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 analyze the eye lens dose and annual effective dose to interventional radiation workers in some hospitals of Xinxiang city from 2020 to 2022, and to ascertain the dose to interventional radiation workers.Methods:By using TLDs, the eye lens dose Hp(3) and annual effective dose Hp(10) were monitored for three consecutive years in six hospitals in Xinxiang city. The lens doses and annual effective doses to intervention radiation workers in different years in different-level hospitals and departments were analyzed. Results:From 2020 to 2022, a total of 117 people were monitored. The left eye lens dose range was 0.12-164.24 mSv, and the right eye lens dose range was 0.07-51.64 mSv. The average annual dose was 8.56 mSv for left eye lens and 4.49 mSv for right eye lens The average annual dose distribution in the MDL-5 mSv range for the left and right eye lens was 60.68% and 73.50%, respectively. 9.41% (11 people) of the left eye lens doses exceeded 20 mSv. The annual effective doses range was 0.11-31.27 mSv, with average annual dose of 2.56 mSv. The proportion of average annual effective doses mainly distributed in the range of MDL to 1.25 mSv was 52.14%, with 2.56% annual effective dose exceeding 20 mSv. There was no significant difference in left and right eye lens dose and annual effective dose between the tertiary hospitals and the secondary hospitals in three years ( P>0.05). Compared with different departments, the cumulative per capita dose in three years was statistically significant (left eye H=11.42, right eye H=13.72, annual effective dose H=25.94, P<0.05). The lens dose and annual effective dose in neurology department were lower than those in cardiology department and comprehensive intervention department ( Zcardiology department=-3.33, -3.78, -4.83, P<0.05; Zcomprehensive intervention department=-2.71, -2.63, -4.39, P<0.05). Conclusions:Most of the annual equivalent dose and annual effective dose to eye lens of the interventional radiation workers in Xinxiang city meet the national limits, but some of them have higher doses and exceed the national limits. It is suggested that the routine and continuous monitoring of eye lens doses to interventional radiologists should be strengthened while routine monitoring of annual effective dose, and attention should be paid to the eye lens and annual effective dose to interventional radiologists in secondary hospitals to improve the awareness of protection.

Objective To analyze the effects of three sterilization methods,namely,pressure steam,low-temperature plasma and ethylene oxide,on the magnetic flux of magnetic surgical devices and their sterilization costs.Methods A total of 234 magnetic surgical devices of different specifications and models(magnetic rings)were randomly divided into Group A,Group B and Group C after the paired number was labelled,and each group consisted of 78 pieces(39 pairs).After packaging each pair of devices according to sterilization specifications,Group A was sterilized by pressure steam,Group B was sterilized by low-temperature plasma,and Group C was sterilized by ethylene oxide.We measured the magnetic flux of three sets of magnetic rings before and after sterilization,and comparatively analyzed the sterilization cost and sterilization time of the single package.Results There was no statistically significant difference in the impact of the three sterilization methods on the magnetic flux of the magnetic surgical devices(P＞0.05),but there was a significant difference in the magnetic flux before and after sterilization for each sterilization method(P＜0.001);the sterilization cost was(1.96±0.16)yuan for Group A,(23.17±0.32)yuan for Group B,and(8.16±0.18)yuan for Group C,showing statistically significant differences among the three groups(P＜0.01).The sterilization time was(65.21±3.36)min for Group A,(45.46±1.39)min for Group B,and(1020.38±12.21)min for Group C,with statistically significant differences among the three groups(P＜0.01).Conclusion None of the three sterilization methods affects the magnetic flux of the magnetic surgical devices.Pressure steam method shows the lowest cost of single package,low-temperature plasma method shows the highest cost of single package,while ethylene oxide method shows the highest sterilization time.Pressure steam should be the preferred sterilization method for magnetic surgical devices.

Objective:To evaluate the effects of different interaction modes on the rehabilitation outcomes of stroke patients, and to provide reference for caregivers to choose the best interaction mode according to the rehabilitation goals.Methods:Computerized search of Web of Science, PubMed, Cochrane Library, EMbase, CNKI, Wanfang Database, VIP Database, and China Biomedical Literature Database for randomized controlled trials (RCTs) of interaction modes to improve rehabilitation outcomes of stroke patients was performed from the year of database construction to January 8, 2024. Two researchers independently screened the literature according to inclusion and exclusion criteria, evaluated the risk of bias in the included studies, and extracted data from them. Stata16.0 was used for a network meta-analysis.Results:A total of 22 articles were included that met the inclusion and exclusion criteria, involving 2 404 patients and 5 interaction modes, namely Cox health behavior interaction mode, doctor-patient interaction mode, King interaction compliance mode, dual track interaction mode, and online interaction mode. The results of the network Meta-analysis showed that in terms of improving self-care ability, the King interaction model [ SMD(95% CI)=0.25(0.05-0.45)], the network interaction model [ SMD(95% CI)=0.27(0.07-0.48)], and the Cox health behavior interaction model [ SMD(95% CI)=0.37(0.07-0.67)] were all superior to conventional nursing (all P<0.05). In terms of improving motor function, except for the dual track interactive mode, all other modes were superior to conventional nursing ( SMD values were -0.52--0.30, all P<0.05). There was no statistically significant difference in the application effects of different modes in improving the quality of life (all P>0.05). The ranking results of the area under the cumulative ranking probability curve (SUCRA) for improving self-care ability, motor fuction and quality of life were Cox health behavior interaction mode (SUCRA=83.7%), doctor-patient interaction mode (SUCRA=89.5%) and King interaction standard mode (SUCRA=78.2%). Conclusions:The Cox health behavior interaction model can improve the self-care ability of stroke patients, the doctor-patient interaction model can improve the motor function of stroke patients, and the King interaction standard model may have more advantages in improving the quality of life of stroke patients. It is suggested to combine the advantages of the three to maximize the rehabilitation effect of stroke patients.

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 relationship between plasma atherogenic index (AIP) trajectory and the risk of hypertension in health examination population.Methods:In this retrospective cohort study, a total of 15 389 subjects who had undergone health examinations at the Health Management Center of the Second Affiliated Hospital of Dalian Medical University three or more times from January 2012 to December 2022 were consecutively selected. The general data, anthropometric parameters and laboratory parameters were collected. The study population without hypertension at baseline inclusion was screened, and AIP trajectory groups of different genders were determined by group-based trajectory modeling. The baseline characteristics and the incidence of hypertension at the end of follow-up were observed in each AIP trajectory group of men and women. Cox proportional hazards regression models were used to analyze the association of AIP trajectories with the risk of hypertension.Results:Four AIP trajectory groups (low level group, low gain group, medium gain group and high gain group) were identified in both male and female subjects, with the highest incidence of hypertension in the low gain group (38.18% in females and 40.92% in males). After adjusting for all confounders, the risk of hypertension was positively associated with increased AIP trajectories in the low ( HR=1.29, 95% CI: 1.02-1.63), medium ( HR=1.66, 95% CI: 1.23-2.23), and high ( HR=1.89, 95% CI: 1.26-2.85) gain groups in women; the risk of hypertension was positively associated with increased AIP trajectories in only the high gain group in men ( HR=1.33, 95% CI: 1.01-1.74). Conclusion:Elevated AIP trajectory is positively correlated with the risk of hypertension in health examination population.

Objective:To construct a recombinant plasmid pET30a-leucine-rich repeat (LRR) containing 15 (LRRC15) of Taenia solium, prokaryotically express and purify the LRRC15 recombinant protein, and prepare a rabbit polyclonal antibody. Methods:The LRRC15 protein encoding gene of Taenia solium was obtained by whole gene synthesis; it was cloned into pET30a vector, and the recombinant plasmid pET30a-LRRC15 was constructed and identified by double-enzyme PCR; the recombinant plasmid was transformed into competent cells of Escherichia coli BL21 (DE3), and the recombinant protein LRRC15 was induced to express by isopropyl-beta-D-thiogalactopyranoside (IPTG), the expression product was analyzed and identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE); the LRRC15 recombinant protein was purified by Ni-IDA affinity columns, the purified recombinant protein was analyzed and identified by SDS-PAGE, and the specificity of the purified recombinant protein was identified by Western blot (WB); the New Zealand rabbits were immunized with purified LRRC15 recombinant protein to prepare polyclonal antibodies against LRRC15, and the potency of the purified polyclonal antibody was determined by indirect enzyme-linked immunosorbent assay (ELISA). Results:After PCR identification, a band with a length of 1 506 bp was amplified, which was consistent with the LRRC15 gene; after SDS-PAGE and WB identification, the LRRC15 target protein with a relative molecular mass ( Mr) of about 55.36 × 10 3 was obtained; after immunizing New Zealand rabbits with purified LRRC15 recombinant protein, a polyclonal antibody against LRRC15 was obtained, and its potency was 1∶1 587 200. Conclusion:The recombinant plasmid pET30a-LRRC15 is successfully constructed, the LRRC15 recombinant protein of Taenia solium is prepared, and a high purity and high potency rabbit anti polyclonal antibody against LRRC15 recombinant protein is obtained.

Objective:To investigate the application of diagnostic criteria for common occupational radiation-induced diseases to radiation workers, in order to provide a basis for the revision, publicity and standardization of the standards.Methods:Radiation workers were selected from 1 city, 7 provinces and 1 corporation by using cluster random sampling method from January 2021 to May 2021. Awareness of the criteria and the effects of ionizing radiation, and the suggestions for diagnostic works were investigated and analyzed.Results:A total of 2 839 radiation workers were investigated. There were differences in the awareness of different diagnostic criteria, the inclusions in complex diagnostic criteria, the materials required for applying for diagnosis, and the ways of knowing the diagnostic criteria( χ2=416.06, 2 924.14, 83.45, 895.67, 815.94, P<0.001). The correct understanding rates of deterministic effects and stochastic effects were 80.63% and 43.64%, respectively. The acceptance rates in applicable materials were 96.79% for occupational exposure history, 94.72% for occupational health monitoring records and 93.55% for individual monitoring of occupational exposure, respectively. Pre-employment training rate was 80.20%, on-job training rate was 81.19%, and untrained rate was 3.77%. The suggestions to the diagnosis of occupational radiation-induced diseases are to strengthen training, pay attention to individual monitoring, occupational health examination, and strengthen health supervision and law enforcement. Conclusions:Radiation workers have a low awareness rate of certain diagnostic standards and a high awareness rate of diagnostic procedures. Publicity and training of health effects of ionizing radiation and diagnostic criteria of occupational radiation-induced diseases should be strengthened. Diagnostic procedure should be optimized.

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 provide reference for safe use of risperidone in clinic. METHODS Data mining and analysis of risperidone-related adverse drug event （ADE） reports from the first quarter of 2017 to the third quarter of 2021 in the United States FAERS database were carried out using reported odds ratio and composite criteria methods from Medicines and Healthcare Products Regulatory Agency. RESULTS There were 101 181 ADE reports with risperidone as the primary suspect drug，involving a total of 33 179 patients. Among those reports，the male-to-female ratio was about 6.21 to 1； most of them were ＜18 years old （15.01%）； ADE was mainly reported by consumers （69.74%） and mainly reported by the United States （79.72%）； oral dosage form was the most used，accounting for 83.71%. A total of 409 ADE signals were obtained，including male breast development， pseudogynecomastia，abnormal increase in body mass，hyperprolactinemia and Wellens syndrome，etc. Twenty-six systems and organs were involved，mainly including reproductive system and breast diseases，various injuries，poisoning and operational complications， mental diseases，metabolic and nutritional diseases，and various nervous system diseases，etc. CONCLUSIONS The common ADE signals of risperidone and the system involved are consistent with the instructions，but we should also be alert to the ADE not recorded in the instruction，such as Wellens syndrome，fibroproliferative endocarditis，cavernous degeneration of portal vein，rabbit syndrome，etc.