[Application of double-layer soft tissue suture closure technique in the surgical treatment of patients with mandible medication-related osteonecrosis of the jaw of early and medium stages].

OBJECTIVE: To investigate the clinical application effect of double-layer soft tissue (DLST) suture closure technique in patients with mandible medication-related osteonecrosis of the jaw (MRONJ) of early and medium stages resulted in application of anti-bone-resorptive drugs. METHODS: Early to medium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking University School and Hospital of Stomatology from October 2021 to September 2022 were included. Clinical information of the patients were collected, including primary disease, concomitant disease, medication regimen (drug type, duration of medication), MRONJ stage, clinical symptoms, imaging manifestations, etc. During surgery, after using marginal mandibulae resection to remove the necrotic bone, the wound was closed using DLST closure technique. Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique, the pain score and functional status of the patiens were evaluated. RESULTS: This study totally included 13 patients, 12 women and 1 man, aged (66.69±13.14) years. Seven patients had osteoporosis, 2 had lung cancer, 3 had breast cancer and 1 had prostate cancer among their primary diseases; 7 had no concomitant diseases, 2 had diabetes mellitus, 2 had cardiovascular disease and 1 had dry syndrome. Intravenous zoledronic acid were used in 9 patients, the average duration was (37.7±20.0) months, and other drugs, such as letrozole tablets were taken in 7 patients at the same time; Denosumab injection was used in 3 patients for an average of (10.3±11.9) months; Alendronate sodium tablets were taken in 5 patients for an average of (55.20±27.20) months, and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 patients. The average post-operative follow-up was 11.9 months (9 to 17 months), and all the 13 patients were cured without complications, such as pus overflow and so forth. The pre-operative score of Karnofsky performance status (KPS) in the patients was 68.46±14.05, and the post-operative score was 82.31±15.36, and the difference was statistically significant (P < 0.05). The pre-operative score of visual analogue scale (VAS) in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51, and the difference had statistical significance (P < 0.001). CONCLUSION: The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the mandible using anti-bone-resorptive drugs alone, and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

[Left mandibular osteonecrosis following herpes zoster of the third branch of left trigeminal nerve: A case report].

Herpes zoster of trigeminal nerve was a common skin disease caused by varicella-zoster virus infection. Simple involvement of the third branch of trigeminal nerve was rare, and so were oral complications such as pulpitis, periodontitis, spontaneous tooth loss, bone necrosis, etc. This article presented a case of herpes zoster on the third branch of the left trigeminal nerve complicated with left mandibular osteonecrosis. We reported the case of a 64-year-old man with sudden pain in the left half of the tongue 1 month ago, and then herpes on the left facial skin appeared following with acute pain.The local hospital diagnosed it as herpes zoster and treated it with external medication. A few days later, he developed gum pain in the left mandibular posterior tooth area. He was admitted to Peking University School and Hospital of Stomatology one week ago with loose and dislodged left posterior tooth accompanied by left mandibular bone surface exposure. Clinical examination showed bilateral symmetry and no obvious restriction of mouth opening. Visible herpes zoster pigmentation and scarring on the left side of the face appeared. The left mandibular posterior tooth was missing, the exposed bone surface was about 1.5 cm×0.8 cm, and the surrounding gingiva was red and swollen, painful under pressure, with no discharge of pus. The remaining teeth in the mouth were all Ⅲ degree loosened. Imageological examination showed irregular low-density destruction of the left mandible bone, unclear boundary, and severe resorption of alveolar bone. The patient was diagnosed as left mandibular osteonecrosis. Under general anesthesia, left mandibular lesion exploration and curettage + left mandibular partial resection + adjacent flap transfer repair were performed. The patient was re-exmained 6 months after surgery, there was no redness, swelling or other abnormality in the gums and the herpes pigmentation on the left face was significantly reduced. Unfortunately, the patient had complications of postherpetic neuralgia. This case indicate that clinicians should improve their awareness of jaw necrosis, a serious oral complication of trigeminal zoster, and provide early treatment. After the inflammation was initially controlled, surgical treatment could be considered to remove the necrotic bone, curettage the inflammatory granulation tissue, and extraction of the focal teeth to avoid further deterioration of the disease.

Bacterial distribution and inflammatory cytokines associated with oral cancer with and without jawbone invasion-a pilot study.

OBJECTIVE: To explore the bacterial and inflammatory variations in oral cancer patients with and without jawbone invasion. MATERIALS AND METHODS: A total of 20 specimens of fresh tumor tissue, including 10 from the tumor-invaded jawbone (JIOC group) and 10 without jawbone invasion (NJIOC group), were collected from oral cancer patients. Meanwhile, 10 specimens from normal oral mucosa were collected from healthy patients (control group). The microbiomic content of each sample was analyzed by 16S rRNA gene sequencing, while the expression of inflammatory cytokines was assessed using protein microarray analysis. RESULTS: There was a significant difference in ß diversity between JIOC and NJIOC groups (P < 0.05), but no difference between NJIOC and control groups. The average relative abundance of Fusobacteria and Spirochaetes was higher, while Firmicutes was lower in the JIOC group than in the NJIOC group (all P < 0.05). The expression of pro-inflammatory cytokines like interleukin (IL)-1α, IL-1ß, IL-4, and IL-8 was upregulated in the JIOC group compared with the NJIOC group, while MCP-1 was decreased (all P < 0.05). Slackia spp. and Howardella spp. were positively correlated with IL-4; Odoribacter spp. and Acidaminococcaceae spp. were negatively correlated with IL-4, and Clostridium XIVa spp. was negatively correlated with IL-1α and IL-1ß. CONCLUSION: Bacterial and inflammatory differences were observed in oral cancer patients with and without jawbone invasion, where the relative abundance of the differential bacteria was associated with the expression of the inflammatory cytokines. CLINICAL RELEVANCE: This study investigated the changes in the flora during jawbone invasion in oral cancer and its effect on inflammatory factors, elucidating the possible mechanisms of jawbone invasion caused by oral cancer, which may lead to new ideas for the clinical prevention and treatment of jawbone invasion in oral cancer.

Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts.

BACKGROUND: Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients. METHODS: The clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket. RESULTS: Patients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib. CONCLUSION: Our findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs.

Bone morphogenetic protein receptor 1α promotes osteolytic lesion of oral squamous cell carcinoma by SHH-dependent osteoclastogenesis.

Oral squamous cell carcinoma (OSCC) is an aggressive tumor that usually invades the maxilla or mandible. The extent and pattern of mandibular bone invasion caused by OSCC are the most important factors determining the treatment plan and patients' prognosis. Yet, the process of mandibular invasion is not fully understood. The following study explores the molecular mechanism that regulates the mandibular invasion of OSCC by focusing on bone morphogenetic protein receptor 1α (BMPR1α) and Sonic hedgehog (SHH) signals. We found that BMPR1α was positively correlated to bone defect of OSCC patients. Mechanistically, BMPR1α signaling regulated the differentiation and resorption activity of osteoclasts through the interaction of OSCC cells and osteoclast progenitors, and this process was mediated by SHH secreted by tumor cells. The inhibition of SHH protected bone from tumor-induced osteolytic activity. These results provide a potential new treatment strategy for controlling OSCC from invading the jawbones.

The Fgl2 interaction with Tyrobp promotes the proliferation of cutaneous squamous cell carcinoma by regulating ERK-dependent autophagy.

Human fibroleukin 2 (Fgl2), a member of the fibrinogen superfamily, can cleave prothrombin to generate thrombin or is secreted in a soluble form as a new type of effector of Tregs with immunomodulatory functions. However, there is little research on the role of Fgl2 in cutaneous squamous cell carcinoma (CSCC) growth. We examined the expression of Fgl2 in samples from CSCC patients and CSCC cell lines. Then, the effect of Fgl2 on CSCC was evaluated in vitro and in animals. Regulation of autophagy by Fgl2 was explored in CSCC. Coimmunoprecipitation (Co-IP) and immunofluorescence colocalization experiments were conducted to identify the regulatory effect of Fgl2 on the downstream protein Tyrobp. Then, gain- or loss-of-function analyses and evaluation of Tyrobp expression were performed to validate its role in autophagy and proliferation promoted by Fgl2. Here, our study demonstrated that Fgl2 promoted the proliferation of CSCC cells in vitro and in vivo. Knocking down Fgl2 reduced CSCC cell proliferation and inhibited autophagy in CSCC. Mechanistically, Fgl2 interacted with Tyrobp and promoted ERK-dependent autophagy, resulting in the proliferation of CSCC cells. Our study suggested that Fgl2 could be a promising prognostic biomarker and useful therapeutic target for CSCC.

pERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells.

BACKGROUND: Cancer stem cells (CSCs) drive tumor initiation and progression and participate in tumor chemoresistance. We recently discovered that oral squamous cell carcinoma (OSCC) cells that highly express CD10 (CD10H cells) present cancer stem cells (CSC)-associated characteristics, which, in turn, affect the tumor growth, epithelial-mesenchymal transition (EMT), and resistance to cisplatin. In this study, we further investigated this mechanism in vitro and in vivo. We hypothesized that IL8 might regulate migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells through the ERK pathway. METHODS: CD10 MicroBead Kit was used to select HN6 cells with high and low expression of CD10. The target protein IL8 was screened via protein chip assay. Lentiviral transduction and specific inhibitor were applied to investigate the signaling pathway. Real-time PCR, Western blot, and immunohistochemistry were used to analyze the mRNA and protein expression; transwell assay, spheroid formation assay, and cell viability assay were used to study the cell biological behavior in vitro; xenograft animal model was used to evaluate the tumor formation rate in vivo. RESULTS: Overexpression of CD10 promoted CSC-related genes expression and enhanced migration, invasion, spheroid formation, and chemoresistance in HN6 cells. Moreover, the overexpression of IL8 was detected in OSCC tumor tissue and cell lines (HN6 and CAL27) overexpressing CD10. IL8 secreted by CD10H HN6 promoted migration and invasion and restored tumor chemosensitivity via the p-ERK signaling pathway, while the inhibition of IL8 increased the chemosensitivity to cisplatin. CONCLUSIONS: IL8 secretion by CD10 positive cells promotes migration, invasion, and cisplatin resistance of OSCC via the p-ERK signaling pathway.

Cancer stemness of CD10-positive cells regulated by Hedgehog pathway promotes the resistance to cisplatin in oral squamous cell carcinoma.

OBJECTIVE: To explore the role of CD10 in cisplatin resistance of oral squamous cell carcinoma (OSCC) and its association with the Hedgehog (Hh) signaling pathway and cancer stem cells (CSCs). METHODS: The correlation between cell viability and CD10 expression was analyzed in different OSCC cell lines after the cisplatin treatment. Genes related to chemotherapy resistance, cancer stem cells and the epithelial-mesenchymal transition were detected by quantitative real-time PCR (qPCR) in CD10high and CD10low OSCC cells. Mouse xenograft model and venous metastasis model were used to explore the potential regulatory mechanism of the resistance effect of CD10 on cisplatin. RESULTS: The higher expression of CD10 gene in different cell lines displayed enhanced cisplatin resistance ability. The expression of genes related to chemotherapy resistance, cell stemness, and the epithelial-mesenchymal transition was significantly higher in CD10high cells compared with CD10low cells. Moreover, the combination of cisplatin and Hh pathway inhibitors significantly reduced the resistance of CD10 to cisplatin in the xenograft model and venous metastasis models. CONCLUSION: CD10-positive cells are implicated in developing cisplatin resistance of OSCC, which could be related to its cancer stem cell characteristics regulated by the Hedgehog pathway.

Recycling of LiCoO2 cathode material from spent lithium ion batteries by ultrasonic enhanced leaching and one-step regeneration.

A novel process for recycling of spent LiCoO2 cathode materials has been developed. The novel process comprises an ultrasonic enhanced leaching and one-step regeneration of LiCoO2 materials with spray drying method. The ultrasonic is novelly applied for effectively improving leaching process of spent LiCoO2 materials in the system of DL-malic acid and H2O2. The leaching efficiencies of 98.13% for Li and 98.86% for Co were presented under the optimal condition of 1.5 mol/L DL-malic acid with 3 vol% H2O2, the solid/liquid ratio of 4 g/L, ultrasonic power of 95 W, temperature of 80 °C and leaching time of 25 min. Based on kinetic analysis, the ultrasonic enhanced leaching process is mainly controlled by the diffusion control model. Meanwhile, the product of Co(C4O5O5)2 formed on particles surface of spent LiCoO2 materials during ultrasonic enhanced leaching process, which is provided from reaction mechanism analysis of scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). Finally, the regenerated LiCoO2 materials are regenerated in one step by spray drying from leaching solution, which present good electrochemical performance.

Reversible Micrometer-Scale Spiral Self-Assembly in Liquid Crystalline Block Copolymer Film with Controllable Chiral Response.

The spiral is a fundamental structure in nature and spiral structures with controllable handedness are of increasing interest in the design of new chiroptical materials. In this study, micrometer-scale spiral structures with reversible chirality were fabricated based on the assembly of a liquid crystalline block copolymer film assisted by enantiopure tartaric acid. Mechanistic insight revealed that the formation of the spiral structures was closely related to the liquid crystalline properties of the major phase of block copolymer under the action of chiral tartaric acid. The chiral spiral structures with controllable handedness were easily erased under ultraviolet light irradiation and restored via thermal annealing. This facile thermal treatment method provides guidance for fabrication of chiral micrometer-scale spiral structures with adjustable chiral properties.

Suppression of G6PD induces the expression and bisecting GlcNAc-branched N-glycosylation of E-Cadherin to block epithelial-mesenchymal transition and lymphatic metastasis.

BACKGROUND: As the rate-limit enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD) plays important roles in tumour progression, but the exact mechanism through which G6PD controls cancer metastasis remains unclear. METHODS: G6PD expression in resected oral squamous cell carcinoma (OSCC) samples was analysed by immunohistochemistry. The effects and mechanism of G6PD suppression on OSCC cell lines were measured by transwell assay, wound healing assay, western and lectin blot, mass spectrometer analysis, ChIP-PCR, and luciferase reporter assay. BALB/c-nude mice were used to establish orthotopic xenograft model. RESULTS: G6PD expression in the tumours of 105 OSCC patients was associated with lymphatic metastasis and prognosis. In vitro cellular study suggested that G6PD suppression impaired cell migration, invasion, and epithelial-mesenchymal transition. Furtherly, G6PD knockdown activated the JNK pathway, which then blocked the AKT/GSK-3ß/Snail axis to induce E-Cadherin expression and transcriptionally regulated MGAT3 expression to promote bisecting GlcNAc-branched N-glycosylation of E-Cadherin. An orthotopic xenograft model further confirmed that dehydroepiandrosterone reduced lymphatic metastatic rate of OSCC, which was partially reversed by JNK inhibition. CONCLUSIONS: Suppression of G6PD promoted the expression and bisecting GlcNAc-branched N-glycosylation of E-Cadherin via activating the JNK pathway, which thus acted on OSCC metastasis.

Investigation of treatment methods in obstructive colorectal cancer.

PURPOSE: The aim of this study was to explore the treatment strategies for patients with obstructive colorectal cancer at different sites. METHODS: Treatment strategies were adopted according to the location of colorectal cancer and the condition of the patients when they were admitted to the hospital. Among a total of 134 patients, 29 patients were subjected to stent placement to relieve the obstruction before undergoing colorectal resection, 15 patients underwent per anum ileus catheterization to alleviate the symptoms of obstruction and waited for removal of the tumor within a limited time; 39 underwent intraoperative colonic lavage and colon resection with anastomosis and the remaining 51 patients were subjected to emergency surgery due to strangulation of the bowel, perforation, septic shock or other conditions before surgery. RESULTS: Stent placement was successfully performed on 23 patients, with a success rate of 79%. Ninety-five of 134 patients (71% had stage I anastomosis and only one case had anastomotic fistula. Infection of incision happened in 9 (7%) cases and 2 (1.5%) patients died of infection. CONCLUSIONS: Individualized treatment for patients with obstructive colorectal cancer can lead to tumor resection and stage I anastomosis, thereby avoiding the suffering of second-stage surgery or colostomy.

Bifidobacterium breve-derived indole-3-lactic acid ameliorates colitis-associated tumorigenesis by directing the differentiation of immature colonic macrophages.

Aim: To elucidate dynamics and functions in colonic macrophage subsets, and their regulation by Bifidobacterium breve (B. breve) and its associated metabolites in the initiation of colitis-associated colorectal cancer (CAC). Methods: Azoxymethane (AOM) and dextran sodium sulfate (DSS) were used to create a CAC model. The tumor-suppressive effect of B. breve and variations of macrophage subsets were evaluated. Intestinal macrophages were ablated to determine their role in the protective effects of B. breve. Efficacious molecules produced by B. breve were identified by non-targeted and targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The molecular mechanism was further verified in murine bone marrow-derived macrophages (BMDMs), macrophages derived from human peripheral blood mononuclear cells (hPBMCs), and demonstrated in CAC mice. Results: B. breve alleviated colitis symptoms, delayed colonic tumorigenesis, and promoted phenotypic differentiation of immature inflammatory macrophages into mature homeostatic macrophages. On the contrary, the ablation of intestinal macrophages largely annulled the protective effects of B. breve. Microbial analysis of colonic contents revealed the enrichment of probiotics and the depletion of potential pathogens following B. breve supplementation. Moreover, indole-3-lactic acid (ILA) was positively correlated with B. breve in CAC mice and highly enriched in the culture supernatant of B. breve. Also, the addition of ILA directly promoted AKT phosphorylation and restricted the pro-inflammatory response of murine BMDMs and macrophages derived from hPBMCs in vitro. The effects of ILA in murine BMDMs and macrophages derived from hPBMCs were abolished by the aryl hydrocarbon receptor (AhR) antagonist CH-223191 or the AKT inhibitor MK-2206. Furthermore, ILA could protect against tumorigenesis by regulating macrophage differentiation in CAC mice; the AhR antagonist largely abrogated the effects of B. breve and ILA in relieving colitis and tumorigenesis. Conclusion: B. breve-mediated tryptophan metabolism ameliorates the precancerous inflammatory intestinal milieu to inhibit tumorigenesis by directing the differentiation of immature colonic macrophages.

Tracking SO2 plumes from the Tonga volcano eruption with multi-satellite observations.

The Hunga Tonga-Hunga Ha'apai (HTHH) volcano eruption received worldwide attention due to its magnitude and potential effects on environment and climate. However, the operational sulfur dioxide (SO2) products mis-estimated SO2 emissions under volcanic conditions due to large uncertainties in the assumptions of SO2 plume altitude. That might have occurred in previous volcanic eruptions and misled understanding of the evolution of sulfate aerosols in the atmosphere and their impact on global climate. Here, we simultaneously retrieved the volcanic SO2 and its plume altitude from the Troposphere Monitoring Instrument (TROPOMI) and the Environment Monitoring Instrument-2 (EMI-2), exploring the SO2 burden, distribution, and evolution from January 14 to 17. We captured multiple eruptions with the second eruption emitting far more SO2 than the first. Total emissions exceeded 900 kt, significantly higher than those from operational products. Our inferred emission fluxes and injection heights offer valuable references for climate modeling and submarine volcano studies.

Advanced Microwave Strategies Facilitate Structural Engineering for Efficient Electrocatalysis.

In the dynamic realm of energy conversion, the demand for efficient electrocatalysis has surged due to the urgent need to seamlessly integrate renewable energy. Traditional electrocatalyst preparation faces challenges like poor controllability, elevated costs, and stringent operational conditions. The introduction of microwave strategies represents a transformative shift, offering rapid response, high-temperature energy, and superior controllability. Notably, non-liquid-phase advanced microwave technology holds promise for introducing novel models and discoveries compared to traditional liquid-phase microwave methods. This review examines the nuanced applications of microwave technology in electrocatalyst structural engineering, emphasizing its pivotal role in the energy paradigm and addressing challenges in conventional methods. The ensuing discussion explores the profound impact of advanced microwave strategies on electrocatalyst structural engineering, highlighting discernible advantages in optimizing performance. Various applications of advanced microwave techniques in electrocatalysis are comprehensively discussed, providing a forward-looking perspective on their untapped potential to propel transformative strides in renewable energy research. It provides a forward-looking perspective, delving into the untapped potential of microwaves to propel transformative strides in renewable energy research.

FD-Net: Feature Distillation Network for Oral Squamous Cell Carcinoma Lymph Node Segmentation in Hyperspectral Imagery.

Oral squamous cell carcinoma (OSCC) has the characteristics of early regional lymph node metastasis. OSCC patients often have poor prognoses and low survival rates due to cervical lymph metastases. Therefore, it is necessary to rely on a reasonable screening method to quickly judge the cervical lymph metastastic condition of OSCC patients and develop appropriate treatment plans. In this study, the widely used pathological sections with hematoxylin-eosin (H&E) staining are taken as the target, and combined with the advantages of hyperspectral imaging technology, a novel diagnostic method for identifying OSCC lymph node metastases is proposed. The method consists of a learning stage and a decision-making stage, focusing on cancer and non-cancer nuclei, gradually completing the lesions' segmentation from coarse to fine, and achieving high accuracy. In the learning stage, the proposed feature distillation-Net (FD-Net) network is developed to segment the cancerous and non-cancerous nuclei. In the decision-making stage, the segmentation results are post-processed, and the lesions are effectively distinguished based on the prior. Experimental results demonstrate that the proposed FD-Net is very competitive in the OSCC hyperspectral medical image segmentation task. The proposed FD-Net method performs best on the seven segmentation evaluation indicators: MIoU, OA, AA, SE, CSI, GDR, and DICE. Among these seven evaluation indicators, the proposed FD-Net method is 1.75%, 1.27%, 0.35%, 1.9%, 0.88%, 4.45%, and 1.98% higher than the DeepLab V3 method, which ranks second in performance, respectively. In addition, the proposed diagnosis method of OSCC lymph node metastasis can effectively assist pathologists in disease screening and reduce the workload of pathologists.

Dehydroepiandrosterone attenuated the immune escape of oral squamous cell carcinoma through NF-κB p65/miR-15b-5p/B7-H4 axis.

OBJECTIVES: We aimed to explore the effects and mechanisms of action of dehydroepiandrosterone (DHEA) on immune evasion of oral squamous cell carcinoma (OSCC) to provide evidence for enhancing the effect of immunotherapy. MATERIALS AND METHODS: A xenograft mouse model and immunohistochemistry were used to reveal the patterns of tumor-infiltrating lymphocytes (TILs). The CAL27 and SCC VII cell lines were used for the in vitro study. Western blotting, qPCR, immunofluorescence, and flow cytometry were used to evaluate the expression of B7-H4. Recombinant mouse B7-H4 protein (rmB7-H4) and PG490, an inhibitor of NF-κB p65 were used for the "rescue study." Gain- and loss-of-function, luciferase reporter, and chromatin immunoprecipitation assays were performed to verify this mechanism. RESULTS: DHEA inhibited tumor growth in an OSCC xenograft mouse model, increased CD8 + cells, and decreased FOXP3 + cells in TILs. DHEA reduced the expression of B7-H4 in CAL27 and SCC VII cells RmB7-H4 reverses the effect of DHEA on tumor growth and TIL patterns. DHEA increased the expression of miR-15b-5p and activated its transcriptional factor NF-κB p65. Further experiments demonstrated that miR-15b-5p inhibited B7-H4 expression by binding to its 3'-UTR regions, and NF-κB p65 activated miR-15b transcription. PG490 reversed the effects of DHEA on tumor growth, antitumor immunity in the OSCC xenograft model, and the expression/phosphorylation of NF-κB p65, miR-15b-5p, and B7-H4. CONCLUSIONS: This study indicates that DHEA attenuates the immune escape of OSCC cells by inhibiting B7-H4 expression, providing new insights for cancer immunotherapy.

Efficacy of submental island flap closing advanced mandibular MRONJ lesion in malignancy patients.

OBJECTIVE: This study evaluated the effectiveness of a submental island flap in closing advanced mandibular medication-related osteonecrosis of the jaw (MRONJ) wounds in patients with malignant tumors. SUBJECTS AND METHODS: A total of 85 patients with stage II and III MRONJ of mandible with malignant tumor as their primary disease were retrospectively analyzed. All patients underwent surgical treatment, and the soft tissue wound closure was performed either with a submental island flap (SIF) or mucoperiosteal flap (MF). Univariate and multifactorial models were applied to analyze the factors influencing patients' prognosis. RESULTS: Univariate analysis (p = 0.004, OR 0.075-0.575, 95% CI) and binary logistic regression (p = 0.017, OR 0.032-0.713, 95% CI) suggested that the surgical prognosis of SIF wound closure was significantly better than that of MF. CONCLUSION: Closure of wound after resection of mandibular MRONJ lesions in patients with malignant tumors using SIF had a better clinical prognosis compared with MF.

A community partitioning algorithm for cyberspace.

Community partitioning is an effective technique for cyberspace mapping. However, existing community partitioning algorithm only uses the topological structure of the network to divide the community and disregards factors such as real hierarchy, overlap, and directionality of information transmission between communities in cyberspace. Consequently, the traditional community division algorithm is not suitable for dividing cyberspace resources effectively. Based on cyberspace community structure characteristics, this study introduces an algorithm that combines an improved local fitness maximization (LFM) algorithm with the PageRank (PR) algorithm for community partitioning on cyberspace resources, called PR-LFM. First, seed nodes are determined using degree centrality, followed by local community expansion. Nodes belonging to multiple communities undergo further partitioning so that they are retained in the community where they are most important, thus preserving the community's original structure. The experimental data demonstrate good results in the resource division of cyberspace.

Influence of two kinds of clearance joints on the dynamics of planar mechanical system based on a modified contact force model.

This study takes the slider-crank mechanism with revolute joint and translational joint as the research object and studies the contact force model of the clearance joint and the influence of the hybrid clearance joints on the nonlinear dynamic behavior of the mechanism. A modified contact force model is established based on the simplified elastic oscillator model, which can be used as a normal force in clearance joint. In the new contact force model, the component n of the indentation depth can be arbitrarily selected and it can support the calculation of contact force for both fully elastic recovery, non-elastic recovery and fully inelastic recovery. Based on the LuGre friction model, the tangential friction model of the clearance joint is given. Thus, the normal force and tangential force during the dynamic contact of the clearance joint are formed. Combining Lagrange's equations of the first kind with the modified normal force and tangential friction force, the dynamic equations of the multi-body system with clearance joints are established. The Baumgarte stabilization method is used to improve the numerical stability. The correctness of the dynamic prediction model in the mechanism with clearance joint is verified by experiment. The dynamic analysis of the slider-crank mechanism with mixed clearance joints shows that the revolute clearance joint has a greater influence on the mechanism than the translational clearance, and the revolute clearance joint plays a leading role in the dynamic response.