Emerging strategies for treating autoimmune disease with genetically modified dendritic cells.

Gene editing of living cells has become a crucial tool in medical research, enabling scientists to address fundamental biological questions and develop novel strategies for disease treatment. This technology has particularly revolutionized adoptive transfer cell therapy products, leading to significant advancements in tumor treatment and offering promising outcomes in managing transplant rejection, autoimmune disorders, and inflammatory diseases. While recent clinical trials have demonstrated the safety of tolerogenic dendritic cell (TolDC) immunotherapy, concerns remain regarding its effectiveness. This review aims to discuss the application of gene editing techniques to enhance the tolerance function of dendritic cells (DCs), with a particular focus on preclinical strategies that are currently being investigated to optimize the tolerogenic phenotype and function of DCs. We explore potential approaches for in vitro generation of TolDCs and provide an overview of emerging strategies for modifying DCs. Additionally, we highlight the primary challenges hindering the clinical adoption of TolDC therapeutics and propose future research directions in this field.

Facile Synthesis and Global Aromaticity of Aza-Superbenzene and Aza-Supernaphthalene at Different Oxidation States.

All-benzenoid polycyclic aromatic hydrocarbons or macrocycles usually display localized aromaticity. On the other hand, incorporation of quinoidal units into the skeleton could lead to effective electron delocalization and global (anti)aromaticity. In this work, fully π-conjugated macrocycle 1 and bismacrocycle 2 containing both para-quinodimethane and triphenylamine units are efficiently synthesized mainly through intermolecular Friedel-Crafts alkylation reaction. They can be considered as a tetraazasuperbenzene and a hexaazasupernaphthalene, respectively, due to their similar geometry and electronic structures to the benzene and naphthalene. X-ray crystallographic analyses reveal a largely planar geometry for both 1 and 2 and variable-temperature NMR measurements disclose slow dynamic processes owing to restricted ring flipping of the phenyl rings. 1 and 2 can be easily oxidized into higher-oxidation-state species. NMR and theoretical calculations indicate that 12+ and 14+ show global anti-aromaticity and aromaticity, respectively, with a dominant 32π and 30π conjugation pathway, while for the bismacrocycle 2, its dication 22+, tetracation 24+ and hexacation 26+exhibit global aromaticity, antiaromaticity, and aromaticity with a 54π, 52π and 50π conjugation pathway along the outermost backbone, respectively.

TIPE2 deficiency prolongs mouse heart allograft survival by facilitating immature DCs-induced Treg generation.

It has been reported that deletion of tumor necrosis factor-α-induced protein-8 like 2 (TNFAIP8L2, TIPE2) facilitates the activation of T-cell receptors. However, the role of TIPE2 in T-cell-mediated acute transplant rejection remains unclear. To illustrate the underlying cellular mechanisms, we transplanted BALB/c hearts into C57BL/6 wild-type (WT) or C57BL/6 mice deficient for TIPE2 (TIPE2-/-) and found that TIPE2-/- recipient mice showed significantly prolonged survival of heart allografts and suppressed maturation of CD11c+ dendritic cells (DCs), which largely abolished the activation and proliferation of alloreactive T cells and their cytotoxic activity. TIPE2-/- DCs increased CD4+CD25+Foxp3+CD127- regulatory T cells (Tregs)generation, likely by inhibiting DCs maturation and CD80 and CD86 expression. Administration of anti-CD25 abolished the allograft survival induced by TIPE2 deficiency. Moreover, TIPE2 deficiency increased IL-10 production in T cells and in recipient serum and allografts. Mechanistic studies revealed that TIPE2-/- restrained the maturation of DCs via inhibition of PI3K/AKT phosphorylation during alloantigen stimulation. Taken together, TIPE2 deficiency in recipient mice inhibited acute rejection by increasing Tregs generated by immature DCs. Thus, TIPE2 could be a therapeutic target for suppressing rejection in organ transplantation.

Colchicine inhibits the proliferation and promotes the apoptosis of papillary thyroid carcinoma cells likely due to the inhibitory effect on HDAC1.

Although the prognosis for papillary thyroid carcinoma (PTC) is generally good, a certain proportion of patients show recurrent or advanced disease, indicating the need for further development of targeted medications. The purpose of this study was to explore the interventional effects of colchicine on PTC and the potential mechanisms or targets. We obtained PTC-related targets from the database and colchicine targets by predicting them. We screened the common targets of colchicine and the PTC-related target histone deacetylase 1 (HDAC1) and verified through molecular docking that colchicine has a good affinity for HDAC1, i.e., colchicine may act on PTC by affecting HDAC1. We then used CCK-8, colony formation, mitochondrial membrane potential and apoptosis assays to confirm that colchicine could inhibit the proliferation and promote the apoptosis of PTC cells and verified by RT‒qPCR, Western blot, and cellular immunofluorescence assays that colchicine could inhibit the expression of HDAC1 in PTC cells. The cytotoxicity and inhibitory effect of colchicine on HDAC1 in PTC cells was stronger than that in normal thyroid cells. We then applied an HDAC1 inhibitor, pyroxamide, to verify that inhibition of HDAC1 inhibits proliferation and promotes apoptosis in PTC cells. Therefore, we conclude that colchicine can inhibit the proliferation and promote the apoptosis of PTC cells likely due to its inhibitory effect on HDAC1. This finding implies that colchicine may be helpful for therapeutic intervention in PTC and that HDAC1 may be a promising clinical therapeutic target.

Comparison of endoscopic bilateral areolar and robotic-assisted bilateral axillo-breast approach thyroidectomy in differentiated thyroid carcinoma: a propensity-matched retrospective cohort study.

BACKGROUND: Robot-assisted and endoscopic thyroidectomy are superior to conventional open thyroidectomy in improving cosmetic outcomes and postoperative quality of life. The procedure of these thyroidectomies was similar in terms of surgical view, feasibility, and invasiveness. However, it remains uncertain whether the robotic-assisted bilateral axilla-breast approach (BABA) was superior to the endoscopic bilateral areolar approach (BAA) thyroidectomy. This study aimed to investigate the clinical benefit of these two surgical procedures to evaluate the difference between these two surgical procedures by comparing the pathological and surgical outcomes of endoscopic BAA and robotic-assisted BABA thyroidectomy in differentiated thyroid carcinoma. METHODS: From November 2018 to September 2021, 278 patients with differentiated thyroid carcinoma underwent BABA robot-assisted, and 49 underwent BAA approach endoscopic thyroidectomy. Of these patients, we analyzed 42 and 135 patients of endoscopic and robotic matched pairs using 1:4 propensity score matching and retrospective cohort study methods. These two groups were retrospectively compared by surgical outcomes, clinicopathological characteristics, and postoperative complications. RESULTS: The mean operation time was significantly longer in the EG than in the RG (p < 0.001), The number of retrieved lymph nodes was significantly lower in the ET group than in the RT group (p < 0.001). The mean maximum diameter of the thyroid was more expansive in the EG than in the RG (p = 0.04). There were no significant differences in the total drainage amount and drain insertion days between the two groups (p = 0.241, p = 0.316, respectively). Both groups showed that cosmetic satisfaction (p = 0.837) and pain score (p = 0.077) were similar. There were no significant differences in complication frequencies. CONCLUSION: Robotic and endoscopic thyroidectomy are similar minimally invasive thyroid surgeries, each with its advantages, both of which can achieve the expected surgical outcomes. TRIAL REGISTRATION: Retrospectively registered.

Expression of CXCR4 and CXCR7 in papillary thyroid carcinoma and adjacent tissues and their relationship with pathologic indicators of tumor aggressiveness.

The receptors of chemokines play a significance role in the aggressiveness of tumor. CXCR4/CXCR7 promote metastasis of papillary thyroid carcinoma (PTC). This study examined the expresssion of chemokine receptors CXCR4/CXCR7 in human tissue specimens of PTC and peritumoral nonmalignant tissues. The correlation between CXCR4/CXCR7 and the clinicopathological factors in PTC was also determined. CXCR4/CXCR7 were examined in 115 PTC tissues from 115 patients using immunohistochemistry. Staining intensity was compared with patients and tumor characteristics including gender, age, tumor size, capsule invasion, multifocality, lymph node metastasis, and nature of paracancerous tissue. [Statistics: rank sum test, Spearman rank order correlation test; p < 0.05]. Higher expression rates of CXCR4/CXCR7 exhibited in PTC compared with peritumoral nonmalignant tissues. The expression of them was correlated in cancer and paracancerous specimens. A trend toward higher CXCR4/CXCR7 expression was found among tumors showing positive lymph nodes and capsule invasion, while no association with sex, age, tumor size, and nature of paracancerous tissue. Number of lymph nodes was associated with higher intensity IHC staining for CXCR4/CXCR7. Intense staining for CXCR4 was also associated with multifocality. Expression of CXCR4/CXCR7 by PTCs was correlated with lymph node metastasis and capsule invasion. Although multiple bias, they were thought to play a significance role in the aggressiveness of PTC, which provides potential targets for therapeutic interventions.

A comparative study of two robotic thyroidectomy procedures: transoral vestibular versus bilateral axillary-breast approach.

OBJECTIVE: To compare the surgical outcomes between the transoral-vestibular robotic thyroidectomy (TOVRT) and bilateral axillo-breast approach robotic thyroidectomy (BABART). METHODS: A total of 99 patients with papillary thyroid carcinoma but no distant metastasis were enrolled in this study from May 2020 to April 2021. Lobectomy or total thyroidectomy with central lymph node dissection were performed in all cases. All 99 patients were received an ultrasound guided fine needle aspiration biopsy prior to surgical intervention, out of which 49 patients underwent TOVRT, while rest 50 patients underwent BABART. During the procedure, intraoperative neuromonitoring system was used and all recurrent laryngeal nerves (RLNs) were preserved, additionally for TOVRT procedure, three intraoral ports or right axillary fold incision was used to allow for fine countertraction of tissue for radical oncological dissection. The clinical data including age, gender, height, weight, BMI, primary tumor size, number of central lymph node removed, central lymph node metastasis, operating time, total hospital stays, postoperative hospital stays, total postoperative drainage volume, postoperative pain score, cosmetic effect and complications were recorded and analyzed. RESULTS: There were no significant differences in gender, height, weight, BMI and removed central lymph nodes between the two groups (P > 0.05). Patients accepted TOVRT were younger and had smaller primary tumor size than those who accepted BABART. The TOVRT group had a longer surgical time than the BABART group, but with smaller postoperative drainage volume and superior cosmetic effect (under visual analogue scale, VAS) (P < 0.05). There was no significant difference in lymph node metastasis, hospital stay and postoperative pain score (under numerical rating scale, NRS) between the two groups (P > 0.05). Last but not least, certain peculiar complications were observed in TOVRT group: paresthesia of the lower lip and the chin (one case), surgical site infection (one case) and skin burn (one case). CONCLUSION: Transoral-vestibular robotic thyroidectomy is safe and feasible for certain patients, which could be considered an alternative approach for patients who require no scarring on their neck.

RPB5-Mediating Protein Promotes Cholangiocarcinoma Tumorigenesis and Drug Resistance by Competing With NRF2 for KEAP1 Binding.

BACKGROUND AND AIMS: Cancer cell survival depends on the balance between reactive oxygen species production and scavenging, which is regulated primarily by NRF2 during tumorigenesis. Here, we demonstrate that deletion of RBP5-mediating protein (RMP) in an autonomous mouse model of intrahepatic cholangiocarcinoma (ICC) delays tumor progression. APPROACH AND RESULTS: RMP-overexpressing tumor cells exhibited enhanced tolerance to oxidative stress and apoptosis. Mechanistically, RMP competes with NRF2 for binding to the Kelch domain of KEAP1 (Kelch-like ECH-associated protein 1) through the E**E motif, leading to decreased NRF2 degradation via ubiquitination, thus increasing NRF2 nuclear translocation and downstream transactivation of antioxidant genes. This RMP-KEAP1-NRF2 axis promotes ICC tumorigenesis, metastasis, and drug resistance. Consistent with these findings, the RMP level in human ICC is positively correlated with the protein level of NRF2 and is associated with poor prognosis. CONCLUSION: These findings reveal that RMP is involved in the oxidative stress defense program and could be exploited for targeted cancer therapies.

Thalidomide with blockade of co-stimulatory molecules prolongs the survival of alloantigen-primed mice with cardiac allografts.

BACKGROUND: Miscellaneous memory cell populations that exist before organ transplantation are crucial barriers to transplantation. In the present study, we used a skin-primed heart transplantation model in mouse to evaluate the abilities of Thalidomide (TD), alone or in combination with co-stimulatory blockade, using monoclonal antibodies (mAbs) against memory T cells and alloantibodies to prolong the second cardiac survival. RESULTS: In the skin-primed heart transplantation model, TD combined with mAbs significantly prolonged the second cardiac survival, accompanied by inhibition of memory CD8+ T cells. This combined treatment enhanced the CD4+Foxp3+ regulatory T cells ratio in the spleen, restrained the infiltration of lymphocytes into the allograft, and suppressed the allo-response of spleen T cells in the recipient. The levels of allo-antibodies also decreased in the recipient serum. In addition, we detected low levels of the constitutions of the lytic machinery of cytotoxic cells, which cause allograft damage. CONCLUSIONS: Our study indicated a potential synergistic action of TD in combination with with mAbs to suppress the function of memory T cells and increase the survival of second allografts in alloantigen-primed mice.

Combination of N, N'-dicyclohexyl-N-arachidonic acylurea and tacrolimus prolongs cardiac allograft survival in mice.

Current immunosuppressive agents for organ transplantation are not ideal because of their strong toxicity and adverse effects. Hence, there is an urgent need to develop novel immunosuppressive agents. The compound N, N'-dicyclohexyl-N-arachidonic acylurea (DCAAA) is a novel highly unsaturated fatty acid from the traditional Chinese medicinal plant Radix Isatidis. In this study, we systematically investigated the toxicity, immunosuppressive effect and mechanisms underlying the activity of DCAAA. The toxicity tests showed that DCAAA treatment did not lead to red blood cell hemolysis and did not affect the liver and kidney functions in mice. The lymphocyte transformation test showed that DCAAA treatment inhibited lymphocyte proliferation in a dose-dependent manner. An in vivo cardiac allotransplantation experiment showed that DCAAA treatment could suppress the immune rejection and significantly prolong the survival of cardiac allografts in recipient mice by reducing the proportion of CD4+ T cells in the spleen and grafts, concentration of interferon-γ in the supernatant and serum and infiltration of inflammatory cells into the grafts. Moreover, a combination treatment with DCAAA and tacrolimus had a synergistic effect in preventing acute rejection of heart transplants. In vitro molecular biology experiments showed that DCAAA treatment inhibited activation of the T-cell receptor-mediated phosphoinostide 3-kinase-protein kinase B pathway, thereby arresting cell cycle transition from the G1 to the S phase, and inhibiting lymphocyte proliferation. Overall, our study reveals a novel, low-toxicity immunosuppressive agent that has the potential to reduce the toxic side effects of existing immunosuppressive agents when used in combination with them.

Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma.

BACKGROUND: Primary cutaneous malignant melanoma is a cancer of the pigment cells of the skin, some of which are accompanied by BRAF mutation. Melanoma incidence and mortality rates have been rising around the world. As the current knowledge about pathogenesis, clinical and genetic features of cutaneous melanoma is not very clear, we aim to use bioinformatics to identify the potential key genes involved in the expression and mutation status of BRAF. METHODS: Firstly, we used UCSC public hub datasets of melanoma (Lin et al., Cancer Res 68(3):664, 2008) to perform weighted genes co-expression network analysis (WGCNA) and differentially expressed genes analysis (DEGs), respectively. Secondly, overlapping genes between significant gene modules and DEGs were screened and validated at transcriptional levels and overall survival in TCGA and GTEx datasets. Lastly, the functional enrichment analysis was accomplished to find biological functions on the web-server database. RESULTS: We performed weighted correlation network and differential expression analyses, using gene expression data in melanoma samples. We identified 20 genes whose expression was correlated with the mutation status of BRAF. For further validation, three of these genes (CYR61, DUSP1, and RNASE4) were found to have similar expression patterns in skin tumors from TCGA compared with normal skin samples from GTEx. We also found that weak expression of these three genes was associated with worse overall survival in the TCGA data. These three genes were involved in the nucleic acid metabolic process. CONCLUSION: In this study, CYR61, DUSP1, and RNASE4 were identified as potential genes of interest for future molecular studies in melanoma, which would improve our understanding of its causes and underlying molecular events. These candidate genes may provide a promising avenue of future research for therapeutic targets in melanoma.

Identification of Potential Key Genes and Pathways in Early-Onset Colorectal Cancer Through Bioinformatics Analysis.

This study was designed to identify the potential key protein interaction networks, genes, and correlated pathways in early-onset colorectal cancer (CRC) via bioinformatics methods. We selected microarray data GSE4107 consisting 12 patient's colonic mucosa and 10 healthy control mucosa; initially, the GSE4107 were downloaded and analyzed using limma package to identify differentially expressed genes (DEGs). A total of 131 DEGs consisting of 108 upregulated genes and 23 downregulated genes of patients in early-onset CRC were selected by the criteria of adjusted P values <.01 and |log2 fold change (FC)| ≥ 2. The gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were accomplished to view the biological process, cellular components, molecular function, and the KEGG pathways of DEGs. Finally, protein-protein interactions (PPIs) were constructed, and the hub protein module was identified. Genes such as ACTA2, ACTG2, MYH11, CALD1, MYL9, TPM2, and LMOD1 were strongly implicated in CRC. In summary, in this study, we indicated that molecular mechanisms were involved in muscle contraction and vascular smooth muscle contraction signaling pathway, which improve our understanding of CRC and could be used as new therapeutic targets for CRC.

Six2 is negatively correlated with prognosis and facilitates epithelial-mesenchymal transition via TGF-ß/Smad signal pathway in hepatocellular carcinoma.

BACKGROUND: Increasing evidence indicates that Six2 contributes to tumorigenesis in various tumor including hepatocellular carcinoma (HCC). This study aimed to determine the role of Six2 in HCC and to elucidate the association of Six2 with clinical pathological characteristics. METHODS: The expressions of Six2 in HCC tumor, para-tumor tissue and portal vein tumor thrombus (PVTT) were detected by tissue microarray technique, immunohistochemistry, real-time RT-PCR and Western blotting. Chi-square and Kaplan-Meier analysis were used to analyze the correlation between Six2 expression and prognosis of HCC patients. Lentivirus mediated Six2 knockdown, spheroid formation assay, proliferation assay and subcutaneous tumor implantation were performed to determine the function of Six2. RESULTS: In 274 HCC samples, Six2 was strongly expressed. Kaplan-Meier analysis revealed that high expression of Six2 was correlated with a shorter overall survival (OS) and disease-free survival (DFS). Moreover, Six2 expression was associated with sex, alpha-fetoprotein, tumor size and portal vein invasion. Six2 was highly expressed in PVTT. Six2 knockdown inhibited HCC cell lines proliferation, migration, and self-renewal in vitro and in vivo. In addition, low-expression of Six2 weakened TGF-ß induced Smad4 activation and epithelial-mesenchymal transition in HCC cell lines. CONCLUSIONS: Elevated Six2 expression in HCC tumor patients was associated with negative prognosis. Upregulated Six2 promoted tumor growth and facilitated HCC metastasis via TGF-ß/Smad signal pathway.

Tracheal injury following robotic thyroidectomy: A literature review of epidemiology, etiology, diagnosis, and treatment and 3 case reports.

Robotic thyroidectomy is one of the most advanced surgical procedures used to manage benign and malignant thyroid nodules. However, complication risks such as tracheal injury still exists. Tracheal injury in robotic thyroidectomy is difficult to detect and is one of the life-threatening complications. This study reviews the current literature on the tracheal injury following robotic thyroidectomy and also discusses our findings on 2060 cases of robotic thyroidectomy via Da Vinci Surgical System performed in our department and finally presents 3 cases treated in our center. PubMed and Web of Science database were searched using Medical Subject Headings (Mesh) related to "tracheal injury" and "robotic thyroidectomy". The search was conducted without publication date limits. We reviewed the literature and summarized common causes, diagnosis and therapeutic options of tracheal injury in robotic thyroidectomy, which has been described in comparison studies or retrospective studies. Tracheal injury is often diagnosed when patients suffer from dyspnea and usually leads to severe postoperative consequences. Tracheal injury can be suspected in all patients having subcutaneous emphysema, pneumomediastinum, pneumothorax or dyspnea after robotic thyroidectomy. Tracheoscopy is necessary to determine the location and size of tracheal injury. In patients whose condition is stable and the injury is contained, conservative treatment is feasible. Certainly, primary closure or tracheotomy is necessary for patients with serious respiratory difficulty or pneumothorax.

Comparison of transoral vestibular robotic thyroidectomy with traditional low-collar incision thyroidectomy.

Transoral vestibular robotic thyroidectomy can really make the patient's body surface free of scar. This study aimed to compare the surgical and patient-related outcomes between the transoral vestibular robotic thyroidectomy and traditional low-collar incision thyroidectomy. The clinical data of 120 patients underwent transoral vestibular robotic thyroidectomy (TOVRT) or traditional low-collar incision thyroidectomy (TLCIT) were collected from May 2020 to October 2021. Propensity score matching analysis was used to minimize selection bias. All these patients were diagnosed with papillary thyroid carcinoma (PTC) through ultrasound-guided fine-needle aspiration prior to surgical intervention and surgical plan was tailored for each patient. An intraoperative recurrent laryngeal nerve (RLN) detection system was used in all patients, whose RLNs were identified and protected. We performed transoral vestibular robotic thyroidectomy with three intraoral incisions. Additional right axillary fold incisions were adopted occasionally to enhance fine reverse traction of tissue for radical tumor dissection. Clinical data including gender, age, tumor size, BMI, operation time, postoperative drainage volume and time, pain score, postoperative length of stay (LOS),number of lymph nodes removed, complications, and medical expense were observed and analyzed. Propensity score matching was used for 1:1 matching between the TOVRT group and the TLCIT group. All these patients accepted total thyroidectomy(or lobectomy) plus central lymph node dissection and all suffered from PTC confirmed by postoperative pathology. No conversion to open surgery happened in TOVRT group. The operative time of TOVRT group was longer than that of TLCIT group (P < 0.05). The postoperative drainage volume of TOVRT group was more than that of TLCIT group (P < 0.05). The drainage tube placement time of TOVRT group were longer than that of TLCIT group (P < 0.05). Significant differences were also found in intraoperative bleeding volume, pain score and medical expense between the two groups (P < 0.05). The incidence of perioperative common complications such as hypoparathyroidism and vocal cord paralysis in the two groups was almost identical (P > 0.05). However, there were some specific complications such as surgical area infection (one case), skin burn (one case), oral tear (two cases), and paresthesia of the lower lip and the chin (two cases) were found in TOVRT group. Obviously, the postoperative cosmetic effect of the TOVRT group was better than TLCIT group (P < 0.05). TOVRT is safe and feasible for low to moderate-risk PTC patients and is a potential alternative for patients who require no scar on their neck. Patients accepted TOVRT can get more satisfaction and have less psychologic injury caused by surgery.

A humanized mouse model for adeno-associated viral gene therapy.

Clinical translation of AAV-mediated gene therapy requires preclinical development across different experimental models, often confounded by variable transduction efficiency. Here, we describe a human liver chimeric transgene-free Il2rg-/-/Rag2-/-/Fah-/-/Aavr-/- (TIRFA) mouse model overcoming this translational roadblock, by combining liver humanization with AAV receptor (AAVR) ablation, rendering murine cells impermissive to AAV transduction. Using human liver chimeric TIRFA mice, we demonstrate increased transduction of clinically used AAV serotypes in primary human hepatocytes compared to humanized mice with wild-type AAVR. Further, we demonstrate AAV transduction in human teratoma-derived primary cells and liver cancer tissue, displaying the versatility of the humanized TIRFA mouse. From a mechanistic perspective, our results support the notion that AAVR functions as both an entry receptor and an intracellular receptor essential for transduction. The TIRFA mouse should allow prediction of AAV gene transfer efficiency and the study of AAV vector biology in a preclinical human setting.

The influence of fixed prosthesis placement on the clinical effectiveness of non-surgical periodontal therapy.

Background/purpose: Fixed prostheses are essential for restoring teeth with compromised structures. However, the margins of prosthesis potentially create an interface that interferes with proper cleaning. This study evaluated whether the fixed prosthesis placement influenced the clinical effectiveness of non-surgical periodontal therapy (NSPT). Materials and methods: Clinical records from 202 patients with generalized chronic periodontitis receiving NSPT at the National Taiwan University Hospital in 2012-2014 were included. The change and improvement ratio (IR) of clinical parameters following NSPT in the entire dentition or posterior region, and all or periodontitis-affected teeth/crowns (T/C) and sites were evaluated. The differences among natural teeth (NT), prosthetic crowns (PC), and abutments (AB) were compared by using Kruskal-Wallis tests followed by Dunn's post-hoc test. Results: Gingival recession (REC) was greater in PC and AB groups than in the NT group before NSPT, while tooth mobility was also lower in the AB group. REC gain was lower in the AB group after NSPT, while mobility reduction was inferior in the PC and AB groups for all or periodontitis-affected T/C and sites. In periodontitis-affected T/C, IRs in probing pocket depth reduction and clinical attachment gain were lower in the PC group, and mobility reduction was lower in the AB group. The tendency in the posterior region is similar but was less pronounced than in the entire dentition. Conclusion: The effectiveness of NSPT and the improvement of periodontal parameters are reduced when fixed prostheses present. MB reduction is inferior in AB teeth relative to NT.

Prospective application of a prediction model for lateral lymph node metastasis in papillary thyroid cancer patients with central lymph node metastasis.

Objective: This study aimed to develop and apply a prediction model to estimate the probability of lateral lymph node metastasis (LLNM) in patients with cN0 unilateral papillary thyroid carcinoma (PTC) with central lymph node metastasis (CLNM). Setting: All study data were collected from a single tertiary hospital. Methods: Univariable and multivariable logistic regression analyses were used to explore independent predictors of LLNM in the derivation and internal validation cohorts, which were used to construct and validate a nomogram. Another 96 patients were included prospectively to evaluate the efficacy of this nomogram. Results: Maximum tumor diameter greater than 1.0 cm (OR, 2.712; 95% CI, 1.412-5.210), multifocality (OR, 2.758; 95% CI, 1.120-6.789), the number of CLNM ≥3 (OR, 2.579; 95% CI, 1.315-5.789), CLNM ratio ≥0.297 (OR, 2.905; 95% CI, 1.396-6.043), and tumors located in the upper portion (OR 2.846, 95% CI 1.151-7.039) were independent predictors associated with LLNM. The prediction model showed excellent discrimination with an AUC of 0.731 (95% CI, 0.635-0.827). Novel risk stratification for LLNM was constructed based on this nomogram. In the prospective cohort, we stratified these patients into three risk subgroups: low-, moderate-, and high-risk subgroups and we found that the probability of LLNM was positively correlated with the total points from the nomogram. Conclusion: This nomogram was applied in prospective clinical practice and distinguished PTC patients with a genuinely high risk of LLNM. Surgeons can use our nomogram to tailor the surgical plan and to credibly determine further postoperative therapy.