Objective To discuss the effect of different particle activities and tumor shrinkage speed on the dosimetric parameters of the target area at the same prescription dose after 125I particle implantation.Methods A 6cm-sized cube tumor model was outlined by using a computerized three-dimensional treatment planning system(3D-TPS)with a prescription dose(PD)of 100 Gy,and 125I particle activities of 0.4 mCi and 0.8 mCi were selected.Assuming that the tumor shrinks centripetally after seed implantation and that the 125I particles were uniformly and centripetally concentrated without shedding or wandering,the tumor volume shrank at different rates every month after implantation(0,5％,10％,15％,20％,25％,30％,35％,40％,45％and 50％),according to the different activities of 125I particles,the experiments were divided into A1-K1 group(0.4 mCi)and A2-K2 group(0.8 mCi).Based on the 125I particle decay law,the validation program(using TPS simulation of the A1-K1 group and A2-K2 group at postoperative 1,2,3,4,5 and 6 months)obtained the dose received by 90％of the target volume(D90)in the two groups with different 125I particle activities at different postoperative time points,the percentages of the target volume covered by the 100％,150％and 90％prescription dose(V100,V150,V90),and the mean dose(Dmean).By comparing the differences in D90,V100,V150,V90 and Dmean after tumor implantation of 125I particles with different activities,the dosimetric impact of the tumor target area shrinking at a rate of 0～50％after implantation of 125I particles with different activities into tumor tissues was analyzed.Results When the monthly shrinkage rate of the tumor target area was≤30％,there was no obvious difference in D90 between the 0.4 mCi group and 0.8 mCi group in 1～6 months after surgery.When the monthly shrinkage rate of the tumor target area was＞30％,the D90 of 0.8 mCi group was higher than that of 0.4 mCi group;when the monthly shrinkage rate of the tumor target area was＜25％,the V90 of 0.4 mCi group was higher than that of 0.8 mCi group,and the changes of V90 of the two groups tended to be the same in the 5th～6th month after surgery.When the monthly shrinkage rate of the tumor target area was ≥30％,the V90 of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more significant,the results of V100 were consistent with those of V90.When the monthly shrinkage rate of tumor target area＜35％,V150 of 0.4 mCi group was higher than that of 0.8 mCi group,when the monthly shrinkage rate of tumor target area ≥35％,V150 of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more prominent.When the monthly shrinkage rate of tumor target area＜25％,Dmean of 0.4 mCi group was higher than that of 0.8 mCi group,when the monthly shrinkage rate of tumor target area ≥25％,Dmean of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more obvious.Conclusion With the same prescription dose,when the tumor target area shrinks at a rate of＜30％per month,the activity of 125I particles has little effect on D90,and all V90,V100,V150 and Dmean in the low activity group are higher than those in the high activity group,meanwhile the homogeneity of the target area is relatively good;when the monthly shrinkage rate of tumor target area ≥35％,all D90,V90,V100,V150 and Dmean in the high activity group are higher than those in the low activity group,and the duration of the presence of high-dose area is long.This difference becomes more obvious with the increasing of the monthly shrinkage rate of the target area.

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 study the changes and mechanism of skin stem cells in microgravity.Methods The skin stem cells of SD rats were used to establish a suspension culture system and compare the proliferation of skin stem cells with 1G gravity.Results The simulated microgravity significantly affected the velocity of skin stem cell sphere proliferation in suspension culture,which was about 12%higher than the 1G gravity group.Transcriptome sequencing showed that 1673 genes were up-regulated and 1409 genes were downregulated;Calcium signaling;cytokine-cytokine receptor interaction and PPAR pathway were different in the two environments.Conclusion Simulation of microgravity can affect the proliferation behavior of skin stem cells in suspension culture by regulating the expression of key signaling pathways,which provides an experimental basis for further research in spatial microgravity environ ment.

Objective To study traditional Chinese medicine(TCM)syndrome pattern of astronauts in long term spaceflight,and to summarize and elucidate the characteristics and evolvement of their holistic functional status based on TCM Pattern Identification and Classification System.Methods The Digital TCM Diagnostic Instrument and TCM Syndrome Diagnosis Scale were used to collect information from 9 astronauts in three manned missions of China Space Station,through diagnostic methods of observation,palpation and inquiry according to CM theory.Data collection was performed at various stages before,during,and after spaceflight,a total of 32 person-time digital images of tongues and facial complexion and over 2 000 data were collected.Through data mining and analysis using four diagnostic feature fusion methods,the distribution characteristics of TCM pattern among astronauts at different stages of flight and with different physical constitutions were proposed,and the health status and evolution trend of astronauts were evaluated based on the health concept of TCM.Results ⑴The astronauts showed related manifestations of 8 TCM syndromes during long term flight,among which 4 syndromes had higher scores,including Liver Depression Transforming into Fire,Liver and Kidney Yin Deficiency,Heart Kidney Disharmony,and Spleen and Kidney Yang Deficiency.However,their syndrome differentiation were mainly based on Yin and Yang in equilibrium,with only a few individuals showing a brief deviation from the equilibrium state at a certain stage.After long-term adaptation and adjustment,they almost had returned to a state of Yin-Yang equilibrium reestablishment.⑵As the flight time increased,the proportion of Liver Depression Transforming into Fire and Qi and Blood Deficiency in Heart and Spleen syndrome increased month by month,indicating that the psychological and emotional changes and insufficient Qi and blood status during long term flight need to be focused on.⑶Physical constitution had a certain impact on the syndrome patterns during flight,the astronauts with biased constitutions had significantly higher total scores for all syndrome patterns than that of individuals with Normal-constitution,astronauts with Yin deficiency had slightly higher scores for Heart Kidney Disharmony than those with Yang(Qi)deficiency,indicating that personalized TCM conditioning measures should be developed based on the pathogenesis of TCM syndrome during different flight periods,combined with factors such as physical constitution,etc.Conclusion The research has verified the scientific nature and effectiveness of TCM pattern analysis based on"four diagnostic"methods,which could be used for achieving quantitative and comprehensive evaluation of astronaut health status from the perspective of TCM in long-term space flight.

As a reversible and dynamic epigenetic marker, N⁶-adenylate methylation (m⁶A) modification is the most common mRNA modification in eukaryotes. This paper briefly described how m⁶A can influence RNA splicing, stability, and translation after transcription, and then participate in a variety of signaling pathways and biological and pathological processes, regulating cell proliferation, apoptosis, epithelial mesenchymal transformation (EMT) processes, and tumor invasion and metastasis. In addition, according to current studies, m⁶A methyltransferases (writers) are believed to promote EMT and tumor development, and readers and erasers both promote and inhibit EMT in different research objects. In this review, we summarized the mechanism of m⁶A modification and its role in cell transformation, and pointed out the direction of disease treatment.

Background Occupational and environmental particulate matter may cause fibrosis, accompanied by RNA m⁶A modification changes. Neodymium oxide (Nd₂O₃) can cause mouse lung fibrosis, which contains a large number of fibroblasts. Objective To investigate m⁶A modification of tumor necrosis factor receptor-associated protein 6/nuclear factor-κB (TRAF6/NF-κB) signaling pathway in fibrosis of human embryonic lung fibroblasts induced by Nd₂O₃, and identify the key m⁶A modification sites of TRAF6. Methods Designed concentrations of Nd₂O₃ (0, 1.563, 3.125, 6.25, 12.5, 25, 50, 100, and 200 mg∙L⁻¹) were infected with HELF cells for 24 and 48 h, and cell viability was detected to determine exposure time and dose. Measurements included indicators of fibrosis [hydroxyproline (HYP) and transforming growth factor-β1 (TGF-β1)], m⁶A methylation level, methyltransferases (METTL3 and METTL14), demethylases (FTO and ALKBH5), reading proteins (YTHDC2 and YTHDF2), fibrosis-associated genes (collagen-І, vimentin, and α-SMA), and proteins related to signaling pathway (TRAF6, NFKB1, P65, and P-P65). The enrichment of m⁶A in TRAF6 mRNA was measured by methylated RNA immunoprecipitation-quantitative real-time PCR (MeRIP-qPCR). Results The results of cell viability indicated that 6.25, 12.5, 25 mg∙L⁻¹ Nd₂O₃ and 48 h exposure time were used for subsequent experiments. After 48 h exposure, compared with the control group, the HYP level in the 25 mg∙L⁻¹ Nd₂O₃ group was increased, and the levels of TGF-β1 in the 6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃ groups were increased (P<0.05); the overall m⁶A methylation levels of HELF cells in the 12.5 and 25 mg∙L⁻¹ Nd₂O₃ groups were increased (P<0.05). At mRNA level, compared with the control group, the mRNA expression levels of methyltransferases METTL3 and METTL14 (6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05); the mRNA expression level of reading protein YTHDF2 (6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃) was increased (P<0.05), while the mRNA expression level of YTHDC2 (25 mg∙L⁻¹ Nd₂O₃) was decreased (P<0.05); the mRNA expression levels of demethylases FTO (12.5 and 25 mg∙L⁻¹ Nd₂O₃) and ALKBH5 (25 mg∙L⁻¹ Nd₂O₃) were decreased (P<0.05); the mRNA expression levels of fibrosis-related genes vimentin, α-SMA, and collagen-Ⅰ (6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05); the mRNA expression levels of pathway-related genes TRAF6 (25 mg∙L⁻¹ Nd₂O₃) and NFKB1 (12.5 and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05). At protein level, compared with the control group, the expression levels of methyltransferases METTL3 (25 mg∙L⁻¹ Nd₂O₃) and METTL14 (12.5 and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05); the expression level of reading protein YTHDF2 (12.5 and 25 mg∙L⁻¹ Nd₂O₃) was increased, while the expression level of YTHDC2 (25 mg∙L⁻¹ Nd₂O₃) was decreased (P<0.05); the expression level of demethylase FTO (25 mg∙L⁻¹ Nd₂O₃) was decreased (P<0.05); the expression level of fibrosis-associated protein vimentin was increased at 25 mg∙L⁻¹ Nd₂O₃, and the expression levels of α-SMA and collagen-Ⅰ were increased at 12.5 and 25 mg∙L⁻¹ Nd₂O₃ (P<0.05); the expression levels of TRAF6 and P-P65 were increased at 25 mg∙L⁻¹ Nd₂O₃ (P<0.05). The MeRIP-qPCR results showed that compared with the control group, the concentrations of m⁶A in all Nd₂O₃ groups were significantly increased (P<0.05). Conclusions Upon exposure of HELF cells to Nd₂O₃, the alterations in fibrosis-related indexes increase the expression of some m⁶A methylases and decrease the expression of demethylases, thereby increasing the m⁶A methylase level, and may promote the progression of fibrosis by activating the TRAF6/NF-κB signaling pathway.

Objective:To evaluate the guidelines on discharged health education for solid organ transplant recipients at home and abroad, analyze the characteristics of each guideline, so as to provide reference for the development of health education for organ transplantation in China.Methods:This was a guideline quality evaluation study. The guidelines on health education for discharged recipients with solid organ transplantation were searched on the websites of clinical practice guidelines, the websites of transplantation professional associations, and Chinese and English databases at home and abroad through computers. The search time limit was from January 1, 2011 to January 1, 2022. The quality of guidelines that met the inclusion and exclusion criteria was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) .Results:A total of 8 guidelines were included. The overall quality evaluation of the guideline was Grade A ( n=2) and Grade B ( n=6) . In terms of standardized scores in six areas of quality evaluation, the average values of scope and purpose, stakeholder involvement, rigour of development, clarity and presentation, applicability as well as editorial independence were 87.62% (70.37%-100.00%) , 75.46% (44.44%-97.22%) , 66.54% (43.75%-93.06%) , 90.16% (77.78%-96.30%) , 48.18% (20.83%-68.75%) and 74.13% (8.30%-97.22%) , respectively. The recommendations of the guidelines covered 9 aspects: team composition and support services, drug management, infection prevention, complication management, diet and nutrition, daily life and social reintegration, contraception and reproduction, psychological guidance and follow-up review. Conclusions:The development of guidelines for different types of solid organ transplantation varies. The overall quality of the guidelines needs to be improved and the content needs to be refined. In the future, we can learn from foreign high-quality guidelines to carry out localization practice, so as to build a health education related guideline for discharge of solid organ transplantation that is suitable for China's national conditions as soon as possible.

Objective:To study the differences in the cumulative dose between deformable image registration (DIR) and simple dose-volume histogram (DVH) summation in the fractionated brachytherapy of cervical cancer, and to analyze the feasibility of the application of DIR in the dosimetry assessment of targets and organs-at-risk (OARs) in the brachytherapy.Methods:A retrospective analysis was conducted for 13 cases with primary cervical cancer treated with four fractions of interstitial brachytherapy guided by CT images. The four CT images of each cases were registered using an intensity-based DIR. Then, the cumulative doses (the D2 cm 3, D1 cm 3, and D0.1 cm 3 of the bladder, rectum, intestine, and colon and the D90for targets) after DIR were calculated and compared to those obtained using simple DVH summation. Afterward, the correlation between the dose difference and dice similarity coefficient (DSC) was analyzed. With the dose difference (the remaining dose of OARs caused by the DIR) as limits, a new plan was made for the latest CT to calculate the dose increase to targets. Results:Compared to simple DVH summation, DIR allowed the cumulative doses of the D2 cm 3 and D1 cm 3 of bladder to be decreased by (2.47±1.92) and (2.82±2.73) Gy, respectively on average ( t=-3.65, -2.93, P < 0.05), those of the D2 cm 3, D1 cm 3, and D0.1 cm 3 of rectum to be decreased by (2.05 ± 1.61) Gy, (1.51 ± 1.58), and (3.21 ± 2.50) Gy, respectively on average ( t=-4.02, -3.02, -4.06, P < 0.05), and those of the D2 cm 3, D1 cm 3, and D0.1 cm 3 to be decreased by (1.42 ± 0.99), (1.55 ± 1.28) Gy, and (2.43 ± 1.95) Gy, respectively on average ( t=-3.52, -2.96, -3.06, P < 0.05). There was no significant statistical difference in the D90 of targets, the D0.1 cm 3 of the bladder, and the D2 cm 3, D1 cm 3, D0.1 cm 3 of the colon ( P > 0.05) between both methods, and there was no distinct correlation between DSC and dose difference ( P > 0.05). The DIR increased the dose to targets, with a median value of 150 cGy. However, the accuracy of the DIR should be improved. Conclusions:In clinical practice of multiple fractions of brachytherapy for cervical cancer, it′s still recommended to adopt the simple dose summation method to assess the doses to targets and OARs.

Objective:To explore the benefit finding and influencing factors of primary caregivers of children with cerebral palsy.Methods:This study adopted the method of random sampling, 158 primary caregivers of children with cerebral palsy in the outpatient and inpatient wards of the Children′s Rehabilitation Department of the Second Affiliated Hospital of Wenzhou Medical University from November 2020 to January 2021 were selected as the research objects. The basic data questionnaire, Chinese version of benefit finding scale, simple coping style questionnaire and perceived social support scale were used to do investigation. The influencing factors of benefit finding of main caregivers of children with cerebral palsy were investigated by single factor analysis, Pearson correlation analysis and multiple linear regression analysis.Results:The score of benefit finding of the main caregivers of children with cerebral palsy was (62.4±7.0),which was above the middle level. The years of diagnosis, the payment method of medical expenses, the place of residence and the length of caring for children had a significant impact on the benefit finding of the main caregivers of children with cerebral palsy ( F=3.45, 3.75, 3.97, 6.60, all P<0.05). The main caregivers′ sense of benefit finding was positively correlated with positive coping style, family support, friend support, others′ support and perceived social support ( r=0.43, 0.20, 0.32, 0.24, 0.30, all P<0.05), and negatively correlated with negative coping style ( r=-0.36, P<0.01).The importance of those factors influencing the benefit finding of the main caregivers of children with cerebral palsy was as follows: positive coping style, place of residence and length of caring for children (standardized regression coefficients were 0.33, 0.22, -0.32, all P<0.05). Conclusions:The main caregivers of children with cerebral palsy have a good sense of benefit finding. The main factors affecting the benefit finding of the main caregivers are the children′s residence, the length of care and coping style.

Objective:To investigate the knowledge, attitude and practice status of ophthalmic nurses on prevention and control of intraocular infection in grade Ⅲ class A hospitals.Methods:A self-made questionnaire was used to investigate the knowledge, attitude and practice of 236 nurses on prevention and control of intraocular infection in the ophthalmology department of 8 grade Ⅲ class A hospitals in Zhengzhou from January to June 2020. The correlation between the knowledge, attitude and practice were analyzed by Pearson correlation analysis and the influencing factors of each term were analyzed by multivariate Logistic regression.Results:The scores of knowledge, attitude, practice of all nurses were (26.08 ± 2.46), (67.45 ± 8.48), (50.31 ± 6.67) points, and the scoring rate were (87.0 ± 8.2)%, (84.3 ± 10.1)%, (83.9 ± 9.8)%, respectively. The scores of each dimension of knowledge, attitude and practice were significantly positively correlated ( r values were 0.26-0.42, all P<0.05), respectively. Multivariate Logistic regression analysis showed that education background, professional title and training experience of infection were the influencing factors of knowledge score ( P<0.05), education background, professional title, training experience of infection and demand were the influencing factors of attitude score ( P<0.05), and nursing age and work post were the influencing factors of practice score ( P<0.05). Conclusions:The level of knowledge, attitude and practice of ophthalmic nurses in grade Ⅲ class A hospitals on prevention and control of intraocular infection is overall good. Hospital management department still needs to make reasonable management countermeasures according to personnel characteristics to improve the knowledge, attitude and practice level of ophthalmic nurses and to reduce post-operative intraocular infection.