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Few cases of patients with Cheng’s type III portal vein tumor thrombus (PVTT) have been reported to achieve radical cure without recurrence over time. In this study, we reported on a 55-year-old male patient with a diagnosis of stage IIIa China liver cancer staging (CNLC), PVTT Cheng’s type III, mild cirrhosis, and chronic viral hepatitis B. TACE combined with radioactive iodine-125 ( 125 I) particle implantation was applied to achieve radical treatment with sequential oral anlotinib hydrochloride capsules. This case might serve as a reference for the treatment of this disease.

First, based on the precipitation data and torrential rain disaster data in Zhangjiajie City of Hunan Province from 2016 to 2020, taking the claim cases of the property and cargo insurance (hereinafter referred to as "property and cargo insurance") from Hunan Branch of the People's Insurance Company of China as the research sample, the Dominance Analysis Method was used to determine the influence weights of disaster-causing factors to establish a comprehensive disaster-causing index (I) model of torrential rain. Second, an exponential function is used to fit the relationship between the number of town or street which filed claims of property and cargo insurance and I, then to determine the threshold of I corresponding to different accident levels. Finally, the claim case caused by torrential rain disaster in Zhangjiajie in the flood season of 2021 were selected to verify the I and its threshold. The results show that the number of property and cargo insurance accidents caused by torrential rain in Zhangjiajie is generally low in east and west but high in middle areas. Among the disaster-causing factors, the weight of the 96-hour accumulated precipitation on the scope of accident is the largest, reaching 28.6%. The simulated grades of the scope of accident, the amount of claim and the number of accidents of property and cargo insurance have a high correlation with the grades of actual disasters, and all passed the test at the 0.01 significance level. The threshold test results show that the consistency rate or accuracy between the predicted level and the actual level of torrential rain disaster-causing cases is 71.4%, in which the predicted values of accuracy for the mild, moderate and severe disaster levels are 70%, 70% and 100%, respectively. Therefore, the threshold of I established in this study can be used for the industrial meteorological services related to the property and cargo insurance in Zhangjiajie.

Head and neck squamous cell carcinoma (HNSCC) usually has a poor prognosis and is associated with a high mortality rate. Its etiology is mainly the result from long-term exposure to either alcohol, tobacco or human papillomavirus (HPV) infection or a combination of these insults. However, HNSCC patients with HPV have been found to show a survival advantage over those without the virus, but the mechanism that confers this advantage is unclear. Due to the large number of HPV-independent HNSCC cases, there is a possibility that the difference in prognosis between HPV-positive (HPV+) and negative (HPV-) patients is due to different carcinogens. To clarify this, we used scRNA data and viral tracking methods in order to identify HPV+ and HPV- cells in the tumour tissues of patients infected with HPV. By comparing HPV+ and HPV- malignant cells, we found a higher level of tumour stemness in HPV- tumour cells. Using tumour stemness-related genes, we established a six-gene prognostic signature that was used to divide the patients into low- and high-risk groups. It was found that HPV patients who were at low-risk of contracting HNSCC had a higher number of CD8+ T-cells as well as a higher expression of immune checkpoint molecules. Correspondingly, we found that HPV+ tumour cells expressed higher levels of CCL4, and these were highly correlated with CD8+ T cells infiltration and immune checkpoint molecules. These data suggest that the stemness features of tumour cells are not only associated with the prognostic risk, but that it could also affect the immune cell interactions and associated signalling pathways.

Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs). Until now, the contributions of circRNAs in chemoresistance of hepatocellular carcinoma (HCC) remain largely unknown. In the present study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We investigated the expression of circRNAs in 5 paired cisplatin-sensitive and cisplatin-resistant HCC tissues by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of circARNT2 in HCC patient tissues and cell lines. Then, the effects of circARNT2 on cisplatin resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. circARNT2 was significantly upregulated in HCC tissues and cell lines. Overexpression of circARNT2 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. In vitro experiments showed that knockdown of circARNT2 inhibited cell proliferation and enhances the cisplatin sensitivity of HCC cells. Furthermore, circARNT2 facilitates HCC progression in vivo. We demonstrated that circARNT2 acts as a sponge for miR-155-5p and verified that PDK1 is a novel target of miR-155-5p. In summary, our study demonstrated that circARNT2 modulates cisplatin resistance through miR-155-5p/PDK1 pathway. Our findings indicated that circARNT2 may serve as a promising therapeutic target for overcoming cisplatin resistance for HCC.

Abstract Background Emerging evidence have illustrated the vital role of long noncoding RNAs (lncRNAs) long intergenic non-protein coding RNA 00511 (LINC00511) on the human cancer progression and tumorigenesis. However, the role of LINC00511 in breast cancer tumourigenesis is still unknown. This research puts emphasis on the function of LINC00511 on the breast cancer tumourigenesis and stemness, and investigates the in-depth mechanism. Methods The lncRNA and RNA expression were measured using RT-PCR. Protein levels were measured using western blotting analysis. CCK-8, colony formation assays and transwell assay were performed to evaluate the cell proliferation ability and invasion. Sphere-formation assay was also performed for the stemness. Bioinformatic analysis, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were carried to confirm the molecular binding. Results LINC00511 was measured to be highly expressed in the breast cancer specimens and the high-expression was correlated with the poor prognosis. Functionally, the gain and loss-of-functional experiments revealed that LINC00511 promoted the proliferation, sphere-formation ability, stem factors (Oct4, Nanog, SOX2) expression and tumor growth in breast cancer cells. Mechanically, LINC00511 functioned as competing endogenous RNA (ceRNA) for miR-185-3p to positively recover E2F1 protein. Furthermore, transcription factor E2F1 bind with the promoter region of Nanog gene to promote it transcription. Conclusion In conclusion, our data concludes that LINC00511/miR-185-3p/E2F1/Nanog axis facilitates the breast cancer stemness and tumorigenesis, providing a vital insight for them.

The remodeling of the extracellular matrix (ECM) in the parenchyma plays an important role in the development of acute respiratory distress syndrome (ARDS), a disease characterized by lung injury. Although it is clear that TGF-β1 can modulate the expression of the extracellular matrix (ECM) through intracellular signaling molecules such as Smad3, its role as a therapeutic target against ARDS remains unknown. In this study, a rat model was established to mimic ARDS via intratracheal instillation of lipopolysaccharide (LPS). A selective inhibitor of Smad3 (SIS3) was intraperitoneally injected into the disease model, while phosphate-buffered saline (PBS) was used in the control group. Animal tissues were then evaluated using histological analysis, immunohistochemistry, RT-qPCR, ELISA, and western blotting. LPS was found to stimulate the expression of RAGE, TGF-β1, MMP2, and MMP9 in the rat model. Moreover, treatment with SIS3 was observed to reverse the expression of these molecules. In addition, pretreatment with SIS3 was shown to partially inhibit the phosphorylation of Smad3 and alleviate symptoms including lung injury and pulmonary edema. These findings indicate that SIS3, or the blocking of TGF-β/Smad3 pathways, could influence remodeling of the ECM and this may serve as a therapeutic strategy against ARDS.

Stroke is a cerebrovascular disease that results in decreased blood flow. Although Panax notoginseng (PN), a Chinese herbal medicine, has been proven to promote stroke recovery, its molecular mechanism remains unclear. In this study, middle cerebral artery occlusion (MCAO) was induced in rats with thrombi generated by thread and subsequently treated with PN. After that, staining with 2,3,5-triphenyltetrazolium chloride was employed to evaluate the infarcted area, and electron microscopy was used to assess ultrastructural changes of the neurovascular unit. RNA-Seq was performed to determine the differential expressed genes (DEGs) which were then verified by qPCR. In total, 817 DEGs were identified to be related to the therapeutic effect of PN on stroke recovery. Further analysis by Gene Oncology analysis and Kyoto Encyclopedia of Genes and Genomes revealed that most of these genes were involved in the biological function of nerves and blood vessels through the regulation of neuroactive live receptor interactions of PI3K-Akt, Rap1, cAMP, and cGMP-PKG signaling, which included in the 18 pathways identified in our research, of which, 9 were reported firstly that related to PN’s neuroprotective effect. This research sheds light on the potential molecular mechanisms underlying the effects of PN on stroke recovery.

Based on the precipitation data and torrential rain disaster data in Zhangjiajie City of Hunan Province from 2Û16 to 2020, taking the claim cases of the property and cargo insurance (hereinafter referred to as "property and cargo insurance") from Hunan Branch of the People's Insurance Company of China as the research sample, the Dominance Analysis Method was used to determine the influence weights of disaster-causing factors to establish a Comprehensive disaster-causing index (I) model of torrential rain. Second, an exponential function was used to fit the relationship between the number of town or street which filed claims of property and cargo insurance and I, then to determine the threshold of I corresponding to different accident levels. The claim cases caused by torrential rain disaster in Zhangjiajie in the flood season of 2021 were selected to verify the I and its threshold. The results showed that the number of property and cargo insurance accidents caused by torrential rain in Zhangjiajie was generally low in east and west but high in middle areas. Among the disaster-causing factors, the weight of the 96-h accumulated precipitation on the scope of accident was the largest, reaching 28. 6%. The simulated grades of the scope of accident, the amount of claim and the number of accidents of property and cargo insurance had a high correlation with the grades of actual disasters, and all passed the test at the 0.01 significance level. The threshold test results showed that the consistency rate or accuracy between the predicted level and the actual level of torrential rain disaster-causing cases was 71.4%, in which the predicted values of accuracy for the mild, moderate and severe disaster levels were 70%, 70% and 100%, respectively. Therefore, the threshold of I established in this study can be used for the industrial meteorological services related to the property and cargo insurance in Zhangjiajie. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a common, non-infectious, chronic nasal mucosal disease primarily mediated by immunoglobulin E (IgE) following allergen exposure. Currently, studies on AR mainly focus on cytokines, IgE and its receptors, basophils, eosinophils, mast cells, and related genes. Among these, an imbalance between T helper (Th) 1 and Th2 cells is considered an important mechanism underlying AR pathogenesis. The most important cytokines in AR are interleukin (Il)-4 and interferon gamma (IFN-γ) which are secreted by Th2 and Th1 cells, respectively. Il-4 and IFN-γ are antagonistic to each other in regulating IgE synthesis. In this study, the expression of extracellular signal-regulated protein kinase (ERK) 1/2 and its phosphorylation from p-ERK1/2, were significantly increased in a cluster of differentiation of 4+ T cells of AR mice, suggesting that the ERK signaling pathway in these cells is involved in the occurrence and development of AR. This result also implies an enhanced expression of deoxyribonucleic acid methyltransferases (DNMTs). To verify the relationship between ERK signaling and DNMT expression, AR mice were treated with PD98059, a specific inhibitor of the ERK1/2 signaling pathway. The results revealed that perturbations in ERK signaling were significantly positively correlated with the downregulation of DNMT1 expression. Pharmacological intervention is key to treating AR. This study demonstrated that Xingbi gel intervention affected both serum IgE levels and AR behavior scores in mice. Based on its effects on IFN-γ gene expression, the regulation of Th1/Th2 balance, and the ERK signaling pathway, research on the effects of Xingbi gel on AR may provide new avenues in its prevention and treatment.

Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were able to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation.

FBXW7 acts as a tumor suppressor through ubiquitination and degradation of multiple oncoproteins. Loss of FBXW7 expression, which could be partially attributed by the genomic deletion or mutation of FBXW7 locus, is frequently observed in various human cancers. However, the mechanisms regulating FBXW7 expression still remain poorly understood. Here we examined the 5' region of FBXW7 gene to investigate the regulation of FBXW7 expression. We identified seven alternative splicing (AS) 5'-UTR forms of FBXW7α that are composed of multiple novel non-coding exons. A significant difference in translational efficiency among these 5'-UTRs variants was observed by in vivo Luciferase reporter assay and Western blot. Furthermore, we found that the mRNA level of the AS form with high translational efficiency was specifically reduced in more than 80% of breast cancer cell lines and in more than 50% of human primary cancers from various tissues. In addition, we also identified mutations of FBXW7 in prostate cancers (5.6%), kidney cancers (16.7%), and bladder cancers (18.8%). Our results suggest that in addition to mutation, differential expression of FBXW7α AS forms with different translational properties may serve as a novel mechanism for inactivation of FBXW7 in human cancer.