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Background: In previous observational studies, food-derived antioxidant vitamins have been suggested to be associated with breast cancer. However, the findings were inconsistent and the causal relationship could not be clearly elucidated. To confirm the potential causal relationship between food-derived antioxidants (retinol, carotene, vitamin C and vitamin E) and the risk of breast cancer, we conducted a two-sample Mendelian randomization (MR) study. Methods: The instrumental variables (IVs) as proxies of genetic liability to food-derived antioxidant vitamins were obtained from the UK Biobank Database. We extracted breast cancer data (122,977 cases and 105,974 controls) from the Breast Cancer Consortium (BCAC). In addition, we studied estrogen expression status categorically, including estrogen receptor positive (ER+) breast cancer (69,501 cases and 105,974 controls) and versus estrogen receptor (ER−) negative breast cancer (21,468 cases and 105,974 controls). We performed two-sample Mendelian randomization study, and inverse variance–weighted (IVW) test was regarded as main analysis. Sensitivity analyses were further conducted to assess heterogeneity and horizontal pleiotropy. Results: The results of IVW showed that among the four food-derived antioxidants, only vitamin E had protective effect on the risk of overall breast cancer (OR = 0.837, 95% CI 0.757–0.926, P = 0.001) and ER+ breast cancer (OR = 0.823, 95% CI 0.693–0.977, P = 0.026). However, we found no association between food-derived vitamin E and ER− breast cancer. Conclusions: Our study suggested food-derived vitamin E can decrease the risk of breast cancer overall and ER+ breast cancer, and the robustness of our results was confirmed by sensitivity analyses. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. In this study, we proposed a severe maternal caloric restriction during late pregnancy, followed by a post weaning high-fat diet in mice. After weaning, normal and high-fat diets were provided to mice to simulate the dietary pattern of modern society. Methods: The pregnant mice were divided into two groups: normal birth weight (NBW) group and low birth weight (LBW) group. After 3 weeks for weaning, the male offspring mice in the NBW and LBW groups were then randomly divided into four subgroups: NC, NH, LC and LC groups. The offspring mice in the NC, NH, LC and LC groups were respectively fed with normal diet, normal diet, high-fat diet and high-fat diet for 18 weeks. After 18 weeks of dietary intervention, detailed analyses of mRNA and protein expression patterns, signaling pathway activities, and promoter methylation states were conducted for all relevant genes. Results: After dietary intervention for 18 weeks, the expressions of CD36, Fabp4, PPARγ, FAS, and ACC1 in the skeletal muscle tissue of the LH group were significantly increased compared with the LC and NH groups (P < 0.05). The level of p-AMPK/AMPK in the skeletal muscle tissue of the LH group was significantly decreased compared with the LC and NH groups (P < 0.05). CPT1 and PGC-1α protein expressions were up-regulated in the LH group (P < 0.05) compared to the LC group. Additionally, the DNA methylation levels of the PGC-1α and GLUT4 gene promoters in the skeletal muscle of the LH groups were higher than those of the LC and NH groups (P < 0.05). However, PPARγ DNA methylation level in the LH group was lower than those of the LC and NH groups (P < 0.05). Conclusions: LBW combined with high-fat diets may increase insulin resistance and diabetes through regulating the CD36-related Fabp4-PPARγ and AMPK/ACC signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. In this study, we proposed a severe maternal caloric restriction during late pregnancy, followed by a post weaning high-fat diet in mice. After weaning, normal and high-fat diets were provided to mice to simulate the dietary pattern of modern society. Methods: The pregnant mice were divided into two groups: normal birth weight (NBW) group and low birth weight (LBW) group. After 3 weeks for weaning, the male offspring mice in the NBW and LBW groups were then randomly divided into four subgroups: NC, NH, LC and LC groups. The offspring mice in the NC, NH, LC and LC groups were respectively fed with normal diet, normal diet, high-fat diet and high-fat diet for 18 weeks. After 18 weeks of dietary intervention, detailed analyses of mRNA and protein expression patterns, signaling pathway activities, and promoter methylation states were conducted for all relevant genes. Results: After dietary intervention for 18 weeks, the expressions of CD36, Fabp4, PPARγ, FAS, and ACC1 in the skeletal muscle tissue of the LH group were significantly increased compared with the LC and NH groups (P < 0.05). The level of p-AMPK/AMPK in the skeletal muscle tissue of the LH group was significantly decreased compared with the LC and NH groups (P < 0.05). CPT1 and PGC-1α protein expressions were up-regulated in the LH group (P < 0.05) compared to the LC group. Additionally, the DNA methylation levels of the PGC-1α and GLUT4 gene promoters in the skeletal muscle of the LH groups were higher than those of the LC and NH groups (P < 0.05). However, PPARγ DNA methylation level in the LH group was lower than those of the LC and NH groups (P < 0.05). Conclusions: LBW combined with high-fat diets may increase insulin resistance and diabetes through regulating the CD36-related Fabp4-PPARγ and AMPK/ACC signaling pathways. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to explore the relationship between vitamin D status and islet function in patients with type 2 diabetes mellitus. Methods: The participants were recruited from Hebei General Hospital. Basic characteristics and blood indicators were collected after fasting overnight. The data were analyzed statistically using SPSS 22.0. Analysis of variance, a nonparametric test, or a trend Chi-square test was used for the comparisons. The association between 25-hydroxy vitamin D and modified homeostasis model assessment-β was assessed using multivariate ordinal logistic regression. Results: One hundred seventy-four patients aged 26 to 79 years with type 2 diabetes mellitus were included in this study. Patients with vitamin D deficiency had a lower modified homeostasis model assessment-β level compared with those without vitamin D deficiency. There were differences in body mass index, diabetes course, glycosylated hemoglobin, fasting blood glucose, fasting blood C-peptide, triglyceride, and 25-hydroxy vitamin D among different modified homeostasis model assessment-β groups based upon the tertiles. 25-hydroxy vitamin D, as continuous or categorical variables, was positively related to modified homeostasis model assessment-β whether or not cofounding factors were adjusted. Conclusion: There is an association between increased 25-hydroxy vitamin D levels and improvement in modified homeostasis model assessment-β function in patients with type 2 diabetes mellitus. Trial registration: Cross-sectional trails ChiCTR2000029391, Registration Date: 29/01/2020. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the reliability and validity of the translated Chinese version of the Communication Complexity Scale (C-CCS) in a Chinese sample of preschool-aged children with minimal verbal skills. A total of 120 children with autism spectrum disorders or children with developmental delays aged 2 to 5 years with minimal verbal skills (i.e., produced less than 20 functional words) were recruited to complete the C-CCS. First, we tested the protocol with 20 children and shortened it based on their results. Second, the interrater reliability, test-retest reliability, and concurrent validity for 100 participants were examined. C-CCS scores were compared with scores from the Chinese Communicative Development Inventories (CCDI) for concurrent validity. Ten C-CCS interactive scripts were administered to 100 participants. Intraclass correlation coefficients (ICC) between independent observers were high. The ICCs for overall optimal scores, optimal BR scores and optimal JA scores were 0.978, 0.971 and 0.977 respectively. Agreement for scores within scripted opportunities and communication level were high-Kappa coefficients 0.869 and 1.000 respectively. The test-retest reliability was high (r = 0.911). A moderate correlation was found between the C-CCS and the CCDI (r = 0.401). The results indicate that C-CCS could be used as a measurement tool in research and clinical practice to describe communication levels in children with minimal verbal skills in China. The Chinese version of the Communication Complexity Scale was developed through a rigorous cultural adaptation process. The evidence shows that the Chinese version of the Communication Complexity Scale is a reliable and valid tool for children with minimal verbal skills in China. The Chinese version of the Communication Complexity Scale can be used in research and clinical practice to assess the general level of social communication skills of Chinese children who mainly communicate using preverbal communication and develop intervention programs. [ABSTRACT FROM AUTHOR]

Objective: Manganese ion (Mn2+) is reported to promote the antitumor immune response by activating the cGAS‐STING pathway, but it is unknown whether Mn2+ can prevent the malignant transformation of precancerous lesions. The effects of Mn2+ in treating oral leukoplakia (OLK) were explored in this work. Methods: Peripheral blood Mn analysis of the patients was performed using inductively coupled plasma atomic emission spectroscopy (ICP–AES). A coculture model of dendritic cells (DCs)/macrophages, CD8+ T cells, and dysplastic oral keratinocytes (DOKs) was employed to analyze the role and mechanism of Mn2+ in a simulated OLK immune microenvironment. Western blot, RT–PCR, flow cytometry, enzyme‐linked immunosorbent assay (ELISA), and lactate dehydrogenase (LDH) assays were adopted to detect the mechanism of Mn2+ in this model. 4‐nitroquinoline oxide (4NQO)‐induced OLK mice were used to assess the role of Mn2+ in suppressing OLK progression, and a novel Mn2+‐loaded guanosine‐tannic acid hydrogel (G‐TA@Mn2+ hydrogel) was fabricated and evaluated for its advantages in OLK therapy. Results: The content of Mn in patients' peripheral blood was negatively related to the progression of OLK. Mn2+ promoted the maturation and antigen presentation of DCs and macrophages and enhanced the activation of CD8+ T cells in the coculture model, resulting in effective killing of DOKs. Mechanistic analysis found that Mn2+ enhanced the anti‐OLK immune response by activating the cGAS‐STING pathway. Moreover, Mn2+ suppressed the development of 4NQO–induced carcinogenesis in the mouse model. In addition, the G‐TA@Mn2+ hydrogel had better anti‐OLK effects. Conclusions: Mn2+ enhanced the anti‐OLK immune response by activating the cGAS‐STING pathway, and the G‐TA@Mn2+ hydrogel is a potential novel therapeutic approach for OLK treatment. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the current evidence on the effectiveness and safety of ureteric stent removal using strings compared to conventional methods. Materials and Methods. The electronic databases PubMed, Embase, China National Knowledge Infrastructure (CNKI), and the Cochrane Library were systematically searched up to March 2020. Two reviewers searched the literature, independently extracted the data, and evaluated the quality of the studies according to the inclusion and exclusion criteria. The data analysis was performed with the software program Review Manager 5.3. Results. Eleven studies with a total of 1809 patients were included in the analysis based on the inclusion criteria. Our meta-analysis showed that visual analogue scale (VAS) scores were significantly lower in the string group than in the conventional group (weighted mean difference (WMD) -2.63; 95% confidence interval (CI) -3.68, -1.58; P < 0.00001). In terms of stent dwell time, the string group had an advantage (WMD -9.53; 95% CI -14.20, -4.86; P < 0.0001). In addition, no significant differences in the occurrence of urinary tract infection (UTI) (odds ratio (OR) 1.03; 95% CI 0.62, 1.72; P = 0.92), emergency room visits (OR 0.99; 95% CI 0.59, 1.67; P = 0.97), or other complications (P > 0.05) were observed between the two groups. Conclusion. Our findings suggest that an extraction string is an effective and safe method for the removal of ureteric stents. This method gives patients the benefits of reduced pain and shortened stent dwell time without increasing the risk of UTI. Nevertheless, these findings should be further confirmed through large-volume, well-designed prospective randomized controlled trials (RCTs). [ABSTRACT FROM AUTHOR]

Purpose: To explore the predictive value of preoperative magnetic resonance imaging structural and diffusion indices of the spinal trigeminal tract (SpTV) on the results of microvascular decompression (MVD) in patients with trigeminal neuralgia (TN). Methods: This retrospective study included patients diagnosed with TN and treated with MVD in the Jining First People's Hospital between January 2020 and January 2021. The patients were divided into good and poor results groups according to postoperative pain relief. Logistic regression analysis was performed to explore independent risk factors for poor results of MVD, and their predictive value was examined using receiver operating characteristic (ROC) curves. Results: A total of 97 TN cases were included, 24 cases with a poor result and 73 with a good result. They were comparable in demographic characteristics. Fractional anisotropy (FA) was lower (P < 0.001), and radial diffusivity (RD) was higher (P < 0.001) in the poor result group compared to the good result group. Patients in the good result group showed a higher proportion of grade 3 neurovascular contact (NVC) (39.7% vs. 16.7%, P = 0.001) and a lower RD (P < 0.001). The multivariate analysis showed that the RD of SpTV (OR = 0.000016, 95% CI: 0.000–0.004, P < 0.001) and NVC (OR = 8.07, 95% CI: 1.67–38.93, P = 0.009) were independently associated with poor results. The area under the curve (AUC) of RD and NVC were 0.848 and 0.710, and their combination achieved an AUC of 0.880. Conclusion: NVC and RD of SpTV are independent risk factors for poor results after MVD surgery, and combining the NVC and RD might achieve relatively high predictive value for poor results. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a very common bone disease in the elderly population and can lead to fractures and disability. Malnutrition can lead to osteoporosis. The geriatric nutritional risk index (GNRI) is a tool used to assess the risk of malnutrition and complications associated with nutritional status in older patients and is a crucial predictor of many diseases. Hence, this study investigated the association between the GNRI and the presence of osteoporosis and assessed the value of this index for predicting osteoporosis in patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional study enrolled 610 elderly patients with T2DM. General and laboratory data of the patients were collected, along with their measurements of bone mineral density (BMD). The GNRI was calculated based on ideal body weight and serum albumin (ABL) levels. Correlation analysis was performed to determine the relationship between the GNRI and BMD and bone metabolism indices. The GNRI predictive value for osteoporosis development was analyzed through logistic regression analysis and by creating a receiver operating characteristic curve (ROC), calculating the area under the curve (AUC). Results: All patients were divided into the no-nutritional risk and nutritional risk groups. Compared with the no-nutritional risk group, the nutritional risk group had a longer diabetes course, older age, higher HbA1c levels, higher prevalence of osteoporosis; lower BMI, ABL,triglyceride (TG),Calcium (Ca),25-hydroxy-vitamin-D(25(OH)D),and parathyroid hormone(PTH) and lower femoral neck BMD,total hip BMD (P < 0.05). All patients were also assigned to the non-osteoporosis and osteoporosis groups. The non-osteoporosis group had higher GNRI values than the osteoporosis group (P < 0.05). Correlation analysis revealed a positive correlation between the GNRI and lumbar BMD, femoral neck BMD, and total hip BMD (P < 0.05). After the adjustment for confounding factors, Spearman's correlation analysis revealed that the GNRI was positively correlated with Ca, 25(OH)D, and PTH and negatively correlated with alkaline phosphatase (ALP) and procollagen of type-1 N-propeptide (P1NP). Regression analysis exhibited that the GNRI was significantly associated with osteoporosis. The ROC curve analysis was performed using the GNRI as the test variable and the presence of osteoporosis as the status variable. This analysis yielded an AUC for the GNRI of 0.695 and was statistically significant (P < 0.05). Conclusions: A lower GNRI among T2DM patients in northern China is associated with a higher prevalence of osteoporosis. [ABSTRACT FROM AUTHOR]

Objective: There were rarely investigations on the effects and molecular mechanisms of oral squamous cell carcinoma (OSCC) cells when treated with isorhamnetin. This article assesses the anti‐cancer effect of isorhamnetin. Methods and materials: Oral squamous cell carcinoma cells were treated with or without isorhamnetin. Cell proliferation, cell cycle arrest, cell migration, cell death, and the related signaling pathways were evaluated. Results: The results revealed that cell proliferation was inhibited in a dose‐ and time‐dependent manner, which was confirmed by diminished cell viability and revealed by decreased in the number of cell colonies. In addition, the cell cycle arrested in the G2/M phase, and the protein levels of cyclin B1 and CDC2 were suppressed. Moreover, the cell migration was inhibited, and the protein levels of related proteins were modulated. Furthermore, it could be observed that abundant cytoplasmic vacuoles existed which that were derived from mitochondria and the endoplasmic reticulum. It was confirmed that cell death did not result from apoptosis and may have which may be apt to paraptosis. Isorhamnetin was observed to upregulate phosphorylated ERK cascades and increase intracellular reactive oxygen species levels. Conclusions: Our study suggested that the anti‐cancer effect of isorhamnetin might trigger paraptosis, which may indicate a new therapeutic approach to OSCC. [ABSTRACT FROM AUTHOR]