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.

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.

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.

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 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.

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.

[Human Umbilical Cord-Derived Mesenchymal Stem Cells Prevent Acute Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation Via Exosome-Mediated MicroRNA and Its Mechanism].

OBJECTIVE: To explore molecular mechanisms by which umbilical cord-derived mesenchymal stem cells suppress the development of GVHD after bone marrow hematopoietic stem cell transplantation. METHODS: A mouse model of aGVHD was constructed after bone marrow hematopoietic stem cell transplantation, and the umbilical cord-derived mesenchymal stem cells were cultured, and then injected into the aGVHD mouse model, so as to investigate its prophylactic efficacy. Prophylactic effect of the exosomes isolated from umbilical cord-derived mesenchymal stem cells on aGVHD mice was assessed. Sequencing analysis of miRNA from exosomes was performed. RESULTS: aGVHD model was successfully constructed after hematopoietic stem cell transplantation. By injecting umbilical cord-derived mesenchymal stem cells into the GVHD mouse model, it was found that the treatment significantly prolonged survival time of mice compared to the untreated group. Injection exosomes derived from umbilical cord-derived mesenchymal stem cells into the GVHD mouse model significantly prolonged the survival time of mice compared to the untreated group. High-throughput sequencing data showed that microRNA such as miR-21 in exosomes isolated from umbilical cord-derived mesenchymal stem cells, which mainly affected the signaling pathways such as cell adhesion, RNA degradation. CONCLUSION: The umbilical cord-derived mesenchymal stem cells can prevent the occurrence of aGVHD after HSCT, which is mediate by MicroRNA in the exosomes derived from umbilical cord-derived mesenchymal stem cells.

[Protective mechanism of electroacupuncture combined with acellular nerve allografts on spinal ganglia in rats with sciatic nerve injury].

OBJECTIVE: To observe the effects of electroacupuncture (EA) combined with acellular nerve allograft (ANA) on the morphological structure of spinal ganglion cells and the protein expressions of nerve growth factor (NGF) and phosphorylated protein kinase B (p-Akt) in rats with sciatic nerve injury (SNI), so as to explore the protective mechanism of EA combined with ANA on spinal ganglia. METHODS: SPF male SD rats were randomly divided into normal, model, single ANA bridging (bridging) and EA + ANA (combination) groups， with 10 rats in each group. The SNI rat model was established by right sciatic nerve transection. Rats in the bridging group were bridged with ANA to the two broken ends of injured sciatic nerves. Rats in the combination group were treated with EA at "Yanglingquan" (GB34) and "Huantiao" (GB30) 2 d after ANA bridging, with dilatational wave, frequency of 1 Hz/20 Hz, intensity of 1 mA, 15 min/d, 7 d as a course of treatment for 4 consecutive courses. Sciatic function index (SFI) was observed by footprint test. Wet weight ratio of tibialis anterior muscle was calculated after weighing. Morphology of rat spinal ganglion cells was observed after Nissl staining. The protein expressions of NGF and p-Akt were detected by immunofluorescence and Western blot. RESULTS: Compared with the normal group, the SFI and wet weight ratio of tibialis anterior muscle were significantly decreased (P<0.05), the number of Nissl bodies in spinal ganglion cells was significantly reduced (P<0.05) with dissolution and incomplete structure， the protein expressions of NGF and p-Akt in ganglion cells were significantly decreased (P<0.05) in the model group. Following the interventions and in comparison with the model group, the SFI and the wet weight ratio of tibialis anterior muscle were significantly increased (P<0.05), the damage of Nissl bodies in ganglion cells was reduced and the number was obviously increased (P<0.05), and the protein expressions of NGF and p-Akt in ganglion cells were significantly increased (P<0.05) in the bridging and combination groups. Compared with the bridging group, the SFI and the wet weight ratio of tibialis anterior muscle were increased (P<0.05), the morphology of Nissl bodies in ganglion cells was more regular and the number was increased (P<0.05), the protein expressions of NGF and p-Akt in spinal ganglion cells were significantly increased (P<0.05) in the combination group. CONCLUSION: EA combined with ANA can improve the SFI and the wet weight ratio of tibialis anterior muscle in SNI rats, improve the morphology and structure of Nissl bodies in spinal ganglion cells, and increase the protein expressions of NGF and p-Akt in spinal ganglion, so as to play a protective role on spinal ganglia.

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.

Rescue of glutaric aciduria type I in mice by liver-directed therapies.

Glutaric aciduria type I (GA-1) is an inborn error of metabolism with a severe neurological phenotype caused by the deficiency of glutaryl-coenzyme A dehydrogenase (GCDH), the last enzyme of lysine catabolism. Current literature suggests that toxic catabolites in the brain are produced locally and do not cross the blood-brain barrier. In a series of experiments using knockout mice of the lysine catabolic pathway and liver cell transplantation, we uncovered that toxic GA-1 catabolites in the brain originated from the liver. Moreover, the characteristic brain and lethal phenotype of the GA-1 mouse model was rescued by two different liver-directed gene therapy approaches: Using an adeno-associated virus, we replaced the defective Gcdh gene or we prevented flux through the lysine degradation pathway by CRISPR deletion of the aminoadipate-semialdehyde synthase (Aass) gene. Our findings question the current pathophysiological understanding of GA-1 and reveal a targeted therapy for this devastating disorder.

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.

TIPE2 knockout reduces myocardial cell damage by inhibiting IFN-γ-mediated ferroptosis.

Acute rejection of the transplanted heart is mediated by oxidative programmed cell death through the synergistic effects of the innate and adaptive immune systems. However, the role of ferroptosis, a newly discovered form of oxidative cell death, has not been widely evaluated. Tumor necrosis factor-α-induced protein-8 like 2 (TNFAIP8L2), also known as TIPE2, is required for maintaining immune homeostasis. To characterize the role of TIPE2 in mediating heart allografts, BALB/c hearts were transplanted into C57BL/6 wild-type (WT) and TIPE2-/- recipient mice. In TIPE2-/- recipient mice, allograft injury in BALB/c allograft hearts was significantly reduced through the inhibition of allograft ferroptosis. On day 3 and day 6 post-transplantation, the numbers of CD3+, CD4+, and CD8+ cells among splenocytes and draining lymph node cells were significantly decreased, and the activation of CD4+ and CD8+ cells in grafts was decreased in TIPE2-/- recipient mice compared with WT mice. Moreover, CD4+ and CD8+ T cells in TIPE2-/- recipient mice were characterized by deficient capacities for interferon-γ (IFN-γ) production through the TBK1 signaling axis and increased glutathione peroxidase 4 (GPX4). In cell experiments, treatment with IFN-γ enhanced ferroptosis-specific lipid peroxidation in myocardial cells and correlated inversely with GPX4 expression. Mechanistically, IFN-γ administration decreased the expression of GPX4 by inhibiting MEK/ERK phosphorylation. In summary, our findings demonstrated that TIPE2 deficiency inhibits T-cell production of IFN-γ to reduce ferroptosis in allografts by restraining lipid peroxidation.

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.

The T-type calcium channel CaV3.2 regulates insulin secretion in the pancreatic ß-cell.

Voltage-gated Ca2+ (CaV) channel dysfunction leads to impaired glucose-stimulated insulin secretion in pancreatic ß-cells and contributes to the development of type-2 diabetes (T2D). The role of the low-voltage gated T-type CaV channels in ß-cells remains obscure. Here we have measured the global expression of T-type CaV3.2 channels in human islets and found that gene expression of CACNA1H, encoding CaV3.2, is negatively correlated with HbA1c in human donors, and positively correlated with islet insulin gene expression as well as secretion capacity in isolated human islets. Silencing or pharmacological blockade of CaV3.2 attenuates glucose-stimulated cytosolic Ca2+ signaling, membrane potential, and insulin release. Moreover, the endoplasmic reticulum (ER) Ca2+ store depletion is also impaired in CaV3.2-silenced ß-cells. The linkage between T-type (CaV3.2) and L-type CaV channels is further identified by the finding that the intracellular Ca2+ signaling conducted by CaV3.2 is highly dependent on the activation of L-type CaV channels. In addition, CACNA1H expression is significantly associated with the islet predominant L-type CACNA1C (CaV1.2) and CACNA1D (CaV1.3) genes in human pancreatic islets. In conclusion, our data suggest the essential functions of the T-type CaV3.2 subunit as a mediator of ß-cell Ca2+ signaling and membrane potential needed for insulin secretion, and in connection with L-type CaV channels.

G6PD inhibition sensitizes ovarian cancer cells to oxidative stress in the metastatic omental microenvironment.

Ovarian cancer (OC) is the most lethal gynecological malignancy, with aggressive metastatic disease responsible for the majority of OC-related deaths. In particular, OC tumors preferentially metastasize to and proliferate rapidly in the omentum. Here, we show that metastatic OC cells experience increased oxidative stress in the omental microenvironment. Metabolic reprogramming, including upregulation of the pentose phosphate pathway (PPP), a key cellular redox homeostasis mechanism, allows OC cells to compensate for this challenge. Inhibition of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, reduces tumor burden in pre-clinical models of OC, suggesting that this adaptive metabolic dependency is important for OC omental metastasis.

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.

Radiographic Evaluation of Regeneration Strategies for the Treatment of Advanced Mandibular Furcation Defects: A Retrospective Study.

Teeth with furcation involvement (FI) present a higher risk of loss and are difficult to maintain. This study evaluated the efficacy of furcation defect regeneration (FDR) as a regeneration strategy. Pre-operative and 6-month postoperative radiographs were collected from patients receiving regeneration therapy for mandibular teeth with degree II and early degree III FI. The linear furcation involvement (LFI), ratio of LFI (RLI), LFI and RLI adjusted bythe alveolar bone crest (ABC), and radiographic intensity were assessed. The effects of demographic characteristics, regeneration treatment strategies, the relationship between furcation and ABC, and adjacent intrabony defect regeneration (AIDR) were evaluated using a generalized linear model and logistic regression. The results demonstrated that 1.5 mm adjusted LFI and 40% adjusted RLI were achieved in both pure furcation defects and combined furcation-angular defects by the combination of bone replacement grafts (BRG) and enamel matrix derivatives (EMD) or collagen membrane (CM); deproteinized bovine bone matrix (DBBM) showed a superior outcome among BRG. In combined furcation-angular defects, EMD appeared more beneficial than CM, and AIDR significantly promoted adjusted LFI and RLI. In conclusion, DBBM with EMD or CM was effective for FDR, and AIDR had a positive effect on FDR in the combined furcation-angular defect.

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.