BACKGROUND:Excessive growth of keratinocytes is the critical event in the etiology of psoriasis. However, the underlying molecular mechanism of psoriatic keratinocyte hyperproliferation is still unclear. OBJECTIVE:This study aimed to figure out the potential contributory role of S-phase kinase-associated protein 2 (SKP2) in promoting the hyperproliferation of keratinocytes in psoriasis. METHODS:We analyzed microarray data (GSE41662) to investigate the gene expression of SKP2 in psoriatic lesion skins compared with their adjacent non-lesional skin. Then, we further confirmed the mRNA and protein expression of SKP2 in human psoriatic skin tissues, imiquimod (IMQ)-induced psoriatic mice back skins and tumor necrosis factor α (TNF-α), interleukin (IL)-17A and IL-6-stimulated keratinocytes by using real-time quantitative polymerase chain reaction and western blot (WB). Furthermore, we explored the potential pathogenic role and its underlying cellular mechanism of SKP2 in promoting keratinocytes hyperproliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle detection, 5-ethynyl-2'-deoxyuridine staining and WB. Finally, we determined whether inhibition of SKP2 can effectively alleviate the keratinocytes hyperproliferation in vivo. RESULTS:We identified that SKP2 is aberrantly upregulated in the psoriatic lesion skin and cytokines-stimulated keratinocytes. Moreover, upregulated SKP2 augments cytokines-induced keratinocytes hyperproliferation. Mechanistically, enhanced SKP2 increased the S phase ratio through inhibiting Cyclin-Dependent Kinase Inhibitor p27 (P27 Kip1) expression. Correspondingly, suppression of SKP2 with SMIP004 can significantly ease the epidermis hyperplasia in vivo. CONCLUSION:Our results suggest that elevated SKP2 can empower keratinocytes proliferation and psoriasis-like epidermis hyperplasia via downregulation of P27 Kip1. Therefore, targeting SKP2-P27 Kip1 axis might be a promising therapeutic strategy for the treatment of psoriasis in future.

Psoriasis (Ps) is one of the most common chronic inflammatory skin disorders with its pathogenesis correlated with dysregulated innate and adaptive system. Even though biological agents have advanced the treatment of psoriasis, however, there are huge limitations, like high adverse reactions and relapse rate. Therefore, it is of great interest in searching clinical resolutions with better safety and efficacy. In the current study, we utilized the adipose-derived mesenchymal stem cell (AD-MSCs) to treat moderate/severe cases of psoriasis in a single-arm clinical study. This AD-MSC treatment has proven to be clinically safe and effective. Interestingly, a trend of adaptome improvement, including increased diversity, elevated uCDR3s and decreased large clone after AD-MSC treatment in a short (2 weeks) and long (12 weeks) terms. In conclusion, allogenic AD-MSC treatment has shown a good safety and efficacy in treating Ps and can effectively improve the compromised adaptive immune system of Ps patients.

结直肠癌是世界范围内发病率和死亡率都位居前列的恶性肿瘤[1],其发病率在我国所有恶性肿瘤中排第3位,死亡率第5位[2],严重威胁着人们的生命健康.结直肠癌发生的途径常有两种,分别是染色体不稳定(chromosomal instability,CN)途径和微卫星不稳定(microsataellite instability,MSI)途径[3].

Lung adenosquamous carcinoma (ASC) is a rare heterogeneous tumor containing two distinct components of adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). The limited biopsy sampling of the primary tumor might have overlooked either the ADC component or the SQCC component, resulting in a misdiagnosis of pure histology. Genotyping for driver mutations is now routinely performed in clinical settings to identify actionable oncogenic mutations and gene arrangements. Additionally, somatic mutations can potentially serve as a marker of clonal relationships. We report a rare case of ASC lung cancer, in which metastases were identified as ADC, while the primary was initially diagnosed as SQCC based on a fibrobronchoscope brush biopsy. The primary and metastatic tumors shared ALK rearrangement and other mutations support they were derived from a single clone origin. Our hypothesis is that the primary tumor contained a minor component of ADC that was not present in the histologic sections of lung biopsy. After sequential ALK-tyrosine kinase inhibitor (TKI) targeted therapy, both the patient's primary lung tumor and the site of metastatic subcutaneous nodules decreased in size, with the metastatic sites demonstrating more noticeable shrinkage. However, after 11 months of targeted therapy, the patient was found to be resistant to ALK-TKIs. Subsequently, the patient's respiratory status deteriorated rapidly, and a cycle of immunotherapy and chemotherapy did not show efficacy. To the best of our knowledge, this is a very rare case of lung ASC, disseminated metastasizing, with distinct morphology between the primary and metastases. Different therapeutic effects of ALK-TKIs were observed in two different morphological sites, with the metastatic cutaneous lesions shrinking more significantly than the primary lung lesions, though they both harbor the same EML4-ALK rearrangement. This case may provide diagnostic and therapeutic insights into lung ASC.

结核病（tuberculosis, TB）,系由结核分枝杆菌感染引起的传染性疾病，可侵犯人体多个脏器。胰腺结核（pancreatic tuberculosis, PTB）的临床表现和影像学表现均与胰腺肿瘤高度相似，因此极易漏诊或误诊。本文回顾性分析1例宏基因组二代测序（mNGS）辅助诊断胰腺结核的病例，并进行文献复习，为诊断该类疾病提供参考。1 临床资料患者，女，60岁，自述10日前突发上腹疼痛，发热寒战，头痛，无头晕，