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The aim of this work is to explore the working conditions of logistics personnel in hospital and provide a new approach for improving the service quality of them in the post-COVID-19 era. Eighty-four logistics personnel in an upper first-class hospital were included in the study, and their working conditions were investigated and analyzed via self-designed questionnaire. 73.8% of all respondents think their work is significantly important to the brand building of the hospital, and 67.9% of them think they are closely related to a harmonious doctor–patient relationship. The compliant rate is higher in security personnel when compared with other personnel and the difference was statistically significant ([Formula: see text]). 94% of the logistics personnel indicate a higher intensity in their work, 39.3% of them constantly face the working pressure and 57.1% come from the risk of infection which accounts for the largest. The largest demand comes for the protective equipment, which is from 69 workers. It would be better for us to pay attention to the hospital culture training and strengthen the sense of identity among logistics personnel of the hospital continuously. Meanwhile we need to enrich the connotation of professional style construction in hospital and promote the efficiency of logistics service. Targeted training is necessary to improve the service capabilities of the security personnel since they receive more complaints. Diversified and personalized support to the logistics personnel based on the grasp of their special demand is also important.

BackgroundA tremendous amount of studies have suggested that post-translational modifications (PTMs) play pivotal roles during tumorigenesis. Compared to other PTMs, lipid modification is less studied. Recently, N-myristoylation, one type of lipid modification, has been paid attention to the field of cancer. However, whether and how N-myristoylation exerts its roles in liver tumorigenesis still remains unclear.MethodsParallel reaction monitoring (PRM) was conducted to evaluate the expression of protein modification enzymes in paired tissues. Liver conditionally knocking NMT1 out mice model was used to assess the critical roles of N-myristoylation during liver tumorigenesis. Proteomics isobaric tags for relative and absolute quantification (iTraq) was performed to identify proteins that changed while NMT1 was knocked down. The click chemistry assay was used to evaluate the N-myristoylation levels of proteins.ResultsHere, N-myristolyation and its enzyme NMT1, but not NMT2, were found to be critical in liver cancer. Two categories of proteins, i.e., N-myristolyation down-regulated proteins (NDP, including LXN, RPL29, and FAU) and N-myristolyation up-regulated proteins (NUP, including AHSG, ALB, and TF), were revealed negatively and positively regulated by NMT1, respectively. Both NDP and NUP could be N-myristolyated by NMT1 indispensable of POTEE. However, N-myristolyation decreased and increased stability of NDP and NUP, respectively. Mechanistically, NDP-specific binding protein RPL7A facilitated HIST1H4H, which has ubiquitin E3 ligase function, to ubiquitinate NDP. By contrast, NUP-specific binding protein HBB prevented NUP from ubiquitination by HIST1H4H. Notably, function of RPL7A and HBB was all NMT1-dependent. Moreover, NDP suppressed while NUP stimulated transformative phenotypes. Clinically, higher levels of NMT1 and NUP with lower levels of NDP had worse prognostic outcome.ConclusionCollectively, N-myristolyation by NMT1 suppresses anti-tumorigenic NDP, whereas it stimulates pro-tumorigenic NUP by interfering their ubiquitination to finally result in a pro-tumorigenic outcome in liver cancer. Targeting N-myristolyation and NMT1 might be helpful to treat liver cancer.

Background : MiR-218-5p is a small non-coding RNA acting as either oncogenes or tumor suppressor genes in human cancer. The expression levels of some miRNAs in human breast cancer plays a potential role in disease pathogenesis. Methods : Thirty pairs of invasive ductal carcinoma and adjacent specimens were included in the study. Breast tissues cell lines MCF-7 and MDA-MB-231 were identified as a breast cancer research cell line. MiR-218-5p mimics, miR-218-5p inhibitor, or negative controls were transfected. Specific antibodies were probed with LRIG1, ErbB2, and EGFR. Proliferation, migration, cell cycle and apoptosis, dual-luciferase reporter assay and immunohistochemistry were used to analyze miR-218-5p、LRIG1 and so on. Results : It was shown that miR-218-5p expression was higher in 30 breast cancer specimens than adjacent normal breast tissues. In human breast cancer cells MCF-7 and MDA-MB-231, restoring miR-218-5p promoted cell proliferation and migration and inhibited cell apoptosis and cell cycle arrest in the G1 stage. Luciferase assays indicated miR-218-5p could bind with its putative target site in the 3'-untranslated region (3'-UTR) of LRIG1. RT-qPCR, western blot, and immunocytochemistry analyses all indicated miR-218-5p overexpression results in LRIG1 downregulation at the mRNA and protein levels. ErbB2 and EGFR were found to be downstream effectors of miR-218-5p. Conclusion : MiR-218-5p promotes ErbB2 and EGFR expression by inhibiting LRIG1 in breast cancer cells, which suggests miR-218-5p and LRIG1 may act as an oncogene in breast cancer and it could be used as a therapeutic target for breast cancer treatments. Keywords: Breast cancer; miR-218-5p; LRIG1; Oncogene

Yang Liu,1 Yue-ru Wang,2 Guang-hui Ding,1 Ting-song Yang,1 Le Yao,1 Jie Hua,1 Zhi-gang He,1 Ming-ping Qian1 1Department of Hepatobiliary Surgery, Shanghai 10th People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Infection, Shanghai First People’s Hospital Affiliated to Jiaotong University, Shanghai, People’s Republic of China Objective: Combination therapy for cancer is more effective than using only standard chemo- or radiotherapy. Our previous results showed that dendritic cell-activated α-fetoprotein (AFP)-specific T-cells inhibit tumor in vitro and in vivo. In this study, we focused on antitumor function of CD8+ T-cells combined with or without JAK2 inhibitor. Methods: Proliferation and cell cycle were analyzed by CCK-8 and flow cytometry. Western blot was used to analyze the expression level of related protein and signaling pathway. Results: We demonstrated reduced viability and induction of apoptosis of tumor cells with combination treatment. Intriguingly, cell cycle was blocked at the G1 phase by using AFP-specific CD8+ T-cells combined with JAK2 inhibitor (AG490). Furthermore, an enhanced expression of BAX but no influence on Fas/FasL was detected from the tumor cells. Conclusion: These results indicate a Fas/FasL-independent pathway for cellular apoptosis in cancer therapies with the treatment of AFP-specific CD8+ T-cells combined with JAK2 inhibitor. Keywords: AFP-specific CD8+ T-cells, JAK2 inhibitor, Fas/FasL signal, antitumor, apoptosis&nbsp

Emerging studies have revealed that O-GlcNAcylation plays pivotal roles in the tumorigenesis of colorectal cancers. However, the underlying mechanism still remains largely unknown. Here, we demonstrated that YY1 was O-GlcNAcylated by OGT and O-GlcNAcylation of YY1 could increase the protein expression by enhancing its stability. O-GlcNAcylation facilitated transformative phenotypes of CRC cell in a YY1-dependent manner. Also, O-GlcNAcylation stimulates YY1-dependent transcriptional activity. Besides, we also identified the oncoproteins, SLC22A15 and AANAT, which were regulated by YY1 directly, are responsible for the YY1 stimulated tumorigenesis. Furthermore, we identified the main putative O-GlcNAc site of YY1 at Thr236, and mutating of this site decreased the pro-tumorigenic capacities of YY1. We concluded that O-GlcNAcylation of YY1 stimulates tumorigenesis in CRC cells by targeting SLC22A15 and AANAT, suggesting that YY1 O-GlcNAcylation might be a potential effective therapeutic target for treating CRC.

Here, bioinformatics data from Sirt1 knock-out (KO) and knock-in (KI) mice suggest that Sirt1 inhibits Wnt/βCatenin signaling in the liver. However, it is unclear how this relationship occurs and how it contributes to malignant phenotypes in liver cancer cells. We found that Sirt1 expression promotes phosphorylation of βCatenin at Ser675, which may subsequently decrease expression of total-βCatenin. Mechanistically, Sirt1 expression elevates phosphorylation of the alpha subunit of protein kinase A (PKAα), and this event is essential for Sirt1-induced phosphorylation of βCatenin. The negative effects of Sirt1 on βCatenin stability are also dependent on PKAα. Stimulating PKAα recruits βTrCP, a well-known ubiquitin E3 ligase for βCatenin, to βCatenin. Interestingly, Sirt1 expression is able to up-regulate βTrCP expression. Finally, we found that malignant phenotypes occur in hepatocytes when Sirt1 and βCatenin are co-overexpressed, and such effects are enhanced by simultaneous knockdown of PKAα. In contrast, malignant phenotypes are abrogated upon knockdown of Sirt1, and this phenotype is magnified by knockdown of βCatenin. Collectively, we conclude that suppression of both Sirt1 and Wnt/βCatenin might be effective in treating liver cancer.

We have identified the most appropriate method of isolating human umbilical cord matrix-derived mesenchymal stem cells (UCM-MSCs) and compared morphological, phenotypic, proliferative, and differentiation characteristics of UCM-MSCs with bone marrow-derived MSCs (BM-MSCs) and umbilical cord blood-derived MSCs (UCB-MSCs). Three explant culture methods and 3 enzymatic methods were compared with regards to time for primary culture, cell number, cell morphology, immune phenotype, and differentiation potential. Morphological, phenotypic, proliferative, and differentiation characteristics of UCM-MSCs, BM-MSCs, and UCB-MSCs were also compared. UCM-MSCs isolated using the 10 mm size tissue explant method led to shorter primary culture time, higher numbers of isolated cells, and higher proliferation rates compared with other isolation methods. Immune phenotype and multilineage differentiation capacity did not differ significantly among 6 groups. UCM-MSCs had similar characteristics as BM-MSCs and UCB-MSCs, including fibroblastic morphology, typical immunophenotypic markers, and multilineage differentiation capacity. In comparison with UCB-MSCs and BM-MSCs, UCM-MSCs have higher proliferative capacity, higher rate of chondrogenic differentiation, and higher expression of CD 146. The results suggest that the 10 mm size tissue culture method is the optimal protocol for the isolation of UCM-MSCs. Given the distinct advantages of UC, such as accessibility, painless acquisition, and abundance of cells obtained, we propose that UC be considered an alternative to BM and UCB as a source of MSCs for cell therapy.

RAB1A acts as an oncogene in various cancers, and emerging evidence has verified that RAB1A is an mTORC1 activator in hepatocellular and colorectal cancer, but the role of RAB1A in breast cancer remains unclear. In this investigation, RAB1A siRNA was successfully transfected in MDA-MB-231 and BT-549 human triple-negative breast cancer cells, and verified by real‑time quantitative polymerase chain reaction and western blotting. Then, MTT cell proliferation, colony formation, cell invasion and wound healing assays were performed to characterize the function of RAB1A in the breast cancer cell lines. Downregulation of RAB1A inhibited cellular growth, cell migration, cell invasion and cell epithelial-mesenchymal transition. Furthermore, compared with NC siRNA transfected cells, RAB1A siRNA transfected breast cancer cells inhibited the phosphorylation of S6K1, the effector molecular of mTORC1. Collectively, our data suggested that RAB1A acts as an oncogene by regulating cellular proliferation, growth, invasion and metastasis via activation of mTORC1 pathway in triple-negative breast cancer.

OBJECTIVES: To observe the expression of nucleotide-binding oligomerization domain 2 (NOD2) in rats with acute pancreatitis (AP). METHODS: Sprague-Dawley rats were randomly divided into sham operation (SO) groups and AP groups. Acute pancreatitis was induced with retrograde infusion of sodium taurocholate into the biliopancreatic duct. They were then killed at 3, 6, 12, 24, and 48 hours after induction of AP. Blood biochemical indicators were detected with automatic biochemistry analyzer. Nuclear factor-κB (NF-κB) was measured by immunohistochemistry. The NOD2 was detected by real-time quantitative polymerase chain reaction and Western blot. Tumor necrosis factor-α (TNF-α) was determined by enzyme-linked immunosorbent assay. RESULTS: Compared with the SO group, the level of messenger RNA and protein of NOD2 in pancreatic tissue and peritoneal white blood cells (PWBCs) in the AP groups significantly declined (P < 0.05). The messenger RNA level of NOD2 in the AP groups was correlated positively with amylase (P < 0.05) and negatively with TNF-α (P < 0.05); TNF-α significantly decreased in the AP groups, whereas NF-κB significantly increased (P < 0.05). CONCLUSIONS: The NOD2 may play an important role in the up-regulation and activation of NF-κB during inflammation reactions in AP.

Stromal cell-derived factor-1 (SDF-1) and its receptor, CXC chemokine receptor-4 (CXCR4), are important regulators in the migration of bone marrow mesenchymal stem cells (BMSCs). However, the mechanisms underlying this effect in acute pancreatitis (AP) have not been investigated. In this study, BMSCs were identified by specific cell surface markers and differentiation potentials, and labeled with chloromethylbenzamido-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (CM-Dil) for in vivo cell tracking. AP was induced by retrograde infusion of sodium taurocholate into the common bile duct in rats. The expression of SDF-1 in the injured pancreas was determined by immunohistochemistry and western blot analysis. BMSCs were incubated with or without anti-CXCR4 antibody and the contribution of SDF-1 to the migration of BMSCs was investigated. Our results demonstrated that the expression of SDF-1 was significantly increased in the injured pancreas, and that these levels peaked on days 5-7 and began to decrease on day 10. SDF-1 induced a dose-dependent migration of BMSCs in an in vitro transwell migration assay, which was almost completely blocked by AMD3100 (CXCR4-specific antagonist) or anti-CXCR4 antibody. In addition, by encouraging the migration of CM-Dil-labeled BMSCs, the SDF-1/CXCR4 axis facilitated the repair of the injured pancreas. This effect was inhibited by the anti-CXCR4 antibody. Taken together, these results indicate that the interaction of locally produced SDF-1 with CXCR4 on BMSCs, has an important regulatory role in the migration of BMSCs towards the injured pancreas in AP.

The objective of our work was to evaluate the effect of interferon-γ (IFN-γ) on cytokine expression in rat acute pancreatitis (AP). AP was introduced to rats which were divided into Control, AP and IFN-γ group. Rats in the AP and IFN-γ group were sacrificed as 6, 12 and 24 h after IFN-γ treatment. The serum amylase (AMA), endotoxin and cytokines were detected. The pathological examination and immunofluorescence staining of pancreas for TNF-α, NF-κB and IL-18 were performed. The serum AMA increased significantly at 6 h and reduced at 48 h after AP. The increase in IFN-γ was higher than that in AMA. IL-18 increased in the AP and IFN group, and IFN increased markedly at 48 h after AP. IL-27 reduced at 24 h after AP compared with AP group. In the AP group, the immunostaining of cytokines increased. In the IFN group, the edema in the pancreas was more severe, and NF-κB and IL-18 expression was higher than that in the other two groups. IFN-γ can increase serum IL-18 and reduce IL-27 in AP. IFN-γ can increase serum IL-18 and reduce serum IL-27 in AP. The increase in NF-κB and IL-18 may exert influence on pro-inflammatory cytokines to deteriorate inflammation in the pancreas. Thus, to control the IFN-γ might has promise to attenuate pancreatitis.

The preprocessing of the Microarray data is a hot topic in the bioinformatics research. The key point of a successful preprocessing method is to remove the noise of nonspecific binding and to keep the information of specific binding as much as possible. One way to solve these problems is to understand the principle of the binding between probes and target sequences, and to distinguish specific binding from nonspecific binding correctly. In this paper, we introduce MM probe intensities into position dependent nearest neighbor (PDNN) model, which contain much information of nonspecific binding.We use two-step model to estimate the parameters,which can simplify the computation. Based on the Wilcoxon rank test, we can determine whether a gene is present, with which we can obtain the training data set for the specific binding and non specific binding parameters. We also apply our model to gene expression data (HGU133plus2.0 and HGU133A) . We find that all these improvements increase the precision and stability, and show better result compared to the other four methods( Mas5.0, dChip, RMA and PDNN ).

The genes for chemokine-like factor ( CKLF ) and four chemokine-like factor super family members ( CKLFSF1–4 ) are tightly linked on chromosome 16, with only 325 bp separating CKLF and CKLFSF1 . We used Northern blotting and RT-PCR to show that these two genes are expressed independently of one another. We then used a novel computational promoter prediction method based on the interaction among transcription factor binding sites (TFBSs) to identify a putative promoter region for the CKLFSF1 gene. Our method predicted a promoter region in the last intron of the upstream gene, CKLF . We PCR amplified the predicted promoter region and used a luciferase assay to show that the region was able to drive the luciferase gene. DNA decoy experiments indicated that 214 bp fragment neighboring the TATA box markedly inhibited CKLFSF1 gene expression. Sequence analysis of the region revealed a typical TATA box (TATATAA) and multiple potential transcription factor binding sites, providing further evidence for this being a functional promoter for CKLFSF1 . This work provides the first evidence of a promoter from one gene located in an intron of another.