G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Objective To establish the quantitative evaluation system on the internal control of drug management, which could reflect the improvement and optimization of the internal control of drug management and be reference for the drug management in the hospital. Methods Brainstorm method was used to design a quantitative evaluation table. The methods of walking test, field inspection and comparative analysis were used to carry out the internal control design and execution effectiveness evaluation. Results Evaluation score increased from 36.50 points in 2015 to 43.75 points in 2021 when the full score was 50 points. The proportion of drug intotal income decreased from 37.97% in 2015 to 21.62% in 2021.The drug markup rate decreased from 14.38% to 0.96%, and the intensity of antibiotic DDDs decreased from 55.48 in 2018 to 39.30 in 2021. The proportion of essential drug prescriptions was higher than the national examination data. Conclusion The optimizing quantitative evaluation system on the internal control of drug management could improve the management specialization, the structure of income and payout and the level of rational drug use, promote the high-quality development of hospitals and safeguard the implementation of the Healthy China strategy.

Since 2016, Binzhou Medical University began to carry out the blended learning reform in the organ-systems based curriculum (OSBC) of the experimental class of clinical medicine. Based on the traditional face-to-face teaching method, the blended learning mode of the integrated course of endocrine system under OSBC has been carried out by using the small private online course (SPOC) of MOOC platform of China universities. Many teaching methods have been adopted and formed, including case-based learning (CBL), problem-based learning (PBL), professional bilingual teaching, scientific research teaching and virtual simulation experiment teaching. The evaluation system for the combination of formative and summary assessment has been also adopted in the whole process to assess the students' academic achievement, and the teaching effect as well. The blended learning mode of the integrated course of the endocrine system under OSBC is still in the exploratory stage. There are some limitations, such as too high requirements for teachers' quality, long preparation time for teaching, and great difficulty in supervising online learning. However, the practice of teaching reform that has been carried out shows that it is effective, feasible, and worth popularizing.

Objective To explore the effect and mechanism of Bajitianwan on preventing D-galactose (D-gal)-induced osteoblast bone loss. Methods Osteoblasts isolated from 24 h old Wistar rats were injured by D-gal and intervened with Bajitianwan extract. The osteoblastic proliferation and differentiation were determined by MTT and alkaline phosphatase (ALP), respectively. The cell reactive oxygen species (ROS) levels were detected by DCFH-DA fluorescent probes. The expression of cellular oxidation-related protein nuclear factor erythroid 2-related factor 2 (Nrf2), phosphorylated protein kinase B (p-AKT), protein kinase B (AKT), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) were detected by Western blotting. The intranuclear expression of Nrf2 protein was measured by immunofluorescence. Results Bajitianwan extract had significantly increased the osteoblastic proliferation and differentiation, and significantly reduced the intracellular ROS level. Bajitianwan extract had activated the PI3K/AKT pathway via activating the phosphorylation of AKT in osteoblasts, and promoted NQO1 and HO-1 expression. In addition, Bajitianwan had significantly promoted the expression of Nrf2 in the nucleus of osteoblasts, activating Nrf2 signaling pathway, and further promoted bone formation. Conclusion This study confirmed that Bajitianwan could prevent D-gal injured osteoblastic bone loss for the first time. The mechanism might be related to the regulation of oxidative stress associated PI3K/AKT and Nrf2 signaling pathway.

Objective:To analyze the differences in clinical outcomes and toxicities between postoperative radiotherapy alone and postoperative radiochemotherapy for soft tissue sarcoma (STS), as well as the related factors affecting clinical prognosis of STS patients.Methods:Retrospective analysis of patients diagnosed with primary STS admitted to Zhejiang Cancer Hospital from May 2012 to May 2019 was performed, who received adjuvant radiotherapy after surgery, combined with or without postoperative chemotherapy. A total of 100 patients were enrolled and divided into postoperative radiotherapy group ( n=52) and postoperative radiochemotherapy group ( n=48). The median follow-up time was 65 months (24-124 months). The local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-related toxicities were recorded in two groups. The survival rate was calculated by Kaplan-Meier analysis. Log-rank test was used for univariate analysis, and Cox model was used for multivariate analysis. Results:In multivariate analysis, the maximum tumor diameter was an independent predictor of local tumor recurrence ( HR=4.80, 95% CI=1.16-19.85, P=0.031), distant metastasis ( HR=4.67, 95% CI=1.53-14.26, P=0.007) and OS ( HR=4.10, 95% CI=1.35-12.48, P=0.013). In addition, the degree of myelosuppression in patients in postoperative radiochemotherapy was significantly higher than that in their counterparts in postoperative radiotherapy group ( P<0.001). Conclusions:In the limited number of patients, radiochemotherapy has no advantages over radiotherapy alone in distant metastasis or survival rate. Besides, it increases toxicities, but the overall tolerability is favorable. It is necessary to conduct prospective randomized studies in a large population and subgroup analysis of histological subtypes, aiming to obtain results with better reference value.

Objective:To analyze the effect of SBAR (situation, background, assessment, and recommendation) sign-out template in the standardized residency training in a neonatal ward.Methods:Based on SBAR communication mode, we designed and optimized neonatal ward sign-out checklist, and a total of 67 residents were trained for 2 weeks from April 2019 to June 2019, with control group (before training) and observation group (after training). The assessment indicators of sign-out information included sign-out duration, the incidence of sign-out errors, quality assessment scores and shift satisfaction (including sign-out satisfaction and self-evaluation) as well as competencies. A total of 1 553 children's morning shift data were collected, and SPSS 22. 0 was used for t test and chi-square test. Results:In the control group, the sign-out duration was (23.4±4.7) min, the incidence of sign-out errors was (43.6±6.6)%, quality assessment scores were (6.3±0.7) points, the satisfaction degree was (76.5±4.6)%, and the self-evaluation scores were (5.2±2.1) points. While, in the observation group, the sign-out duration was (15.9±3.2) min, the incidence of sign-out errors was (21.1±2.3)%, quality assessment scores were (8.9±0.9) points, the satisfaction degree was (94.1±2.9)%, and the self-evaluation scores were (8.9±0.8) points, with statistically significant difference ( P<0.05). There were statistically significant differences between the two groups in clinical skills and medical service ability [(2.2±0.1) vs. (3.8±0.3)], interpersonal communication ability [(2.6±0.5) vs. (4.2±0.1) points], teamwork ability [(3.1±0.2) vs. (4.6±0.3)], information and management ability [(2.5±0.5) vs. (4.2±0.2)] ( P<0.05). Conclusion:The SBAR template can improve sign-out process and the clinical skills of standardized training residents.

Objective:To assess the efficacy and safety of common medication treatments on Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA).Methods:PubMed, Embase, Web of Science, CNKI and Wanfang database were searched to find out the observational studies on medication treatment of KHE and TA. R-3.6.2 was used for calculate the pooled response rate and pooled adverse events rate. Meta analyses were performed according to KHE and TA with and without Kasabach-Merritt phenomenon (KMP) respectively. SPSS 22.0 was used to compare the pooled rates among each therapy.Results:A total of 30 studies regarding the medication treatment of KHE and TA were identified in this meta-analysis. Analyzed medicines included glucocorticoid, vincristine, sirolimus, propranolol, combination therapy of vincristine and glucocorticoid. The pooled results indicated that when referring therapy on KHE and TA with KMP, the pooled response rate of combination therapy (98.34%) and sirolimus (96.43%) was higher than that of other therapies, and the difference was statistically significant. The pooled adverse events rate of sirolimus (5.53%) was relatively higher than other modalities, with no statistically significance. As for therapy on KHE and TA without KMP, sirolimus (94.23%) had higher pooled response rate than glucocorticoid (31.25%), vincristine (46.15%) and propranolol (22.86%), with statistically significant differences. The pooled adverse events rate of sirolimus was 23.81%.Conclusions:Our findings indicate that for KHE and TA with KMP, combination therapy (sirolimus + glucocorticoid) and vincristine have the best efficacy, while the adverse events rate of sirolimus is relatively high. For KHE and TA without KMP, sirolimus has the highest response rate, but there is also a risk of serious adverse events. Glucocorticoid and vincristine have comparable response rate, which both inferior to sirolimus.

Objective:To assess the efficacy and safety of common medication treatments on Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA).Methods:PubMed, Embase, Web of Science, CNKI and Wanfang database were searched to find out the observational studies on medication treatment of KHE and TA. R-3.6.2 was used for calculate the pooled response rate and pooled adverse events rate. Meta analyses were performed according to KHE and TA with and without Kasabach-Merritt phenomenon (KMP) respectively. SPSS 22.0 was used to compare the pooled rates among each therapy.Results:A total of 30 studies regarding the medication treatment of KHE and TA were identified in this meta-analysis. Analyzed medicines included glucocorticoid, vincristine, sirolimus, propranolol, combination therapy of vincristine and glucocorticoid. The pooled results indicated that when referring therapy on KHE and TA with KMP, the pooled response rate of combination therapy (98.34%) and sirolimus (96.43%) was higher than that of other therapies, and the difference was statistically significant. The pooled adverse events rate of sirolimus (5.53%) was relatively higher than other modalities, with no statistically significance. As for therapy on KHE and TA without KMP, sirolimus (94.23%) had higher pooled response rate than glucocorticoid (31.25%), vincristine (46.15%) and propranolol (22.86%), with statistically significant differences. The pooled adverse events rate of sirolimus was 23.81%.Conclusions:Our findings indicate that for KHE and TA with KMP, combination therapy (sirolimus + glucocorticoid) and vincristine have the best efficacy, while the adverse events rate of sirolimus is relatively high. For KHE and TA without KMP, sirolimus has the highest response rate, but there is also a risk of serious adverse events. Glucocorticoid and vincristine have comparable response rate, which both inferior to sirolimus.

Staring from the definition of medical humanity education,this paper expounded the influence and challenges medical humanity education faced in the "Internet Plus" age from three aspects of the values,discourse system and teaching mode.With the "Internet Plus" as platform for teaching innovations,constructing the new teaching mode of medical humanity education through integrating resources standardly,setting up relevant courses,strengthening the training teachers and other measures can improve the humanistic quality of medical students and guide medical students to apply humanistic care into clinical work.Therefore,choosing various teaching methods and strategies which are suitable for medical humanity education and can stimulate students' subjective initiative is the effective way to improve the clinical thinking ability of medical students.

The graphene prepared by chemical vapor deposition onto copper foils was transferred onto a poly(ethylene terephthalate) (PET) soft substrate by the aid of poly-methyl methacrylate (PMMA).The soft G/AuNPs/GOD composite electrode based on PET substrate was fabricated using a protocol in which the uniform distribution of Au nanoparticles (AuNPs) was firstly obtained by controlling the evaporation of gold sol on a graphene surface, then thioglycolic acid (TGA) was modified on the AuNPs through Au-S bond, and finally glucose oxidase (GOD) was immobilized on the surface of AuNPs through acylation reaction between TGA and the GOD.Glucose was detected in the linear range from 0.05 to 10.55 mmol/L with a linear correlation coefficient (r) of 0.9955.The detection was performed in phosphate buffer solution (pH 7) at 25℃ with a working potential of 0.6 V (vs.SCE electrode), and the detection limit was 1 μmol/L (3σ).The G/AuNPs/GOD flexible electrode based on PET substrate provided a new pathway to detect glucose in special environments using wearable equipment, which enlarged the applied field of glucose detection.