Influencing factors of medical device-related pressure ulcers in medical personnel during the COVID-19 pandemic: A systematic review and meta-analysis.

OBJECTIVE: To determine the influencing factors of medical device related pressure injury (MDRPU) in medical staff by meta-analysis. METHODS: A comprehensive literature search was conducted by PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, CBM, and WanFang Data (from inception to July 27, 2022). Two researchers independently performed literature screening, quality evaluation and data extraction, and meta-analysis was conducted with RevMan 5.4 and Stata12.0 software. RESULTS: Total of 11215 medical staff were included in 9 articles. Meta analysis showed that gender, occupation, sweating, wearing time, single working time, department of COVID-19, preventive measures, and level 3 PPE were the risk factors for MDRPU in medical staff (P < 0.05). CONCLUSION: The outbreak of COVID-19 led to the occurrence of MDRPU among medical staff, and the influencing factors should be focused on. The medical administrator can further improve and standardize the preventive measures of MDRPU according to the influencing factors. Medical staff should accurately identify high-risk factors in the clinical work process, implement intervention measures, and reduce the incidence of MDRPU.

Association of Thiamine Intake with Human Papillomavirus (HPV) Infection in American Women: A Secondary Data Analysis Based on the National Health and Nutrition Examination Survey from 2003 to 2016.

BACKGROUND Studies have shown that thiamine intake is associated with cervical cancer, but the relationship between thiamine and HPV infection remains unclear. In the present study, we used the National Health and Nutrition Examination Survey (NHANES) database to investigate whether HPV infection was associated with thiamine intake. MATERIAL AND METHODS A total of 13 471 women ages 18-59 years were selected from the NHANES database from 2003 to 2016. Using thiamine intake as the independent variable, HPV infection as the dependent variable, and sociodemographic data and other data as the covariates, we analyzed the relationship between thiamine and HPV infection by conducting a weighted logistic regression model in a cross-sectional research design. RESULTS The two-piecewise linear model indicated the inflection point of thiamine intake was 2.07 mg. On the left side of the inflection point, the difference in the thiamine intake of log2 conversion was related to the difference of 0.82 in HPV infection, which means that the increase of every 1 unit increase in thiamine intake is associated with the decrease of the HPV infection by 18%. On the right side of the inflection point, we did not observe a correlation between HPV infection and thiamine intake. CONCLUSIONS Thiamine intake is negatively correlated with HPV infection. Intake of an appropriate amount of thiamine can prevent HPV infection. The best preventive effect can be achieved when the intake is about 2 mg, and excessive intake will not increase the preventive effect.

Exchange protein directly activated by cAMP (Epac) protects against airway inflammation and airway remodeling in asthmatic mice.

BACKGROUND: ß2 receptor agonists induce airway smooth muscle relaxation by increasing intracellular cAMP production. PKA is the traditional downstream signaling pathway of cAMP. Exchange protein directly activated by cAMP (Epac) was identified as another important signaling molecule of cAMP recently. The role of Epac in asthmatic airway inflammation and airway remodeling is unclear. METHODS: We established OVA-sensitized and -challenged acute and chronic asthma mice models to explore the expression of Epac at first. Then, airway inflammation and airway hyperresponsiveness in acute asthma mice model and airway remodeling in chronic asthma mice model were observed respectively after treatment with Epac-selective cAMP analogue 8-pCPT-2'-O-Me-cAMP (8pCPT) and Epac inhibitor ESI-09. Next, the effects of 8pCPT and ESI-09 on the proliferation and apoptosis of in vitro cultured mouse airway smooth muscle cells (ASMCs) were detected with CCK-8 assays and Annexin-V staining. Lastly, the effects of 8pCPT and ESI-09 on store-operated Ca2+ entry (SOCE) of ASMCs were examined by confocal Ca2+ fluorescence measurement. RESULTS: We found that in lung tissues of acute and chronic asthma mice models, both mRNA and protein expression of Epac1 and Epac2, two isoforms of Epac, were lower than that of control mice. In acute asthma mice model, the airway inflammatory cell infiltration, Th2 cytokines secretion and airway hyperresponsiveness were significantly attenuated by 8pCPT and aggravated by ESI-09. In chronic asthma mice model, 8pCPT decreased airway inflammatory cell infiltration and airway remodeling indexes such as collagen deposition and airway smooth muscle cell proliferation, while ESI-09 increased airway inflammation and airway remodeling. In vitro cultured mice ASMCs, 8pCPT dose-dependently inhibited, whereas ESI-09 promoted ASMCs proliferation. Interestingly, 8pCPT promoted the apoptosis of ASMCs, whereas ESI-09 had no effect on ASMCs apoptosis. Lastly, confocal Ca2+ fluorescence examination found that 8pCPT could inhibit SOCE in ASMCs at 100 µM, and ESI-09 promoted SOCE of ASMCs at 10 µM and 100 µM. In addition, the promoting effect of ESI-09 on ASMCs proliferation was inhibited by store-operated Ca2+ channel blocker, SKF-96365. CONCLUSIONS: Our results suggest that Epac has a protecting effect on asthmatic airway inflammation and airway remodeling, and Epac reduces ASMCs proliferation by inhibiting SOCE in part.

Cardioprotective effect of nicorandil against myocardial injury following cardiac arrest in swine.

INTRODUCTION: Nicorandil, a vasodilatory drug used to treat angina, was reported to protect against myocardial ischemia-reperfusion injury in various animal models. However, its cardioprotective action following cardiac arrest is unknown. We examined the cardioprotective effects of nicorandil in a porcine model of cardiac arrest and resuscitation. METHODS: Ventricular fibrillation was induced electrically for 4min in anesthetized domestic swine, followed by cardiopulmonary resuscitation. Sixteen successfully resuscitated animals were randomized to saline control (n=8) or nicorandil (n=8) groups. Nicorandil (150µg/kg) was administered by central intravenous injection at onset of restoration of spontaneous circulation (ROSC), followed by 3µg/kg/min infusion until reperfusion end. Sham-operated animals received surgery only (n=4). Hemodynamic parameters were monitored continuously. Blood samples were taken at baseline, 5, 30, 180, and 360min after ROSC. Left ventricular ejection fraction was assessed by echocardiography at baseline and 6h after ROSC. The animals were euthanized 6h after ROSC, and the cardiac tissue was removed for analysis. RESULTS: 6 h after ROSC, nicorandil had significantly improved all hemodynamic variables (all P<0.05) except the maximum rate of left ventricular pressure decline and heart rate (P>0.05) compared with the control group. Control animals showed elevated cardiac troponin I and lactate levels compared with sham animals, which were significantly decreased following nicorandil treatment (P<0.05). In the saline control group, the adenosine triphosphate (ATP) content was largely reduced but subsequently rescued by nicorandil (P<0.05). Histopathologic injury was reduced with nicorandil treatment. Nicorandil reduced cardiomyocyte apoptosis as evidenced by reduced terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, decreased Bax and caspase-3 expression, and increased Bcl-2 expression in the myocardium (all P<0.05). CONCLUSION: Nicorandil exhibited cardioprotective effects on myocardial injury following cardiac arrest via improvement in post-resuscitation myocardial dysfunction and energy metabolism, reduction in myocardial histopathologic injury, and antiapoptotic effects.

Targeted delivery of pexidartinib to tumor-associated macrophages via legumain-sensitive dual-coating nanoparticles for cancer immunotherapy.

Tumor-associated macrophage (TAM) is regarded as an appealing cell target for cancer immunotherapy. However, it remains challenging to selectively eliminate M2-like TAM in tumor microenvironment. In this work, we employed a legumain-sensitive dual-coating nanosystem (s-Tpep-NPs) to deliver CSF-1R inhibitor pexidartinib (PLX3397) for targeting TAM therapy. The PLX3397-loaded NPs exhibited uniform size of ∼240 nm in diameter, good drug loading capacity and efficiency, as well as sustained drug release profile. Compared to non-sensitive counterpart ns-Tpep-NPs, s-Tpep-NPs showed distinguished selectivity upon M1 and M2 macrophage uptake with relation to incubation time and dose. Besides, the selectivity of anti-proliferation effect was also identified for s-Tpep-NPs against M1 and M2 macrophage. In vivo imaging demonstrated that s-Tpep-NPs exhibited much higher tumoral accumulation and TAM recognition specificity as compared to non-sensitive ns-Tpep-NPs. In vivo efficacy verified that s-Tpep-NPs formulation was much more effective than ns-Tpep-NPs and other PLX3397 formulations to treat B16F10 melanoma via targeting TAM depletion and modulating tumor immune microenvironment. Overall, this study provides a robust and promising nanomedicine strategy for TAM-targeted cancer immunotherapy.

Legumain protease-sheddable PEGylated, tuftsin-modified nanoparticles for selective targeting to tumour-associated macrophages.

Tumour-associated macrophages (TAMs) represent an attractive cell target for anticancer therapy. However, selective and efficient targeting of TAMs remains difficult. Here, we constructed a novel dually functionalised nanoparticle platform (s-Tpep-NPs) by surface co-modification of nanoparticles (NPs) with tuftsin (Tpep) and legumain protease-sheddable polyethylene glycol 5k (PEG5k) to achieve selective targeted delivery to TAMs. The fluorescence resonance energy transfer experiment and in vitro cellular uptake assay confirmed that s-Tpep-NPs can responsively shed PEG5k and transform into active Tpep-NPs upon the cleavage of legumain that is overexpressed on TAM surfaces, which then promotes TAM phagocytosis through Fc receptor-mediated pathways. Owing to the shielding effect by legumain-sheddable PEG5k, s-Tpep-NPs can effectively decrease the Tpep-induced non-specific accumulation in mononuclear phagocyte system (MPS) organs during systemic circulation. Moreover, s-Tpep-NPs can significantly enhance the tumoural accumulation and improve the specificity and efficiency of targeting to TAMs, as compared with both controls of Tpep-NPs and non-sheddable ns-Tpep-NPs. Overall, this study provides a robust nanoplatform with a novel avenue for improved selectivity of targeted delivery to TAMs.

Legumain protease-activated tuftsin-functionalized nanoparticles for dual-targeting TAMs and cancer chemotherapy.

M2 tumor-associated macrophages (TAMs) play a pivotal role in cancer progression and therapy resistance. Inhibition of TAMs is of great significance to reshape the protumor environment to benefit therapeutic outcomes. In this work, we developed a novel TAMs and tumor cells dual-targeting nanoparticle (ATpep-NPs) system for cancer chemotherapy by integrating a docetaxel (DTX)-loaded nanocarrier and a multi-function peptide ATpep, which is composed of a phagocytosis-stimulating peptide-tuftsin (Tpep) fused with a substrate peptide-alanine-alanine-asparagine (AAN) of endoprotease legumain. In vitro protelytic and cellular uptake assays confirmed ATpep-NPs can be responsively activated into Tpep-NPs by cleavage of legumain that is overexpressed in both tumor cells and TAMs, which then promoted tumor cells internalization and TAMs phagocytosis through neuropilin-1/Fc receptor pathways. Due to AAN deactivation effect, ATpep-NPs can effectively decrease the Tpep-induced non-specific uptake by M1-polarized and normal macrophage during systemic circulation. Our results of in vivo experiments demonstrated ATpep-NPs outperformed Tpep-NPs in tumor and TAMs dual-targeting delivery efficiency with markedly enhanced efficacy against both tumor growth inhibition and TAMs depletion. Overall, this study offers a novel approach for development of multitargeted delivery vehicle for improved cancer chemotherapy.

Problematic Internet Usage and Self-Esteem in Chinese Undergraduate Students: The Mediation Effects of Individual Affect and Relationship Satisfaction.

The aim of this cross-sectional study was to examine the mediating effects of individual affect and relationship satisfaction on the relationship between self-esteem and Problematic Internet Use (PIU). Affect was measured using the Positive and Negative Affect Schedule (PANAS), relationship satisfaction was assessed using a positive and negative semantic dimension scale, self-esteem was measured using the Rosenberg Self-Esteem Scale, and PIU was measured using the Problematic Internet Use scale with a sample of 507 Chinese university students (Mage = 20.41 years, SD = 2.49). The relationships between the variables were tested using structural equation modelling with a multiple mediation model. The results revealed that negative affect and the negative semantic dimensions of relationship satisfaction mediated the relationship between self-esteem and PIU. The implications of the results and the study's theoretical contributions are discussed.

Matrix Metalloproteinase-3 induces proteoglycan degradation in gouty arthritis model.

BACKGROUND: Gout is an inflammatory arthritis resulting from precipitation of monosodium urate (MSU) crystals in joints and surrounding tissues. However, the mechanism underlying high levels of uric acid inducing gouty arthritis has not been clarified. OBJECTIVE: The purpose was to investigate the role of Matrix Metalloproteinase-3 (MMP-3) in the development of gouty arthritis from hyperuricemia. METHOD: MSU crystal-induced gouty arthritis model and chondrocytes were used to evaluate changes of MMP-3 levels. Western blot, qPCR and ELISA were performed to detect MMP-3, Tissue Inhibitors of Metalloproteinase-1 (TIMP-1) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs-4 (ADAMTS-4) expressions in rabbit chondrocytes. Expression of proteoglycan was determined through toluidine blue staining. Concentrations of glycosaminoglycan, Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß) and Tumor Necrosis Factor-α (TNF-α) in chondrocytes were assessed via ELISA kits. Concentration of uric acid in supernate was tested by Automatic Analyzer. RESULTS: MMP-3 was significantly increased in rat serum, synovial fluid, cartilages and chondrocytes treated with high-level uric acid. Increased concentration of glycosaminoglycancould be observed in chondrocytes incubated with MMP-3, as well as the remarkable downregulation of proteoglycan expression. Furthermore, high-level uric acid contributed to the degradation of proteoglycan via the activation of MMP-3. IL-6, IL-1ß and TNF-α concentrations were increased significantly in 35 °C compared to 37 °C with MMP-3 and high-level uric acid. CONCLUSION: Our study showed that MMP-3 was enhanced by high levels of uric acid, which promoted proteoglycan degradation, and induced MSU crystallization in turn. A low temperature environment is an important factor in the development of gout.

Non-Lactobacillus-Dominated Vaginal Microbiota Is Associated With a Tubal Pregnancy in Symptomatic Chinese Women in the Early Stage of Pregnancy: A Nested Case-Control Study.

The features of the vaginal microbiota (VM) community can reflect health status, and they could become new biomarkers for disease diagnosis. During pregnancy, domination of bacteria of the genus Lactobacillus in the VM community is regarded as a keystone because they stabilize the VM by producing antimicrobial compounds and competing adhesion. An altered VM composition provides a marker for adverse pregnancy outcomes. This nested case-control study aimed to characterize the VM in women with a tubal pregnancy (TP) presenting with pain and/or uterine bleeding in early pregnancy. Chinese women with a symptomatic early pregnancy of unknown location were the study cohort. 16S rDNA gene-sequencing of V3-V4 variable regions was done to assess the diversity, structures, taxonomic biomarkers, and classification of the VM community. The primary outcome was the location of the early pregnancy. The VM community in women with a TP showed higher diversity (PD-whole-tree, median: 8.26 vs. 7.08, P = 0.047; Shannon Diversity Index, median: 1.43 vs 0.99, P = 0.03) and showed different structures to those in women with an intrauterine pregnancy (IUP) (R = 0.23, P < 0.01). Bacteria of the genus Lactobacillus were significantly enriched in the IUP group, whereas bacteria of the genera Gardnerella and Prevotella were significantly enriched in the TP group. Lactobacillus abundance could be used to classify the pregnancy location (AUC = 0.81). Non-Lactobacillus-dominated microbiota (≤ 0.85% Lactobacillus) was significantly associated with a TP (adjusted odds ratio: 4.42, 95% confidence interval: 1.33 to 14.71, P = 0.02). In conclusion, among women with a symptomatic early pregnancy, a higher diversity and lower abundance of Lactobacillus in the VM is associated with a TP.

Caprin-1 promotes HepG2 cell proliferation, invasion and migration and is associated with poor prognosis in patients with liver cancer.

The present study aimed to investigate the role of caprin-1 in liver cancer and its association with the clinicopathological features and prognosis of liver cancer, as well as the underlying mechanism of caprin-1 function. Caprin-1 expression levels in a tissue microarray containing 40 liver cancer tissues, 10 peritumoral tissues and 20 normal liver tissues were analyzed using immunohistochemistry. The clinical data of 154 patients with liver cancer were also collected from The Cancer Genome Atlas database. Kaplan-Meier analysis and a Cox proportional hazards regression model were used to assess the association between caprin-1 expression levels and survival in patients with liver cancer. The effects of caprin-1 knockdown on the mRNA levels of cyclin D1 and cyclin D2 as well as the proliferation, invasion and migration of HepG2 cells were also investigated. The expression level of caprin-1 in liver cancer tissues was significantly higher compared with normal liver tissues or cells (P<0.01). High caprin-1 expression levels were associated with advanced clinical stage (P<0.001) and enhanced tumor invasion (P<0.001). Kaplan-Meier analysis showed that the overall survival time and disease-free survival time in patients with liver cancer with high caprin-1 expression were significantly shorter compared with patients with low caprin-1 expression levels (P=0.002 and P=0.033, respectively). The Cox proportional hazards regression model showed that high caprin-1 expression levels were an independent prognostic factor for liver cancer (P<0.001). Knockdown of caprin-1 in HepG2 cells significantly downregulated mRNA expression levels of cyclin D1 and cyclin D2, inhibited cell proliferation and invasion and the cells were arrested at G0/G1 phase. In conclusion, caprin-1 may be a novel prognostic indicator for patients with liver cancer.

Different effects of acetyl-CoA carboxylase inhibitor TOFA on airway inflammation and airway resistance in a mice model of asthma.

BACKGROUND AND OBJECTIVE: Acetyl CoA carboxylase (ACC) regulates the differentiation of Th1, Th2, Th17 cells and Treg cells, which play a critical role in airway inflammation of asthma. Here we investigated the role of ACC in the pathogenesis of asthma. METHODS: Chicken Ovalbumin-sensitized and -challenged mice were divided into three groups, PBS group, DMSO (solvent of TOFA) group and ACC inhibitor 5-tetradecyloxy-2-furoic acid (TOFA) + DMSO group. Airway inflammation was assessed with histology, percentages of CD4+T cell subsets in lung and spleen was assessed with flow cytometry, and airway responsiveness was assessed with FinePointe RC system. The expression of characteristic transcription factors of CD4+T cell subsets was evaluated with real-time PCR. Cytokine levels in bronchoalveolar lavage fluid (BALF) and serum was determined with ELISA. RESULTS: In asthma mice, the expression of ACC increased, while the expression of phosphorylated ACC (pACC) decreased. TOFA had no significant effect on pACC expression. TOFA reduced serum IgE, airway inflammatory cells infiltration and goblet cell hyperplasia, but dramatically increased airway responsiveness. TOFA significantly reduced the percentages of Th1, Th2, Th17 cells in lung and spleen, the expression of GATA3 and RORγt in lung, and IFN-γ, IL-4, IL-17A levels in BALF and serum. TOFA had no significant effect on the percentage of Treg cells, IL-10 level and the expression of T-bet and Foxp3. CONCLUSION: Acetyl-CoA carboxylase inhibitor TOFA might have a distinct effect on asthmatic airway inflammation and airway hyperresponsiveness.

Optimal harvesting of a competitive n-species stochastic model with delayed diffusions.

In this study, we propose an n-species stochastic model which considers the influences of the competitions and delayed diffusions among populations on dynamics of species. We then investigate the stochastic dynamics of the model, such as the persistence in mean of the species, and the asymptotic stability in distribution of the model. Then, by using the Hessian matrix and theory of optimal harvesting, we investigate the optimal harvesting problem, obtaining the optimal harvesting effort and the maximum of expectation of sustainable yield (ESY). Finally, we numerically discuss some examples to illustrate our theoretical findings, and conclude our study by a brief discussion.

Downregulation of lncRNA TUBA4B is Associated with Poor Prognosis for Epithelial Ovarian Cancer.

A host of studies have revealed that long non-coding RNAs (lncRNAs) are critically involved in the development and progression of epithelial ovarian cancer. LncRNA TUBA4B is recently identified to be a critical mediator in non-small cell lung cancer. However, the clinical roles and biological functions of lncRNA TUBA4B in epithelial ovarian cancer have yet to be fully clarified. The present study was conducted to explore the expression of lncRNA TUBA4B in human epithelial ovarian cancer tissues and potential roles of lncRNA TUBA4B in ovarian cancer cells. The matched epithelial ovarian cancer specimens and adjacent normal tissues were employed to detect the expression of lncRNA TUBA4B. The prognostic value of lncRNA TUBA4B for tumor progression and survival rate was investigated. The effects of lncRNA TUBA4B on ovarian cancer cell proliferation and migration were also explored. The expression of lncRNA TUBA4B was significantly decreased in epithelial ovarian cancer tissue specimens. The low lncRNA TUBA4B level was closely related with pathological grade, FIGO stage and lymph node metastases, and serum CA125 level. Enforced expression of lncRNA TUBA4B obviously reduced the proliferation of SKOV3 cells, and attenuated the activation of ERK and Akt signaling pathways. Our data demonstrate for the first time that lower lncRNA TUBA4B may be a novel independent prognostic biomarker for overall survival of epithelial ovarian cancer. Overexpression of lncRNA TUBA4B inhibits the proliferation of ovarian cancer cells. LncRNA TUBA4B may be an important target for therapeutic intervention in ovarian cancer.

Overexpression of salusin-ß is associated with poor prognosis in ovarian cancer.

Ovarian cancer is recognized as one of the worst gynecologic malignancies associated with rapid metastasis and poor overall survival rate. The identified valuable molecular biomarkers criticize importance of timely diagnosis for ovarian cancer. Salusin-ß levels are dramatically increased in women with polycystic ovarian syndrome. However, the roles of salusin-ß in ovarian cancer have yet to be fully elucidated. A total of 57 paired ovarian cancer specimens and matched adjacent normal tissues were used to measure the salusin-ß levels. The prognostic value of salusin-ß for tumor progression and survival rate was investigated. The effects of salusin-ß on ovarian cancer cell proliferation and epithelial-mesenchymal transition were also explored. The expression of salusin-ß was significantly increased in ovarian cancer tissue specimens compared with matched normal adjacent tissue (P<0.05). The high salusin-ß level was closely related with FIGO stage and lymph node metastases. The ovarian cancer patients with high salusin-ß had a shorter overall survival (P<0.05). Salusin-ß obviously enhanced the proliferation and epithelial mesenchymal-transition of SKOV3 cells. Furthermore, salusin-ß substantially decreased the expression of p-GSK-3ß and GSK-3ß, but stimulated the ß-catenin expression and downstream genes of wnt/ß-catenin including cyclin D1 and C-myc. Our data demonstrated for the first time that upregulated salusin-ß may be a novel independent prognostic biomarker for overall survival of ovarian cancer. Salusin-ß accelerated the proliferation and epithelial mesenchymal transition of ovarian cancer cells at least partly via activation of Wnt/ß-catenin signaling pathway. Salusin-ß may be an important target for therapeutic intervention in ovarian cancer.

Neuroprotective effect of interleukin-6 regulation of voltage-gated Na(+) channels of cortical neurons is time- and dose-dependent.

Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL) and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours) by studying voltage-gated Na(+) channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na(+) currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na(+) channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.