A four-hypoxia-genes-based prognostic signature for oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most common maligancies of the head and neck. The prognosis was is significantly different among OSCC patients. This study aims to identify new biomarkers to establish a prognostic model to predict the survival of OSCC patients. METHODS: The mRNA expression and corresponding clinical information of OSCC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus. Additionally, a total of 26 hypoxia-related genes were also obtained from a previous study. Univariate Cox regression analysis and LASSO Cox regression analysis were performed to screen the optimal hypoxia-related genes which were associated with the prognosis of OSCC. to establish the predictive model (Risk Score) was established for estimating the patient's overall survival (OS). Multivariate Cox regression analysis was used to determine whether the Risk Score was an independent prognostic factor. Based on all the independent prognostic factors, nomogram was established to predict the OS probability of OSCC patients. The relative proportion of 22 immune cell types in each patient was evaluated by CIBERSORT software. RESULTS: We determined that a total of four hypoxia-related genes including ALDOA, P4HA1, PGK1 and VEGFA were significantly associated with the prognosis of OSCC patients. The nomogram established based on all the independent factors could reliably predict the long-term OS of OSCC patients. In addition, our resluts indicated that the inferior prognosis of OSCC patients with high Risk Score might be related to the immunosuppressive microenvironments. CONCLUSION: This study shows that high expression of hypoxia-related genes including ALDOA, P4HA1, PGK1 and VEGFA is associated with poor prognosis in OSCC patients, and they can be used as potential markers for predicting prognosis in OSCC patients.

Selection and evaluation of quality markers from Yinlan capsule and its LXRα-mediated therapy for hyperlipidemia.

BACKGROUND: The selection of active compounds for the quality evaluation of traditional Chinese medicine (TCM), specifically complex formulas, remains a challenge for researchers, as components selected as indexes usually have no clear relation with the therapeutic effects of interest. As a suggested resolution, quality control markers (Q-markers) showed good perspective for discriminating numerous compounds found for specific efficacies. In the presented study, the components of the Yinlan (YL) capsule, a TCM patent formula comprising four ingredients, were evaluated and selected for their lipid regulatory effects using principles for Q-marker selection. PURPOSE: The mechanism of TCM therapeutic effects involves several pathways and targets that combine to become an integrated action in the body. Therefore, it is assumed that specific compounds in YL should have good affinity for related targets and obvious effects (both up- and downregulating). Thus, a series of experiments, including cytobiology, animal-based pharmacodynamics, computer-assisted drug design, conventional content determination and pharmacokinetics, would be helpful for the selection and final confirmation of Q-markers. METHODS: The capsule was first administered to Wistar mice fed a high-fat diet and tested for their triglycerides (TG) and total cholesterol (TC) values to evaluate the effectiveness of YL. Then, liver tissue was extracted for gene expression. According to the results, the compounds in YL with good affiliation were selected and determined using UHPLC-MS-MS, and those with adequate results in the capsule were chosen as Q-marker candidates. Finally, pharmacokinetics research was performed; the candidates with desirable metabolite and bioavailability parameters were confirmed as Q-markers of YL. RESULTS: YL capsule was capable of lowering TG and TC levels. For target selection, the expression of LXR mRNA increased significantly at all three tested dosages. Downstream genes, such as LCAT, CYP7A1, and ABCA1, and intestinal FXR mRNA also showed significant increases in expression. For screening of the Q-marker candidates, 5 compounds were selected according to abovementioned results. The pharmacokinetics research demonstrated that the rats exploited lupeol and ginsenoside Rb3 in a desirable pattern with adequate bioavailability, which confirmed their roles as lipid regulatory Q-markers. CONCLUSION: The YL capsule was demonstrated to have obvious lipid regulatory effects, which are mainly exerted by targeting LXR and its related pathway. Lupeol and ginsenoside Rb3 were validated as Q-markers that represent the anti-hyperlipidemia activity of the capsule.

[Clinical evaluation of the five-digit numerical recording system for classification of cleft lip and palate deformities].

OBJECTIVE: To evaluate the five-digit numerical recording system (LAPAL system) for classification of cleft lip and palate. METHODS: Fourteen young doctors took part in the study after receiving one-hour instruction twice for the LAPAL system. Photographs of 200 cases of untreated cleft lip and palate were used for the evaluation. The diagnostic codes of the patient were recorded and compared with the teacher's standard diagnosis. The basic criterion of the LAPAL system was that the clefts were arranged in five anatomical components in order of right lip (L), right alveolus and primary palate (A), secondary palate (P), left alveolus and primary palate (A), and left lip (L). The degrees of the cleft severity were recorded with Arabic number 0 for the intact, 1 for the subcutaneous or submucous cleft, 2 for clefts smaller than half of a component, 3 for clefts larger than half of a component, 4 for complete clefts. RESULTS: The rate of the diagnostic coincidence was 88% (2475/2800) totally. The higher coincidence appeared in degree 4 of cleft lip and in degree 4 of cleft alveolar and cleft primary palate as 99% (707/714) and 100% (546/546), respectively. The lower coincidence appeared in degree 2 and degree 3 of clefts of the alveolus and primary palate as 70% (98/140) and 82% (103/126), respectively. Among the 17 types of possible cleft combination, 14 types were found in the present study. CONCLUSIONS: The LAPAL system is easily understood and grasped in a short time. Clefts on the border of adjoin degrees may cause confusion in diagnosis. More training or simplified modification is suggested.