Recent advances in dysphagia treatment have given us many methods of stimulating swallowing function, but no attempt has been made to systematically classify them all. In this review, we provide an exhaustive description of all the techniques and stimulatory substances that stimulate swallowing that have so far been reported in the scientific literature, irrespective of their level of evidence, and we have tried to classify them with the objective of encouraging the future development of research in this direction. The Preferred Reporting Items for Systematic Reviews and Meta-analysis were followed for retrieval of relevant research. A total of 237 records were screened for this literature review. One record was excluded for being published in a language other than English, and 59 articles were excluded for having no original data. Of the 177 records that were assessed for eligibility in this review, 31 were excluded for reasons related to other inclusion and exclusion criteria. Finally, 146 records were classified. We found stimuli related to swallowing published in the literature could be divided into physical and chemical stimuli. Each stimulus had both peripheral and central stimuli when we assessed the main site of action. Physical stimuli included electric, magnetic and thermal stimulations and acupuncture. Chemical stimuli included spices activating transient receptor potential channels, several categories of medications, taste and flavor, and olfactory stimulants. Medications modifying substance P and the dopaminergic system are thought to be peripheral and central stimuli, respectively. This classification may pave the way to discover means to improve swallowing.

Osteosarcoma is a primary malignancy of mesenchymal origin, and its metastasis and multidrug resistance remain major problems affecting the therapeutic effect. This study aimed to evaluate the efficacy and underlying mechanism of monoacylglycerol lipase (MAGL) on osteosarcoma progression. MAGL expression was downregulated by shMAGL or JZL184 (an MAGL inhibitor) and upregulated through plasmid. RT-PCR and Western blot were utilized to determine the expression of target molecules. CCK-8 assay, transwell assay and ROS assay were performed to investigate the inhibitory effect of MAGL on the growth and metastasis of osteosarcoma cells. The role of JZL184 on tumor growth was examined in cisplatin-resistant MG-63 (MG-63/R) xenograft model. MAGL was highly expressed in osteosarcoma cells and tissues. MAGL knockdown significantly impeded the proliferation, clone formation, invasion and migration of MG-63 cells, whereas opposite result was observed in 143B cells with MAGL overexpression. Likewise, an MAGL inhibitor JZL184 displayed reduced viability, clone formation, invasion and migration of osteosarcoma cells. Western blot of the epithelial mesenchymal transition (EMT)-related proteins indicated that MAGL knockdown or JZL184 could upregulated E-cadherin expression and downregulated vimentin expression. In vitro and in vivo experiments indicated that JZL184 re-sensitized MG-63/R cells to cisplatin. In summary, MAGL regulated osteosarcoma by modulating EMT, and JZL184 might be a promising agent for osteosarcoma patients who are resistant to cisplatin.

Esophageal squamous cell carcinoma (ESCC) showed limited treatment outcome and poor prognosis. This study aimed to screen potential biomarkers and drugs in ESCC. Firstly, GSE26886, GSE111044 and GSE77861 were downloaded from the Gene Expression Omnibus (GEO) database. Next, the differentially expressed genes (DEGs) between cancer and noncancerous tissues were analyzed by the GEO2R. The Gene Ontology (GO) annotation, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, the protein-protein interaction (PPI) analysis and hub genes screened were conducted by some bioinformatic methods, respectively. Lastly, the hub genes and potential drugs were verified by the GEPIA2 and the QuartataWeb database. The results showed that 13 up-regulated genes and 81 down-regulated genes were identified. In GO terms, DEGs were mainly associated with cell proliferation, cell migration and cell differentiation. DEGs did not cluster into the KEGG pathway. After hub genes validated, nine genes (FLG, COL1A1, COL1A2, PSCA, SCEL, PPL, ACPP, CNFN, and A2ML1) expression trends showed no change. Moreover, higher COL1A1 or COL1A2 expression for ESCC patients showed poor prognosis. Finally, five drugs used for promoting blood coagulation were identified. Probably, these drugs could show anticancer effects by promoting blood coagulation or inhibiting vascular formation in cancers, which offers a novel idea for the treatment of ESCC.

Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and the absence of pancreatic autoimmune markers. MODY-causing mutations have been identified in 14 genes, and carboxyl ester lipase (CEL) has been implicated in MODY8. We report a Japanese patient with MODY who harbored a heterogeneous mutation in CEL exon 2 (NM_001807.4:c.146_147delCT; NP_001798.2:p.Ser49CysfsTer52). A 13-year-old girl experienced her first episode of diabetic ketoacidosis, during which her endogenous insulin secretion was poor. However, her insulin secretion had apparently recovered 2 months after the commencement of insulin treatment, and no further treatment was required for the following 2 years. Diabetic ketoacidosis recurred when the patient was 15 years old, when her insulin secretion was again poor. Since that time, the patient, who is now 18 years old, has been undergoing continuous insulin treatment. The large fluctuations in her insulin secretory capacity led us to suspect MODY. MODY8 patients that carry a mutation in the variable number of tandem repeats in the last exon of the CEL gene typically show pancreatic exocrine dysfunction. However, in the present case, which features premature termination, there is no involvement of exocrine dysfunction, potentially demonstrating a genotype-phenotype correlation.

The number of elderly patients with hepatocellular carcinoma (HCC) has been increasing, but it remains unclear whether hepatectomy can be performed using the same criteria as in younger patients. Furthermore, the appropriate preoperative evaluation for hepatectomy in elderly patients is not yet clearly defined. Here, we investigated the applicability of preoperative assessment using the Controlling Nutritional Status (CONUT) score to help improve hepatectomy outcomes in elderly patients with HCC. This was a single-center retrospective analysis, and the study population comprised 64 consecutive patients who underwent hepatectomy for HCC between January 2012 and August 2016. We compared the preoperative assessment and perioperative outcomes between elderly (≥ 75 years old) and younger (< 75 years old) patients. A total of 61 patients were reviewed. Poor preoperative CONUT score was associated with a longer postoperative hospital stay in elderly patients undergoing hepatectomy for HCC. In addition, although elderly patients had similar perioperative outcomes to younger patients, the incidence of delirium was significantly higher, and univariate analysis confirmed that old age is a risk factor for delirium among the preoperative factors. Hepatectomy for HCC in the elderly can be safely performed with appropriate preoperative nutritional assessment using CONUT score and prevention of postoperative delirium. Preoperative nutritional assessment using the CONUT score was useful in predicting prolonged hospitalization for elderly hepatectomy with HCC.

Triglyceride/high-density lipoprotein (HDL) cholesterol ratio (TG/HDL-C), triglyceride-glucose index (TyG), and non-HDL cholesterol level (non-HDL-C) have been proposed as surrogate markers for predicting metabolic syndrome (MetS). This study investigated whether these lipid-derived surrogate markers can predict MetS in Korean children and adolescents. Data from 1,814 participants were analyzed from the 2013-2016 Korean National Health and Nutrition Examination Survey. MetS was defined using three sets of criteria: Cook et al. (MetS1), de Ferranti et al. (MetS2), and the International Diabetes Federation (MetS3). The prevalence of MetS1, MetS2, and MetS3 was 4.6%, 11.3%, and 2.7%, respectively. In receiver operating characteristic curve analysis of MetS and lipid-derived surrogate markers, TG/HDL-C (0.937 for MetS1, 0.894 for MetS2, and 0.897 for MetS3) had the largest area under the curve (AUC), followed by TyG (0.906 for MetS1, 0.864 for MetS2, and 0.887 for MetS3), and non-HDL-C (0.752 for MetS1, 0.708 for MetS2, and 0.703 for MetS3) (all P < 0.001). The cutoff values for detecting MetS with TG/HDL-C, TyG, and non-HDL-C were 2.64, 8.52, and 111.6 for MetS1; 2.23, 8.47, and 110.7 for MetS2; and 2.64, 8.74, and 110.8 for MetS3, respectively. In conclusion, TG/HDL-C and TyG were similarly predictive of MetS. We propose using TG/HDL-C and TyG as surrogate markers for assessing MetS in Korean children and adolescents.

Since knowledge of medical communication education and objective structured clinical examination (OSCE) is increasing, a greater number of simulated patients/standardized patients (SPs) will undoubtedly be needed throughout Japan. At Tokyo Medical University in Japan, non-medical professional school staff members have acted as SPs in post-clinical clerkship OSCEs. However, except for academic or medical staff, no other staff members were reported to have acted as SPs. Therefore, the significance of the large numbers of solely medical school staff acting as SPs needs to be investigated. The purpose of this study was to determine how acting as SPs affects medical school staff’s understanding of student education and whether it is useful for university staff to know what kind of education is being provided at their own school. A mixed-method study was utilized to investigate what kind of attitudinal changes occurred among medical school staff after their SP experiences. Accordingly, the researchers conducted a questionnaire survey with staff members after they acted as SPs. The questionnaire was developed through semi-structured interviews. The majority of the participants’ responses were positive. They claimed that they had gained knowledge on the testing of students and now understood the importance of doctors’ communication skills. Furthermore, many stated that all staff members at medical schools should experience acting as SPs. Medical school staff understands students’ education processes better after acting as SPs. Japan’s SPs are aging and becoming fewer; however, these SP numbers could be supplemented by medical school staff members.

Suicide is an important public health issue for adolescents. To investigate the risk and protective factors for adolescent suicide, a cross-sectional questionnaire-based survey was conducted at a junior high school (n = 379) in Japan in 2018. After obtaining survey data, we conducted univariate and logistic regression analyses to test for associations between suicidal ideation and several factors, including worries (i.e., about school life, interpersonal relationships at school, family life, interpersonal relationships at home, and academic performance), perceived support from school staff and family members, and social capital. In this context, the existence of trustful relationships between classmates was used as indicators of social capital. The results showed that the prevalence of suicidal ideation was 10.5%. The risk of suicidal ideation was increased by worries about 1) interpersonal relationships at school, 2) interpersonal relationships at home, and 3) academic performance, but was decreased by social support from family members and trusting relationships. Further, the rate of suicidal ideation was higher among students who expressed all these three worries when compared to those who expressed two or fewer worries. In addition, looking at students who expressed all these three worries simultaneously, the rate of suicidal ideation was higher among those with lower levels of support from family members and fewer trustful relationships. Our results suggest that the prevention of adolescent suicide should include strategies for reducing worries about interpersonal relationships at school/home and academic performance while finding ways to enhance family support and classmate social capital.

Mizoribine may be a safe and effective treatment for children with steroid-dependent nephrotic syndrome (SDNS). However, predictors of treatment response and long-term outcomes after mizoribine discontinuation remain unknown. We retrospectively reviewed the clinical course of 22 children aged ≤ 10 years (median age, 5.3 years) with SDNS who received high-dose mizoribine as the initial steroid-sparing agent (SSA). Mizoribine was administered at a single daily dose of 10 mg/kg (maximum, 300 mg/day) after breakfast. The dose was adjusted to maintain 2-h post-dose mizoribine levels of > 3 μg/mL and was tapered off after 12 months of steroid-free remission. Patients who regressed to SDNS were switched from mizoribine to other SSAs. The primary endpoint was probability of survival without regression to SDNS after mizoribine initiation. Ten patients were able to discontinue SDNS (response group), whereas twelve were switched from mizoribine to other SSAs (non-response group) during a median observation period of 6.0 years after mizoribine. The steroid-dependent dose prior to mizoribine was significantly lower in the response group than in the non-response group (p < 0.05). The Kaplan-Meier analysis revealed that the probability of regression-free survival was significant higher in patients with steroid-dependent dose of < 0.25 mg/kg/day than in those with steroid-dependent dose of ≥ 0.25 mg/kg/day (p < 0.05). During a median follow-up of 5.5 years after mizoribine discontinuation, all but one patient did not develop SDNS. High-dose mizoribine may be an attractive treatment option as initial SSA in young children with low steroid-dependent dose for improved long-term outcomes.