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Early metastasis of pancreatic cancer (PC) leads to high mortality, and the underlying mechanism of metastasis remains unclear. Tumor necrosis factor superfamily member 9 (TNFSF9) is associated with poor prognosis in PC. Here, we investigated the effect of TNFSF9 on PC proliferation and apoptosis, and focused on the effect of TNFSF9 on PC metastasis and its potential mechanism. We found that TNFSF9 promotes PC metastasis in vivo and in vitro, and may be partially dependent on the Wnt/Snail signaling pathway. In addition, TNFSF9 also regulates the release of cytokines IL-10 and transforming growth factor-β (TGF-β) in pancreatic cancer cells through Wnt signaling to induce the M2 polarization of macrophages and promote the migration of PC cells. Overall, our study found that TNFSF9 may directly promote PC metastasis or indirectly promote PC metastasis through macrophage M2 polarization. Our study provides a new costimulatory target for the treatment of PC.

Perfluorobutane ultrasound contrast agent as a new type of contrast agent has a good performance in the diagnosis of hepatocellular carcinoma (HCC). This study aim to evaluate the accuracy and reliability of Perfluorobutane contrast-enhanced ultrasonography (P-CEUS) in the diagnosis of HCC with a systematic review and meta-analysis. Web of Science, EMBASE, Cochrane, Clinical Key, Wan Fang, CBM and CNKI databases were systematically searched and checked for studies using P-CEUS in HCC, from 2007 to 2020. Data necessary to construct 2 × 2 contingency tables were extracted from included studies. The QUADAS tool was utilized to assess the methodologic quality of the studies. Meta-analysis included data pooling, subgroup analyses, meta-regression and investigation of publication bias was comprehensively performed. Nine studies were included in this meta-analysis and the overall diagnostic accuracy in characterization of HCC was as follows: pooled sensitivity, 0.90 (95% confidence interval: 0.82–0.95); pooled specificity, 0.97 (0.93–0.98); pooled positive likelihood ratio, 27.2 (14.1 to − 52.3); and pooled negative likelihood ratio, 0.10 (0.06–0.18). The area under the comprehensive receiving operation characteristic curve was 0.98 (0.97–0.99). The sensitivity and specificity of P-CEUS are more valuable than other imaging techniques (such as computer tomography or magnetic resonance imaging). However, due to the large differences in the data samples collected in this study, statistical heterogeneity results. P-CEUS can significantly improve the diagnostic efficiency of previous contrast-enhanced ultrasound for HCC. PROSPERO registration number: PROSPERO (CRD42020200040).

Obesity is a growing epidemic worldwide, and it is also considered a major environmental factor contributing to the pathogenesis of inflammatory skin diseases, including psoriasis (PSO) and atopic dermatitis (AD). Moreover, obesity worsens the course and impairs the treatment response of these inflammatory skin diseases. Emerging evidence highlights that hypertrophied adipocytes and infiltrated immune cells secrete a variety of molecules, including fatty acids and adipokines, such as leptin, adiponectin, and a panel of cytokines/chemokines that modulate our immune system. In this review, we describe how adipose hypertrophy leads to a chronic low-grade inflammatory state in obesity and how obesity-related inflammatory factors are involved in the pathogenesis of PSO and/or AD. Finally, we discuss the potential role of antimicrobial peptides, mechanical stress and impairment of epidermal barrier function mediated by fast expansion, and dermal fat in modulating skin inflammation. Together, this review summarizes the current literature on how obesity is associated with the pathogenesis of PSO and AD, highlighting the potentially important but overlooked immunomodulatory role of adipose tissue in the skin.

The aim of this study was to elucidate the mechanism of action of the insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) on the phenotype of the liver cancer stem cells (LCSCs). To gain ...

To explore the role of metastasis-related long noncoding RNA (lncRNA) signature for predicting the prognosis of clear cell renal cell carcinoma (ccRCC) patients. Firstly, metastasis-associated genes were identified to establish a metastasis-related lncRNA signature by statistical analysis. Secondly, the ccRCC patients were grouped into high-risk or low-risk group according to the established signature, and the different pathways between the 2 groups were identified by gene set enrichment analysis (GSEA). Finally, investigations involving PCR, transwell migration and invasion assay were carried out to further confirm our findings. The metastasis-related lncRNA signature was successfully constructed according to 7-metastasis-related genes (ADAM12, CD44, IL6, TFPI2, TGF-β1, THBS2, TIMP3). The diagnostic efficacy and the clinically predictive capacity of the signature were evaluated. Most of the values of the area under the time‐dependent receiver‐operating characteristic (ROC) were greater than 0.70. The nomogram constructed by integrating clinical data and risk scores confirmed that the risk score calculated from our signature was a good prognosis predictor. GSEA analysis showed that some tumor-related pathways were enriched in the high-risk group, while metabolism-related pathways were enriched in the low-risk group. In carcinoma tissues, the SSR3-6, WISP1-2 were highly expressed, but the expression of UBAC2-6 was low there. Knocking down SSR3-6 decreased the ability of migration and invasion in ccRCC cells. In conclusion, we successfully constructed a metastasis-related lncRNA signature, which could accurately predict the survival and prognosis of ccRCC patients.

We performed in vitro and in vivo experiments to explore the role of protein kinase C-binding protein 1 (PICK1), an intracellular transporter involved in oxidative stress-related neuronal diseases, in sepsis-related acute kidney injury (AKI). Firstly, PCR, western blotting, and immunohistochemistry were used to observe the expression of PICK1 after lipopolysaccharide- (LPS-) induced AKI. Secondly, by inhibiting PICK1 in vivo and silencing PICK1 in vitro, we further explored the effect of PICK1 on AKI. Finally, the relationship between PICK1 and oxidative stress and the related mechanisms were explored. We found that the expression of PICK1 was increased in LPS-induced AKI models both in vitro and in vivo. PICK1 silencing significantly aggravated LPS-induced apoptosis, accompanied by ROS production in renal tubular epithelial cells. FSC231, a PICK1-specific inhibitor, aggravated LPS-induced kidney injury. Besides, NAC (N-acetylcysteine), a potent ROS scavenger, significantly inhibited the PICK1-silencing-induced apoptosis. In conclusion, PICK1 might protect renal tubular epithelial cells from LPS-induced apoptosis by reducing excessive ROS, making PICK1 a promising preventive target in LPS-induced AKI.

Osteosarcoma is the most common primary malignant bone tumor; its standard treatment includes neoadjuvant chemotherapy combined with surgery. Neoadjuvant chemotherapy has significantly improved the 5-year survival and limb salvage rates in osteosarcoma since the 1870s. The survival rate of patients with limb salvage was not inferior to that of amputees, and therefore, limb salvage has become the main surgical option for patients with osteosarcoma. The 5-year survival rate for osteosarcoma has plateaued. However, new advances in limb salvage therapy in osteosarcoma, including adjuvant chemotherapy, ablation techniques, bone transport techniques, and computer navigation techniques, are now available. This report summarizes the recent advances in limb salvage therapy for osteosarcoma over the past decade.

Serum C-reactive protein (CRP) and genetic variation of CRP gene have been reported as a strong, independent predictor of myocardial infarction and stroke. But there is rare association evidence of CRP genetic variation and hypertension (HT).A community-based case-control study including 1331 cases with HT and 1400 controls was used to evaluate the association of tagSNPs covered CRP gene, CRPP1 gene and 40kb upstream with HT in a Chinese Han population. Haplotypes and stratification analysis were applied to further evaluate relationships between the screened SNPs and HT and general linear model (GLM) was applied to compare blood pressure levels between genotypes.In stage 1, five SNPs had positive association with HT (P0.05) and entered stage 2 and two SNPs rs876537 and rs10737175 polymorphisms showed significant association with HT in joint sample. Haplotype analysis showed that comparing with common haplotype T-C which was constructed by rs6677719 and rs10737175, haplotype T-T significantly associated with HT after adjusted covariates. Stratification analysis found significant associations of HT for rs876537, rs2808630, rs6677719 and rs10737175 in ≥50years group, rs876537, rs10737175 in female, rs876537 and rs10737175 in non-smoking and non-drinking populations as well as rs2808630 in non-drinking population. Furthermore, quantitative trait analysis indicated significant differences of SBP and DBP between the genotypes of rs10737175, rs876537 and rs2808630 in non-treatment hypertensive cases and control population.The findings of this study support that CRP gene polymorphisms have significant association with genetic susceptibility of HT and quantitative traits of blood pressure.