Mechanism of Huangwu Ganfu Ointment in Treatment of Peripheral Inflammatory Hyperalgesia of Knee Osteoarthritis Based on TRPV1 / 中国实验方剂学杂志

ObjectiveTo observe the regulatory effect of Huangwu Ganfu ointment on transient receptor potential anchor protein 1 （TRPV1） receptor expression， macrophage polarization， and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway in synovial tissue of knee osteoarthritis （KOA） rats with yang deficiency and cold coagulation syndrome and explore the mechanism of relieving peripheral inflammatory hyperalgesia of KOA. MethodForty-eight male SD rats were randomly divided into blank group， model group， high-dose， middle-dose， and low-dose groups of Huangwu Ganfu ointment （9.3， 4.65， 2.325 g·kg-1）， and celecoxib group （20.82 mg·kg-1）. The KOA rat model of yang deficiency and cold coagulation syndrome was established through climate box and swimming for two weeks combined with an injection of sodium iodoacetate （MIA） in the articular cavity. After continuous administration for four weeks， the general condition of rats in each group was observed， and the pain withdrawal threshold （PWT） and joint diameter induced by mechanical stimulation were recorded. The expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） inflammatory factor were detected by enzyme-linked immunosorbent assay （ELISA）， and the histopathological changes of synovial tissue of the knee joint were observed by hematoxylin-eosin （HE） staining. Western blot was used to detect the protein expression of TRPV1， p38 MAPK， and p-p38 MAPK in synovial tissue of the knee joint， and immunofluorescence （IF） was used to evaluate the polarization of M1/M2 macrophages. ResultCompared with that in the blank group， the overall mental state of the model group was worse， and the autonomous activity was decreased. The body mass was lower， and the joint diameter was increased. The X-ray showed that the osteophyte at the edge of the joint proliferated， and the articular surface was obviously rough. The articular cavity was significantly narrowed， and the PWT was significantly decreased （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in serum and synovium Krenn score increased significantly （P<0.01）. The protein expression of TRPV1 and p-p38 MAPK/p38 MAPK increased significantly （P<0.01）， and the proportion of M1 macrophages and M1/M2 increased （P<0.01）， while the proportion of M2 macrophages decreased （P<0.01）. Compared with model group， the body mass in the low， middle， and high dose groups of Huangwu Ganfu ointment increased to different degrees （P<0.05， P<0.01）. The diameter of the knee joint in the high dose group of Huangwu Ganfu ointment and celecoxib group decreased （P<0.01）. The recovery of PWT in the high and middle dose groups of Huangwu Ganfu ointment groups was more obvious （P<0.05）. The contents of IL-1β and CGRP in the serum of rats in each administration group were significantly decreased （P<0.01）， and the content of serum TNF-α in the celecoxib group and high dose group of Huangwu Ganfu ointment decreased significantly （P<0.05）. The content of serum NGF in the middle dose group of Huangwu Ganfu ointment decreased significantly （P<0.05）， and the synovium Krenn score decreased in the high dose group of Huangwu Ganfu ointment （P<0.05）. In addition， the protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in synovial tissue decreased significantly in all groups of Huangwu Ganfu ointment （P<0.01）. The proportion of M1 macrophages in synovial tissue in the celecoxib group and all groups of Huangwu Ganfu ointment decreased （P<0.01）， and the proportion of M2 macrophages in the high dose group of Huangwu Ganfu ointment increased （P<0.05）. The M1/M2 in the middle and high dose groups of Huangwu Ganfu ointment decreased （P<0.05）. ConclusionHuangwu Ganfu ointment can mediate the polarization of macrophages to reduce the inflammatory reaction of KOA， alleviate the release of inflammatory pain mediators， and lower the protein expression of TRPV1. The mechanism may be related to the p38 MAPK signaling pathway， so as to improve the peripheral hyperalgesia of KOA.

Analysis on Mechanism of Huangwu Ganfu Ointment in Relieving Knee Osteoarthritis Pain Based on Network Pharmacology and Experimental Verification / 中国中医药信息杂志

Objective To analyze the mechanism of Huangwu Ganfu Ointment in relieving pain of knee osteoarthritis(KOA)based on network pharmacology;To verify it in animal experiments.Methods The active components of Huangwu Ganfu Ointment were obtained by TCMSP database,PubChem database and SwissADME platform,the effective components were screened,and the targets were obtained from SEA database.KOA disease-related targets were obtained from GeneCards,OMIM and other databases,and the intersection targets were obtained.A effective component-target-disease network was constructed using Cytoscape 3.9.0 Software.Protein-protein interaction(PPI)network was constructed by STRING database and core targets were screened.GO and KEGG enrichment analysis of intersection targets were analyzed using DAVID platform.The KOA rat model with cold and damp syndrome was established,and the intervention of Huangwu Ganfu Ointment was carried out.The efficacy was observed and the core target expressions were detected.Results Totally 104 effective components were screened from Huangwu Ganfu Ointment,and 59 potential targets were obtained for treating KOA.PPI network interaction analysis obtained the important targets of IL6,IL1B and PTGS2.KEGG enrichment results showed that Huangwu Ganfu Ointment may involve 84 signaling pathways such as IL-17,TNF,TRP and NF-κB in the treatment of KOA,most of which were related to inflammation.The results of animal experiments showed that Lecuesne MG scores increased in the model rats(P<0.05),and paw withdrawal threshold(PWT)significantly decreased(P<0.05).Compared with model group,PWT in Huangwu Ganfu Ointment medium-and high-dosage groups were significantly recovered,and synovitis Krenn score decreased(P<0.05).The Mankin score of cartilage tissue of Huangwu Ganfu Ointment high-dosage group decreased(P<0.05).The contents of IL-6 and IL-1β in all Huangwu Ganfu Ointment groups decreased(P<0.01).Huangwu Ganfu Ointment medium-and high-dosage groups could down-regulate the expression of TRPV1 protein(P<0.05,P<0.01).Conclusion The mechanism of Huangwu Ganfu Ointment in alleviating the pain of KOA may be related to reducing inflammatory response,reducing the release of inflammatory factors of IL-1β and IL-6,alleviating inflammatory pain sensitivity of KOA,and down-regulating the expression level of TRPV1.

A research on epilepsy source localization from scalp electroencephalograph based on patient-specific head model and multi-dipole model / 生物医学工程学杂志

Accurate source localization of the epileptogenic zone (EZ) is the primary condition of surgical removal of EZ. The traditional localization results based on three-dimensional ball model or standard head model may cause errors. This study intended to localize the EZ by using the patient-specific head model and multi-dipole algorithms using spikes during sleep. Then the current density distribution on the cortex was computed and used to construct the phase transfer entropy functional connectivity network between different brain areas to obtain the localization of EZ. The experiment result showed that our improved methods could reach the accuracy of 89.27% and the number of implanted electrodes could be reduced by (19.34 ± 7.15)%. This work can not only improve the accuracy of EZ localization, but also reduce the additional injury and potential risk caused by preoperative examination and surgical operation, and provide a more intuitive and effective reference for neurosurgeons to make surgical plans.

Emergency training need and effect evaluation analysis of novel coronavirus pneumonia in centers of disease control and prevention / 中华预防医学杂志

A questionnaire was used to investigate the emergency training needs of novel coronavirus pneumonia of disease prevention and control institutions in provinces, deputy provincial level regions and cities specifically designated in the state plan, and the effect evaluation of emergency training activities conducted by Chinese Center for Disease Control and Prevention (China CDC). The results showed that 67.4% of 47 disease prevention and control institutions (31/46) believed that the emergency training at the initial stage of the epidemic should be conducted as soon as possible, and the form of network training should be given priority. The training should focus on the urgently needed technologies such as epidemiological investigation, formulation and response of prevention and control strategies, laboratory testing, etc. The teaching materials should highlight pertinence and practicability and be presented in the form of electronic video. The average satisfaction score of the video training conducted by China CDC was (8.81±1.125) and the score of audio-video courseware was (8.97±0.893). The needs analysis and evaluation of novel coronavirus pneumonia prevention and control in disease prevention and control institutions could provide reference for the follow-up training and improve the emergency training management.

Influencing factors of serum insulin-like growth factor binding protein-3 level in radiological workers in medical institutions / 中华放射医学与防护杂志

Objective:To investigate the influence of low-dose ionizing radiation on the expression level of serum insulin-like growth factor binding protein-3 (IGFBP-3) in radiation workers in hospitals.Methods:183 radiation workers were randomly selected and grouped by work type including interventional radiology ( n=37), nuclear medicine ( n=43), radiotherapy ( n=48), and diagnostic radiology ( n=55). The content of IGFBP-3 in the serum of radiation workers was detected by ELISA assay. Results:It was observed that the expression level of serum IGFBP-3 in the four groups had significant differences ( F=6.056, P<0.05), and the content of serum IGFBP-3 in the interventional radiology group was significantly higher than that of nuclear medicine, radiotherapy, and diagnostic radiology groups ( t= 2.815, 3.611, 3.936, P<0.05). The concentration of IGFBP-3 in the serum of radiation workers among different annual effective dose groups was statistically different ( F=8.380, P<0.05), which gradually increased with the increase of annual effective dose and length of service ( rs=0.202, 0.151, P<0.05). Conclusions:The expression level of serum IGFBP-3 has the potential to be used as a biomarker to reflect the cumulative exposure of long-term chronic low-dose ionizing radiation.

Influence factors of chromosomal aberration levels in radiation workers in hospitals / 中华放射医学与防护杂志

Objective:To explore the influence factors of chromosomal aberration levels in radiation workers in hospitals.Methods:Two hundred and fourteen age- and sex- matched hospital radiation workers were recruited by stratified random sampling method. According to the job title, the individuals were divided into four groups including diagnostic radiology group ( n=57), radiotherapy group ( n=49), nuclear medicine group ( n=52) and interventional radiology group ( n=56). Chromosomal aberrations in peripheral blood lymphocytes from the subjects were measured using conventional cytogenetic analysis method, and the influence factors of chromosomal aberrations were analyzed. Results:There was significant difference in the frequencies of acentric fragment, translocation and total chromosome-type aberrations among the four groups ( χ2=9.906, 19.965, 32.824, P<0.05), and the rates of aberrations were significantly higher in the interventional radiology group and the nuclear medicine groups than those in the diagnostic radiology (interventional group: χ2=4.711, 10.798, 10.845, P<0.05; nuclear medicine group: χ2=3.853, 7.674, 7.708, P<0.05) and the radiotherapy groups (interventional group: χ2=9.209, 9.772, 21.330, P<0.05; nuclear medicine group: χ2=8.010, 6.969, 10.812, P<0.05). The rates of translocation and total aberrations ( χ2=7.706, 6.667, P<0.05) and the frequencies of acentric fragment, translocation and total aberrations ( χ2=12.263, 15.360, 21.478, P<0.01) were dependent on the length of service and the dose among different groups. The rates of translocation and total aberrations significantly increased along with exposure doses ( r=0.347, 0.263, P<0.01). Poisson regression analysis indicated that the job titles and annual effective dose partly affected the levels of chromosomal aberrations[ IRR=1.797 (nuclear medicine group), 2.136 (interventional group) and 1.422 (0.5-1 mSv group); P<0.05]. Conclusions:The frequencies of chromosomal aberrations in the radiation workers of interventional and nuclear medicine groups remain higher levels in hospital, thus it is necessary to strengthen the radiation protection on these radiation workers.

The feasibility of using automatic micronucleus assay to test micronucleus in lymphocyte of radiation workers / 中华放射医学与防护杂志

Objective:To explore the feasibility of using a High-Throughput Chromosome Automatic Scanning System (Metafer 4) to carry out automatic micronucleus detection for radiation workers.Methods:A total of 2 005 radiation workers selected were divided into five groups in terms of diagnostic radiology, radiotherapy, nuclear medicine, interventional radiology and industrial application.The Metafer 4 was used to assay micronuclei in peripheral blood lymphocytes from the subjects, with the factors affecting micronuclei analyzed. A total of 200 micronucleus samples collected by stratified random sampling were manually assayed for comparison of micronuclei frequency and detection efficiency between automatic and manual analysis.Results:The mean micronuclei frequency in 2 005 radiation workers were measured to be (0.92±0.02) ×10 -3. There was significant difference in the frequencies of micronuclei among the five groups ( χ2=11.054, P<0.05), with higher micronuclei frequency in interventional radiology group(1.00±0.03) ×10 -3 than in other groups ( χ2=5.568, 5.334, 7.689, P<0.05). Statistically significant difference could be observed in annual effective dose, length of service and micronuclei frequency among the radiation workers in different medical applications ( F=3.026, χ2=11.582, 8.878, P<0.05). A positive correlation between annual effective dose and micronucleus frequency was shown by Pearson analysis ( r=0.106, P<0.05). Multiple linear regression analysis showed that the automatic assay-based micronuclei frequencies were associated with length of service and work categories( r=9.485×10 -6, 5.660×10 -5, P<0.05), significantly lower when compared with manual analysis ( χ2=169.259, P<0.05). There was a consistency (ICC=0.713, P<0.05) between the two assay methods, but automatic analysis can increase the assayed micronucleus frequency by about 5 folds. Conclusions:The micronucleus frequency tested by automatic detection reflects genetic damage from low-dose chronic radiation exposure, and there may be feasibility of using automatic analysis to assay micronucleus of radiation workers.

Serum 8-hydroxy-2-deoxyguanosine level of radiation workers in hospitals / 中华放射医学与防护杂志

Objective To explore the influence of long-term low-dose ionizing radiation on 8-hydroxy-2-deoxyguanosine(8-OHdG) level in the serum of radiation workers in hospitals.Methods 307 age-and sex-matched hospital radiation workers were recruited by stratified random sampling method.After deleting the subjects without dosage information,230 individuals were divided into four groups according to their job title [including diagnostic radiology (n =75),radiotherapy (n =60),nuclear medicine (n =41) and interventional radiology (n =54)].Serum 8-OHdG level was measured by ELISA assay.Results According to the statistical analysis,there was significant difference in the serum 8-OHdG level among four groups (F =9.071,P ＜ 0.05),and the content of serum 8-OHdG was significantly higher in the interventional radiology group than that in the groups of diagnostic radiology,radiotherapy and nuclear medicine (t =-4.473,-3.011,-2.189,P ＜ 0.05).There were significant differences in serum 8-OHdG level among different dose groups and working period groups(F =7.659,3.058,P ＜ 0.05).The serum 8-OHdG levels significantly increased along with exposure dose and working period (r =0.300,0.142,P ＜ 0.05).Conclusions Serum 8-OHdG may be a potential biomarker of oxidative DNA damage in radiation workers exposed to low-dose ionizing radiation.