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Extracellular vesicles (EVs) are nanoparticles that include exosomes, microvesicles, and apoptotic bodies; they interact with target cell surface receptors and transport contents, including mRNA, proteins, and enzymes into the cytoplasm of target cells to function. The biological fingerprints of EVs practically mirror those of the parental cells they originated from. In the bone remodeling microenvironment, EVs could act on osteoblasts to regulate the bone formation, promote osteoclast differentiation, and regulate bone resorption. Therefore, there have been many attempts wherein EVs were used to achieve targeted therapy in bone-related diseases. Periodontitis, a common bacterial infectious disease, could cause severe alveolar bone resorption, resulting in tooth loss, whereas research on periodontal bone regeneration is also an urgent question. Therefore, EVs-related studies are important for periodontal bone remodeling. In this review, we summarize the current knowledge of mesenchymal stem cell-EVs involved in periodontal bone remodeling and explore the functional gene expression through a comparative analysis of transcriptomic content.

With the advancement of society and people’s knowledge of oral health, the prevention of oral illnesses such as dental caries, periodontal disease, oral cancer, oral mucosal disease, salivary gland disease, and so on has become the primary focus of current health status and treatment. Although treatment for these diseases has focused on removing lesions or inhibiting progression, early detection has always been the focus of clinical research. And the non-invasive diagnosis is now the primary goal of clinical diagnosis. Meanwhile, the electrochemical approach can satisfy this need while also achieving a speedy and reliable diagnosis, giving patients a more comfortable option. And noninvasive detection of specific diseases can be achieved by detecting markers carried in body fluids. Therefore, in the context of disease, pathophysiological progress and electrochemical-assisted diagnosis form a close relationship, providing a basis for the detection of oral disease related indicators. As a result, this review comprehensively summarizes the detection and diagnosis of common oral diseases using electrochemical sensing technology and provides important insights for the development of electrochemical biosensors for the early detection of common oral diseases.

It is well understood that maintaining viable pulp is critical for tooth retention. This review focused on cell-free therapy based on extracellular vesicles (EVs), a novel minimally invasive treatment strategy for endodontic restoration.This study was conducted by searching mainstream electronic databases such as Web of Science and PubMed for relevant studies on the therapeutic role of odontogenic EVs in pulp healing published in the last five years.We selected 89 relevant articles and discovered that dental stem cells (DSCs) derived EVs (DSC-EVs) have become a research hotspot in oral regenerative medicine, with significant advantages over cell transplantation in terms of low immunogenicity, ease of isolation, preservation, and management. Here, we introduce in detail the therapeutic effects of DSC-EVs for pulp restoration from three perspectives: excellent odontogenic properties, clinical applications, and possible molecular mechanisms.This article contributes a new viewpoint to the field of regenerative endodontics.

Aims and objectives The purpose of this study was to understand the emotional intelligence level (EI) and negative emotional status of the front-line nurses in the epidemic situation and to further explore the relationship between them. Background During the COVID-19 epidemic, under the influence of multiple factors, nurses were vulnerable to negative emotions. While previous studies have explored, the role of emotional intelligence in negative emotions, the relationship between the two has not been sufficiently discussed in the context of COVID-19. Design The study carried out a cross-sectional survey. The STROBE was selected as the checklist in this study. Methods 202 nurses from Wuhan makeshift hospital participated in the questionnaire survey. Data collection tools included a general data questionnaire designed by the researchers, Chinese version of EI scale (WLEIS-C) and Chinese version of Depression Anxiety Stress Scale (DASS-21). Descriptive statistics, single factor analysis and correlation analysis were used to analyse the data. Results The emotional intelligence of the front-line nurses was in the upper middle range. Among the negative emotions, anxiety was the most prominent symptom. Conclusions Managers should pay attention to the negative emotional problems of front-line nurses, improve their EI level and promote mental health and the progress of epidemic prevention. Relevance to clinical practice Improving the level of emotional intelligence can reduce the frequency and intensity of negative emotions. In clinical work, emotional intelligence can be used as a skill to carry out relevant training, which is conducive to playing a positive role in future emergencies.

BackgroundThe significance of spiritual care competence among nurses has been emphasized across countries and cultures in many studies. However, there were few studies on correlations among spiritual care competence, spiritual care perceptions, and spiritual health of nurses in China.ObjectiveTo investigate spiritual care competence, spiritual care perceptions, and spiritual health, and examine the correlations among spiritual care competence, spiritual care perceptions and spiritual health, and the mediating role of spiritual health between other two variables of Chinese nurses.MethodsA cross-sectional and correlational design was implemented, and the STROBE Checklist was used to report the study. A convenience sample of 2,181 nurses were selected from 17 hospitals in 3 provinces, China. Participants provided data on sociodemographic by completing the Chinese Version of the Spiritual Care Competence Scale, the Chinese Version of the Spiritual Care-Giving Scale, and the Spiritual Health Scale Short Form. Descriptive statistics, univariate, multiple linear regression, and Pearson correlation analysis were used to analyze data.ResultsThe total scores of spiritual care competence, spiritual care perceptions, and spiritual health were 58.25 ± 16.21, 144.49 ± 16.87, and 84.88 ± 10.57, respectively, which both were moderate. Spiritual care competence was positively correlated with spiritual care perceptions (r = 0.653, p < 0.01) and spiritual health (r = 0.587, p < 0.01). And spiritual health played a mediating role between the other two variables (accounting for 35.6%).Significance of resultsThe spiritual care competence, spiritual care perceptions, and spiritual health of Chinese nurses need to be improved. It is recommended that nursing managers should pay attention to spiritual care education of nurses, and improve spiritual care perceptions and spiritual health in multiple ways, so as to improve their spiritual care competence and to maximize the satisfy spiritual care needs of patients in China.

The etiology of nasopharyngeal carcinoma (NPC) is multifactorial, complex and not fully characterized yet. MicroRNAs (miRNAs or miRs) have been found to contribute to the development and progression of NPC. Here, we aimed to investigate the putative role of miR-129-5p in NPC lymphangiogenesis and lymph node metastasis (LNM), including the involvement of its target gene ZIC2 and the Hedgehog signaling pathway. The expression of miR-129-5p and ZIC2 in primary NPC tissues was assessed using RT-qPCR and Western blot analyses, followed by LNM and lymph vessel density (LVD) correlation analyses. A direct interaction between miR-129-5p and ZIC2 was verified using a dual-luciferase reporter assay. Gain- and loss-of-function experiments were conducted to investigate the effects of miR-129-5p and ZIC2 expression on NPC cell invasion, migration and proliferation in vitro, as well as on LDV and LNM in nude mice in vivo. Additionally, RT-qPCR and Western blot analyses were performed to determine the expression levels of Hedgehog signaling pathway-related factors. We found that ZIC2 was highly expressed, and miR-129-5p was lowly expressed, in primary NPC tissues. In addition, we found that miR-129-5p can directly bind to and reduce ZIC2 expression. LVD was found to be negatively correlated with miR-129-5p and to be positively correlated with ZIC2 expression. Concomitantly, we found that miR-129-5p abrogated activation of the Hedgehog signaling pathway via ZIC2 targeting, leading to suppression of NPC cell invasion, migration and proliferation in vitro as well as suppression of LNM and LVD in vivo. From our data we conclude that miR-129-5p, by decreasing ZIC2 expression, may inhibit NPC lymphangiogenesis and LNM through suppression of the Hedgehog signaling pathway.

Extracellular vesicles (EVs) are 30-150 nm in diameter vesicles released by cells that serve important intercellular regulatory functions. EVs include exosomes and microvesicles. Exosomes form in multivesicular bodies and are released extracellularly as the multivesicular bodies fuse with the plasma membrane. Microvesicles bud directly from the plasma membrane. Here, we examine methods that are available or emerging to detect and study EVs during orthodontic tooth movement (OTM). EV's involvement in regulating bone remodelling associated with OTM may be demonstrated by adding isolated EVs to an animal model to change the rate of tooth movement. Exosomes in multivesicular bodies might be detected by immunogold labelling of markers in sections from the tooth and jaw and detection by electron microscopy. Gingival crevicular fluid (GCF) is enriched in EVs. Detection and characterization of EVs released by osteoclasts during resorption have been described, and this information could be used to analyse EVs in OTM models. Regulatory EVs may be enriched in the GCF from teeth that are being moved or are undergoing root resorption. Emerging approaches, including nanoparticle tracking, ExoView and micro- and nanofluidics, show promise for studying EVs in the GCF. Techniques that amplify signal, including polymerase chain reaction (PCR), provide the sensitivity necessary to utilize EVs from GCF as biomarkers. Studies of the role of EVs in OTM will provide fresh insight that may identify means for enhancing OTM procedures. EVs in GCF may include biomarkers for bone remodelling during OTM, orthodontic-associated root resorption, and other dental pathologies.

Compared with men, female accounts for a larger proportion of patients with depression. Behavioral genetics researches find gender differences in genetic underpinnings of depression. We found that gender differences exist in heritability and the gene associated with depression after reviewing relevant research. Both genes and gene-environment interactions contribute to the risk of depression in a gender-specific manner. We detailed the relationships between serotonin transporter gene-linked promoter region (5-HTTLPR) and depression. However, the results of these studies are very different. We explored the reasons for the contradictory conclusions and provided some suggestions for future research on the gender differences in genetic underpinnings of depression.

Extracellular vesicles (EVs) are 30-150 nm in diameter and are released by cells into the extracellular environment. They facilitate intercellular communication and may be involved in cell survival. Although serum-dependent cells are not obviously affected by depletion of EVs from the serum, we previously reported that cells in serum that contain EVs were more resistant to the drugs, enoxacin and bis-enoxacin, compared to cells in serum without EVs. This change in resistance led us to examine whether EVs are sufficient to maintain serum dependent cells in vitro. Here, we tested the effect of EVs on the survival RAW 264.7 cells and on 4T1 murine breast cancer cells. EVs were isolated by differential centrifugation. EVs were counted over various time periods. Cells were grown in alpha or Dulbecco’s minimal essential media supplemented with FBS, EVs from various sources, or with no supplements. Cell growth was determined by cell counts. In media without supplementation, the RAW 264.7 cells and 4T1 cells died by three days. Media supplemented with EVs from FBS allowed the cells to survive in the absence of FBS for one week or more. Being able to perform experiments on cells supported by EVs will simplify the interpretation of experiments. Efforts are underway to determine their mechanism by which EVs support cell survival.

Renal ischemia/reperfusion (I/R) is a common cause of acute renal failure in many clinical settings. Our study aimed to elucidate the role of lentiviral vector-mediated KSR1 gene silencing in inflammatory factor expression and proliferation of renal tubular epithelial cells (RTECs) in a rat model of I/R injury. Male Sprague-Dawley (SD) rats were used for I/R model establishment and subject to different treatments, followed by the measurement of neurological severity score (NSS), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, 47-kDa heat-shock protein (HSP47), KSR1, and factors related to the Ras/MAPK pathway, as well as cell apoptosis. As compared with the blank group, the neurologic impairment induced by I/R in the siKSR1, U0126, and siKSR1 + U0126 groups was alleviated. Compared with the control group, the other five groups showed increased levels of TNF-α, IL-6, IL-1β, HSP47, N-ras, Raf-1, c-fos, TNF-α, IL-6, p38 MAPK, and cell apoptosis, accompanied by a declined mRNA and protein level of Bcl-2. As compared with the blank and NC groups, the siKSR1, U0126, and siKSR1 + U0126 groups showed decreased levels of TNF-α, IL-6, IL-1β, HSP47, N-ras, Raf-1, c-fos, TNF-α, IL-6, p38 MAPK, cleaved caspase-3, cleaved caspase-9, p53, and cell apoptosis, accompanied by an increased mRNA and protein level of Bcl-2. Our findings demonstrated that KSR1 gene silencing might inhibit the expression of inflammatory factors in RTECs and promote their proliferation by inactivating the Ras/MAPK pathway in the rat model of I/R injury.

Aucubin, an iridoid glycoside found in several plants, such as Eucommia ulmoide and Rehmannia, has various pharmacological effects. Bone formation is a complex process in which osteoblast differentiation plays an important role. This study aimed to investigate the promotion effects of aucubin on osteoblast differentiation in MG63 cells, a human osteoblast-like cell line. Aucubin not only improved osteoblast differentiation, as shown by enhanced ALP (alkaline phosphatase) concentration and mineralization in cells, but increased the expression of various cytokines, including collagen I, osteocalcin, osteopontin, integrin β1, and Osterix. Aucubin strongly enhanced the levels of BMP2 (bone morphogenetic proteins-2) in MG63 cells, which play a central role during osteoblast differentiation. Further data show that aucubin exposure after 1 day, 7 days, and 14 days enhanced the expression of Smad1, 5, and 8, and the phosphoresced levels of MAPKs (mitogen-activated protein kinases) family Erk (extracellular signal–regulated kinases), JNK (c-Jun-NH2-terminal kinases), P38, and Akt (serine/threonine protein kinase)/mTOR (mammalian target of rapamycin)/p70s6k in MG63 cells. This study shows the improved effects of aucubin on osteoblast differentiation in MG63 cells, related to the signaling of BMP2-mediated Smads (drosophila mothers against decapentaplegic proteins), MAPKs, and Akt/mTOR/p70S6K. This study indicates the potential of aucubin for osteoporosis treatment.

Background: Healthcare services are increasingly shifting from inpatient to outpatient settings. Outpatient settings such as emergency departments (EDs), oncology clinics, dialysis clinics, and day surgery often involve invasive procedures with the risk of acquiring healthcare-associated infections (HAIs). As a leading cause of HAI, Clostridioides difficile infection (CDI) in outpatient settings has not been sufficiently described in Canada. The Canadian Nosocomial Infection Surveillance Program (CNISP) aims to describe the epidemiology, molecular characterization, and antimicrobial susceptibility of outpatient CDI across Canada. Methods: Epidemiologic data were collected from patients diagnosed with CDI from a network of 47 adult and pediatric CNISP hospitals. Patients presenting to an outpatient setting such as the ED or outpatient clinics were considered as outpatient CDI. Cases were considered HAIs if the patient had had a healthcare intervention within the previous 4 weeks, and they were considered community-associated if there was no history of hospitalization within the previous 12 weeks. Clostridioides difficile isolates were submitted to the National Microbiology Laboratory for testing during an annual 2-month targeted surveillance period. National and regional rates of CDI were stratified by outpatient location. Results: Between January 1, 2015, and June 30, 2019, 2,691 cases of outpatient-CDI were reported, and 348 isolates were available for testing. Most cases (1,475 of 2,691, 54.8%) were identified in outpatient clinics, and 72.8% (1,960 of 2,691) were classified as community associated. CDI cases per 100,000 ED visits were highest in 2015, at 10.3, and decreased to 8.1 in 2018. Rates from outpatient clinics decreased from 3.5 in 2016 to 2.7 in 2018 (Fig. 1). Regionally, CDI rates in the ED declined in Central Canada and increased in the West after 2016. Rates in outpatient clinics were >2 times higher in the West compared to other regions. RT027 associated with NAP1 was most common among ED patients (26 of 195, 13.3%), whereas RT106 associated with NAP11 was predominant in outpatient clinics (22 of 189, 11.6%). Overall, 10.4% of isolates were resistant to moxifloxacin, 0.5% were resistant to rifampin, and 24.2% were resistant to clindamycin. No resistance was observed for metronidazole, vancomycin, or tigecycline. Compared to CNISP inpatient CDI data, outpatients with CDI were younger (51.8 ± 23.3 vs 64.2 ± 21.6; P < .001), included more females (56.4% vs 50.9%; P < .001), and were more often treated with metronidazole (63.0% vs 56.1%; P < .001). Conclusions: For the first time, CDI cases identified in outpatient settings were characterized in a Canadian context. Outpatient CDI rates are decreasing overall, but they vary by region. Predominant ribotypes vary based on outpatient location. Outpatients with CDI are younger and are more likely female than inpatients with CDI.Funding: NoneDisclosures: Susy Hota reports contract research for Finch Therapeutics.

Background Hypospadias, as a congenital disorder of the urethra, is the second most common birth abnormality of the male reproductive system. This study primarily investigates the effects of microRNA-494 (miR-494) on the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway and on the development of hypospadias by binding to neural precursor cell expressed developmentally downregulated gene 4-like (Nedd4L). Methods We induced a mouse model of hypospadias through di-(2-ethylhexyl) phthalate treatment. The underlying regulatory mechanisms of miR-494 in this model were analyzed upon treatment of miR-494 mimic, miR-494 inhibitor, or small interfering RNA against Nedd4L in urethral epithelial cells isolated from mice with hypospadias. We then verified the binding site between miR-494 and Nedd4L and applied a gain- and loss-of-function approach to determine the effects of miR-494 on cell proliferation, cycle distribution, and apoptosis. Results Male mice with hypospadias exhibited significantly higher miR-494 expression and lower Nedd4L expression in urethral tissues than normal male mice. Nedd4L was verified as a target gene of miR-494. Treatment with miR-494 inhibitor suppressed the activation of the TGF-β1/Smads signaling pathway, whereas down-regulation of miR-494 exerted protective effects on urethral epithelial cells by impeding cell proliferation and inducing cell apoptosis. Conclusions The study indicates that downregulation of miR-494 inhibits the TGF-β1/Smads signaling pathway and prevents the development of hypospadias through upregulating Nedd4L.

Constrained optimization problems are common in theoretical study and engineering practice. The constraint functions can be equality or inequality, convex or non-convex, which makes it difficult to find a constrained optimal solution. Evolutionary algorithms are powerful tools for constrained optimization problems. The balance between constraints and objective functions is always a difficult task and hotspot in EA-community. Many EA-based constraint handling methods have been proposed, but this problem is far to be completely solved.This paper presents a new view of constraint handling: A bi-level differential evolutionary algorithm (BLDE). BLDE has a bi-level structure, which deals with the constraints and searches optimal solutions separately. In the lower level, the objective is to find a population of candidate feasible solutions, and in the upper level, the objective is to search the global optimal solution. The proposed BLDE gets competitive results in 13 benchmark functions, with a comparison of two state-of-the-art constraint handling algorithms. BLDE shows the following advantages: 1) it is efficient in search constrained optimal solutions; 2) it is easy to implement and requires few hyper-parameters; 3) it can guarantee the obtained solutions are feasible or close to feasible.

Liver fibrosis is a common pathological process of various chronic liver injury. It is the early stage of liver cirrhosis. Therefore, It is particularly important to diagnose and monitor liver fibrosis. Liver biopsy is the gold standard for diagnosis of liver fibrosis and liver cirrhosis, but cannot be used as the first choice for screening because of its invasiveness. Elastography has unique advantages. Including the simple method, no radiation, no trauma and real time, so it has been widely recognized by clinicians. This paper introduces the elastography technology used in the diagnosis of hepatic fibrosis, including transient elastography, real-time tissue elastography, acoustic radiation force impulse imaging (ARFI) and real-time shear wave elastography. Its application, advantages and disadvantages are also reviewed.

Objective: To explore the application value of real-time elastography (RTE) in the diagnosis of breast cancer. Methods: Forty patients with breast cancer who were treated by the first hospital of Jilin University were selected. All the patients were diagnosed by RTE and pathology. The pathological diagnosis was used as the gold standard to evaluate the benign and malignant tumors. The receiver operating characteristic curve (ROC curve) was used to evaluate the value of RTE in the diagnosis of breast lesions. Results: Of the 52 lesions, 33 were benign and 19 were malignant. Ratio-max and Ratio-mean were significantly different between the benign and malignant groups (P

The optimization of a complex system with multiple subsystems is a tough problem. In this paper, a Decentralized differential evolutionary algorithm (DDEA) is proposed. The simulations for both DDEA and centralized DE on three benchmark functions are carried out. The numerical results show that DDEA is efficient to solve decentralized optimization problems. On these problems, the proposed DDEA outperforms centralized DE in convergence.

In the present study, we aimed to evaluate the single or conjoint effects of Lactococcus lactis (L. lactis) L19 and Enterococcus faecalis (E. faecalis) W24 isolated from the intestine of Channa argus (C. argus) on digestive enzyme activity, antioxidant capacity, intestinal microbiota and morphology of C. argus (initial weight, 9.50 ± 0.03 g). The fish were fed for 56 days with a basal diet (CK) or diets supplemented with 1.0 × 108 CFU/g of L. lactis (L19), E. faecalis (W24), L. lactis + E. faecalis (L + W). Results indicated that these three lactic acid bacteria (LAB) supplementary diets especially the L19 produced significant improvement in the digestive enzyme activity (protease, amylase and lipase) in liver, stomach and intestine compared with control (P

This study aimed to investigate the expression of c-Fos and matrix metallopeptidase 9 (MMP-9) in dental pulp of patients receiving orthodontic treatment via wire appliance.Fifteen patients (30 teeth in total) were randomly assigned to five groups: t = 0, t = 1, t = 4, t = 8 and t = 12 (n = 6). The first maxillary premolars of patients in the t = 0 group were extracted without any orthodontic treatment. An intrusive force of 300 g was applied on first maxillary premolars in the other four groups via wire appliances. This force was maintained for 1 week for t = 1 group, 4 weeks for t = 4 group, 8 weeks for t = 8 group, or 12 weeks for t = 12 group, before the teeth were extracted.The expression of c-Fos and MMP-9 in the pulps of each group was analyzed by immunohistochemical staining and real-time PCR. The relationship in the protein expression between c-Fos and MMP-9 in the dental pulp was analyzed by Pearson correlation analysis.Intrusive force of 300 g increased the expression of both c-Fos and MMP-9 in the dental pulp. The protein expression of MMP-9 in the dental pulp was significantly correlated with the expression of c-Fos (P < .001).Extreme intrusive force upregulates c-Fos and MMP-9 expression in the dental pulp. Moreover, protein expression of c-Fos and MMP-9 is significantly correlated under intrusive force.

Enoxacin and its bone-seeking bisphosphonate derivative, bis-enoxacin, have recently captured attention as potential therapeutic agents for the treatment of cancer and bone disease. No differences in growth or survival of 4T1 murine breast cancer cells were detected at a concentration of 50 µM of enoxacin or bis-enoxacin. Growth was perturbed at higher concentrations. Both 50 µM enoxacin and bis-enoxacin stimulated increases in the number of GW/Processing bodies, but there were minimal changes in microRNA levels. Extracellular vesicles (EVs) released from 4T1 cells treated with 50 µM enoxacin or 50 µM bis-enoxacin stimulated proliferation of RAW 264.7 cells, and both significantly inhibited osteoclastogenesis in calcitriol-stimulated mouse marrow. EVs from 4T1 cells treated with enoxacin and bis-enoxacin displayed small reductions in the amount of microRNA (miR)-146a-5p and let-7b-5p. In marked contrast, miR-214-3p, which has been shown to regulate bone remodeling, was increased 22-fold and 30-fold respectively. We conclude that enoxacin and bis-enoxacin trigger the release of EVs from 4T1 cancer cells that inhibit osteoclastogenesis.

Objective: To evaluate the accuracy and clinical application value of color Doppler ultrasound in the diagnosis of accessory renal artery (ARA) stenosis. Methods: a retrospective analysis on 80 patients from January 2014 to November 2017, due to hypertension in our hospital. All of them accepted ultrasound examination, preliminary diagnosis with suspected accessory renal artery or accessory renal artery stenosis and underwent CTA scan within 2 weeks. We record the number of accessory renal artery, origin, course, stenosis. Results: 80 cases of patients with 86 accessory renal arteries. Taking CTA as the reference standard, in the 54 right accessory renal arteries, 36 with stenosis confirmed by CTA, ultrasound confirmed 34(34/36), the diagnosis rate was 94.4%, 32 left accessory renal arteries, 20 with stenosis confirmed by CTA, ultrasound diagnosed 12(12/20) with diagnosis rate 60%. Conclusion: color Doppler ultrasound can be used as the main means of screening accessory renal artery and accessory renal artery stenosis, but in ectopic origin of accessory renal artery, with relatively higher missed diagnosis rate, if necessary with CTA or DSA.

Tongue cancer is one of the most common and deadly types of head and neck cancer. The incidence of tongue cancer has been particularly high and remained been increasing in some countries. A main reason for poor prognosis and clinical outcome for tongue cancer was its resistance to chemotherapies, behind which the mechanisms have been not clear. In this review, we summarized literatures published in recent years and listed the proteins, biomacromolecules, and signaling pathways related to this drug resistance. We hoped that this summary could provide reference for researchers to develop new treatment strategies for tongue cancer.