Gender differences in risk factors for ischemic stroke: a longitudinal cohort study in East China.

OBJECTIVES: Epidemiological studies of stroke and its risk factors can help develop strategies to prevent stroke. We aimed to explore the current gender-specific prevalence of stroke and associated risk factors. METHODS: Data were collected using a structured precoded questionnaire designed by the Stroke Screening and Prevention Programme of the National Health and Wellness Commission Stroke Prevention and Control Project Committee, between June 2020 and November 2021. A total of 7394 residents took part in the study, 187 of whom had a stroke. The baseline information of each participant was obtained and included in this study. The chi-square test and Kruskal-Wallis tests were used to examine the relationship between these indicators and stroke, and then multivariate logistic regression was used to construct the prediction scale between different genders. RESULTS: of 7394 participants,4571 (61.82%) were female. The overall prevalence of stroke patients in the study population was 2.53%, Multivariate analysis found that residence status (OR = 0.43, p = 0.002) 、HCY (OR = 0.962, p = 0.000)、Previous TIA (OR = 0.200, p = 0.002) 、Hypertension (OR = 0.33, p = 0.000) and Dyslipidemia (OR = 0.668, p = 0.028) were significant predictors of stroke. there are gender differences in the traditional risk factors for stroke, and women have more risk factors. ROC analysis confirmed the accuracy of the stroke risk model, and the AUC of the stroke risk model for the general population was 0.79 with p < 0.05. In the gender model, the female AUC was 0.796 (p < 0.05). and the male AUC was 0.786 with p < 0.05. CONCLUSION: The prevalence of stroke in adults aged 40 years and above is high in eastern China were high. management of risk factors can effectively prevent the occurrence of most strokes. more attention should be paid to gender differences associated with stroke.

MicroRNA-142-5p induces cancer stem cell-like properties of cutaneous squamous cell carcinoma via inhibiting PTEN.

Cutaneous squamous cell carcinoma (cSCC) is a malignancy of keratinocyte-derived skin tumor, which is regarded as the second most common skin cancer worldwide. Accumulating evidence has established that microRNAs (miRNAs) can play a critical role in tumor initiation, progression, and metastasis including cSCC. Abnormal expression of hsa-miR-142-5p has been elaborated in various tumors. Nevertheless, its expression and function in the development of cSCC remain unclear. In our study, we found that the expression of hsa-miR-142-5p in cSCC cells were greatly overexpressed compared to human benign epidermal keratinocyte cells. Moreover, inhibited hsa-miR-142-5p can repress cSCC cell growth and induce apoptosis while upregulated hsa-miR-142-5p exhibited a reverse phenomenon. Recently, cancer stem cells (CSCs) which possess the ability of self-renewal and proliferation and are able to produce cancer cells have been widely reported. However, the correlation between hsa-miR-142-5p and CSCs in cSCC is still unknown. Interestingly, we observed that overexpressing hsa-miR-142-5p can induce CSC-like properties in cSCC via activating Wnt signaling. In addition, the luciferase reporter assay data and bioinformatics analysis demonstrated that hsa-miR-142-5p can target the 3'UTR of PTEN mRNA. Taken these together, we draw a conclusion that hsa-miR-142-5p can trigger cancer stem cell-like properties of cSCC through inhibition of PTEN. Our findings may provide hsa-miR-142-5p as a new therapeutic target for cSCC.

Establishment and validation of a nomogram model for predicting the specific mortality risk of melanoma in upper limbs based on the SEER database.

For patients with upper limb melanoma, the significance of specific death is more important than that of all-cause death, and traditional survival analysis may overestimate the mortality rate of patients. Therefore, the nomogram model for predicting the specific mortality risk of melanoma in the upper limbs was developed. A population with melanoma in the upper limbs, diagnosed from 2010 to 2015, were selected from the National Cancer Institute database of Surveillance, Epidemiology, and End Results (SEER). The independent predictive factors of specific death were confirmed by the competing risk model of one-factor analysis and multi-factor analysis, and the nomogram was constructed according to the independent predictive factors. 17,200 patients with upper limb melanoma were enrolled in the study (training cohort: n = 12,040; validation cohort: n = 5160). Multi-factor analysis of the competing risk model showed that age, marital status, gender, tumor stage, T stage, M stage, regional lymph node surgery information, radiotherapy, chemotherapy, mitotic cell count, ulcer and whether there were multiple primary cancers, were independent factors affecting the specific death of upper limb melanoma patients (P < 0.05). The nomogram has good predictive ability regarding the specific mortality risk of melanoma in the upper limbs, and could be of great help to formulate prognostic treatment strategies and follow-up strategies that are conducive to survival.

Exosome-delivered circRPS5 inhibits the progression of melanoma via regulating the miR-151a/NPTX1 axis.

BACKGROUND: Circular RNAs (circRNAs) have been reported to exert critical functions in tumorigenesis and development. However, the underlying mechanism by which circRNAs regulate melanoma progression remain to be elucidated. METHODS: The differentially expressed circRNAs were first identified by circRNA-seq, and circRNAs were validated via qRT-PCR and Sanger sequencing. Then, the impact of circRPS5, miR-151a and NPTX1 expression on the progression of melanoma cell were determined by gain- and loss-of-function assays. The relationship between circRPS5, miR-151a, and NPTX1 was predicted by StarBase website and authenticated by luciferase reporter assay. The melanoma cells-derived exosomes were characterized using nanoparticle tracking analysis (NTA) and western blot. RESULTS: CircRPS5 was significantly downregulated in melanoma tissues and cell lines. Functionally, circRPS5 suppressed the proliferation, migration, and invasion of melanoma cells, and induced cell cycle arrest and apoptosis in vitro. Mechanistically, circRPS5 harbor miR-151a, acting as miRNA sponge, and then miR-151a targeted the 3'-UTR of NPTX1. Finally, circRPS5 was mainly incorporated into exosomes to inhibit the progression of melanoma cells. CONCLUSIONS: This finding reveal circRPS5 suppressed the progression of melanoma through miR-151a/NPTX1 pathway, and may provide a promising therapeutic strategies for melanoma.

[Positron emission tomography plus VEEG in the localization of epileptic foci in negative-MRI interact epilepsy].

OBJECTIVE: To explore the application value of positron emission tomography (PET) in the localization of magnetic resonance imaging (MRI)-negative epileptogenic focus. METHODS: Brain images of 18fluoro-2-deoxy-D-glucose (18F-FDG) and 13N-NH3·H2O-PET, MRI and video electroencephalography (VEEG) were obtained in 65 patients. Preoperative and postoperative localizations were compared in MRI-negative patients. And the results of PET and VEEG were compared between the MRI-positive and MRI-negative groups. RESULTS: MRI scans were normal in 26 cases and abnormal in 35 cases. Sixty-one patients had interictal epileptiform discharge on VEEG (brain regions, n = 12; multiple brain areas, n = 16; hemisphere, n = 13; unspecified location, n = 20) and interictal PET imaging (brain regions, n = 23; multiple brain areas, n = 28; hemisphere, n = 5; unspecified location, n = 6). And 17 MRI-negative patients underwent operations and 12 of them reached the Engels I-II level standard. Both PET and VEEG were compared between the MRI-positive and MRI-negative groups. No significant differences existed between two group (P < 0.05). A comparison of PET and VEEG showed statistical significance in two group (P > 0.05). CONCLUSIONS: PET imaging is both sensitive and effective in the detection and localization of epileptogenic foci. Especially for MRI-negative cases, it is an indispensable tool of localizing epileptogenic foci.

Mild cold stress specifically disturbs clustering movement of DFCs and sequential organ left-right patterning in zebrafish.

In poikilothermic animals, the distinct acclimatization ability of different organs has been previously addressed, while the tissue-specific role of cold stress in early development is largely unknown. In this study, we discovered that despite its role in delaying embryonic development, mild cold stress (22°C) does not disturb multiple-organ progenitor specification, but does give rise to organ left-right (LR) patterning defects. Regarding the mechanism, the data showed that mild cold stress downregulated the expression of cell-adhesion genes cdh1 and cdh2 during gastrulation, especially in dorsal forerunner cells (DFCs), which partially disturbed the clustering movement of DFCs, Kupffer's vesicle (KV) morphogenesis, and ciliogenesis. As a result, the defects of KV/cilia disrupted asymmetric nodal signaling and subsequent heart and liver LR patterning. In conclusion, our data novelly identified that, in early development, DFCs are more sensitive to mild cold stress, and mild cold stress repressed the expression of cell adhesion-related gene cdh1 and cdh2. This role partially disturbed the clustering movement of DFCs, which resulted in defective KV/cilia development and sequential organ LR patterning defects.

TCF21 regulates miR-10a-5p/LIN28B signaling to block the proliferation and invasion of melanoma cells.

BACKGROUND AND AIM: Some research has suggested that miRNA-10a (miR-10a-5p) had an inhibitory function in proliferation and invasion of cancers. Whereas the role of miR-10a-5p in melanoma has not been fully explored. This study aims to confirm LIN28B as the targeted gene of miR-10a-5p which was explored in melanoma cells. In addition, upstream regulatory molecule of miR-10a-5p was also investigated in melanoma cells. METHODS: Real-time Quantitative polymerase chain reaction (RT-qPCR) was adopted to analyze miR-10a-5p expression level in melanoma and the normal human epidermal melanocyte cells. Several biological assays were performed to evaluate miR-10a-5p influences on cell proliferation, migration and invasion ability in A375 and B16-F10 cells. Gene prediction of miRNA targeting and a dual luciferase assay were applied to assess miR-10a-5p-targeted LIN28B. Western blot assessed the impacts of miR-10a-5p on the protein expression of LIN28B. Western blot analyzed the TCF21 effects on the expression of LIN28B and RT-qPCR assessed the influence of TCF21 on the expression level of miRNA-10a. In addition, Chromatin Immunoprecipitation (ChIP) Assay and JASPAR databases were employed to explore the regulatory relationship between TCF21 and miR-10a-5p. RESULTS: We discovered that miR-10a-5p expression was lower in melanoma cells and high expression of miR-10a-5p suppressed the proliferation, migration and invasion abilities of melanoma cells. We also discovered that miR-10a-5p targeted the LIN28B mRNA 3'UTR area and diminished LIN28B protein expression. We found that LIN28B expression was strongly decreased by TCF21 upregulation in the two melanoma cells. The qRT-PCR assay showed that miR-10a-5p expression level was obviously boosted by increased TCF21 expression. The results also demonstrated that TCF21 directly regulated miR-10a-5p at transcript levels. CONCLUSION: TCF21 induced miRNA-10a targeting LIN28B could affect the progression and growth of melanoma.

MicroRNA-373 promotes cell migration via targeting salt-inducible kinase 1 expression in melanoma.

It is well established that altered expression of microRNAs (miRs) is critical in numerous human cancer types. Nevertheless, the molecular mechanisms of many miRs are yet to be elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction and western blot analyses, and cell migration assays were performed to verify dysregulation of miR-373 in melanoma and its biological function. The transcriptional level of miR-373 was identified to be upregulated in melanoma tissues and cell lines compared with nevus and normal melanocytes. miR-373 was identified to function as an oncomiR, promoting melanoma cell migration. Notably, miR-373 was observed to suppress its downstream gene salt-inducible kinase 1 (SIK1) through directly binding the 3'-untranslated region of SIK1 expression. Furthermore, reduced SIK1 expression was identified to be responsible for the oncogenic effect of miR-373. In conclusion, the present study indicates that miR-373 functions as an oncomiR to promote melanoma progression through targeting SIK1 expression. This may provide a new therapeutic approach for melanoma.

Identification of Biomarker for Cutaneous Squamous Cell Carcinoma Using Microarray Data Analysis.

Cutaneous squamous cell carcinoma (CSCC) is one of the most malignant tumors worldwide. We aimed to explore the molecular mechanism of this CSCC and screen feature genes that can function as the biomarker of CSCC and thus provide a theoretical basis for the pathogenesis research and development of medicine. The method of microarray data analysis was used in this study to explore the differentially expressed genes between tissues of normal specimens and tissues of patients with CSCC. Besides, functional enrichment analysis and signal pathway were performed on these genes to screen the feature genes that are closely associated with CSCC can function as the potential biomarkers of CSCC.A total of 53 samples from two datasets, GSE45216 and GSE45164, were used in the differentially expressed analysis. And as a result, a total of 833 genes were screened out, including 465 up-regulated genes and 215 down-regulated genes. Candidate genes, including up-regulated genes like S100A12, MMP1, DEFB4B/DEFB4A, KRT16 and PI3, and down-regulated genes like EGR3, LRP4, C14orf132, PAMR1, CCL27, and KRT2 were screened out. All these genes were testified in the dataset of GSE66359. The result showed that only three genes, KRT16, PI3 and EGR3, were mostly differentially expressed and only EGR3 had the same expression pattern with both datasets, GSE45216 and GSE45164.Of note, EGR3 gene was found to be the most differentially expressed gene in cutaneous squamous cell carcinoma, which had the potential to function as the candidate genes and help in the diagnosis and prognostic treatments of CSCC.