Plumbagin has an inhibitory effect on the growth of TSCC PDX model and it enhances the anticancer efficacy of cisplatin.

BACKGROUND: Head and neck squamous cell carcinomas are the sixth most common malignant tumors worldwide. Tongue squamous cell carcinoma is a common malignant tumor of this type, and it is associated with poor prognosis, a high rate of recurrence and a low survival rate. Plumbagin is derived from Plumbago zeylanica L, several studies report that plumbagin could inhibit cell, tumor metastasis, induce apoptosis in various cancer cells. Patient-derived xenograft (PDX) model can maintain the heterogeneity and microenvironment of human tumors, is a powerful research tool for developing potentially effective therapies for TSCC. METHODS: Tumor tissues obtained from TSCC patients were implanted into immunodeficient mice to establish TSCC PDX models. Subsequently, the PDX models were used to evaluate the anti-tumor effects of plumbagin on TSCC. Furthermore, we conducted next-generation sequencing (NGS) and explored the mRNA expression profiles between the treatment and control groups. We selected eight mRNAs related to the characteristics and prognosis of TSCC patients for further analysis. RESULTS: Plumbagin could inhibit the growth of TSCC PDX models and inhibit expression of Akt/mTOR pathway. In addition, plumbagin was shown to increase drug sensitivity to cisplatin. The eight mRNAs selected for further analysis, AXL, SCG5, VOPP1, DCBLD2 and DRAM1 are cancer-promoting genes, DUSP1, AQP5 and BLNK are cancer suppressor genes. And they were related to the diagnosis, growth, prognosis, and immune cell infiltration in TSCC patients. CONCLUSION: Plumbagin exhibits an inhibitory effect on the growth of the PDX model of TSCC. Moreover, plumbagin enhances the inhibitory effects of cisplatin.

Construction of prognostic signature of patients with oral squamous cell carcinoma based on pyroptosis-related long non-coding RNAs.

Background and objective: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the head and neck, and its morbidity and mortality are increasing year by year. Changes in key genes are thought to be closely related to the occurrence and development of OSCC. Pyroptosis is an inflammatory form of programmed cell death that has been implicated in malignancies and inflammatory diseases. Changes in the expression of long noncoding RNAs may also affect tumorigenesis and progression. In this study, our main objective was to evaluate the association between pyroptosis-related lncRNAs and prognosis in patients with OSCC. Methods: The RNA-seq data and clinicopathological data of OSCC patients are from The Cancer Genome Atlas database. The pyroptosis gene set is obtained from Gene Set Enrichment Analysis database. Univariate COX, Lasso and multivariate COX regression analyses were used for the construction of risk prognostic models of OSCC, eight lncRNAs were incorporated into prognostic models. The Kaplan-Meier method and log-rank test were used to evaluate the differences of overall survival between patients in high-risk and low-risk groups. The reliability of predictions across the dataset was analyzed by receiver operating characteristic (ROC) curves. The immune signature score was calculated using the single-sample gene set enrichment analysis. Results: Eight pyroptosis-related lncRNAs were used to construct prognostic signature of OSCC, including AC136475.2, AC024075.2, JPX, ZFAS1, TNFRSF10A-AS1, LINC00847, AC099850.3 and IER3-AS1. According to this prognostic signature, patients with OSCC were divided into high-risk and low-risk groups. Kaplan-Meier survival analysis showed that the survival rate of the high-risk group was significantly lower than the low-risk group. ROC area for risk score was 0.716, and ROC area of the 8 lncRNAs are all between 0.5 and 1, implied that these lncRNAs had high accuracy in predicting the prognosis of OSCC patients. Immune Infiltration findings suggested that these lncRNAs affected immune responses in the microenvironment of OSCC. Conclusion: The prognostic signature based on pyroptosis-related lncRNAs potentially serves as an independent prognostic indicator for OSCC patients. And this signature facilitates research on targeted diagnosis and treatment of patients diagnosed with OSCC.

lncRNA SNHG26 promoted the growth, metastasis, and cisplatin resistance of tongue squamous cell carcinoma through PGK1/Akt/mTOR signal pathway.

Tongue squamous cell carcinoma (TSCC) is closely linked to head and neck cancers. Here, we sought to explore the role and mechanism of lncRNAs in the occurrence and progression of TSCC and cisplatin resistance. The results of next-generation transcriptomic sequencing revealed that lncRNA-SNHG26 was differentially expressed and was associated with TSCC cisplatin resistance. The Cancer Genome Atlas dataset and tumor tissue analysis revealed that high SHNG26 expression was associated with the occurrence, progression, and poor prognosis of TSCC. Evidence from cell and animal experiments showed that SNHG26 expression was positively correlated with TSCC proliferation, epithelial-mesenchymal transformation, migration, invasion, and cisplatin resistance. Furthermore, in TSCC cells, SNHG26 was found to bind directly to the PGK1 protein, inhibiting its ubiquitination and activating the Akt/mTOR signaling pathway. These findings suggest that lncRNA-SNHG26 may be a promising target for inhibiting TSCC progression and improving sensitivity to cisplatin chemotherapy in TSCC.

Quantile regression analysis of the association between parental rearing and interpersonal sensitivity in Chinese adolescents.

BACKGROUND: Parental rearing is well documented as an important influencing factor of interpersonal sensitivity (IS). However, little research has focused on the extent by which various aspects of parental rearing in fluence IS. This study aimed to analyze the effects of parental rearing on IS, using quantile regression. We analyzed the extent of the influence of parental rearing on IS by quantile regression to provide definitive evidence on the family education of adolescents with IS problems. METHODS: The multiple cross-sectional studies were conducted among 3345 adolescents from Harbin, China, in 1999, 2006, 2009 and 2016. Furthermore, a multistage sampling method (stratified random cluster) was used to select participants. IS was assessed using a subscale of the Symptom Checklist-90-Revision. Perceived parental rearing was assessed using the Egna Minnen av. Barndoms Uppfostran. The ordinary least squares (OLS) linear regression was used to determine the average effect of parental rearing on IS. The quantile regression was conducted to examine the established associations and to further explain the association. RESULTS: Paternal emotional warmth was found to be associated with IS across the quantile, especially after the 0.6 quantiles; however, this association was not found for maternal emotional warmth. Paternal punishment was associated with IS at the 0.22-0.27 and 0.60 quantile; however, maternal punishment had no significant effect on IS. QR method found that paternal overinvolvement was associated with IS at the 0.48-0.65 quantiles, but paternal overprotection was associated with IS across the quantile; however, maternal overinvolvement and overprotection was positively correlated with IS at the 0.07-0.95 quantiles. The correlation between paternal rejection and IS was found at the 0.40-0.75 and > 0.90 quantiles; maternal rejection was associated with IS within the 0.05-0.92 quantiles. CONCLUSIONS: Parental rearing practices predict different magnitudes of IS at varying levels. This study provides suggestions for parents to assess purposefully and systematically, intervene, and ameliorate adolescent IS problems. We also highlight the role of paternal rearing in children's IS problems, providing new ideas for family education.

Dynamics of parenting styles of adolescent students from the perspective of intergenerational conflict / 中国学校卫生

Objective@#To explore dynamics of parenting styles of adolescents from 1999 to 2019 from the perspective of intergenerational conflict, to provide support for family education and adolescent healthy development.@*Methods@#Using a multistage stratified cluster random sampling method, the unified questionnaire was administered to 2 590 students in the same sampling junior and senior high schools in 1999, 2009, and 2019 using the Egna Minnen av Barndoms Uppfostran own memories of parental rearing practices in childhood(EMBU).@*Results@#Overall there were differences in the nine factors of parenting styles across generations ( F = 12.07-72.52, P <0.01), with decreasing ratings of warmth and understanding of father and mother (F1, M1), over interference of father (F3) over generations(F1:46.72±9.41, 45.87±11.33, 43.61±11.27; M1:51.56±9.38, 51.03±11.59, 46.23± 12.27 ; F3:19.03±4.00, 18.29±4.32, 17.95±4.51), and all other parenting styles rated higher in 2019 than in 2009 and 1999(except for the over protection and over interference of mother, and punishment, firm control of mother). Parenting styles across generations (except for the rejection and denial of father among girls) showed gender difference.The overall gender trend coincided with the total population trend. Parenting styles across generations varied significantly among middle and high school students( F =3.92-47.27, P <0.05 ), changes in F1 and F3 factors coincided with the overall decreasing trend. Factor analysis showed that parenting styles could be classified into two dimensions, with varied factor loading across generation.@*Conclusion@#Intergenerational decreases in parental emotional warmth and paternal interfering are observed in a sex and grade specific manner. Based on the diversity of needs and population differentiation, optimal intervention for comprehensive health development of adolescents are in great need to keep pace with the times and promoting the high quality development of adolescents.

Components of the Endocannabinoid System and Effects of Cannabinoids Against Bone Diseases: A Mini-Review.

Background: The endocannabinoid system (ECS) is involved in multiple physiological processes, including appetite regulation, pain perception, motor function development, and immune response regulation. Cannabinoids have been approved for the clinical treatment of nausea and vomiting caused by cytostatic therapy or cancer chemotherapy, loss of appetite in HIV/AIDS-associated cachexia, refractory spasms induced by multiple sclerosis, chronic pain, and urinary incontinence. Methods: Check out the research on ECS and bone diseases in the past 20 years. Results: Many studies have demonstrated that endocannabinoids (eCBs) and cannabinoid receptors (CBRs) are expressed in bone and synovial tissues, playing important roles in bone metabolism. Preclinical studies using cannabis-based therapies in animal models have shown that cannabinoids (CBs) can alleviate the development of osteoarthritis (OA), prevent osteoporosis (OP), reduce cancer-induced osteolytic destruction, and improve fracture healing, highlighting the therapeutic potential of CBs for human bone diseases. Conclusions: The present review summarizes various components of the ECS in bone diseases and their potential as a therapeutic target.

A competing risk nomogram for predicting cancer-specific death of patients with buccal mucosa cancer.

OBJECTIVES: Our aim was to develop and validate a competing risk nomogram to determine the probability of cancer-specific death in buccal mucosa cancer (BMC) patients. MATERIALS AND METHODS: We examined the records of BMC patients in the Surveillance, Epidemiology, and End Results (SEER) Program and First Affiliated Hospital of Nanchang University (China). We adopted the cumulative incidence function and Fine-Gray proportional hazards model based on univariate and multivariate analyses by R-software to identify the risk factors associated with cancer-specific death. Subsequently, a nomogram was developed and validated to predict the 3- and 5-year probability of cancer-specific death. RESULTS: In 1,286 BMC patients identified from SEER database, cumulative incidences of cancer-specific death after diagnosis were 33.4% and 35.5% for 3 and 5 years, respectively. In the training cohort (n = 902) from SEER database, the Fine-Gray model indicated that age, Tumor Node Metastasis (TNM) stages, grade, surgery, and histological type were independent risk factors associated with cancer-specific death, based on which a prognostic nomogram was developed. In the internal validation cohort from SEER database (n = 384) and the external validation cohort from our medical center (n = 174), the nomogram was well calibrated and showed remarkable prediction performance. CONCLUSION: The nomogram created herein may prove to be a good assistant tool for assessing the prognosis of BMC patients.

Comparison of clinical effects of the Yu flap and the Karapandzic flap in repairing greater than 2/3 lower lip defects / 口腔疾病防治

Objective@#To compare the clinical effect of the Yu flap and the Karapandzic flap in repairing greater than 2/3 defects of the lower lip and to provide a reference for clinical application.@*Methods@#Ten patients with greater than 2/3 lower lip defects after surgical resection of lower lip tumors and vascular malformations were enrolled: 5 patients were repaired with the Yu flap (Yu flap group) and 5 patients were repaired with the Karapandzic flap (Karapandzic flap group). Follow-up for at least 1 year was conducted to evaluate the morphology (symmetry, stoma, exposure of vermilion) and function (sensory function, motor function) of the reconstructed lower lip.@*Results @#All the flaps survived, and all wounds showed primary healing. The lower lips reconstructed with the Yu flap or the Karapandzic flap obtained similar satisfactory oral function. The sensory function was essentially restored. There were no obvious obstacles in speech and expression, and no saliva leakage occurred. In the Yu flap group, only 1 patient had slight microstomia. In the Karapandzic flap group, 2 patients had slight microstomia and 3 patients had moderate microstomia. 90% (9/10) of the patients were very satisfied with the postoperative outcome, and 1 patient in the Karapandzic flap group was basically satisfied. @*Conclusion@#Both the Yu flap and the Karapandzic flap can be used to repair greater than 2/3 lower lip defects and reliable outcomes can be achieved. These two methods can achieve similar oral functions, but the effect of the Karapandzic flap is inferior to that of the Yu flap in terms of aesthetic appearance, and microstomia often occurs, while the Yu flap can generally maintain the original size of the mouth cleft.

Establishment of a Jaw Fibrosarcoma Patient-Derived Xenograft and Evaluation of the Tumor Suppression Efficacy of Plumbagin Against Jaw Fibrosarcoma.

Background: Head and neck fibrosarcoma is a rare malignant tumor, accounting for about 1% of all head and neck tumors. It can also occur in the jaw bone, for which surgical resection is the main treatment but the recurrence rate is high and the prognosis is usually poor. Due to the lack of models mimicking the biological characteristics of the tumor, there is little progress in the research of the pathogenesis and treatment of fibrosarcoma. Therefore, there is an urgent need to explore a high-fidelity model that can reflect the biological characteristics of fibrosarcoma for the sake of improving the therapeutic outcome and prognosis, and preventing recurrence. Patient-derived xenografts (PDX) may more accurately reflect the human disease, and is an attractive platform to study disease biology and develop treatments and biomarkers. In this study we describe the establishment of jaw fibrosarcoma PDX models and compare PDX tumors to those of human origin. Methods: Tumor biopsies from a patient with jaw fibrosarcoma were implanted in immunodeficient mice. Primary and PDX tumors were characterized extensively by histology, immunohistochemistry and humanized identification. Based on the finding of our previous preliminary research that plumbagin had an anti-tumor effect against head and neck cancer, we used this model in the present study to evaluate the anti-tumor effect of plumbagin on jaw fibrosarcoma. Results: The established PDX model maintained the histological and immunohistochemical characteristics of the primary tumor. Plumbagin significantly inhibited the tumor growth in the jaw fibrosarcoma PDX model. Conclusion: We successfully established a PDX model of jaw fibrosarcoma and demonstrated that this PDX model preserved the important molecular characteristics of the human primary tumor, thus providing a powerful tool for treatment research and new drug development of jaw fibrosarcoma. In addition, plumbagin was found to have an inhibitory effect on the growth of PDX modeled jaw fibrosarcoma, which provides a preliminary research basis for its clinical application.

Association between microRNA-125b expression in formalin-fixed paraffin-embedded tumor tissues and prognosis in patients with melanoma.

Melanoma is an invasive and malignant type of tumor with unsatisfactory therapeutic outcomes. The present study aimed to detect the expression levels of microRNA (miR)-125b in formalin-fixed paraffin-embedded (FFPE) melanoma tissues and the association of its expression levels with the clinical features, diagnosis and prognosis of melanoma. Expression levels of miR-125b in 29 FFPE melanoma specimens (16 primary and 13 metastatic tumors), and 16 intradermal nevus (IDN) specimens as a control, were detected by reverse transcription-quantitative PCR. Associations among miR-125b expression and mortality, patient age and sex, tumor location and size, lymph node metastasis (LNM) and TNM stage were analyzed by t-test. The diagnostic value of miR-125b for melanoma was evaluated by receiver operating characteristic (ROC) curve analysis. Prognosis of patients in the microRNA-125b low- and high-expression groups was analyzed by Fisher's exact test. The association between miR-125b expression and the overall survival of patients with melanoma was assessed using Kaplan-Meier curve analysis and a Cox proportional hazards model. The results revealed that the expression levels of miR-125b in primary and metastatic melanomas were significantly lower than those in the IDN control group (P<0.05), and the expression levels of miR-125b in the metastatic group were significantly lower than those in the primary group (P<0.05). In addition, the expression levels of miR-125b were significantly associated with LNM (P=0.001) and TNM stage (P=0.004), but not with age, sex, tumor size or location (P>0.05). ROC curve analysis revealed that the area under the curve (AUC) was 0.880, with a 95% CI of 0.777-0.984 (P<0.05). The overall survival rate of the patients with a low expression level of miR-125b (20.0%) was lower than that of patients with a high expression level of miR-125b (64.3%) (P<0.05). miR-125b expression was an independent predictor of overall survival in patients with melanoma [hazard ratio (HR), 0.252; 95% CI, 0.087-0.729]. Overall, these findings indicated that a low expression level of miR-125b was associated with higher LNM and TNM stage in patients with melanoma, and that this has a certain diagnostic value. miR-125b may be used for the early screening of melanoma and determining the prognosis of patients with melanoma, and may be a potential target for the treatment of the disease.

Inhibition of USP4 attenuates pathological scarring by downregulation of the TGF­ß/Smad signaling pathway.

Pathological scarring is a result of the hypertrophy of scar tissue during tissue repair following trauma. The aim of the present study was to assess the effect of ubiquitin­specific protease 4 (USP4) silencing on pathological scarring, and to evaluate the mechanistic basis for the effect. An MTT assay was used to assess cell viability. Immunoprecipitation (IP) was used to determine ubiquitination levels of the TGF­ß receptor (TßR)I and Smad7. Tumor formation was assessed by injecting keloid fibroblasts. Hematoxylin and eosin staining was used to detect pathological changes in tumor tissue. Reverse transcription quantitative polymerase chain reaction and western blot analysis assays were used to evaluate the expression levels of TßRI and Smad7. Compared with the untreated control animals, cell viability and the expression of TßRI and Smad7 increased significantly in animals treated with TGF­ß. Short hairpin RNA for USP4 (shUSP4) decreased the cell viability of negative control cells, TGF­ß­induced cellular proliferation, and the expression of TßRI and Smad7. IP experiments indicated that the ubiquitination level of TßRI was decreased following USP4 silencing. There was no remarkable difference in the structure of scar tissue among the various animal groups at 14 days following treatment, while the necrotic area of the scar tissue in the shUSP4 and vialinin A (USP inhibitor)­treated animals increased significantly at the 28th and 42nd day compared with the control animals. At days 14, 28 and 42, the expression levels of TßRI and Smad7 in the shUSP4 and vialinin A­treated animals were significantly decreased compared with the control animals (P<0.05). In summary, interference with or inhibition of USP4 prevented the activity of the TGF­ß/Smad pathway signaling and inhibited the formation of pathological scars.