation of mitochondrial autophagosome were observed by transmission electron microscopy. Mito tracker red cmxros and lyso tracker green staining were used to observe the localization of mitochondria and lysosomes. The formation intensity of ROS was detected with a DCFH-DA ROS fluorescent probe. The expression levels of mitochondrial autophagy genes (Tomm20 and Timm23) and the PINK1/Parkin pathway were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression levels of mitochondrial autophagy proteins (Tomm20 and Timm23) and PINK1/Parkin protein were detected by Western blot. Results EBSS starvation for 30 min induced the strongest activation of hPDLCs mitochondrial autophagy, increased the expression of ROS, downregulated the expression of mitochondrial autophagy-related genes (Tomm20 and Timm23) (P<0.001), and upregulated the PINK1/Parkin pathway (P<0.001). After NACinhibited ROS production, mitochondrial autophagy was also inhibited. Meanwhile, the expression of Tomm20 and Timm23 was upregulated (P<0.001 and P<0.05), and the expression of the PINK1/parkin pathway (P<0.001 and P<0.05) was down regulated. When cyclosporin A inhibited the expression of the PINK1/Parkin pathway (P<0.05 and P<0.05), it reversed the mitochondrial autophagy of hPDLCs (P<0.001 and P<0.01) and also upregulated the expression of Tomm20 and Timm23 (P<0.001 and P<0.01). Conclusion ROS enhanced the mitochondrial autophagy of hPDLCs primarily through the PINK1/Parkin pathway under starvation conditions.

Objective The expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in human periodontal ligament cells (HPDLCs) was investigated by cell culture under continuous static pressure. Methods HPDLCs were primarily cultured by tissue explant method and divided into three groups: group A (13-18 years old), group B (19-29 years old), and group C (30-44 years old). CCK-8 was used to detect the proliferation of HPDLCs. The senescence of HPDLCs was detected by senescence-associated β-galactosidase staining. Cells in the three groups were respectively given 0, 1.5, 3, 6, 12, 24, 48, and 72 h of continuous static pressure in vitro. The expression of OPG and RANKL in the supernatant was detected by enzyme-linked immunosorbent assay. Results After continuous static pressure in vitro for stimulation, the expression of OPG and RANKL changed. The expression of OPG increased with time and age (P<0.01). The expression of RANKL increased with time and decreased with age (P<0.01). The ratio of OPG/RANKL initially decreased, increased with time, and then continued to rise with age (P<0.01). Conclusion Aging could increase the expression of OPG and the ratio of OPG/RANKL and decrease the expression of RANKL in HPDLCs under continuous static pressure in vitro.

Objective This work aimed to synthesize a novel injectable alginate impression material and evaluate its accuracy. Methods Certain proportions of sodium alginate, trisodium phosphate dodecahydrate, potassium fluorotitanate, diatomaceous earth, and other ingredients were dissolved in water and mixed evenly with a planetary centrifugal mixer to obtain a certain viscosity base paste. Certain proportions of calcium sulfate hemihydrate, magnesium oxide, glycerin, and polyethylene glycol (PEG) 400 were mixed evenly with a planetary centrifugal mixer to obtain the reactor paste with the same viscosity as the base paste. The base and reactor pastes were poured into a two-cylinder cartridge at a 2∶1 volume ratio. A gun device was used to accomplish mixing by compressing materials into a mixing tip. The samples were divided into three groups: injectable alginate impression materials (IA group) as the experimental group, and Jeltrate alginate impression materials (JA group) and Silagum-putty/light addition silicone rubber impression materials (SI group) as the two control groups. Results Scanning electron microscopy (SEM) showed that the injectable alginate impression materials had a denser structure and fewer bubbles than the commercial alginate impression material. The accuracy of the three kinds of impression materials was evaluated by 3D image superposition. The deviations between the three test group models and the standard model (trueness) were 49.58 μm±1.453 μm (IA group), 54.75 μm±7.264 μm (JA group), and 30.92 μm±1.013 μm (SI group). The deviations of the models within each test group (precision) were 85.79 μm±8.191 μm (IA group), 97.65 μm±11.060 μm (JA group), and 56.51 μm±4.995 μm (SI group). Significant differences in trueness and precision were found among the three kinds of impression materials (P<0.05). Conclusion The accuracy of the new injectable alginate impression material was better than that of the traditional powder-type alginate impression material but worse than that of the addition silicone rubber impression materials. The novel injec-table alginate impression material demonstrated good operation performance and impression accuracy, showing broad application prospect.

Objective The purpose of the study was to evaluate the effect of hydroxyapatite (HA)-based desensiti-zing agents and determine their influence on the bonding performance of mild universal adhesives. Methods Mid-coronal dentin samples were sectioned from human third molars and prepared for a dentin-sensitive model. According to desensitizing applications, they were randomly divided into four groups for the following treatments: no desensitizing treatment (control), Biorepair toothpaste (HA-based desensitizing toothpaste) treatment, Dontodent toothpaste (HA-based desensitizing toothpaste) treatment, and HA paste treatment. Dentin tubular occlusion and occluded area ratios were evaluated by scanning electron microscopy (SEM). Furthermore, All-Bond Universal, Single Bond Universal, and Clearfil Universal Bond were applied to the desensitized dentin in self-etch mode. The wettability and surface free energy (SFE) of desensitized dentin were evaluated by contact angle measurements. Bonded specimens were sectioned into beams and tested for micro-tensile bond strength to analyze the effect of desensitizing treatment on the bond strength to dentin of universal adhesives. Results SEM revealed that the dentin tubule was occluded by HA-based desensitizing agents, and the area ratios for the occluded dentin tubules were in the following order: HA group>Biorepair group>Dontodent group (P<0.05). Contact angle analysis demonstrated that HA-based desensitizing agents had no statistically significant influence on the wettability of the universal adhesives (P>0.05). The SFE of dentin significantly increased after treatment by HA-based desensitizing agents (P<0.05). The micro-tensile bond strength test showed that HA-based desensitizing toothpastes always decreased the μTBS values (P<0.05), whereas the HA paste group presented similar bond strength to the control group (P>0.05), irrespective of universal adhesive types. Conclusion HA-based desensitizing agents can occlude the exposed dentinal tubules on sensitive dentin. When mild and ultra-mild universal adhesives were used for subsequent resin restoration, the bond strength was reduced by HA-based desensitizing toothpastes, whereas the pure HA paste had no adverse effect on bond strength.

Objective This study aimed to build a surgical navigation system based on mixed reality (MR) and optical positioning technique and evaluate its clinical applicability in craniomaxillofacial trauma bone reconstruction. Me-thods　We first integrated the software and hardware platforms of the MR-based surgical navigation system and explored the system workflow. The systematic error, target registration error, and osteotomy application error of the system were then analyzed via 3D printed skull model experiment. The feasibility of the MR-based surgical navigation system in craniomaxillofacial trauma bone reconstruction was verified via zygomatico-maxillary complex (ZMC) reduction experiment of the skull model and preliminary clinical study. Results The system error of this MR-based surgical navigation system was 1.23 mm±0.52 mm, the target registration error was 2.83 mm±1.18 mm, and the osteotomy application error was 3.13 mm±1.66 mm. Virtual surgical planning and the reduction of the ZMC model were successfully conducted. In addition, with the guidance of the MR-based navigation system, the frontal bone defect was successfully reconstructed, and the clinical outcome was satisfactory. Conclusion The MR-based surgical navigation system has its advantages in virtual reality fusion effect and dynamic navigation stability. It provides a new method for doctor-patient communications, education, preoperative planning, and intraoperative navigation in craniomaxillofacial surgery.

Objective This study aimed to evaluate the efficacy of three methods in root canal retreatment to remove the filling material in the root canals. Methods Ninety tooth roots filled by gutta percha or plasticized material (n=45, each) were randomly divided into three groups (n=15). WaveOne (WaveOne group), 1^#P drill+WaveOne (1^#P+WaveOne group), and ultrasound P5 working end ET25+ProTaper Universal (P5+ProTaper Universal group) were used to remove the root canal filling material and prepare for root canal. The operating time of each canal was recorded and the percentage of residual filling material area was measured on the root canal wall of the mesial and distal dissected root section. The degree of deviation of the root canal after operation was measured for the root samples filled by gutta percha. Results The type of root filling material and the method of root canal retreatment had no significant effect on the percentage of residual area of the filling material (P>0.05). However, the remaining filling material area of apical 1/3 of the root canal was significantly higher than that of cervical 1/3 of the root canal (P<0.05). The average operating times for removing gutta-percha or plasticized material in the W and 1^#P+WaveOne groups were significantly less than that in the P5+ProTaper Universal group (P=0.000). The root canal retreatment methods had no significant effect on the curvature of the root canal (P=0.650). Conclusion WaveOne single file's cleaning ability and center positioning ability were similar to those of ProTaper Universal. Moreover, WaveOne can be independently used for most root canals without a pathway when removing the root canal fillings, thereby simplifying the process of root canal retreatment.

Objective To evaluate the effectiveness of an acellular dermal matrix or a connective tissue autograft in the treatment of multiple adjacent gingival recessions through Meta-analysis. Methods Randomized controlled trials were screened in four electronic databases in English according to the inclusion and exclusion criteria until April 20, 2022. The main outcome indicators were keratinized gingival tissue width, recession depth, probing depth, clinical attachment level, complete root coverage, and root coverage esthetic score. Results Seven randomized controlled trials were included. After 12 months, the connective tissue graft in the control group could increase the keratinized gingival tissue width [mean difference (MD)=-0.28 (-0.47, -0.08), P=0.006], reduce the gingival recession depth [MD=0.23 (0.12, 0.35), P<0.000 1], and improve the complete root coverage [risk ratio=0.80, 95% confidence interval (0.69, 0.93), P=0.003] compared with the acellular dermal matrix in the experimental group. No significant difference was found in probing depth, clinical attachment level, and root coverage esthetic score between groups. Conclusion Connective tissue grafts have advantages in increasing the keratinized gingival tissue width, reducing the gingival recession depth, and improving the complete root coverage in surgeries for treating multiple adjacent gingival recessions. Acellular dermal matrices also have some clinical value in terms of operation simplicity and similar effectiveness.

Objective This study aimed to investigate the accuracy of model superimposition and automatic analysis for upper and lower dentition widths in iTero Progress Assessment during the clear aligner process. Methods Nineteen cases were included in this retrospective case control study. Pretreatment dental cast (T0) and post treatment dental cast after staged treatment (T1) were available for three-dimensional (3D) model superimposition. The movements of maxillary teeth in the horizontal plane (cross section) after staged treatment and the widths of upper and lower dentitions were measured by 3D model superimposition in real world and iTero Progress Assessment. The data collected from the two methods were compared. Results The movements [Median (upper and lower quartiles)] of maxillary teeth in the horizontal plane after staged treatment were 2.31 (1.59, 3.22) and 1.79 (1.21, 3.03) mm in iTero Progress Assessment and 3D model analysis, respectively. Significant difference was observed between the two groups (P<0.05). In the measurement of upper and lower dentition width, four indicators were measured, including intercanine width upper, intermolar width upper, intercanine width lower, and intermolar width lower. Before treatment, the measurement of iTero Progress Assessment were (35.78±2.49), (56.21±2.51), (27.43±1.38), (52.26±2.91) mm, respectively, and actual measurement were (35.77±2.53), (56.17±2.47), (27.40±1.41), (52.30±2.86) mm, respectively, without significant difference (P>0.05). After stage treatment, the measurement of iTero Progress Assessment were (37.37±2.86), (57.76±2.56), (28.89±2.00), (54.16±2.19) mm, respectively, and actual measurement were (37.29±2.94), (57.71±2.63), (28.88±2.05), (54.01±2.15) mm, respectively, and there was no significant difference (P>0.05). Conclusion The data from iTero Progress Assessment did not coincide with the model superimposition results with palate as reference. The accuracy of model superimposition in iTero Progress Assessment needs further investigation, whereas the arch width analysis is accurate. Therefore, iTero Progress Assessment results should be interpreted with caution by orthodontists in clinical applications.

Objective This work aimed to construct N6-methyladenosine (m⁶A) regulator-based prognostic signature and evaluate the prognostic value and the intervention on tumor immune microenvironment of this m⁶A risk signature. Methods Using transcriptome and clinical data of head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA), we profiled m⁶A regulators and constructed an m⁶A risk signature. The relationship between m⁶A modulation and immune function was studied by differential gene expression, cell type enrichment, and correlation analyses. Results Fifteen m⁶A regulators had aberrant expression in HNSCC. A three-gene m⁶A prognostic signature (i.e., YTHDC2, IGF2BP2, and HNRNPC) was constructed and identified as an independent prognostic indicator for HNSCC. The m⁶A regulator signature-based high-risk group revealed pro-tumoral immune microenvironment due to the dysregulation of immune-related gene expression, abnormal enrichment of multiple immunocytes, and production of immunoregulatory factors. Conclusion This comprehensive analysis of m⁶A regulators and tumor immune landscape in HNSCC revealed that the m⁶A signature of YTHDC2, IGF2BP2, and HNRNPC could serve as a promising biomarker for monitoring HNSCC development and may be a potential target for tumor therapy in the future.

Objective This study aims to explore the clinical and pathological characteristics of congenital granular cell tumors and provide some references for clinical diagnosis, differential diagnosis, and treatment. Methods Nine ca-ses of congenital granular cell tumors who visited the Children’s Hospital of Zhejiang University School of Medicine from February 2008 to March 2022 were retrospectively analyzed. Herein, its clinical characteristics, pathological characteristics, treatment, and prognosis were summarized and analyzed. Results We found that nine patients were all female, aged 1‑38 days when they saw the doctor. Three of them were attached in maxillary and the other six were attached in mandible. Meanwhile, six tumors were found during the mother's pregnancy at 28-39 weeks and three tumors were found at the baby's birth. One case was excised surgically under local anesthesia, and the other cases were excised surgically under general anesthesia. After 1 month to 12 years of follow-up, patients have no recurrence, however, two cases emerged new teeth from the tumor resection site. Histopathology of all excised lesions was congenital granular cell lesion. Conclusion Congenital granular cell tumor is a benign tumor and the prognosis is good. Therefore, surgical resection of the tumor can be done without extensive resection, and it generally does not relapse. Thus, ultrasonography during pregnancy is an important method for the early detection of congenital granular cell epulis.

Dens invaginatus (DI) is a developmental anomaly as a result of a deepening or invagination of the enamel organ into the dental papilla during tooth development. In addition, DI is a malformation with varying anatomical features, which poses numerous challenges to treatment. Endodontic treatment of dens in dente is one of the most complica-ted cases of DI. Herein, an immature lateral incisor that employed regenerative endodontic treatment was presented. The mentioned tooth was diagnosed with DI, pulp necrosis, and chronic apical periodontitis. Hence, a favorable prognosis has been shown by a 2-year review with cone beam computed tomography. The tooth was functional with normal periodontal parameters and exhibited a normal response to the electric pulp sensibility test. Thus, regenerative endodontic treatment can also be recommended to endodontists for teeth with DI.

Radiation-induced oral mucositis is an oral mucosal injury caused by radiation ionizing radiation, which often manifests as oral mucosal congestion, erosion, and ulcers. Radiation-induced oral mucositis manifesting as vascular proliferative changes in the oral mucosa has not been reported. We report a case of oral mucosal atypical vascular proliferation after radiotherapy for a malignant maxillofacial tumor. We discussed the mechanism and treatment of aty-pical vascular proliferation in the oral mucosa secondary to radiotherapy, including diagnosis, treatment, and previous literature.

Warthin tumor is a benign salivary gland tumor comprising ductal epithelium and lymphoid stroma. To date, reports about the malignant transformations of intraepithelial and lymphoid components in Warthin tumor are extremely rare; lymphoid malignant transformation into B-cell lymphoma is particularly rare in combination with T-cell lymphoma. The case of Warthin tumor complicated with T-lymphoblastic lymphoma is reported to emphasize the importance of a careful light microscopic evaluation of lymphoid tissue in Warthin tumor for identifying occult lymphoma presence, reducing misdiagnosis and missed diagnosis, and determining a timely treatment.

This article reports a case of using immediate implant placement and immediate restoration combined with measurable implant surgical guides to restore compromised maxillary incisors caused by dental trauma. Target restoration was designed in the exoCAD software preoperatively, intraoral measurements were obtained in three directions, and the correct position of virtual implants was determined in BlueSky Plan 4. Afterward, measurable implant guides were designed and fabricated by 3D printing. Under the guidance of the measurable implant surgical guides and intraoperative measurement, the entry point was determined, the axial direction was verified when drilling to half the depth, and the 3D position was verified when drilling to total depth. Implants were inserted followed by verification once again. The temporary restoration, which was designed based on the target restoration and emergence profile of the original teeth and milled preoperatively, was connected to the implant immediately after surgery. Postoperative accuracy analysis showed that the mean linear deviations between the actual implant position and the pre-planned position were (0.57±0.17) mm at the entry point and (0.82±0.27) mm at the apex, and the mean angular deviation was (1.86±0.89) °, demonstrating that precise implant placement and immediate restoration were implemented.