1.GRK2 inhibits Flt-1+ macrophage infiltration and its proangiogenic properties in rheumatoid arthritis.
Xuezhi YANG ; Yingjie ZHAO ; Qi WEI ; Xuemin ZHU ; Luping WANG ; Wankang ZHANG ; Xiaoyi LIU ; Jiajie KUAI ; Fengling WANG ; Wei WEI
Acta Pharmaceutica Sinica B 2024;14(1):241-255
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 GRK2f/fLyz2-Cre+/- mice. Synovial inflammation and M1 polarization were improved in GRK2f/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.
2.Effects of three sterilization methods on the magnetic flux of magnetic surgical devices and analysis of sterilization cost
Feng MA ; Aihua SHI ; Xiaoyan ZENG ; Fang BAI ; Ningxia JIA ; Hao XUE ; Fengling WANG ; Yan LI ; Xufeng ZHANG ; Yi LÜ ; Lingling SHI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(4):669-673
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.
3.Analysis of the eye lens dose and annual effective dose to some interventional radiation workers in Xinxiang city
Yuxuan MAO ; Bingjie ZHANG ; Yulong LIU ; Xuan WANG ; Tongzhen LIU ; Tianhe JIA ; Fengling ZHAO ; Quanfu SUN ; Dianhui WANG
Chinese Journal of Radiological Medicine and Protection 2024;44(3):216-222
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.
4.Network Meta-analysis of the effects of different interactive modes of intervention on the rehabilitation of stroke patients
Shui LIU ; Fengling WANG ; Tiantian JIA ; Yunfen SUN
Chinese Journal of Practical Nursing 2024;40(31):2413-2421
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.
5.Association between plasma atherogenic index trajectories and risk of hypertension in health examination population
Yu ZHOU ; Hui ZHAO ; Cuicui WANG ; Xueni JIA ; Yulong ZHAO ; Fengling XIN
Chinese Journal of Health Management 2024;18(8):587-592
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.
6.Cost-effectiveness analysis of enzalutamide in the treatment of metastatic prostate cancer
Lei YANG ; Fengling WANG ; Ling HUANG ; Yan LI ; Hanrui ZHENG ; Lingli ZHENG ; Li CHEN
Chinese Journal of Pharmacoepidemiology 2024;33(3):269-276
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.
7.Evaluation and analysis on diagnostic criteria for common occupational radiation-induced diseases among radiation workers in some provinces and cities of China
Wei GUO ; Fengling ZHAO ; Zhiwei XING ; Ling HE ; Wei LIU ; Yulong LIU ; Shouzheng WANG ; Zaiqing HE ; Wei CHEN ; Guizhi CHEN
Chinese Journal of Radiological Medicine and Protection 2023;43(8):620-626
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.
8.Effect analysis of PDCA cycle on prophylactic use of antibiotics in laparoscopic cholecystectomy during perioperative period
Jingjing ZHANG ; Fengling WANG ; Xiangyun MENG ; Dan SU
China Pharmacy 2023;34(13):1632-1636
OBJECTIVE To evaluate the effect of PDCA cycle on prophylactic use of antibiotics in laparoscopic cholecystectomy during perioperative period and to conduct pharmacoeconomic analysis. METHODS Using retrospective analysis method, 80 discharged patients of each group underwent laparoscopic cholecystectomy were randomly selected from Hefei Second People’s Hospital before PDCA cycle (from May to June 2019), after the first round of PDCA cycle (from May to June 2020), after the second round of PDCA cycle (from May to June 2021) according to real or basic reasons for irrational drug use. The rationality of prophylactic use of antibiotics for patients was evaluated. The general situation, antibiotic use, clinical efficacy and treatment cost of patients were compared before cycle and after the first and second rounds of PDCA cycle. Cost-effectiveness analysis method and sensitivity analysis method were adopted to evaluate pharmacoeconomic significance of PDCA cycle. RESULTS After two rounds of PDCA cycle, the irrational rate of antibiotics, cost ratio of antibiotics, the number of days of antibiotics use, DDDs, drug utilization index, the frequency of antibiotics use per capita, the total amount of antibiotics, the cost of antibiotics, the total amount of drugs, and the total cost of hospitalization all decreased significantly (P<0.05). The results of cost-effectiveness analysis indicated that the pharmacoeconomic effect was the best after two rounds of PDCA cycle; the results of sensitivity analysis were consistent with it, which confirmed the reliability of the research results. CONCLUSIONS PDCA CPA- cycle promotes the rational use of antibiotics of laparoscopic cholecystectomy during perioperative period, reduces the cost of antibiotics and relieves the economic burden of patients.
9.Implementation and revision of the Measures for the Management of Radiation Workers’ Occupational Health
Shiyue CUI ; Yinping SU ; Fengling ZHAO ; Zhiwei XING ; Li LIANG ; Juan YAN ; Yuanyuan ZHANG ; Bo WANG ; Jianxiang LIU ; Changsong HOU ; Erdong CHEN ; Jun DENG ; Quanfu SUN
Chinese Journal of Radiological Health 2023;32(3):335-340
Since the implementation of the Measures for the Management of Radiation Workers’ Occupational Health in November 2007, it has played an extremely important role in protecting the occupational health of radiation workers. There are more than 700 000 radiation workers in about 100 000 workplaces with potential radiation exposure, as well as a large number of miners exposed to high levels of radon. As the radiation health monitoring project suggests, measures of occupational health management such as personal dose monitoring and occupational health examination of radiation workers have been widely implemented and achieved good results in the protection of radiation workers. However, the risks of chromosomal aberration and specific turbidity of the eye lens of radiation workers have increased in high-risk positions such as interventional radiology, nuclear medicine, and industrial flaw detection. The control of high radon exposure in miners needs to be strengthened. It is necessary to adapt to the new situation in view of new challenges and actively promote the revision of the Measures for the Management of Radiation Workers’ Occupational Health, so as to further improve the occupational health management of radiation workers in China.
10.Mining and analysis of risperidone adverse event signals based on FAERS database
Ling HUANG ; Fengling WANG ; Li CHEN ; Xinming WANG ; Li CHEN
China Pharmacy 2023;34(3):350-354
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.

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