Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

Objective To investigate the correlation of serum calmodulin(CaM)level with the con-dition and prognosis of patients with severe traumatic brain injury(sTBI).Methods A total of 208 elderly sTBI patients admitted to the Geriatric Hospital and Puren Hospital Affiliated to Wuhan University of Science and Technology from January 2021 to June 2023 were enrolled,and after 3 months'follow-up,192 cases were finally included in this study.According to their progno-sis,they were divided into poor prognosis group(n=56)and good prognosis group(n=136).Their general data were collected,and serum CaM level was measured by ELISA.Pearson correla-tion analysis was used to study the correlation between the level and the disease condition.Multi-variate logistic regression model was employed to screen the prognosis related factors of sTBI pa-tients,and restricted cubic spline was applied to fit the relationship between serum CaM level and prognosis of sTBI patients.Results Midline shift,significantly lower CaM level and acute physi-ology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,and obviously higher Glasgow Coma Scale(GCS)score and albumin level were observed in the good prognosis group than the poor prognosis group(P＜0.05,P＜0.01).Pearson correlation analysis showed that serum CaM level was negatively correlated with condition of sTBI(r=-0.804,P＜0.05).Multivariate logistic analysis indicated that APACHE Ⅱ score(OR=1.248,95％CI:1.076-1.447,P=0.003)and ser-um CaM level(OR=1.030,95％CI:1.017-1.044,P=0.001)were risk factors for prognosis,while,GCS score(OR=0.730,95％CI:0.536-0.994,P=0.045)and serum albumin level(OR=0.730,95％CI:0.649-0.822,P=0.001)were protective factors for poor prognosis in sTBI pa-tients.Restricted cubic spline revealed that there was a linear dose-response relationship between serum CaM level and prognosis of sTBI patients(X2=27.080,P＜0.01).Conclusion Serum CaM level is correlated with sTBI disease and prognosis.

Objective To evaluate the cost-effectiveness of enzalutamide in the treatment of metastatic prostate cancer from the perspective of healthcare in China.Methods Based on the published phase Ⅲ randomized controlled trial(ENZAMET),the disease process of metastatic prostate cancer was classified into three states:progression-free survival,progression survival and death,and the model period was defined as 28 days,and the study period was lifelong,and a Markov model was established to evaluate the cost-effectiveness of the treatment of enzalutamide versus standard antiandrogen drugs in metastatic prostate cancer.Setting the willingness-to-pay(WTP)threshold at 3 times our 2022 gross domestic product(GDP)per capita and the robustness of the model analysis was verified by sensitivity analysis.Results Compared to the control group standard antiandrogen therapy,the incremental effect of enzalutamide was 0.92 quality-adjusted life years(QALYs),the incremental cost was 311 863.30 yuan,and the incremental cost-effectiveness ratio(ICER)was 338 981.85 yuan/QALY,which was higher than WTP threshold(257 094 yuan/QALY).The results of univariate sensitivity analyses showed that the total cost of the enzalutamide group,the PFS utility value,the cost of the PD status of enzalutamide group,and the unit price of enzalutamide had a greater impact on the model results.The results of the probabilistic sensitivity analysis suggested that the enzalutamide treatment regimen was not economical within the willingness-to-pay threshold of 3 times our 2022 GDP per capita.Conclusion Compared with the standard anti-androgen drugs,enzalutamide does not offer a cost-effectiveness advantage in the treatment of metastatic prostate cancer.

Objective To investigate the effects of laparoscopic radiofrequency ablation(LRFA)and percutaneous radiofrequency ablation(PRFA)on anti-tumor immunity,complication rate and recurrence rate in patients with primary liver cancer.Methods A total of 81 patients with primary liver cancer treated in Dazhou Central Hospital from January 2020 to August 2022 were selected and divided into observation group(LRFA,n=42)and control group(PRFA,n=39)according to the treatment plan.Compare the total ablation rate,postoperative complication rate,recurrence rate of the two groups,as well as tumor necrosis factor-α(TNF-α),carbohydrate antigen 199(CA199),interleukin-6(IL-6),Golgi protein 73(GP73),C-reactive protein(CRP),alpha-fetoprotein(AFP)and peripheral blood T lymphocyte subpopulation levels before and after surgery.Results There was no significant difference between the observation group(95.24％)and the control group(92.31％)(P＞0.05).At 1 d postoperatively,IL-6 was(124.63±45.41)pg/ml and(168.28±51.26)pg/ml,CRP was(19.14±5.03)ng/L and(28.26±7.47)ng/L,and TNF-α was(94.32±18.49)pg/ml and(108.41±20.11)pg/ml;at 3 d postoperatively,IL-6 was(92.37±24.11)pg/ml and(105.83±27.45)pg/ml in the observation group and the control group,respectively,CRP was(14.87±4.37)ng/L and(17.25±5.06)ng/L,and TNF-α was(75.41±12.10)pg/ml and(82.64±16.83)pg/ml,which were all higher than that of preoperative period(P＜0.05).At 7 d postoperatively,CD3+in the observation group and control group were(66.27±7.82)％and(65.14±7.63)％,AFP was(156.23±30.27)μg/mland(160.84±32.33)μg/ml,GP73 was(65.21±10.26)μg/L and(67.44±11.03)μg/L,CA199 was(44.89±11.41)U/L and(45.12±13.07)U/L,CD4 was(32.02±6.03)％and(31.53±6.11)％,and CD4+/CD8+was(1.31±0.39)and(1.29±0.37)respectively;at 14 d postoperatively,CD3+was(71.25±6.83)％and(70.89±6.76)％,AFP was(48.52±18.31)μg/ml and(50.11±19.12)μg/ml,GP73 was(48.25±8.46)μg/L and(49.12±10.12)μg/L,CA199 was(19.27±5.16)U/L and(20.07±5.39)U/L,and CD4 was(38.25±7.7)U/L and(20.07±5.39)U/L,respectively,in the observation and control groups.g/L,CA199 was(19.27±5.16)U/L and(20.07±5.39)U/L,CD4 was(38.25±7.45)％and(37.61±7.92)％,and CD4+/CD8+was(1.49±0.42)and(1.47±0.45),respectively,which were higher than that of preoperative period(P＜0.05),but the difference between the two groups was not statistically significant(P＞0.05).The postoperative complication rate of 42.86％and recurrence rate of 2.38％in the observation group were lower than 66.67％and 17.95％in the control group(P＜0.05).The 12-month postoperative survival rate of 97.62％in the observation group was not statistically significant compared with 94.87％in the control group(P＞0.05).Conclusion The efficacy of LRFA and PRFA in the treatment of primary hepatocellular carcinoma is comparable,which can effectively improve the body's anti-tumor immunity and reduce the release of serum tumor markers;however,LRFA has less stressful reaction,reduces the occurrence of postoperative complications,and has a lower recurrence rate,which is especially advantageous in the treatment of hepatocellular carcinoma at special sites.

The rehabilitation compliance of stroke patients is generally low.Evaluating the rehabilitation motivation of patients is helpful to promote the rehabilitation management of patients,enhance the rehabilitation enthusiasm and compliance of patients,and improve the rehabilitation outcome.This paper reviews the existing stroke patients rehabilitation motivation assessment tools,and expounds the main contents,application status,characteristics and limitations of stroke patients rehabilitation motivation assessment tools,in order to provide references for the appropriate selection of clinical assessment tools,the rehabilitation management of stroke patients and the development of domestic localized stroke rehabilitation motivation assessment tools.

Objective: To construct a human G protein-coupled receptor kinase 2 ( GRK2) eukaryotic expression system． Methods: The primers were designed ，and the His-GRK2 target gene was amplified by PCR using the Pans-EGFP-GrK2 (full-length) gene as the template．The His-GRK2 target gene was connected to the pcDNA3．1EGFP eukaryotic expression vector． The pcDNA3. 1-EGFP-His-GRK2 plasmid was transfected into HEK 293T cells．48 h later，the expression of GRK2 protein was detected by Western blot，and the GRK2 protein was purified by nickel chelated magnetic bead method．The purification of GRK2 protein was detected by Coomassie bright blue staining and Western blot，and the activity of GRK2 protein was detected by His pull down. Results : The results of double enzyme digestion and sequencing showed that pcDNA3. 1-EGFP-His-GRK2 eukaryotic expression plasmid was successfully constructed．Western blot analysis showed that the molecular weight of GRK2 protein was about 80 ku，indicating that GRK2 protein was successfully expressed in HEK 293T cells (t = 6. 433，P = 0. 003) ．GRK2 protein was purified by nickel chelated magnetic beads．His pull down experiment results showed that GRK2 was bound to prostaglandin E2 receptor 4 (EP4) ，suggesting that GRK2 protein had biological activity (t = 13. 5，P = 0. 000 2) ． Conclusion The pcDNA3．1-EGFP-His-GRK2 eukaryotic expression plasmid was correctly sequenced and the GRK2 recombinant plasmid was successfully constructed．The GRK2 recombinant plasmid was successfully expressed in eukaryotic cells HEK 293T and the protein expressed was biologically active.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.

Objective:To investigate the relationship between prolonged PR interval and carotid atherosclerosis(CAS)in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 537 middle-aged and elderly inpatients with T2DM in the Southern Branch of the Sixth People′s Hospital of Shanghai Jiaotong University from January 2019 to January 2021 were selected as the research objects. Color Doppler ultrasound was used to detect bilateral carotid artery intima-media thickness(CIMT). The subjects were divided into carotid atherosclerosis group(CAS group, n=352)and non-carotid atherosclerosis group(NCAS group, n=185). The difference in the PR interval of ECG between the two groups was compared. Pearson or Spearman rank correlation analysis was used for evaluating the correlation of PR interval and CAS lesions with various clinical index. The relationship between PR interval and CAS lesions was adopted by multivariate logistic regression analysis. Results:The average PR interval of middle-aged and elderly patients with T2DM was(164.57±23.02)ms. The average PR interval in CAS group was significantly higher than that in NCAS group [(169.76±24.28) vs (154.70±16.42)ms, P<0.01]. The results of multifactorial logistic regression analysis showed that age, low density lipoprotein-cholesterol, serum osteocalcin, and PR interval were independent factors influencing the development of CAS lesions in middle-aged and elderly patients with T2DM( OR=1.079, 1.936, 0.879, 1.039, respectively, P<0.05 or P<0.01)where each 1 ms increase in PR interval was associated with a 3.9% increase in the risk of CAS in middle-aged and elderly patients with T2DM( OR=1.039, 95% CI 1.006-1.073, P=0.020). Multivariate logistic regression analysis showed that middle-aged and elderly type 2 diabetic patients with PR interval≥158 ms were 4.072 times more likely to have CAS lesions than those with PR interval<158 ms( OR=4.072, 95% CI 1.417-11.702, P<0.01). Conclusion:The PR interval of electrocardiogram is correlated with CAS lesions in middle-aged and elderly patients with T2DM. Middle-aged and elderly type 2 diabetic patients with significantly prolonged PR interval should be reminded to screen for CAS lesions early.

Objective:To investigate the association of surrogate indexes of insulin resistance with the risk of nonalcoholic fatty liver disease(NAFLD)and advanced liver fibrosis in newly diagnosed patients with type 2 mellitus.Methods:A total of 429 newly diagnosed type 2 diabetic patients hospitalized in the Department of Endocrinology and Metabolism, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from June 2018 to June 2020 were included. The patients were divided into NAFLD group( n=263)and non-NAFLD group( n=166)according to the results of abdominal ultrasound, NAFLD patients were divided into advanced liver fibrosis group( n=33)and non-advanced liver fibrosis group( n=230)according to the NAFLD fibrosis score(NFS). The correlation of the triglyceride/high density lipoprotein-cholesterol ratio(TG/HDL-C), triglyceride glucose index(TyG), visceral adiposity index(VAI), triglyceride glucose-body mass index(TyG-BMI), homeostasis model assessment of insulin resistance index(HOMA-IR)with NAFLD and the occurrence of advanced liver fibrosis were analyzed. Results:The prevalence of NAFLD in newly diagnosed type 2 diabetic patients was 61.3%, and the prevalence of advanced liver fibrosis was 12.5%. After adjusting the potential confounders, multivariate logistic regression analysis showed that TG/HDL-C, TyG, VAI, TyG-BMI, and HOMA-IR were independently and positively correlated with NAFLD, and only TyG-BMI was independently and positively correlated with advanced liver fibrosis( OR=1.021, 95% CI 1.009-1.034, P<0.01). The receiver operating characteristic analysis showed that the area under the curue of TyG-BMI was more than those of TG/HDL-C, TyG, VAI and HOMA-IR for predicting the occurrence of NAFLD in newly diagnosed type 2 diabetic patients(0.83 vs 0.73, 0.74, 0.73, 0.67, P<0.01), but had no predictive value for advanced liver fibrosis. Conclusion:TyG-BMI is superior to TG/HDL-C, TyG, VAI and HOMA-IR for predicting the occurrence of NAFLD in newly diagnosed type 2 diabetic patients, and it is also an independent risk factor for advanced liver fibrosis.

Wechat has been widely used in nursing clinical clerkship teaching now. The application of Wechat in nursing clinical teaching mainly takes the form of Wechat group chat, Wechat public signal platform, Wechat friendship circle, online test and so on. Among them, Wechat group chat and Wechat public signal platform are used widely. Wechat enriches the teaching way, and improve the effectiveness of teaching, moreover, it facilitates the relationship between teachers and students. However, there are the ongoing challenges such as lacking of supervision and protection of intellectual property rights.