Immune microenvironment: novel perspectives on bone regeneration disorder in osteoradionecrosis of the jaws.

Osteoradionecrosis of the jaws (ORNJ) is a severe complication that occurs after radiotherapy of head and neck malignancies. Clinically, conservative treatments and surgeries for ORNJ exhibited certain therapeutic effects, whereas the regenerative disorder of the post-radiation jaw remains a pending problem to be solved. In recent years, the recognition of the role of the immune microenvironment has led to a shift from an osteoblasts (OBs) or bone marrow mesenchymal stromal cells (BMSCs)-centered view of bone regeneration to the concept of a complicated microecosystem that supports bone regeneration. Current advances in osteoimmunology have uncovered novel targets within the immune microenvironment to help improve various regeneration therapies, notably therapies potentiating the interaction between BMSCs and immune cells. However, these researches lack a thorough understanding of the immune microenvironment and the interaction network of immune cells in the course of bone regeneration, especially for the post-operative defect of ORNJ. This review summarized the composition of the immune microenvironment during bone regeneration, how the immune microenvironment interacts with the skeletal system, and discussed existing and potential strategies aimed at targeting cellular and molecular immune microenvironment components.

[Design of Individualized Oral Radiotherapy Stent Based on 3D Printing Technique].

This paper introduces the individual design of oral radiotherapy stent based on 3D printing technology, and expounds its design principle. The modeling of the device is based on CT images and Mimics software, which builds a set of 3D printing oral stent technology. The instrument has more advantage in high precision, fast modeling, individualized production and digital storage. The results show that the construction of 3D printed dental stent is feasible, which provides a new idea and method for the production of oral stents.

Integrated soil-fruit-climate management system to improve apple production stability.

Unstable agricultural systems, such as unreliable fruit production, threaten global food security and could negatively impact human nutrition. However, methods of maintaining a stable fruit supply have received little attention. Therefore, this study explored the impact of a systematic service model on the establishment of an integrated soil-fruit-climate management (ISM) approach and stabilization of apple yield based on a fixed-effects model using sample data from Fuji apple farmers in China for six consecutive years (2016-2021). The results showed that the systematic service model dramatically improved the adoption of ISM-based technology. By 2021, the rate of ISM technology adoption among farmers reached 84.4 %, especially pendulous branch-fruiting technology and Osmia pollination, which increased by 82.2 % and 37.8 %, respectively, compared to that in 2016. With the adoption of the ISM approach, apple yields and tree loadings stabilized over time. For example, the yield change rate and tree loading change rate were 14.8 % and 7.3 % lower, respectively, in 2021 than in 2016. We demonstrated through a fixed-effects analysis that the ISM approach exerts a fully mediated effect on the mechanism of action of service measure quantity disclosure, which positively impacted the rate of change in yield and tree loadings. This finding indicated that the six-in-one systematic service model of soil testing, pest and disease diagnosis, course training, meteorological monitoring, on-site guidance, and experimental demonstration established by the Science and Technology Backyard model resolved the information, goal, and hardware gaps that limited the adoption of this technology by farmers and promoted the construction of an integrated soil-fruit-climate management approach, which in turn has stabilized the apple production system.

Response to nivolumab combining radiotherapy and nimotuzumab in metastatic oral squamous cell carcinoma patient with strong PD-L1 expression: a case report.

Immune checkpoint inhibitors (ICIs) have been approved for the treatment of oral squamous cell carcinoma (OSCC). However, not all patients would benefit from ICIs. Thus, in order to improve the response rate, the efficacy and safety of combination immunotherapy is still under evaluation. We report a 71-year-old female patient with a recurrent metastatic oral cavity cancer. Immunohistochemical examination showed more than 50% of tumor cells to express the programmed cell death receptor ligand 1 (PD-L1). The patient received nivolumab plus radiotherapy and nimotuzumab. Both clinically and radiologically response was observed and the patient reached a partial response (PR). This is the first case describing the efficacy and safety of nivolumab plus radiotherapy and nimotuzumab in an OSCC patient with a strong PD-L1 expression, showing a tolerable safety profile and a promising response. The combination immunotherapy may be a potential treatment option for patients with OSCC.

The NRF2/KEAP1 Pathway Modulates Nasopharyngeal Carcinoma Cell Radiosensitivity via ROS Elimination.

PURPOSE: Radioresistance is a vital obstacle for the prognosis of human nasopharyngeal carcinoma (NPC), but the underlying mechanism is still unknown. Here, we explored the role of the NRF2/KEAP1 pathway in radioresistance of NPC cell lines. MATERIALS AND METHODS: We selected NPC cell lines CNE-1 and CNE-2, treated them with ionization, and subsequently determined the levels of NRF2, KEAP1, antioxidant enzymes, and ROS. We then evaluated the effect of NRF2 or KEAP1 inhibition on cell proliferation, colony formation, and radiosensitivity in CNE2 cells. RESULTS: We discovered that the NRF2/KEAP1 signaling pathway can be activated by radiotherapy in NPC cells, while NRF2 knockdown enhances the sensitivity of CNE-2 cells to radiation treatment. In contrast, the silencing of KEAP1 inhibits the sensitivity of CNE-2 cells to radiation treatment. CONCLUSION: Our results suggest that NRF2/KEAP1 signaling may serve as an essential regulator of the radioresistance of NPC and may be applied as a novel therapeutic approach for the sensitization of NPC to radiation.

SMARCAD1 Promotes Pancreatic Cancer Cell Growth and Metastasis through Wnt/ß-catenin-Mediated EMT.

Pancreatic cancer (PC) is one of the most lethal diseases, characterized by early metastasis and high mortality. Subunits of the SWI/SNF complex have been identified in many studies as the regulators of tumor progression, but the role of SMARCAD1, one member of the SWI/SNF family, in pancreatic cancer has not been elucidated. Based on analysis of GEO database and immunohistochemical detection of patient-derived pancreatic cancer tissues, we found that SMARCAD1 is more highly expressed in pancreatic cancer tissues and that its expression level negatively correlates with patients' survival time. With further investigation, it shows that SMARCAD1 promotes the proliferation, migration, invasion of pancreatic cancer cells. Mechanistically, we first demonstrate that SMARCAD1 induces EMT via activating Wnt/ß-catenin signaling pathway in pancreatic cancer. Our results provide the role and potential mechanism of SMARCAD1 in pancreatic cancer, which may prove useful marker for diagnostic or therapeutic applications of PC disease.

Expression of miR-146a-5p in breast cancer and its role in proliferation of breast cancer cells.

In the present study, the expression level of microRNA-146a-5p (miR-146a-5p) in breast cancer tissue and cell lines was investigated and its effects on proliferation of breast cancer cells. miR-146a-5p expression was detected by reverse transcription-quantitative polymerase chain reaction in breast cancer tissues, paraneoplastic tissue (collected by The Department of Oncology of Changhai Hospital from January 2014 to June 2015), breast cancer cell line MCF-7 and normal breast epithelial cell line MCF 10A. Bioinformatics analysis was conducted to forecast target genes of miR-146a-5p, which was further verified by fluorescent reporter gene detection. The results demonstrated the expression level of miR-146a-5p in breast cancer tissue was significantly higher, compared with paraneoplastic tissue (P<0.01), and the expression level of miR-146a-5p in MCF-7 cells was significantly higher, compared with MCF 10A cells (P<0.01). Overexpression of miR-146a-5p in MCF-7 cells can promote the proliferation, and low expression miR-146a-5p in MCF-7 can inhibit the proliferation. BRCA1 was further identified as a target gene of miR-146a-5p by bioinformatics analysis and fluorescent reporter gene detection. It was concluded that miR-146a-5p is expressed in breast cancer tissue and breast cancer cell line and may regulate the proliferation of MCF-7 via BRCA1.

Positron imaging for verification of irradiation field during radiotherapy.

AIM OF STUDY: The present study was designed to investigate the application of positron images from photonuclear reactions to verify the location of targeted radiation in vivo. MATERIALS AND METHODS: The phantom study was conducted with distilled water, porcine muscle, porcine adipose tissue, and graphite; these subjects were irradiated separately with 50 MV photons generated by an MM50 Racetrack Microtron. The positron emission activity was measured using a Geiger counter, and the radioactive decay curves for each of the irradiated materials were then established. The positron emission tomography (PET) images of the three tissue models were also achieved using the same radiation conditions. The in vivo PET imaging study was also conducted in tumor-bearing rabbits. RESULTS: Our results demonstrated that the PET imaging could be used to verify the position of the irradiation field in vivo. The dose distribution images of photonuclear reactions of 11 C and 15 O were uniform, using 2-Gy 50 MV photons. CONCLUSIONS: The factors influencing the half-life of radiation activity in various tissues were different from the first order kinetic reaction in physics.