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The most prevalent oral cancer globally is oral squamous cell carcinoma (OSCC). The invasion of adjacent bones and the metastasis to regional lymph nodes often lead to poor prognoses and shortened survival times in patients with OSCC. Encouraging immunotherapeutic responses have been seen with immune checkpoint inhibitors (ICIs); however, these positive responses to monotherapy have been limited to a small subset of patients. Therefore, it is urgent that further investigations into optimizing immunotherapies are conducted. Areas of research include identifying novel immune checkpoints and targets and tailoring treatment programs to meet the needs of individual patients. Furthermore, the advancement of combination therapies against OSCC is also critical. Thus, additional studies are needed to ensure clinical trials are successful. Mice models are advantageous in immunotherapy research with several advantages, such as relatively low costs and high tumor growth success rate. This review paper divided methods for establishing OSCC mouse models into four categories: syngeneic tumor models, chemical carcinogen induction, genetically engineered mouse, and humanized mouse. Each method has advantages and disadvantages that influence its application in OSCC research. This review comprehensively surveys the literature and summarizes the current mouse models used in immunotherapy, their advantages and disadvantages, and details relating to the cell lines for oral cancer growth. This review aims to present evidence and considerations for choosing a suitable model establishment method to investigate the early diagnosis, clinical treatment, and related pathogenesis of OSCC.

Background: The world’s age-related health concerns continue to rise. Audio-vestibular disorders, such as hearing loss, tinnitus, and vertigo, are common complaints in the elderly and are associated with social and public health burdens. Various preventative measures can ease their impact, including healthy food consumption, nutritional supplementation, and lifestyle modification. We aim to provide a comprehensive summary of current possible strategies for preventing the age-related audio-vestibular dysfunction. Methods: A PubMed, Embase, and Cochrane review databases search was conducted to identify the relationship between diet, lifestyle, and audio-vestibular dysfunction. “Diet”, “nutritional supplement”, “lifestyle”, “exercise”, “physical activity”, “tinnitus”, “vertigo” and “age-related hearing loss” were used as keywords. Results: Audio-vestibular dysfunction develops and progresses as a result of age-related inflammation and oxidative stress. Diets with anti-inflammatory and antioxidant effects have been proposed to alleviate this illness. A high-fat diet may induce oxidative stress and low protein intake is associated with hearing discomfort in the elderly. Increased carbohydrate and sugar intake positively correlate with the incidence of audio-vestibular dysfunction, whereas a Mediterranean-style diet can protect against the disease. Antioxidants in the form of vitamins A, C, and E; physical activity; good sleep quality; smoking cessation; moderate alcohol consumption; and avoiding noise exposure are also beneficial. Conclusions: Adequate diet or nutritional interventions with lifestyle modification may protect against developing audio-vestibular dysfunction in elderly individuals.

Self-management is an important skill for patients with diabetes, and it involves frequent monitoring of glucose levels and behavior modification. Techniques to enhance the behavior changes of diabetic patients have been developed, such as diabetes self-management education and telehealthcare. Although the patients are engaged in self-management activities, barriers to behavior changes remain and additional work is necessary to address the impact of electronic media and telehealthcare on patient self-care behaviors. The aims of this study were to (1) explore the behaviors of diabetic patients interacting with online applications, (2) determine the impact of a telehealthcare program among 7 self-care behaviors of the patients, and (3) determine the changes in glycosylated hemoglobin (HbA1c) levels. A telehealthcare program was conducted to assist the patients with 7 self-care activities. The telehealthcare program lasted for 18 months and included the use of a third-generation mobile telecommunications glucometer, an online diabetes self-management system, and a teleconsultant service. We analyzed the data of 59 patients who participated in the telehealthcare program and 103 who did not. The behavioral assessments and the HbA1c data were collected and statistically analyzed to determine whether the telehealthcare services had an impact on the patients. We divided the 18-month period into 3 6-month intervals and analyzed the parameters of patients assisted by the telehealthcare service at different time points. We also compared the results of those who were assisted by the telehealthcare service with those who were not. There was a significant difference in monitoring blood glucose between the beginning and the end of the patient participation (P=.046) and between the overall period and the end of patient participation (P<.001). Five behaviors were significantly different between the intervention and control patients: being active (P<.001), healthy eating (P<.001), taking medication (P<.001), healthy coping (P=.02), and problem solving (P<.001). Monitoring of blood glucose was significantly different (P=.02) during the 6-12 month stage of patient participation between the intervention and control patients. A significant difference between the beginning and the 6-12 month stage of patient participation was observed for the mean value of HbA1c level (P=.02), and the differences between the overall HbA1c variability and the variability of each 6-month interval was also significant. Telehealthcare had a positive effect on diabetic patients. This study had enhanced blood glucose monitoring, and the patients in the program showed improvements in glycemic control. The self-care behaviors affect patient outcomes, and the changes of behavior require time to show the effects.

Almost all children in Singapore complete 1 year of preschool before entering primary school. However, preschool education (PSE) is not compulsory and is provided primarily by the private sector. Taking the national agenda for reforming PSE at the start of the twenty-first century as the point of departure, this paper describes and discusses the policies and strategies that have been introduced and implemented for preschool quality enhancement in the past 15 years. Three major waves of preschool policy reviews were undertaken in 2000, 2008, and 2012 attesting to the seriousness the government attaches to improving PSE for encouraging a strong start for every child. The key recommendations of these reviews were related to uplifting teacher, center, and program quality, and enhancing the affordability and accessibility of PSE. Opportunities and challenges associated with implementing recommendations for quality enhancement are discussed and suggestions to further enhance PSE in Singapore are explored.

Epigenetic reprogramming has been associated with the functional plasticity of cancer-initiating cells (CICs); however, the regulatory pathway has yet to be elucidated. A siRNA screen targeting known epigenetic genes revealed that G9a profoundly impairs the chemo-resistance, self-renewal and metastasis of CICs obtained from patients with colorectal cancer (CRC). Patients with elevated G9a were shown to face a high risk of relapse and poor survival rates. From a mechanistic perspective, G9a binds with and stabilizes RelB, thereby recruiting DNA methyltransferase 3 on the Let-7b promoter and repressing its expression. This leads to the activation of the K-RAS/β-catenin pathway and regulates self-renewal and function of CICs. These findings indicate that the G9a/RelB/Let-7b axis acts as a critical regulator in the maintenance of CIC phenotypes and is strongly associated with negative clinical outcomes. Thus, these findings may have diagnostic as well as therapeutic implications for the treatment of chemotherapy-resistant or metastatic CRC. Cha et al.  report that the G9a/RelB axis represses Let-7b through DNMT3A, and sustains K-RAS and β-catenin signalling, thereby controlling the maintenance and function of colorectal-cancer-initiating cells.

Background Head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide. Emerging evidence indicates that alteration of epigenetics might be a key event in HNSCC progression. Abnormal expression of histone methyltransferase G9a, which contributes to transcriptional repression of tumor suppressors, has been implicated in promoting cancerous malignancies. However, its role in HNSCC has not been previously characterized. In this study, we elucidate the function of G9a and its downstream mechanism in HNSCC. Methods We investigated the clinical relevance of G9a in HNSCC using immunohistochemistry (IHC) staining. In vitro cell proliferation and tumorigenesis ability of G9a-manipulated HNSCC cells were examined with MTT assays, clonogenic assays, and soft agar assays. We examined different routes of cell death in HNSCC cells induced by G9a-depletion or enzymatic inhibition by immunoblot, flow cytometry, fluorescent and transmission electron microscopy analysis. Specific targets of G9a were identified by affymetrix microarray and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Lastly, functions of G9a in vivo were confirmed with a xenograft tumor model. Results G9a expression is positively correlated to proliferation marker Ki-67 and to poor prognosis in HNSCC patients. Genetic or pharmacological inhibition of G9a reduced cell proliferation without inducing necrosis or apoptosis. Instead, autophagic cell death was the major consequence, and our investigation of mechanisms suggested it is mediated via the dual specificity phosphatase-4 (DUSP4) dependent ERK inactivation pathway. An orthotopic tumor model further confirmed the growth inhibiting effect and induction of autophagy that followed suppression of G9a. Conclusions In this study, we provide evidence that G9a confers the survival advantage of HNSCC. Genetic or pharmacological inhibition of G9a induces autophagic cell death; this finding provides a basis for new therapeutic targets for treating HNSCC.

Angiopoietin-like protein 1 (ANGPTL1) is a potent regulator of angiogenesis. Growing evidence suggests that ANGPTL family proteins not only target endothelial cells but also affect tumor cell behavior. In a screen of 102 patients with lung cancer, we found that ANGPTL1 expression was inversely correlated with invasion, lymph node metastasis, and poor clinical outcomes. ANGPTL1 suppressed the migratory, invasive, and metastatic capabilities of lung and breast cancer cell lines in vitro and reduced metastasis in mice injected with cancer cell lines overexpressing ANGPTL1. Ectopic expression of ANGPTL1 suppressed the epithelial-to-mesenchymal transition (EMT) by reducing the expression of the zinc-finger protein SLUG. A microRNA screen revealed that ANGPTL1 suppressed SLUG by inducing expression of miR-630 in an integrin α(1)β(1)/FAK/ERK/SP1 pathway-dependent manner. These results demonstrate that ANGPTL1 represses lung cancer cell motility by abrogating the expression of the EMT mediator SLUG.

Laryngeal photographs from 165 Taiwanese subjects were taken during microlaryngoscopy. Photographs of the vocal fold during the open phase were chosen. For measuring the vocal fold length, both the photograph of a ruler and the larynx were taken under the operating microscope, thus forming a ‘new scale’. Photographs of the vocal fold and the ruler were then processed at the same power of magnification. The length of the vocal folds was measured with the ‘new scale’. In 100 patients receivingdirect laryngoscopy under neuroleptic anaesthesia, the vocal fold length was 14.6 ± 1.2 mm (n = 35) for males and 11.1 ± 1.0 mm (n = 65) for females. In 65 patients under general anaesthesia, the vocal fold length was 15.3 ± 1.6 mm (n = 23) for males and 13.5 ± 1.3 mm (n = 42) for females. Statistical analysis revealed a significant difference between both groups and both sexes. Elongation of the vocal fold under general rather than neuroleptic anaesthesia may be important when performing functional surgery of the vocal fold.

Medical resources are important and necessary in health care. Recently, the development of methods for improving the efficiency of medical resource utilization is an emerging problem. Despite evidence supporting the use of order sets in hospitals, only a small number of health information systems have successfully equipped physicians with analysis of complex order sequences from clinical pathway and clinical guideline. This paper presents a data-mining framework for transnational healthcare system to find alternative practices, including transfusion, pre-admission tests, and evaluation of liver diseases. However, individual countries vary with respect to geographical location, living habits, and culture, so disease risks and treatment methods also vary across countries. To realize the difference, a service-oriented architecture and cloud-computing technology are applied to analyze these medical data. The validity of the proposed system is demonstrated in including Taiwan and Mongolia, to ensure the feasibility of our approach.

Purpose The aim of this study was to investigate whether physical evaluations could be used for predicting the presence and severity of obstructive sleep apnea (OSA) in non-obese snoring patients. Methods This is a retrospective study, and a total of 244 non-obese (body mass index, BMI, <27 kg/m 2 ) snoring patients (178 men and 66 women; mean age = 43.1 ± 12.1 years) were included. Each patient underwent polysomnography and a thorough physical examination, including flexible nasopharyngoscopy and Müller maneuver. Patients were divided into four groups based on apnea–hypopnea index (AHI) scores: normal (simple snoring), AHI < 5; mild OSA, 5 ≦ AHI < 15; moderate OSA, 15 ≦ AHI < 30; severe OSA, AHI ≧ 30. Logistic regression was used to identify risk factors for OSA severity. Results Fifty-nine patients (24%) were simple snorers. The prevalence of sleep apnea (mild, moderate, or severe OSA) for our non-obese snoring patients was 76%. Univariate logistic analyses showed that higher BMI, male gender and retropalatal Müller grades were significantly associated with OSA severity. Multivariate logistic regression analysis identified male gender and retropalatal Müller grade as risk factors for OSA in non-obese snoring patients. Conclusions Physical examination may be useful for studying the upper airway in non-obese snoring patients. Flexible nasopharyngoscopy with Müller maneuver appears to be useful for evaluating the severity of OSA in non-obese patients. Retropalatal Müller grade is highly related to both the presence and severity of OSA, particularly in males.