OBJECTIVE:Fangcang shelter hospital is a form of large temporary hospital developed in China to tackle public health events. Through the case study and analysis of managing a nursing unit in a huge Fangcang shelter hospital transformed from the National Exhibition and Convention Center during the Omicron wave in Shanghai, China between April 9, 2022 and May 24, 2022, this paper aimed to highlight critical implications of public health nurses in health emergencies.DESIGN:A case study was conducted using data collected from a nursing unit with 570 beds. The five characteristics of management were organized as follows: human resource management, establishment and optimization of the core workflow, safety management of high-risk patients, the grid cooperation mechanism with patient volunteers, as well as humanistic nursing.RESULTS:Analysis of the data of the nursing unit indicated close team cooperation, efficient and orderly process scheduling, good outcomes of patients, and the indispensable role of volunteers.CONCLUSION:Practice indicated that nursing unit management in a large Fangcang shelter hospital is important to ensure medical order and efficiency. This practical experience can provide valuable reference and data to support for the nursing management of large-scale public health events, such as infectious disease epidemics.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Understanding the mechanisms mediating secondary nonimmune renal injury in lupus nephritis (LN) is important for therapeutic development. Cytotoxic granule-associated RNA-binding protein 1 (T-cell-resrticted intracellular antigen 1, TIA1) plays potential roles in infiltrating immune cells in LN. However, the regulatory targets and mechanisms underlying TIA1 activity in renal nonimmune cells remain unclear. Here, TIA1 was overexpressed in a human renal tubular epithelial cell line (HK-2). Then, RNA sequencing and bioinformatic analysis were performed to compare the expression profile and alternative splicing pattern in TIA1-overexpressing (TIA1-OE) and control cells. Additionally, the expression of Tia1 and the genes that it may regulate in the kidney tissues of LN mice was analysed. The results showed TIA1-OE increased and decreased the transcript levels of 101 and 452 genes in HK-2 cells, respectively. Gene Ontology (GO)analysis showed that the downregulated genes were significantly enriched in several terms associated with the cellular response to stress. Moreover, TIA1-OE changed the pattern of 2,035 alternative splicing events that occurred in 1,420 genes in HK-2 cells. GO analysis showed t genes were significantly enriched in DNA repair and cellular response to DNA damage stimulus terms. These results demonstrate that TIA1 mediates secondary nonimmune renal injury by regulating the expression and alternative splicing of stress-related genes in renal tubular epithelial cells, which provides a reference for targeted therapy for renal injury in LN.

Abstract LncRNAs take extensive effects in immune cells to mediate various autoimmune diseases. However, its potential role in development of SLE remains uncertain. We screened out candidate lncRNA in exosomes from SLE patients and the healthy, and was further validated in mouse model by histological examinations in vivo. Additional morphological verification was exploited to validate its biological functions by construction of plasmids in vitro. H19 in serum exosomes of patients was escalated, and could also promote the proliferation and migration of macrophages. Additionally, H19 mainly recruited miR-145-5p and promotes the expression of downstream targeted protein PAI-1. It further promoted the release of SLE-associated proinflammatory factors via Jak2-STAT3 axis, and in turn facilitated the polarization of M1 macrophages. Our study uncovered a potential mechanism of lncRNA H19 in mediating macrophage polarization and leading to the release of proinflammatory factors, providing a new intervention target for treating SLE.

BACKGROUND:Certain circRNAs could be used as biomarkers to determine the risk of development and/or severity of systemic lupus erythematosus, and their new function in the regulation of gene expression has motivated us to investigate their role in SLE METHODS: Experimental methods including qRT-PCR, RNA immunoprecipitation (RIP), pulldown, dual luciferase reporter assay, RNA interference and cell transfection, RNA fluorescence in situ hybridization, western blotting, and mass spectrometry were used to assessed circGARS (hsa_circRNA_0009000) for immune functions and defined mechanisms by which circGARS promotes the progression in SLE.RESULTS:Our results demonstrated that the levels of circGARS was remarkably upregulated in SLE and correlated with clinicopathological features. CircGARS directly combined with microRNA-19a (miR-19a). Functionally, circGARS downregulated the expression of TNFAIP3 (A20, tumor necrosis factor alpha-induced protein 3) to mediate the activation of immune responses that were regulated by the nuclear factor-κB (NF-κB) pathway as a negative feedback mechanism. In addition, miR-19a regulated A20 (TNFAIP3) degradation by downregulating the expression of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2).CONCLUSIONS:The circGARS sponges miR-19a to regulate YTHDF2 expression to promote SLE progression through the A20/NF-κB axis and may act as an independent biomarker to help the treatment of SLE patients.

BACKGROUND:Non-small cell lung cancer (NSCLC) is characterized by high morbidity and mortality in the world. Growth and differentiation factor 15 (GDF15) has been proved to play an important role in regulating tumor progression. However, the influence of GDF15 on NSCLC remains unclear.OBJECTIVE:We aimed to investigate the regulatory role of GDF15 in NSCLC.METHODS:The correlation between GDF15 expression and prognosis, stage of NSCLC was examined with bioinformatics method. The cell proliferation was detected with CCK8 and EdU staining. Wound healing, Transwell, flow cytometry assays were used to measure cell migration, invasion, and apoptosis, respectively.RESULTS:High expression of GDF15 is correlated with worse survival and malignant progression of NSCLC. Knockdown of GDF15 restrained the proliferation, invasion, migration, but accelerated apoptosis of lung cancer cells through regulating PTEN/PI3K/AKT signaling pathway. sh-GDF15 suppressed epithelial mesenchymal transition (EMT) process and promoted the chemotherapy sensitivity of lung cancer cells.CONCLUSION:GDF15 plays an important role in NSCLC progression. GDF15 mediated PTEN/PI3K/AKT signaling pathway might be the potential therapeutic targets for the prevention and treatment of GDF15.

Background Non-coding RNAs (ncRNAs), including small nucleolar RNAs (snoRNAs), are widely involved in the physiological and pathological processes of human beings. While up to date, although considerable progress has been achieved in ncRNA-related pathogenesis of non-small cell lung cancer (NSCLC), the underlying mechanisms and biological significance of snoRNAs in NSCLC still need to be further clarified. Methods Quantitative real-time polymerase chain reaction or RNAscope was performed to verify the expression of Small Nucleolar RNA, H/ACA Box 38B (SNORA38B) in NSCLC cell lines or clinical samples. BALB/c nude mice xenograft model or C57BL/6J mice syngeneic tumor model were estimated to detect the effects of SNORA38B in tumor growth or tumor immune microenvironment in vivo. Cytometry by time of flight, enzyme-linked immunosorbent assay and flow cytometry assay were conducted to clarify the effects and mechanisms of SNORA38B-mediated tumor immunosuppressive microenvironment. The binding activity between SNORA38B and E2F transcription factor 1(E2F1) was detected by RNA immunoprecipitation and RNA pull-down assays. Then, bioinformatics analysis and chromatin immunoprecipitation were utilized to demonstrate the regulation of GRB2-associated-binding protein 2 (GAB2) by E2F1. Moreover, the combinatorial treatment of SNORA38B locked nucleic acid (LNA) and immune checkpoint blockade (ICB) was used to treat murine Lewis lung carcinoma-derived tumor burden C57BL/6J mice to clarify the effectiveness of targeting SNORA38B in NSCLC immunotherapy. Results SNORA38B was found highly expressed in NSCLC tissues and cell lines, and associated with worse prognosis. Further results showed that SNORA38B functioned as an oncogene via facilitating cell proliferation, migration, invasion, and inhibiting cell apoptosis in vitro and promoting tumorigenesis of NSCLC cells in vivo. SNORA38B could also recruit the CD4(+)FOXP3(+) regulatory T cells by triggering tumor cells to secrete interleukin 10, which in turn reduced the infiltration of CD3(+)CD8(+) T cells in NSCLC tumor microenvironment (TME), favoring tumor progression and poorer immune efficacy. Mechanistically, SNORA38B mainly distributed in the nucleus, and promoted NSCLC progression by regulating GAB2 transcription to activate protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway through directly binding with E2F1. Moreover, we found that SNORA38B LNAs were able to ameliorate CD3(+)CD8(+) T cell infiltration in TME, which sensitized NSCLC to the treatment of ICB. Conclusions In conclusion, our data demonstrated that SNORA38B functioned as an oncogene in NSCLC both in vitro and in vivo at least in part by regulating the GAB2/AKT/mTOR pathway via directly binding to E2F1. SNORA38B could also sensitize NSCLC to immunotherapy, which may be a critical therapeutic target for NSCLC.

Background Accumulating evidence supports the implication of circular RNAs (circRNAs) in systemic lupus erythematosus (SLE). However, little is known about the detailed mechanisms and roles of circRNAs in the pathogenesis of SLE. Methods Quantitative real-time PCR was used to determine the levels of circLOC101928570 and miR-150-5p in peripheral blood mononuclear cells of SLE. Overexpression and knockdown experiments were conducted to assess the effects of circLOC101928570. Fluorescence in situ hybridization, RNA immunoprecipitation, luciferase reporter assays, Western blot, flow cytometry analysis and enzyme-linked immunosorbent assay were used to investigate the molecular mechanisms underlying the function of circLOC101928570. Results The results showed that the level of circLOC101928570 was significantly downregulated in SLE and correlated with the systemic lupus erythematosus disease activity index. Functionally, circLOC101928570 acted as a miR-150-5p sponge to relieve the repressive effect on its target c-myb, which modulates the activation of immune inflammatory responses. CircLOC101928570 knockdown enhanced apoptosis. Moreover, circLOC101928570 promoted the transcriptional level of IL2RA by directly regulating the miR-150-5p/c-myb axis. Conclusion Overall, our findings demonstrated that circLOC101928570 played a critical role in SLE. The downregulation of circLOC101928570 suppressed SLE progression through the miR-150-5p/c-myb/IL2RA axis. Our findings identified that circLOC101928570 serves as a potential biomarker for the diagnosis and therapy of SLE.

Long noncoding RNAs (lncRNAs) play essential roles in various biological processes. Nevertheless, advance exploration is warranted to elaborate the therapeutic implications and detailed mechanisms of lncRNAs in non-small cell lung cancer (NSCLC). In the present study, lncRNA PP7080 is found highly expressed and correlated with a poorer prognosis for NSCLC. Knockout of PP7080 diminishes cell proliferation, migration, and invasion, but accelerates cell apoptosis in vitro, and impeded tumor growth in vivo. While elevated PP7080 facilitates cell proliferation, migration and invasion, repressed cell apoptosis in vitro, and accelerated xenograft tumor growth in vivo. Additionally, downregulated DNMT1 is found contributing the higher PP7080 expression via regulation of DNA methylation at PP7080 promoter-regions in NSCLC. Furthermore, PP7080 directly bound with TFAP2C and facilitated TFAP2C phosphorylation at Ser434 site, and then upregulated PDCD6 expression through binding with its promoters. Furthermore, highly expressed PP7080/PDCD6 correlated with immune-suppressing tumor microenvironment (TME) in NSCLC. Collectively, the results identified PP7080 mainly localized in the nucleus and functioned its oncogenic role via regulating NSCLC initiation, advancement, and contributing to an immune-resistant TME through TFAP2C/PP7080/PDCD6 axis, implying PP7080 as a novel therapeutic target for NSCLC.

Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease of unknown etiology. The epigenetic regulation of N6-methyladenosine (m6A) modification in immunity is emerging. However, few studies have focused on SLE and m6A immune regulation. In this study, we aimed to explore a potential integrated model of m6A immunity in SLE. The models were constructed based on RNA-seq data of SLE. A consensus clustering algorithm was applied to reveal the m6A-immune signature using principal component analysis (PCA). Univariate and multivariate Cox regression analyses and Kaplan–Meier analysis were used to evaluate diagnostic differences between groups. The effects of m6A immune-related characteristics were investigated, including risk evaluation of m6A immune phenotype-related characteristics, immune cell infiltration profiles, diagnostic value, and enrichment pathways. CIBERSORT, ESTIMATE, and single-sample gene set enrichment analysis (ssGSEA) were used to evaluate the relative immune cell infiltrations (ICIs) of the samples. Conventional bioinformatics methods were used to identify key m6A regulators, pathways, gene modules, and the coexpression network of SLE. In summary, our study revealed that IGFBP3 (as a key m6A regulator) and two pivotal immune genes (CD14 and IDO1) may aid in the diagnosis and treatment of SLE. The potential integrated models of m6A immunity that we developed could guide clinical management and may contribute to the development of personalized immunotherapy strategies.

Dendritic epidermal T cells (DETCs) are the main source of insulin-like growth factor-1 (IGF-1) in epidermal tissue, which promote re-epithelialization and wound healing. In refractory wounds, IL-1β has been shown to activate NF-κB and suppress IGF-1 expression in DETCs. Nevertheless, the underlying mechanisms remain unclear. In this study, chromatin immunoprecipitation analysis revealed that IL-1β did not inhibit NF-κB binding to IGF-1 promoter, indicating that IL-1β/NF-κB may suppress IGF-1 expression by alternative mechanisms. MiRNAs negatively regulate gene expression predominantly by base pairing to the 3' untranslation region (UTR) of target mRNAs. Let-7f-5p, miR-1a-3p, and miR-98-5p have been identified as IGF-1-specific miRNAs that can bind directly to the 3'UTR of IGF-1 mRNA and dysregulate IGF-1 mRNA and protein levels. In IL-1β-treated epidermis around wounds or DETCs in vitro, NF-κB promoted the expression of let-7f-5p, and IGF-1 expression was impeded via NF-κB/let-7f-5p pathway. As pre-let-7f-5p, let-7f-1 is located in the 3'UTR of LOC118568094, and let-7f-2 is located in the intron of HUWE1. We discovered that NF-κB p65 bound to the promoters of LOC118568094 and HUWE1 to accelerate let-7f-5p expression, but NF-κB p65 did not affect the methylation levels of LOC118568094 and HUWE1 CpG islands. Injections of Let-7f-5p antagomir into IL-1β-treated and ischemic wound margins restored IGF-1 secretion in DETCs and promoted wound healing. In conclusion, we demonstrated that NF-κB signaling pathway activated by IL-1β could increase let-7f-5p expression to inhibit IGF-1 production in DETCs and delay wound healing. And let-7f-5p antagomir utilized in wound margin could effectively promote refractory wound healing.

Monocyte subsets, including classical, intermediate and non-classical monocytes, are involved in the pathogenesis of inflammatory or autoimmune diseases. The pathogenic role of monocytes in the peripheral blood mononuclear cells (PBMCs) of patients with rosacea remains unclear. This study aimed to assess frequencies of monocyte subsets in PBMCs from rosacea patients before and after clinical treatment. We applied flow cytometry to examine frequencies of monocyte subsets in 116 patients with rosacea，while patients with 26 systemic lupus erythematosus (SLE), 28 acne and 42 normal healthy subjects without skin problems (HC) were recruited as controls. Expression of CCR2 on monocytes and plasma levels of CCL2, HMGB-1, IL-1β and TNF-α were measured in HC and rosacea patients before and after treatment. The frequency of classical monocytes, but not intermediate or non-classical monocytes, was higher in rosacea as compared with HC, which decreased after treatment. Frequencies of monocyte subsets showed no gender difference, while increased with age in patients but not in HC. Frequencies of classical monocytes in patients with erythromatotelangiectatic rosacea (ETR) and ETR-papulopaustula rosacea (PPR) overlap were significantly higher than HC or patients with only PPR or phytomatous rosacea (PhR). There was a significant higher expression of CCR2 in classical monocytes, with higher plasma levels of CCL2, HMGB-1, IL-1β and TNF-α in patients than in HC, which all significantly decreased after treatment. Our data indicated a possible association between abnormal classical monocytes frequencies and rosacea.

An amendment to this paper has been published and can be accessed via the original article.

Objective To investigate the role of long non-coding RNA (lncRNA) RP11-288L9.1 in systemic lupus erythematosus (SLE) and its potential mechanism. Methods Transcriptome sequencing (RNA-seq) was used to screen the differentially expressed lncRNAs in peripheral blood mononuclear cells (PBMCs) of SLE patients, and the expression levels of these lncRNAs in 8 pairs of SLE patients and healthy controls were further verified by qRT-PCR. The knockdown as well as over-expression models of RP11-288L9.1 were constructed respectively by transfecting recombinant lentivirus into macrophages, and the transfection efficiency was determined subsequently. The subcellular distribution of RP11-288L9.1 was detected by fluorescence in situ hybridization (FISH) technique. Moreover, CCK-8 assay and Annexin V-FITC apoptosis detection kit were applied to examine the proliferation and apoptosis of macrophages in both models, and qRT-PCR was conducted to detect the expression of macrophage-related inflammatory cytokines, IL-1β, IL-6, IL-4, IL-10 and TGF-β1 after the transfection. Results Six differentially expressed lncRNAs were found (P < 0.05), in which RP11-288L9.1 was significantly up-regulated (P < 0.01), and mainly located in the cytoplasm of macrophages. The over-expression of RP11-288L9.1 promoted the apoptosis and inhibited the proliferation of macrophages (P < 0.05), increasing the levels of IL-1β and IL-6, and decreasing those of IL-4, IL-10 and TGF-β1 (P < 0.01). In contrast, the knockdown of RP11-288L9.1 significantly induced the proliferation of macrophages and inhibited the apoptosis (P < 0.05), with lowered levels of IL-1β and IL-6 and elevated IL-4, IL-10 and TGF-β1 (P < 0.01). Conclusion RP11-288L9.1 is highly expressed in the PBMCs of SLE patients, and regulates immune response in macrophages by affecting the synthesis of inflammatory cytokines, which may contribute to the occurrence of SLE.

PKR, also known as EIF2AK2, is an IFN-stimulated gene (ISG) and shows a higher expression in probands with systemic lupus erythematosus (SLE), which is likely responsible for the impaired translational and proliferative responses to mitogens in T cells from SLE patients. In this study, we overexpressed EIF2AK2 in HeLa cells to study EIF2AK2-regulated genes using RNA-seq technology, followed by bioinformatic analysis of target genes of EIF2AK2-regulated transcriptional factors (TFs). Overexpression of EIF2AK2 promotes HeLa cell apoptosis. EIF2AK2 selectively represses the transcription of histone protein genes associated with SLE, immune response genes and TF genes, which was validated by RT-qPCR experiments. Analysis of motifs overrepresented in the promoter regions of EIF2AK2-regulated genes revealed eighteen EIF2AK2-regulated TFs involved in establishing the EIF2AK2 network. Eight out of these predicted EIF2AK2-regulated TFs were further verified by RT-qPCR selectively in both HeLa and Jurkat cells, and most such as HEY2, TFEC, BATF2, GATA3 and ATF3 and FOXO6 are known to regulate immune response. Our results suggest that the dsRNA-dependent kinase EIF2AK2 selectively regulates the transcription of immune response and SLE-associated histone protein genes, and such a selectivity is likely to be operated by EIF2AK2-targeted TFs. The EIF2AK2-TFs axis potentially offers new therapeutic targets for counteracting immunological disease in the future.

It has been demonstrated that various long non-coding RNAs (lncRNAs) may have key roles in various types of cancer. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of all RCCs, accounting for 70-80% of all cases. The present study identified a novel lncRNA and investigated its clinical significance and physiological function in ccRCC. The expression pattern of the novel lncRNA LOC389332 in 30 ccRCC tissue samples was examined using reverse-transcription quantitative polymerase chain reaction. The results demonstrated that LOC389332 expression was markedly lower in ccRCC tissues compared with that in matched adjacent non-tumor tissues. Of note, downregulation of LOC389332 expression was significantly associated with the tumor American Joint Commission on Cancer stage (P=0.001), Fuhrman grade (P=0.001) and lymph node metastasis (P<0.001). Furthermore, patients with ccRCC with lower levels of LOC389332 expression had a shorter overall survival time than those with higher LOC389332 expression. A gain-of-function study was used to evaluate the biological function of LOC389332 in ccRCC and the results suggested that restoration of LOC389332 expression inhibited the growth and migration of the 786-O and 769-P cell lines. Therefore, the results of the present study demonstrated that LOC389332 is a novel lncRNA involved in ccRCC progression and may be a potential diagnostic and prognostic biomarker. Ectopic overexpression of LOC389332 may represent a therapeutic strategy for ccRCC.

Hepatocyte nuclear factor 4-α (HNF4α), a nuclear receptor, is expressed at lower levels in colon carcinoma tissues than in adjacent normal tissues. However, the relation between HNF4α and colon cancer progression and the underlying molecular mechanisms remain unclear. Here, we investigated the role of HNF4α in the progression of colon carcinoma. We showed that HNF4α mRNA and protein were downregulated in colon carcinoma specimens. HNF4α expression was related to pT classification (P < 0.001), lymph node metastasis (P = 0.002), distant metastasis (P < 0.001) and clinical stage (P < 0.001) in colon carcinoma patients. Patients with low or negative HNF4α expression had worse 3-year progression-free survival (PFS, P = 0.006) and overall survival (OS, P = 0.005) than patients with high HNF4α expression. Low HNF4α expression was an independent prognostic factor for 3-year PFS (hazard ratio 2.94; 95% confidence interval 1.047-8.250; P = 0.041). Ectopic expression of HNF4α inhibited colon carcinoma cell (HT29, LoVo, and SW480) proliferation, migration, and invasion, induced G2/M phase arrest and promoted apoptosis. Ectopic expression of HNF4α upregulated E-cadherin and downregulated vimentin in vitro, and suppressed SW480 xenograft tumor growth and liver metastasis in vivo. Furthermore, HNF4α overexpression downregulated the expression of snail, slug and twist. HNF4α inhibited EMT through its effect on the Wnt/β-catenin signaling pathway, and HNF4α downregulation may be mediated by promoter methylation in cancer tissues. Our results suggest that downregulation of HNF4α plays a critical role in the aggravation of colon carcinoma possibly by promoting EMT via the Wnt/β-catenin signaling pathway and by affecting apoptosis and cell cycle progression.