Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL-6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro.

BACKGROUND: Dexamethasone (Dexa) and potassium canrenoate (Cane) modulate nociceptive behavior via glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) by two mechanisms (genomic and nongenomic pathways). This study was designed to investigate the Dexa- or Cane-mediated nongenomic and genomic effects on mechanical nociception and inflammation-induced changes in interleukin-6 (IL-6) mediated signaling pathway in rats. METHODS: Freund's complete adjuvant (FCA) was used to trigger an inflammation of the right hind paw in male Sprague-Dawley rats. First, the mechanical nociceptive behavioral changes were examined following intraplantar administration of GR agonist Dexa and/or MR antagonist Cane in vivo. Subsequently, the protein levels of IL-6, IL-6Rα, JAK2, pJAK2, STAT3, pSTAT3Ser727 , migration inhibitory factor, and cyclooxygenase-2 were assessed by Western blot following intraplantar injection of Dexa or Cane or the combination. Moreover, the molecular docking studies determined the interaction between Dexa, Cane, and IL-6. The competition binding assay was carried out using enzyme-linked immunosorbent assays (ELISA). RESULTS: Administration of Dexa and Cane dose-dependently attenuated FCA-induced inflammatory pain. The sub-additive effect of Dexa/Cane combination was elucidated by isobologram analysis, accompanied by decrease in the spinal levels of IL-6, pJAK2, and pSTAT3Ser727 . The molecular docking study demonstrated that both Dexa and Cane displayed a firm interaction with THR138 binding site of IL-6 via a strong hydrogen bond. ELISA revealed that Dexa has a higher affinity to IL-6 than Cane. CONCLUSIONS: There was no additive or negative effect of Dexa and Cane, and they modulate the IL-6/JAK2/STAT3 signaling pathway through competitive binding with IL-6 and relieves hypersensitivity during inflammatory pain.

Research on Cognition and Training Needs of Sex Education during Pregnancy among Obstetricians and Obstetric Nurses in Guangdong Province Based on Mixed Research Perspective.

Objective: The purpose of this study was to understand the current status and existing responses of obstetricians and obstetric nurses in Guangdong Province regarding sex education during pregnancy and to understand their acceptance of sex education during pregnancy and the knowledge and information they would like to obtain in sex education courses. Methods: A phenomenological research method was used to conduct in-depth interviews with 12 obstetricians and obstetric nurses in a tertiary hospital in Guangdong Province to understand their perceptions and attitudes toward providing sex education to pregnant women. A self-designed questionnaire was used to survey 462 obstetricians and obstetric nurses in Guangdong Province to understand their needs for sex education. Results: Three themes were summarized: insufficient awareness of sex education during pregnancy; negative attitudes of obstetricians and obstetric nurses toward sex education during pregnancy; and the need for a long-term process for the development and popularization of sex education during pregnancy. We obtained the required scores of obstetricians and obstetric nurses on 11 aspects of sex education during pregnancy with a coefficient of variation ≤25%. Conclusion: There is an urgent need to improve the awareness and related competencies of obstetricians and obstetric nurses about sex education during pregnancy, and the purpose and content of sex education courses should be in line with the clinical reality.

LUNAR :Drug Screening for Novel Coronavirus Based on Representation Learning Graph Convolutional Network.

An outbreak of COVID-19 that began in late 2019 was caused by a novel coronavirus(SARS-CoV-2). It has become a global pandemic. As of June 9, 2020, it has infected nearly 7 million people and killed more than 400,000, but there is no specific drug. Therefore, there is an urgent need to find or develop more drugs to suppress the virus. Here, we propose a new nonlinear end-to-end model called LUNAR. It uses graph convolutional neural networks to automatically learn the neighborhood information of complex heterogeneous relational networks and combines the attention mechanism to reflect the importance of the sum of different types of neighborhood information to obtain the representation characteristics of each node. Finally, through the topology reconstruction process, the feature representations of drugs and targets are forcibly extracted to match the observed network as much as possible. Through this reconstruction process, we obtain the strength of the relationship between different nodes and predict drug candidates that may affect the treatment of COVID-19 based on the known targets of COVID-19. These selected candidate drugs can be used as a reference for experimental scientists and accelerate the speed of drug development. LUNAR can well integrate various topological structure information in heterogeneous networks, and skillfully combine attention mechanisms to reflect the importance of neighborhood information of different types of nodes, improving the interpretability of the model. The area under the curve(AUC) of the model is 0.949 and the accurate recall curve (AUPR) is 0.866 using 10-fold cross-validation. These two performance indexes show that the model has superior predictive performance. Besides, some of the drugs screened out by our model have appeared in some clinical studies to further illustrate the effectiveness of the model.

Effect of Gua Sha therapy on patients with diabetic peripheral neuropathy: A randomized controlled trial.

OBJECTIVE: To examine the effect of Gua Sha therapy in the treatment of diabetic peripheral neuropathy (DNP). DESIGN: An open-label randomized controlled study was conducted with usual care as the control (60 subjects in Gua Sha group and 59 subjects in usual care group). Outcome measures included Toronto Clinical Scoring System (TCSS), Vibration Perception Threshold (VPT), Ankle Brachial Index (ABI), and fasting plasma glucose (FPG). There were 12 consecutive sessions of Gua Sha, one session per week. RESULTS: After the first cycle of Gua Sha intervention, only performance of sensory function measured by the VPT, and peripheral artery disease symptoms by the ABI were statistically significant differences between the two groups (both P values < 0.01), and the total TCSS score and the FPG level were no group differences (P = 0.14, and 0.25, respectively). At the eight-week and 12-week post intervention assessment, Gua Sha therapy significantly reduced severity of neuropathy symptoms, improved performance of sensory function, reduced peripheral artery disease, and better controlled plasma glucose by comparing with the control group (all P values < 0.01). The changes of mean scores of TCSS, VPT, ABI and the plasma glucose levels in the Gua Sha group showed a significant change from baseline to week 12, indicating that Gua Sha therapy induced progressive improvement in the management of DPN symptoms, sensory function, peripheral artery disease and glucose levels. No serious adverse events were reported in either arm. Gua Sha therapy in this study was effective, safe and well tolerated by patients. CONCLUSION: Gua Sha therapy appears to be effective at reducing the severity of DPN in a clinically relevant dimension, and at improving other health outcomes in patients with DPN. While this study found that Gua Sha therapy is a promising treatment in reducing the symptoms of patients with DPN, further, larger sample studies are required to confirm the effects of Gua Sha therapy in patients with DPN.