Application of direct observation of operational skills in nursing skill evaluation of pressure injury: A randomized clinical trial.

This was a non-blinded, single-centre, randomized, controlled clinical trial that compared the effectiveness of direct observation of procedural skills (DOPSs)with traditional assessment methods in pressure injury (PI) care skills. The study population included 82 nursing professionals randomly assigned to the study group (n = 41) and the control group (n = 41). Both groups of nurses underwent a 6-month training in PI care skills and were subsequently evaluated. The main outcome variables were the PI skill operation scores and theoretical scores. Secondary outcome variables included satisfaction and critical thinking abilities. Independent sample t-tests and chi-square tests were used to assess differences between the two groups of nurses. The results showed no statistically significant difference in PI skill operation scores between the two groups of nurses (p > 0.05). When comparing the PI theoretical scores, the study group scored higher than the control group, and this difference was statistically significant (p < 0.05). In terms of satisfaction assessment, the study group and the control group showed differences in improving self-directed learning, enhancing communication skills with patients, improving learning outcomes and increasing flexibility in clinical application (p < 0.05). When comparing critical thinking abilities between the two groups of nurses, there was no statistically significant difference at the beginning of the training, but after 3 months following the training, there was a statistically significant difference between the two groups (p < 0.01).The results indicated that the DOPS was effective in improving PI theoretical scores, increasing nurse satisfaction with the training and enhancing critical thinking abilities among nurses.

Chemically modified liposomes carrying TRAIL target activated hepatic stellate cells and ameliorate hepatic fibrosis in vitro and in vivo.

At present, no satisfactory anti-liver fibrosis drugs have been used clinically due to the poor targeting ability and short half-life period. This study aimed to explore the effects of a new TRAIL (TNF-related apoptosis-inducing ligand) preparation that can target aHSCs (activated hepatic stellate cells) on liver fibrosis and explain the possible underlying mechanism. Using our self-made drug carrier pPB-SSL that specifically targets aHSCs, recombinant human TRAIL (rhTRAIL) protein was embedded in (named as pPB-SSL-TRAIL) and applied to treat liver fibrotic mice as well as 3T3 fibroblast cells and aHSCs. Through in vitro and in vivo experiments, we found that, compared with the groups treated with TRAIL (free rhTRAIL) and SSL-TRAIL (rhTRAIL capsulated within unmodified liposome), the group treated with pPB-SSL-TRAIL nanoparticles showed significantly lower cell viability and higher cell apoptosis in vitro. The targeting delivering system pPB-SSL also significantly enhanced the anti-fibrotic effect, apoptosis induction and long circulation of rhTRAIL. After the treatment with pPB-SSL-TRAIL, apoptosis of aHSCs was notably increased and hepatic fibrosis in mice was remarkably alleviated. In vitro, pPB-SSL-TRAIL nanoparticles were mainly transported and located on membrane or into cytoplasm, but the particles were distributed mainly in mouse fibrotic liver and most on the cell membrane of aHSCs. In conclusion, rhTRAIL carried by pPB-SSL delivering system has prolonged circulation in blood, be able to target aHSCs specifically, and alleviate fibrosis both in vitro and in vivo. It presents promising prospect in the therapy of liver fibrosis, and it is worthwhile for us to develop it for clinical use.

MAP Kinase-Interacting Kinase 1 Promotes Proliferation and Invasion of Hepatocellular Carcinoma and Is an Unfavorable Prognostic Biomarker.

BACKGROUND Hepatocellular carcinoma (HCC) accounts for one of the most prevalent tumor types in the world. The MAP kinase-interacting kinase 1 (MNK1) functions downstream of MAP kinases such as p38 and ERK, and its potential role in cancer development is being uncovered. The aim of this study was to investigate the expression and function of MNK1 in HCC. MATERIAL AND METHODS Immunohistochemical staining and quantitative PCR were performed to explore the expression of MNK1 in both HCC tissues and adjacent normal liver tissues. Chi-square test, univariate analysis, and multivariate analysis were conducted to statistically evaluate clinical significance of MNK1 in HCC. Proliferation, migration, and invasion capacities of HCC cells were assessed after overexpressing or silencing MNK1. RESULTS Both the RNA and protein levels of MNK1 were upregulated in HCC tissues compared to normal liver tissues. High expression of MNK1 was correlated with advanced tumor stage and poor overall survival. Moreover, MNK1 was identified as a novel independent prognostic factor for HCC patients. Cellular studies showed that MNK1 can enhance the proliferation, migration, and invasion capacities of HCC cells, thereby promoting tumor progression. CONCLUSIONS High expression of MNK1 is frequent in HCC tissues, which promotes tumor proliferation and invasion, and is correlated with a poor overall survival. Targeting MNK1 may be a novel direction for the drug development of HCC therapy.

Clinical Significance of Ubiquitin Specific Protease 7 (USP7) in Predicting Prognosis of Hepatocellular Carcinoma and its Functional Mechanisms.

BACKGROUND Hepatocellular carcinoma (HCC) accounts for one of the most prevalent cancer types in the world. The ubiquitin specific protease 7 (USP7), a kind of deubiquitylating enzyme, has been reported to play multifaceted roles in different tumor types. The aim of this study was to investigate the expression and function of USP7 in HCC. MATERIAL AND METHODS Immunohistochemical staining and quantitative PCR were performed to explore the expression of USP7 in both HCC tissues and adjacent normal liver tissues. Chi-square test, univariate analysis, and multivariate analysis were conducted to statistically evaluate the clinical significance of USP7 in HCC. Proliferation, migration, and invasion capacities of HCC cells were assessed after overexpressing or silencing USP7. RESULTS Both the RNA and protein levels of USP7 were upregulated in HCC tissues compared to normal liver tissues. High expression of USP7 was correlated with advanced tumor stage and poor overall survival. Moreover, USP7 was identified as a novel independent prognostic factor for HCC patients. Cellular studies showed that USP7 could enhance the proliferation, migration, and invasion capacities of HCC cells, thereby promoting tumor progression. CONCLUSIONS High expression of USP7 is frequent in HCC tissues, which promotes tumor proliferation and invasion, and is correlated with a poor overall survival. Targeting USP7 may be a novel direction for the drug development of HCC therapy.

The effect of telemedicine interventions on patients with diabetic foot ulcers: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The meta-analysis was performed to evaluate the effectiveness of telemedicine interventions on patients with diabetic foot ulcers(DFU). APPROACH: The authors conducted a comprehensive search across eight databases. The aim was to identify randomized controlled trials examining the effectiveness of telemedicine for patients with DFU. Methodological qualities of included studies were assessed using Cochrane Handbook for Systematic Reviews of Intervention.. Subsequently, a meta-analysis was conducted using RevMan 5.3 to synthesize the findings. RESULTS: Ten studies involving 1678 patients with DFU were included in the meta-analysis. In comparison to the face-to-face intervention group, telemedicine interventions significantly reduced the amputation rate (risk ratio (RR) = 0.64, 95% confidence interval (CI) = 0.44－0.92, p = 0.02), decreased costs (mean difference (MD) = -4158.51, 95% CI = -7304.69－-1012.34, p = 0.01), better controlled fasting blood glucose( FPG)(MD = -0.89, 95% CI = -1.43－-0.36, p = 0.001), achieved superior glycated hemoglobin(HbA1c) control (MD = -0.71, 95% CI = -1.01－-0.41, p ˂ 0.00001). No significant differences were observed between the telemedicine group and the face-to-face group in terms of healing rate, mortality, and healing time.  Innovations: Our study suggests that telemedicine is a viable strategy for managing DFU. CONCLUSIONS: The meta-analysis indicates that telemedicine interventions have a positive effect on DFU. Nevertheless, more well-designed and high-quality studies are needed to reach a conclusion with greater confidence.

Enhancing therapeutic effects of murine cancer vaccine by reshaping gut microbiota with Lactobacillus rhamnosus GG and jujube powder.

Cancer vaccines have gained widespread attention in recent years as an emerging treatment for tumors. However, most therapeutic cancer vaccines have failed in phase III clinical trials due to faint clinical benefits. In this study, we funded that a specific synbiotic composing Lactobacillus rhamnosus GG (LGG) and jujube powder significantly enhanced the therapeutic effects of whole cells cancer vaccine in MC38 cancer cells bearing-mouse. The utilization of LGG increased the abundance of Muribaculaceae, which is conductive to an enhanced anti-tumor effect, but reduced microbial α-diversity. The use of jujube nursed probiotic microorganisms in Lachnospiaceae and enriched microbial diversity, as indicated by increased Shannon and Chao index. The reshaped gut microbiota by this synbiotic improved lipid metabolism conductive to intensified infiltration of CD8+ T cells in the tumor microenvironment and enhanced the potency of above-mentioned cancer vaccine. These encouraging findings are helpful for further efforts towards enhancing the therapeutic effects of cancer vaccines through nutritional intervention.

Boosting HSA Vaccination with Jujube Powder Modulating Gut Microbiota Favorable for Arginine Metabolism.

Whereas vaccination is established as one of the most effective and available methods against seasonal flu and holds high potential for many infectious diseases, immune response may differ among individuals and regions. In this study we examined the effects of gut microbiota on vaccination with human serum albumin (HSA) as the model vaccine in C57BL/6J mice. We observed that a two-week antibiotic cocktail (ABX) treatment hampered HSA-specific IgG1 in serum, whereas fecal microbiota transplantation (FMT) restored the gut microbiota impaired by the ABX treatment and consequently increased the proportions of macrophages in the mesenteric lymph nodes (MLNs), plasma cells in the peripheral blood, and HSA-specific immunoglobulin G1 (IgG1) in the serum. A week of daily application of jujube powder (800 mg/kg) to ABX-treated mice achieved a significantly higher HSA-specific IgG1 concentration in the serum compared with the ABX treatment group. Of particular note was that the administration of the jujube powder did not increase the myeloid cells, indicating a different mechanism of vaccination compared with FMT. More interestingly, daily pre-administration of jujube powder (800 mg/kg) to healthy mice one week ahead of vaccination boosted their immune response, as evidenced by the proportion of macrophages in the MLNs, B cells in the spleen, plasma cells and memory B cells in the peripheral blood, and HSA-specific IgG1 concentration in the serum. The 16S rRNA sequencing of gut microbiota revealed that the administration of jujube powder increased the abundance of Coriobacteriaceae associated with the metabolism of amino acids. The Kyoto encyclopedia of genes and genomes (KEGG) analysis suggested the altered microbiota is more favorable for arginine and proline metabolism, which may promote macrophages in the MLNs. These results indicate a high potential for boosting vaccination by manipulating gut microbiota with natural products.

Promoting intestinal IgA production in mice by oral administration with anthocyanins.

While recent years have witnessed ever-growing evidence on the prebiotic attributes of anthocyanins for treatment of microbiota-associated diseases, the complex interplay between anthocyanin uptake, the gut microbiota, and the intestinal mucosal immune system remains poorly understood. Here, we investigate the effects of bilberry anthocyanins on the gut microbiota composition and metabolism, and the intestinal mucosal immune system of mice. We observed an increased proportion of IgA-producing plasma cells in the mesenteric lymph nodes (MLNs) and an enhanced secretion of secretory immunoglobulin A (sIgA) and antimicrobial peptides in the small intestine. Small intestine transcriptome analysis further suggested that anthocyanins influenced IgA production. We found that oral administration of anthocyanins altered the gut microbiota through maintaining the anaerobic intestinal environment, promoting the secretion of sIgA and antimicrobial peptides, and downregulating cell motility and mobile genetic elements of commensal bacteria. These observations suggest that the oral administration of anthocyanins helps in maintaining intestinal homeostasis and thus it may find applications in immunotherapy and related fields.

Sex-Biased Immune Responses to Antibiotics during Anti-PD-L1 Treatment in Mice with Colon Cancer.

Colitis is a frequently occurred side effect of immune checkpoint inhibitors (ICIs), which are increasingly used in cancer treatment, whereas antibiotics are widely used to treat colitis, their effectiveness in ICI-associated colitis remains controversial. In this study, we firstly assessed the effectiveness of several commonly used antibiotics and antibiotic cocktails in alleviating of dextran sulfate sodium- (DSS-) induced colitis. We observed that two narrow-spectrum antibiotics, neomycin and metronidazole, were more effective in alleviating colitis, as evidenced by the remission of loss of the body weight, enlargement of the spleen, shortening of the colon, secretion of proinflammatory cytokines, and histological score of the colon tissue. Moreover, these two antibiotics resulted in better relief of colitis symptoms in the MC38 tumor-bearing male mice receiving the anti-PD-L1 mAb (αPD-L1) treatment, compared to the females. In the meantime, an enhanced response to αPD-L1 efficiency against mice colon cancer was observed in the male mouse group upon the application of these two antibiotics. In contrast, both neomycin and metronidazole showed destructive effects on the antitumor efficiency of αPD-L1 in female mice, despite relief from colitis. We found that antibiotic treatment attenuated the increased infiltration of granulocytes and myeloid cells in colon tissue induced by DSS in female mice, while reducing the proportion of Th17 cells in male mice. These differences were further associated with the sex-biased differences in the gut microbiota. These findings indicated that sex-dependent alterations in the gut microbiota should be considered when applying antibiotics for the treatment of ICI-associated colitis.

Jujube Powder Enhances Cyclophosphamide Efficiency against Murine Colon Cancer by Enriching CD8+ T Cells While Inhibiting Eosinophilia.

Cyclophosphamide (CTX) is widely applied in cancer treatment. However, the outcome is often compromised by lymphopenia, myelosuppression, and gut dysbiosis. Here, we used jujube powder to enhance CTX efficiency through nurturing gut microbiota in order to facilitate favorable metabolisms. It was observed that the oral administration of jujube powder enriched CD8+ T cells in mouse MC38 colon tumor microenvironment and increased the diversity of gut microbiota and the abundance of Bifidobacteriales, which is helpful to the production of butyrate in the cecum content. The application of jujube powder also stimulated the production of white blood cells, especially CD8+ T cells in peripheral and bone marrow, while inhibiting the growth of eosinophils in peripheral blood and the production of IL-7 and GM-CSF in serum. All these are conductive to the significant inhibition of the tumor growth, suggesting the high potential of nurturing gut microbiota with natural products for improving the efficiency of chemotherapy.

Ultrafine Jujube Powder Enhances the Infiltration of Immune Cells during Anti-PD-L1 Treatment against Murine Colon Adenocarcinoma.

Whereas dietary intervention with natural nutrients plays an important role in activating the immune response and holds unprecedented application potential, the underpinning mechanism is poorly understood. The present work was dedicated to comprehensively examine the effects of ultrafine jujube powder (JP) on the gut microbiota and, consequentially, the effects associated with the response rate to anti-PD-L1 treatment against murine colon adenocarcinoma. A murine colon adenocarcinoma model with anti-PD-L1 immunotherapy was established to evaluate how dietary interventions affect the microbiota. In vitro and in vivo experiments confirmed the role of SCFAs in the immune response. Oral administration of JP greatly improves the response of anti-PD-L1 treatment against murine colon adenocarcinoma. Such an improvement is associated with the alteration of gut microbiota which leads to an increased abundance of Clostridiales, including Ruminococcaceae and Lachnospiraceae, an elevated SCFA production, and an intensified infiltration of CD8+ T cells to the tumor microenvironment. This work demonstrates that JP is particularly effective in modulating the gut microbiota for an improved immune checkpoint blockage therapy by boosting cytotoxic CD8+ T cells in tumor-infiltrating lymphocytes. The experimental findings of the present study are helpful for the development of dietary intervention methods for cancer immunotherapy using natural nutrients.

Downregulating testosterone levels enhance immunotherapy efficiency.

Low response rates to certain tumor types remain a major challenge for immune checkpoint blockade therapy. In this study, we first conducted an integrated biomarker evaluation of bladder cancer patients from confirmatory cohorts (IMvigor210) and found that no significant differences exist between sexes before acceptance of anti-PD-L1 treatment, whereas male patients showed a better response. Thus, we then focused on sex-related changes post anti-PD-L1 treatment and found no obvious impact on the gut microbiota in male mice but a significant decrease in the sex hormone levels. Further, castration dramatically enhanced the antitumor efficacy against murine colon adenocarcinoma in male mice. Moreover, a narrow-spectrum antibiotic, colistin was innovatively used for deregulation of testosterone levels to enhance the immunotherapy efficiency in male mice. These findings indicate that the impact on the sex hormone levels in males may contribute to the sexual dimorphism in response and provide a promising way to enhance immunotherapy efficiency.

Validity of Chinese Version of Attitudes Toward Interprofessional Health Care Teams Scale.

OBJECTIVE: Effective teamwork can provide safe and effective care in various medical systems. Thus, there is increasing recognition of the value of interprofessional collaborative practice. The Attitudes Toward Interprofessional Health Care Teams Scale (ATIHCTS) has been applied to a wide variety of health professions for evaluating attitudes toward health care teams. The ATIHCTS has been widely used internationally, but no Chinese version has been developed. The aim of this study was to adapt a Chinese version of the ATIHCTS among Chinese health care professionals and to test its validity. METHODS: The English version of the ATIHCTS was translated into Chinese, back-translated, and modified for cultural adaptation according to Brislin's guideline. A total of 306 health professionals in a Shanghai tertiary hospital were investigated using the Chinese version of the ATIHCTS to test its validity. RESULTS: The Chinese version of the ATIHCTS was adjusted based on expert review and pilot testing. According to expert opinions, the text that did not conform to the Chinese language habits and the Chinese medical environment was adjusted. A total of five adjustments were made. After the pilot testing, minor corrections were made to improve the sentence structure of the scale instructions to make it easier to understand. Factor analysis was subsequently conducted with 306 respondents. The Chinese version of the ATIHCTS had 14 items. Exploratory factor analysis extracted two common factors, quality of care and time constraints, with the cumulative variance contribution rate reaching 70.011% and the load value of each entry on its common factor > 0.4. In addition, for scale confirmatory factor analysis (CFA), the chi-square/degrees of freedom ratio (X2/df) was 1.46, the normed fit index (NFI) was 0.97, the Tucker-Lewis index (TLI) was 0.99, the incremental fit index (IFI) was 0.99, the comparative fit index (CFI) was 0.99, and the root mean square error of approximation (RMSEA) was 0.04. The fitting values all met the judgment criteria, and the scale had good structural validity. Cronbach's α of the Chinese version of the ATIHCTS was 0.861, and the Cronbach's α values of each factor were 0.949 and 0.838, respectively. The split-half reliability was 0.644, and the Guttman split-half coefficients of each factor were 0.904 and 0.779, respectively. CONCLUSION: The Chinese version of the ATIHCTS has good validity. It is a valuable tool for evaluating attitudes toward interprofessional health care teams among the health care professionals in China.

The lncRNA ENSG00000254041.1 promotes cell invasiveness and associates with poor prognosis of pancreatic ductal adenocarcinoma.

Pancreatic cancer (PC) mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. Long non-coding RNAs (lncRNAs) are well known as a class of transcripts involved in cancer occurrence and progression. The process of epithelial to a mesenchymal (EMT) phenotype in tumor cell increases their migratory and invasive properties, resulting in facilitating metastasis. Here, we reanalyzed RNA-seq data from the TCGA PC database and identified that ENSG00000254041.1 increasingly expressed in samples with elevated EMT signature score. Then, the evaluated expression and prognostic significance of ENSG00000254041.1 were verified in our cohort. Meanwhile, multivariate analysis suggested that ENSG00000254041.1 was independent factors for predicting the prognosis of PC, apart from advanced stage (III/IV). Moreover, functional assay revealed that knock down of ENSG00000254041.1 significantly decreased proliferation, invasion and chemoresistance of PC cells (SW1990 and BxPC-3), while overexpression of ENSG00000254041.1 in PC cells (Panc-1) resulted in the opposite effects. Western blot showed that knockdown of ENSG00000254041.1 expression in PC cells caused a significant downregulation of vimentin, Snail and SOX4, and upregulation of E-cadherin; also, ENSG00000254041.1 overexpression in PC cells resulted in opposite effects. In conclusion, these findings indicated that ENSG00000254041.1 promotes PC progression, and might provide a potential biomarker for predicting the prognosis of PC.

The long coding RNA AFAP1-AS1 promotes tumor cell growth and invasion in pancreatic cancer through upregulating the IGF1R oncogene via sequestration of miR-133a.

Long non-coding RNAs (lncRNAs) have been shown to play a significant role in the progression of many cancers, including pancreatic cancer (PC). However, the biological function and regulatory mechanisms of lncRNAs in PC remains largely unclear. The aim of this study was to identify and evaluate the potential functions of lncRNAs in PC and reveal the underlying mechanisms of their effects. Screening of published microarray data (GEO accession Nos. GSE16515 and GSE32688), revealed lncRNA AFAP1-AS1 to be one of the most upregulated lncRNAs in PC tissues. High expression of AFAP1-AS1 was correlated with advanced stages, tumor size and lymph node metastasis, as well as with poorer overall survival in patients with PC. Functionally, knockdown of AFAP1-AS1 by transfection with siRNA inhibited the proliferative and invasive capacities of PaCa-2 and SW1990 PC cells, promoted apoptosis of PC cells in vitro, and impaired in-vivo tumorigenicity. In particular, it was hypothesized that AFAP1-AS1 may act as a competitive endogenous RNA (ceRNA), effectively becoming a sink for miR-133a whose expression was found to be downregulated in PC tissues and cell lines, and which was negatively correlated with the expression of AFAP1-AS1. We also found that the IGF1R oncogene which is an important regulator of MEK/ERK signaling pathway, was positively regulated by AFAP1-AS1 through ameliorating miR-133a-mediated IGF1R repression in PC tissues. Moreover, we demonstrated that knockdown of IGF1R by transfection with si-IGF1R suppressed cell proliferation, invasion and migration of PaCa-2 and SW1990 PC cells, suggesting that IGF1R may function as an oncogene in PC cells. Further investigations revealed that miR-133a reversed the biological effects of AFAP1-AS1 on PC cells. Collectively, the findings provide new evidence that AFAP1-AS1 could regulate the progression of pancreatic cancer by acting as a ceRNA, and suggest it has potential for use as both a biomarker for the early detection PC and for the development of individualized therapies for PC.