Recent advances in immunotherapy, as a part of the multidisciplinary therapy, has gradually gained more attention. However, only a small proportion of patients who sensitive to the therapy could gain benefits. An increasing number of studies indicate that intestinal microbiota could enhance the efficiency of cancer immunotherapy. As one of the main probiotics, Bifidobacterium plays an important role in immune regulation, which has been proved by animal research and human clinical study. But the detailed mechanism was not clearly elucidated. Here we found oral administration of Bifidobacterium breve (B. breve) lw01 could significantly inhibit tumor growth and up-regulate tumor cell apoptosis, which relied on the recruitment of tumor-infiltrating lymphocytes and dendritic cells (DCs) in tumor microenvironment, but not Lactobacillus rhamnosus (L. rhamnosus) CGMCC 1.3724 or Escherichia coli (E. coli) MG1655. In the in situ ligated intestine loop model, B. breve’s stimulation triggered the upregulated expression of DC-related chemokine CCL20 and recruited more DCs in the intestinal villi. Further study revealed the enhancement of interleukin 12 (IL-12) secretion derived from DCs is essential to B. breve’s antitumor effect, which was counteracted by the treatment of neutralizing antibody for IL-12. Meanwhile, the modulation of intestinal microbiota caused by exogenous B. breve might enhance its antitumor effect. This study provides a simple and easy way to promote antitumor immunity via B. breve.

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. Source codes will be released at https://github.com/MrXueyuZhang/FD-Net .

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.

The authors described a new procedure for secondary mandibular reconstruction with a free fibular flap using digital techniques involving surgical navigation, which have the potential to improve the clinical outcomes of this procedure.

Objective: Refractory infection is an important factor affecting the progression of medication-related osteonecrosis of the jaw (MRONJ) from clinical stage I to stage II/III. The aim of this study was to explore the distribution of bacteria and their association with the inflammatory pathway of stage II/III MRONJ. Materials and Methods: Nine specimens of fresh inflammation tissue, located next to the necrotic bone or sequestrum, were collected from MRONJ patients. Nine specimens from normal oral mucosa were collected from healthy patients. The 16S rRNA gene sequencing method was used to determine the distribution characteristics of the bacterial colony. The protein microarray analysis was used to detect the expression of inflammatory cytokines. Results: The average relative abundance of Bacteroidetes, Spirochaetes, Synergistetes, and Tenericutes was higher, while Proteobacteria and Actinobacteria were lower in the MRONJ group. Most pro-inflammatory cytokines were up-regulated in the MRONJ group; yet, only IFNγ, TNFα, and IL8 showed statistical differences (P < 0.05). Porphyromonas and Treponema were positively correlated with IL8, and Mogibacterium was positively correlated with IFNγ and TNFα. Conclusions: IL8/IFNγ/TNFα pro-inflammatory effect caused by Porphyromonas, Treponema, and Mogibacterium may be the leading cause of advancing MRONJ and thus may be used as a new target for infection control.