Radiotherapy is one of the most common treatments for oral cancer. However, in the clinic, recurrence and metastasis of oral cancer occur after radiotherapy, and the underlying mechanism remains unclear. Cancer stem cells (CSCs), considered the "seeds" of cancer, have been confirmed to be in a quiescent state in most established tumours, with their innate radioresistance helping them survive more easily when exposed to radiation than differentiated cancer cells. There is increasing evidence that CSCs play an important role in recurrence and metastasis post-radiotherapy in many cancers. However, little is known about how oral CSCs cause tumour recurrence and metastasis post-radiotherapy. In this review article, we will first summarise methods for the identification of oral CSCs and then focus on the characteristics of a CSC subpopulation induced by radiation, hereafter referred to as "awakened" CSCs, to highlight their response to radiotherapy and potential role in tumour recurrence and metastasis post-radiotherapy as well as potential therapeutics targeting CSCs. In addition, we explore potential therapeutic strategies targeting these "awakened" CSCs to solve the serious clinical challenges of recurrence and metastasis in oral cancer after radiotherapy.

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The rate of brucellosis, a zoonotic disease, has rapidly increased in humans brucellosis(HB) in recent years. In 1950–2018, a total of 684,380 HB cases (median 2274/year (interquartile range (IQR) 966–8325)) were reported to the National Infectious Disease Surveillance System in mainland China. The incidence of HB peaked in 2014 (4.32/100,000), and then showed a downward trend; we predict that it will maintain a steady downward trend in 2019–2020. Since 2015, the incidence of HB has shown opposite trends in the north and south of China; rates in the north have fallen and rates in the south have increased. In 2004–2018, the most significant increases in incidence of HB were in Yunnan (IQR 0.002–0.463/100,000), Hubei (IQR 0.000–0.338/100,000), and Guangdong (IQR 0.015–0.350/100,000). The areas where HB occurs have little overlap with areas with high per capita GDP in China. The “high–high” clusters of HB are located in northeastern China (Inner Mongolia, Heilongjiang, Jilin, Liaoning, Ningxia, Shanxi, and Gansu), and the “low–low” clusters of HB are located in southern China (Yunnan, Jiangxi, Shanghai, Guangxi, Guangdong, Zhejiang, Guizhou, and Hunan). In recent years, the incidence of HB in China has been controlled to some extent, but the incidence of HB has increased in southern China, and the disease has spread geographically in China from north to south. Further research is needed to address this change and to continue to explore the relationship between the incidence of HB and relevant factors.

Due to the natural resistance of nontuberculous mycobacteria (NTM) against multiple antibiotics, treatment of infections caused by them is often long-course and less successful. The main objective of our study was the evaluation of in vitro susceptibility of 209 isolates consisting of different NTM species against bedaquiline and delamanid. Furthermore, reference strains of 33 rapidly growing mycobacterium (RGM) species and 19 slowly growing mycobacterium (SGM) species were also tested. Bedaquiline exhibited strong in vitro activity against both reference strains and clinical isolates of different SGM species, as the majority of the strains demonstrated MICs far below 1 μg/ml. Bedaquiline (Bdq) also exhibited potent activity against the recruited RGM species. A total of 29 out of 33 reference RGM strains had MICs lower than 1 μg/ml. According to the MIC distributions, the tentative epidemiological cutoff (ECOFF) values, and the pharmacokinetic data, a uniform breakpoint of 2 μg/ml was temporarily proposed for NTM’s Bdq susceptibility testing. Although delamanid (Dlm) was not active against most of the tested reference strains and clinical isolates of RGM species, it exhibited highly variable antimicrobial activities against the 19 tested SGM species. Eleven species had MICs lower than 0.25 μg/ml, and 7 species had MICs greater than 32 μg/ml. Large numbers of M. kansasii (39/45) and M. gordonae (6/10) clinical isolates had MICs of ≤0.125 μg/ml. This study demonstrated that bedaquiline had potent activity against different NTM species in vitro, and delamanid had moderate activity against certain species of SGM. The data provided important insights on the possible clinical application of Bdq and Dlm to treat NTM infections.

BackgroundDespite their high accuracy to recognize oral potentially malignant disorders (OPMDs) with cancer risk, non‐invasive oral assays are poor in discerning whether the risk is high or low. However, it is critical to identify the risk levels, since high‐risk patients need active intervention, while low‐risk ones simply need to be follow‐up. This study aimed at developing a personalized computational model to predict cancer risk level of OPMDs and explore its potential web application in OPMDs screening.MethodsEach enrolled patient was subjected to the following procedure: personal information collection, non‐invasive oral examination, oral tissue biopsy and histopathological analysis, treatment, and follow‐up. Patients were randomly divided into a training set (N = 159) and a test set (N = 107). Random forest was used to establish classification models. A baseline model (model‐B) and a personalized model (model‐P) were created. The former used the non‐invasive scores only, while the latter was incremented with appropriate personal features.ResultsWe compared the respective performance of cancer risk level prediction by model‐B, model‐P, and clinical experts. Our data suggested that all three have a similar level of specificity around 90%. In contrast, the sensitivity of model‐P is beyond 80% and superior to the other two. The improvement of sensitivity by model‐P reduced the misclassification of high‐risk patients as low‐risk ones. We deployed model‐P in web.opmd-risk.com, which can be freely and conveniently accessed.ConclusionWe have proposed a novel machine‐learning model for precise and cost‐effective OPMDs screening, which integrates clinical examinations, machine learning, and information technology.

As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.