The efficacy and mechanism of positive psychological intervention on well-being for colostomy patients: a randomized controlled trial.

AIMS: The positive psychology intervention (PPI) is an effective therapy designed to motivate individuals' positive quality and power, to help them survive in an adverse situation, and to establish a high-quality personal and social life. This study aims to evaluate the efficacy and mechanism of PPI on the psychological capital, psychological distress, and life satisfaction among colostomy patients. METHODS: Patients (n = 120) with permanent stomas were recruited and randomly assigned into two groups. Patients in the experimental group (n = 60) received standard care and PPI, whereas patients in the control group (n = 60) only received standard care. The psychological capital, psychological distress, and life satisfaction were measured and compared between two groups before the intervention, the immediate post-intervention, and follow-up. RESULTS: All 120 patients completed the study. The hope, optimism, resilience, psychological distress, and life satisfaction score of the experimental group were significantly higher than those of the control group at T1 and T2 (P < 0.05). Self-efficacy score of the experimental group had no significant difference at the two time points after the intervention than the control group (P > 0.05). Changes in hope and resilience which belong to psychological capital mediated the intervention's efficacy on changes in PPI on life satisfaction (ß = 0.265, P = 0.005; ß = 0.686, P = 0.002). CONCLUSIONS: PPI could effectively improve psychological capital, psychological distress, and life satisfaction among patients with stomas. Besides, our findings add novel support that increased hope and resilience are the active ingredients that promote intervention change.

Network meta-analysis of the optimal time of applying enteral immunonutrition in esophageal cancer patients receiving esophagectomy.

BACKGROUND: Enteral immunonutrition (EIN) has been extensively applied in cancer patients; however, its role in esophageal cancer (EC) patients receiving esophagectomy remains unclear. We performed this network meta-analysis to investigate the impact of EIN on patients undergoing surgery for EC and further determine the optimal time of applying EIN. METHODS: We searched PubMed, EMBASE, Cochrane library, and China National Knowledgement Infrastructure (CNKI) to identify eligible studies. Categorical data was expressed as the odds ratio with 95% confidence interval (CI), and continuous data was expressed as mean difference (MD) with 95% CI. Meta-analysis with head-to-head approach and network meta-analysis was performed to evaluate the impact of EIN on clinical outcomes using RevMan 5.3 and ADDIS V.1.16.8 software. The surface under the cumulative ranking curve (SUCRA) was calculated to rank all nutritional regimes. RESULTS: Total 14 studies involving 1071 patients were included. Meta-analysis with head-to-head approach indicated no difference between EIN regardless of the application time and standard EN (SEN); however, subgroup analyses found that postoperative EIN was associated with decreased incidence of total infectious complications (OR = 0.47; 95%CI = 0.26 to 0.84; p = 0.01) and pneumonia (OR = 0.47; 95%CI = 0.25 to 0.90; p = 0.02) and shortened the length of hospitalization (LOH) (MD = - 1.01; 95%CI = - 1.44 to - 0.57; p < 0.001) compared to SEN, which were all supported by network meta-analyses. Ranking probability analysis further indicated that postoperative EIN has the highest probability of being the optimal option in terms of these three outcomes. CONCLUSIONS: Postoperative EIN should be preferentially utilized in EC patients undergoing esophagectomy because it has optimal potential of decreasing the risk of total infectious complications and pneumonia and shortening LOH. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/KJ9UY.

Dynamical response and vibrational resonance of a tri-stable energy harvester interfaced with a standard rectifier circuit.

This paper investigates the dynamical response and vibrational resonance (VR) of a piecewise electromechanically coupled tri-stable energy harvester (TEH), which is driven by dual-frequency harmonic excitations. To achieve a stable DC output, the TEH is interfaced with a standard rectifier circuit. Using the harmonic balance method combined with the separation of fast and slow variables, a steady-state response together with the analytical expressions of displacement and harvested power is derived. The multi-solution feature in the amplitude-frequency response is observed and can improve the harvesting performance of the TEH under a low-frequency environment. There is an optimal time constant ratio and electromechanical coupled coefficient to maximize the harvested DC power. Meanwhile, the VR phenomenon of the TEH is explored through the response amplitude of the low-frequency input signal, which implies that an appropriate combination can induce the occurrence of VR and improve the rectified voltage. Similarly, the nonlinear stiffness coefficients can be adjusted by changing the magnet distance to induce the appearance of VR. The theoretical solutions are well supported by numerical simulation and experimental verification. Specifically, the theoretical analysis and experimental evidence illustrate that the harvested power under the VR effect is much higher than that without VR.

The chain mediating role of social support and stigma in the relationship between mindfulness and psychological distress among Chinese lung cancer patients.

PURPOSE: Psychological distress greatly impaired the psychological and physical well-being of lung cancer patients. Identification of protective and risk factors is a prerequisite of developing effective psychological treatment protocol. The study aims to determine the relationship of mindfulness and psychological distress and further clarify the mechanism of mindfulness against psychological distress through perceived stigma and social support among Chinese lung cancer patients. METHOD: A cross-sectional survey study involving 441 valid Chinese lung cancer patients was conducted from September 2018 to August 2019. After all validated questionnaires that measured psychological distress, level of mindfulness, social support, and perceived stigma were returned by patients, we firstly performed correlation analysis to assess the associations between mindfulness, social support, perceived stigma, and psychological distress. Then structural equation modelling analysis was conducted to further clarify the mediating effects of perceived stigma and social support on the relationship between mindfulness and psychological distress. RESULTS: According to our hypothesis and further modification, our revised model adequately fits to data. Mindfulness (ß = - 0.107, p = 0.008) and social support (ß = - 0.513, p < 0.001) had a direct effect on psychological distress. Meanwhile, mindfulness had a direct effect on perceived stigma (ß = - 0.185, p < 0.001), and perceived stigma had a direct effect on social support (ß = - 0.373, p < 0.001). Furthermore, mindfulness had also the indirect effect on psychological distress through the chain mediating role of stigma and social support among lung cancer patients. CONCLUSIONS: Mindfulness has direct negative effect on psychological distress and has also indirectly negative psychological distress through impacting social support and perceived stigma.

CircRNA hsa_circ_0030018 regulates the development of glioma via regulating the miR-1297/RAB21 axis.

Circular RNAs (circRNAs) play a crucial role in tumor occurrence and progression. And the dysregulated circRNAs are reported to be relevant to glioma development. Nevertheless, the function and regulatory mechanism of hsa_circ_0030018 in glioma progression are largely indistinct. The abundances of hsa_circ_0030018, miR-1297, and RAB21 were detected using quantitative real-time polymerase chain reaction or western blot. Cell proliferation was assessed via colony formation assay and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis and cell cycle progression were evaluated by flow cytometry. Cell migration and invasion were examined using transwell assay and wound healing assay. The protein levels were measured by western blot. The interaction between miR-1297 and hsa_circ_0030018 or RAB21 was validated via dual-luciferase reporter analysis, RNA immunoprecipitation (RIP), and RNA pull-down assays. A xenograft model experiment was performed to analyze the function of hsa_circ_0030018 on tumor growth in vivo. hsa_circ_0030018 and RAB21 levels were enhanced, and the miR-1297 level was reduced in glioma tissues and cells. The silence of hsa_circ_0030018 or overexpression of miR-1297 impeded cell proliferation, metastasis, and expedited cell apoptosis and cycle arrest in glioma cells. Furthermore, hsa_circ_0030018 modulated glioma malignant behaviors via sponging miR-1297, and miR-1297 suppressed glioma development via targeting RAB21. Moreover, hsa_circ_0030018 knockdown inhibited tumor growth in vivo. The hsa_circ_0030018 knockdown repressed glioma progression by mediating the miR-1297/RAB21 pathway, providing potential therapeutic targets for glioma treatment.

Development and psychometric evaluation of the colostomy disgust scale in patients with colostomy.

OBJECTIVE: To establish and validate the Colostomy Disgust Scale (CDS) for assessing disgust in colostomy patients. DESIGN: Triphasic, cross-sectional psychometric study. SETTING: A total of 423 patients with colostomy (222 first samples and 201 s samples) were recruited from a tertiary hospital between January 2015 and April 2016. METHODS: Three phases were undertaken: (a) item generation, (b) item selection and (c) evaluation and validation. The evaluation and validation of the CDS were performed through feasibility and initial item analysis, exploratory factor analysis, confirmatory factor analysis and internal consistency. RESULTS: Following item generation and item selection, a 22-item CDS was generated. Principal axis factoring indicated a two-factor solution for the proposed CDS model, which was also verified by confirmatory factor analysis. Moreover, the proposed CDS had a high internal consistency. CONCLUSION: The CDS is a self-report instrument with initial evidence for its validity and reliability. It is a promising tool to identify the triggers of disgust in colostomy contexts, which can be of great importance for promoting the mental health of colostomy patients.

Extracting non-Gaussian governing laws from data on mean exit time.

Motivated by the existing difficulties in establishing mathematical models and in observing state time series for some complex systems, especially for those driven by non-Gaussian Lévy motion, we devise a method for extracting non-Gaussian governing laws with observations only on the mean exit time. It is feasible to observe the mean exit time for certain complex systems. With such observations, we use a sparse regression technique in the least squares sense to obtain the approximated function expression of the mean exit time. Then, we learn the generator and further identify the governing stochastic differential equation by solving an inverse problem for a nonlocal partial differential equation and minimizing an error objective function. Finally, we verify the efficacy of the proposed method by three examples with the aid of the simulated data from the original systems. Results show that our method can apply to not only the stochastic dynamical systems driven by Gaussian Brownian motion but also those driven by non-Gaussian Lévy motion, including those systems with complex rational drift.

Self-disgust and stigma both mediate the relationship between stoma acceptance and stoma care self-efficacy.

AIM: This paper is a report of a study exploring the relationship between stoma acceptance and stoma care self-efficacy in patients with colostomy and whether self-disgust and stigma play mediating roles in this relationship. DESIGN: A cross-sectional survey design. METHOD: In all, 476 participants were recruited from a tertiary hospital and completed structured, anonymous, self-report measures of stoma acceptance, self-disgust, stigma, and stoma care self-efficacy between January 2016-March 2017. RESULTS: Stoma acceptance was significantly negatively associated with personal disgust (r = -.640, p<.001), behavioural disgust (r = -.384, p<.001), and stigma (r = -.309, p<.001) and significantly positively associated with stoma care self-efficacy (r = .689, p<.001). Furthermore, regression-based mediation modelling showed that personal disgust and stigma had significant mediating effects on stoma acceptance and stoma care self-efficacy. CONCLUSION: We demonstrated, for the first time, that emotional responses (self-disgust and stigma) play important roles in the association between stoma acceptance and stoma care self-efficacy. Addressing concerns about emotional disorder should become part of the routine care for patients with stoma. IMPACT: Patients with colostomy must cope with many challenges and undergo profound changes in daily life. Acceptance of the existence of the stoma and effective management of the stoma can aid patients in the return to a full and active life. Illness acceptance and psychological states have been widely reported to be correlates of the ability to successfully reconstitute a meaning of life, but these have not been specifically explored in patients with colostomy. This study examined the effect of stoma acceptance on stoma care self-efficacy with the mediation role of self-disgust and stigma. Evidence of the relationship between illness acceptance and self-efficacy could offer practitioners to consider emotional factors like self-disgust and stigma when aiming to improve stoma care and management.

Questionnaire for the Assessment of Self-Disgust: The psychometric testing among mental disorders in China.

Research on self-disgust is relevant to psychopathologic tendencies because it has been shown to play a critical role in several mental disorders. Examining self-disgust and exploring its role in mental health are significant goals. The purpose of this study was to translate the Questionnaire for the Assessment of Self-Disgust (QASD) into Chinese and evaluate its validity and reliability. The translation and validation of the QASD were guided by the World Health Organization's Process of Translation and Adaptation of Instruments. Three phases were undertaken: (a) professional translation and expert panel review, (b) pretesting, and (c) psychometric evaluation. The psychometric evaluation was tested among 1,068 patients who were recruited from two psychiatric hospitals and three psychological clinics of tertiary hospitals. In this study, multigroup confirmatory factor analysis (CFA) supported the two-factor structure of the original QASD construct. Measurement invariance showed that the QASD is invariant across the patients with heterogeneous mental health diagnoses. The correlation of QASD with the Self-Esteem Scale (SES) and the Trait Anger Scale (TAS) showed that it has good convergent validity and discriminative validity. Internal consistency and test-retest yielded acceptable results. Thus, the findings suggest that the Chinese version of the QASD is a reliable and valid instrument with adequate psychometric properties for assessment of self-disgust among patients with mental disorders in China.

Stochastic resonance and bifurcations in a harmonically driven tri-stable potential with colored noise.

Stochastic resonance (SR) and stochastic bifurcations are investigated numerically in a nonlinear tri-stable system driven by colored noise and a harmonic excitation. The power spectral density, signal-to-noise ratio, stationary probability density (SPD), and largest Lyapunov exponent (LLE) are calculated to quantify SR, P-bifurcation, and D-bifurcation, respectively. The effects of system parameters, such as noise intensity and correlation time, well-depth ratio, and damping coefficient, on SR and stochastic bifurcations are explored. Numerical results show that both noise-induced suppression and SR can be observed in this system. The SPD changes from bimodal to trimodal and then to the unimodal structure by choosing well-depth ratio, correlation time, and noise intensity as bifurcation parameters, which shows the occurrence of stochastic P-bifurcation. The stochastic D-bifurcation is found through the calculation of LLE. Moreover, the relationship between SR and stochastic bifurcation is explored thoroughly. It indicates that the optimal SR occurs near D-bifurcation and can be realized with weak chaos by adjusting the proper parameters. Finally, the tri-stable energy harvester is chosen as an example to show the improvement of the system performance by exploiting SR and stochastic bifurcations.

Stochastic resonance in a delayed triple-well potential driven by correlated noises.

In this paper, we investigate stochastic resonance (SR) in a delayed triple-well potential subject to correlated noises and a harmonic signal. The stationary probability density, together with the response amplitude of the system, is obtained by using the small time delay approximation. It is found that the time delay, noise intensities, and the cross-correlation between noises can induce the occurrence of the transition. Moreover, the appropriate choice of noise intensities and time delay can improve the output of the system, enhance the SR effect, and lead to the phenomenon of noise enhanced stability. Especially, the stochastic multi-resonance phenomenon is observed when the multiplicative and additive noises are correlated. Finally, the theoretical results are well verified through numerical simulations.

Dyadic effects of perceived stress, relationship satisfaction and distress disclosure on emotional distress in colorectal cancer patients and their family caregivers: An actor-partner interdependence mediation model.

Objective: This study adopted a dyadic analysis method to examine the effect of perceived stress on emotional distress and determine whether relationship satisfaction and distress disclosure act as mediators in colorectal cancer (CRC) enterostomy patient-caregiver dyads. Methods: A total of 312 patient-caregiver dyads completed measures assessing perceived stress, relationship satisfaction, distress disclosure, and emotional distress. The data were analyzed using the actor-partner interdependence mediation model. Results: This study found that the perceived stress of patients and caregivers both had direct and indirect actor effects on emotional distress (through relationship satisfaction). Another important finding is that perceived stress had indirect actor-partner effects (through distress disclosure) on emotional distress. Conclusions: This study highlights that perceived stress, relationship satisfaction, and distress disclosure of patients and their caregivers are key factors that can be considered for improving emotional distress. It also partially confirmed the interdependence of patients with CRC and their caregivers.

Sleep quality, social rhythms, and depression among people living with HIV: a path analysis based on social zeitgeber theory.

Background: People living with HIV frequently report sleep disturbances. The social zeitgeber theory, which proposes that stressful life events can interfere with sleep and even depression by destabilizing daily routines, provides new insights into identifying predictors of sleep disturbances and improving sleep in people living with HIV. Objective: To explain the pathways affecting sleep quality in people living with HIV based on social zeitgeber theory. Methods: A cross-sectional study was conducted to assess sleep quality, social rhythms, depression, social support, and coping styles from December 2020 to February 2021. The hypothetical model was tested and respecified by performing path analysis and a bias-corrected bootstrapping method using IBM AMOS 24 software. The report of this study followed the STROBE checklist. Results: A total of 737 people living with HIV participated in the study. The final model presented a good fit (goodness of fit = 0.999, adjusted goodness of fit index = 0.984, normed fit index = 0.996, comparative fit index = 0.998, Tucker-Lewis index = 0.988, root mean square error of approximation = 0.030, chi-squared/degree of freedom = 1.646), explaining 32.3% of the variance in sleep quality among people living with HIV. Lower social rhythm stability was directly associated with poorer sleep quality, and depression mediated the relationship between social rhythms and sleep quality. Social support and coping styles affected sleep quality through social rhythms and depression. Limitation: The cross-sectional study design precludes making assumptions about causality among factors. Conclusion: This study validates and extends the applicability of the social zeitgeber theory in the HIV context. Social rhythms have direct and indirect effects on sleep. Social rhythms, sleep, and depression is not simply linked in a cascading sequence but is theoretically linked in a complex way. More studies are needed to explore the predictors of social rhythms, and interventions for stabilizing social rhythms have the potential to alleviate sleep disturbances and depression in people living with HIV.

Effectiveness and moderators of cancer patient-caregiver dyad interventions in improving psychological distress: A systematic review and meta-analysis.

Objective: As patients and family caregivers are increasingly viewed as a dyadic whole, growing studies have emerged that identify ways to improve the two parties' emotional distress. However, the specific effectiveness, quality, and optimal intervention details of these studies are unclear. Our objective is to synthesize the effectiveness of existing dyadic interventions for improving the psychological distress of cancer patient-caregiver dyads and identify potential moderators that influence intervention effectiveness. Methods: PubMed, Cochrane Library, Web of Science, CINHAL, Embase, and Clinical Trials were searched to identify all randomized controlled trials from inception until June 2021. Two reviewers performed the process independently. The Cochrane Risk of Bias tool was used for quality assessment. We calculated effect sizes (Hedges' adjusted g) by standard mean difference. Potential moderators influencing the intervention effects were explored. Results: We included 28 articles, of which 12 were available for meta-analysis. In total, 4784 participants were included, who were primarily middle-aged (M â€‹= â€‹58 years old), with the highest proportion reporting a diagnosis of "mixed cancer" (30%). Patients' anxiety (g â€‹= â€‹-0.31; 95% CI: â€‹-0.51 to -0.12; P â€‹= â€‹0.001; I 2 â€‹= â€‹17%) and cancer-related distress (g â€‹= â€‹-0.32; 95% CI: â€‹-0.46 to -0.18; P â€‹< â€‹0.0001; I 2 â€‹= â€‹0%) were statistically significantly improved from baseline to post-intervention. Interventionist, delivery type, duration, and frequency were potential moderators for psychosocial interventions on negative emotions. Conclusions: Face-to-face, relatively shorter interventions led by psychologists in moderator analysis seem to have better performance. Cancer dyad-based interventions were efficacious in improving the emotional distress of both parties in the dyad, but the effect was more apparent in patients than in family caregivers. However, the long-term effects were modest for both groups.

Circ-CREBBP promotes cell tumorigenesis and glutamine catabolism in glioma by regulating miR-375/glutaminase axis.

Circular RNA CREB-binding protein (circ-CREBBP) has been reported to involve in the tumorigenesis of glioma. However, the role and underlying molecular mechanism of circ-CREBBP in glioma glutamine catabolism remain unclear. The expression of circ-CREBBP, microRNA (miR)-375 and glutaminase (GLS) was detected using quantitative real-time polymerase chain reaction and western blot. The 3­(4, 5­dimethylthiazol­2­y1)­2, 5­diphenyl tetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays were used to determine the effects of them on glioma cell malignant biological behaviors in vitro. Glutamine metabolism was analyzed using assay kits. Murine xenograft model was established to investigate the role of circ-CREBBP in vivo. The binding interactions between miR-375 and circ-CREBBP or GLS were confirmed by the dual-luciferase reporter assay. Circ-CREBBP was highly expressed in glioma tissues and cells, and high expression of circ-CREBBP predicted poor prognosis. Circ-CREBBP knockdown suppressed cell proliferation, migration, invasion and glutamine metabolism while expedited cell apoptosis in glioma in vitro, as well as impeded tumor growth in vivo. Circ-CREBBP directly targeted miR-375, which was demonstrated to restrain glioma cell growth, motility and glutamine metabolism. Moreover, miR-375 inhibition reverted the anticancer effects of circ-CREBBP knockdown on glioma cells. GLS was a target of miR-375, GLS silencing or the treatment of GLS inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) impaired glioma cell malignant phenotypes and glutamine metabolism. Importantly, GLS up-regulation weakened the tumor-suppressive functions of miR-375 on glioma cells. Mechanistically, circ-CREBBP indirectly regulated GLS expression through sponging miR-375. In all, circ-CREBBP expedited glioma tumorigenesis and glutamine metabolism through miR-375/GLS axis, suggesting a promising target for combined glioma therapy.

Effects of continuous care on health outcomes in patients with stoma: A systematic review and meta-analysis.

Objective: Continuing care, which is an extension of post-discharge care, is recognized as a crucial element of high-quality health services and is essential to patients. This systematic review aims to identify the effectiveness of continuing care for patients with stomas. Methods: PubMed, EMBASE, Cochrane Trial Register and Web of Science databases were searched. Study selection and quality appraisal were performed independently by two reviewers. We calculated the mean differences (MD) or the relative risk (RR) with 95% confidence intervals and assessed heterogeneity. Results: Nine studies (1134 participants) met the inclusion criteria. This meta-analysis revealed that, in the continuous care group, the stoma self-efficacy (MD â€‹= â€‹6.46; 95% CI â€‹= â€‹3.81-9.11; P â€‹< â€‹0.001; I 2 â€‹= â€‹0%), and the quality of life (MD â€‹= â€‹7.48; 95% CI â€‹= â€‹5.13-9.82; P â€‹< â€‹0.001; I 2 â€‹= â€‹0%) increased significantly 1 month after discharge; stoma adjustment and care satisfaction also showed a trend toward improvement while stoma complications (RR â€‹= â€‹0.71; 95% CI â€‹= â€‹0.58-0.87; P â€‹= â€‹0.001; I 2 â€‹= â€‹25%) decreased significantly. Continuing care did not decrease hospital readmission rates or medical costs. Conclusions: Continuing care showed beneficial effects in improving health outcomes and care satisfaction for patients with stomas compared with routine care. We proposed an integrated continuing care program with different elements and recommendations for its implementation.

Antidepressant-like activity of oroxylin A in mice models of depression: A behavioral and neurobiological characterization.

Depression is a mood disorder which causes a huge economic burden to both families and societies. However, those monoamine-based antidepressants used in clinical practice have been found to have various limitations. Therefore, currently it is very necessary to explore novel antidepressant targets and medications. As a main active component extracted from Scutellariae radix, oroxylin A possesses many pharmacological functions such as anti-cancer, anti-inflammation and neuroprotection. Here, the present study aims to investigate whether oroxylin A possess antidepressant-like actions using the chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) models of depression, forced swim test, tail suspension test, open field test, sucrose preference test, western blotting, immunofluorescence and viral-mediated gene interference. Our results revealed that treatment of oroxylin A fully prevented both the CUMS-induced and CRS-induced depressive-like behaviors in mice. Moreover, the protecting effects of oroxylin A against CUMS and CRS on mice behaviors were accompanied with a significant enhancement on the levels of brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine kinase B (pTrkB), phosphorylated cAMP-response element binding protein (pCREB) and neurogenesis in the hippocampus. Furthermore, genetic knockdown of BDNF and TrkB in the hippocampus remarkably abolished the antidepressant-like efficacy of oroxylin A in both the CUMS and CRS models of depression, proving that the hippocampal BDNF-TrkB system participates in the antidepressant mechanism of oroxylin A. In summary, our findings are the first evidence showing that oroxylin A possesses potential of being an antidepressant candidate.

PDE4D targeting enhances anti-tumor effects of sorafenib in clear cell renal cell carcinoma and attenuates MAPK/ERK signaling in a CRAF-dependent manner.

Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer and effective treatment regimens are yet to be established. Tyrosine kinase inhibitors (TKI) have widely been used as ccRCC therapeutics, but their efficacy is limited due to accompanying resistance mechanisms. Previous studies have provided substantial evidence for crosstalk between cAMP and the MAPK/ERK signaling pathway. Low levels of intracellular cAMP have been found in several human malignancies and some data suggest that elevation of cAMP expression can be achieved by phosphodiesterase 4 (PDE4) inhibition, resulting in cell growth arrest and/or cell death. The effects of crosstalk between cAMP and the MAPK/ERK pathway on the development progression in ccRCR, however, remain to be fully understood. In this study, we sought to explore the involvement of PDE4 in ccRCC and to assess its potential as a target for therapeutic intervention. We demonstrated that PDE4D is the predominant subtype of PDE4 expressed in healthy and cancerous renal cell lines, particularly in metastatic Caki-1 cells. We generated a CRISPR/Cas9-mediated PDE4D-KO Caki-1 cell model and showed that PDE4D depletion reduced cell proliferation and recovered cAMP expression in these cells. PDE4D-KO and/or PDE4 inhibition with the FDA approved PDE4 inhibitor, roflumilast, also attenuated MAPK/ERK signaling in a CRAF-dependent manner. Most interestingly, we showed that PDE4D-KO enhanced the effectiveness of the TKI, sorafenib, to stunt cell survival. In conclusion, we provide preliminary evidence of PDE4 involvement in ccRCC and suggest a rationale for dual tyrosine kinase/PDE4D targeting in patients with CRAF-dependent MAPK activation.

[Establishment of a multiplex PCR detection method for four foodborne pathogens].

OBJECTIVE: To establish a multiplex PCR method for simultaneous detection of Salmonella, Shigella, Staphylococcus aureus and Listeria monocytogenes in food. METHOD: The primers were designed according to the sequences of invA gene of Salmonella, ipaH gene of Shigella, nuc gene of Staphylococcus aureus and hly gene of Listeria monocytogenes, and the reaction system was optimized. RESULTS: No false positive and false negative results occurred during the test of 15 target strains and 17 non-target strains of bacteria, and the molecular weight of PCR products were consistent with expected. The detection limits for each pathogen were at least 1 pg/microl. The sequence analysis of PCR products showed the same sequences with target genes. The test result of 319 samples showed that 4 raw milk samples were contaminated by staphylococcus aureus, and 1 raw pork sample by Salmonella. CONCLUSION: The established method showed good specificity, and provided an important method for the rapid detection of foodborne pathogens.

Instruments for Detecting Moral Distress in Clinical Nurses: A Systematic Review.

Moral distress (MD) has become a seriously negative problem experienced by healthcare professionals, especially clinical nurses. Early and accurate detection of MD by the validated and reliable instrument is critically important to further develop an effective intervention strategy. We performed the current systematic review to comprehensively summarize the evidence of instruments for the detection of MD in clinical nurses. The research design was a systematic literature review. We assigned 2 investigators to independently search potential studies in PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) from their inception to June 2020. We used data extraction table extracting essential information, and the modified critical appraisal tool evaluating the reliability and validity of eligible instruments. Finally, we qualitatively summarized results of all included instruments. No ethical approval was required because this systematic review was performed based on published studies. We included 16 eligible studies covering 10 original and 6 revised or modified instruments for the final analysis. The overall quality of all instruments was moderate because test-retest reliability was inadequately examined in most instruments. Of 16 instruments, MDS-revised (MDS-R) was broadly validated and employed in different working or cultural settings. Meanwhile, it also extensively expands to specifically detect MD. Moreover, other instruments including moral distress risk scale (MDSR) and moral distress thermometer (MDT) should be further validated and utilized because it covered the gap missed by most instruments. Although several instruments have been made available for clinical nurses, some of them have inadequate psychometric properties test, especially test-retest reliability evaluation. Meanwhile, most of them have not be validated and employed in other working or cultural settings. We therefore suggested further studies to validate the psychometric properties of existing instruments and then employed instruments with high reliability and validity to detect MD in clinical nurses.