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.

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 characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

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.

Objective:To investigate the influencing factors of surgical site infection (SSI) after abdominal surgery.Methods:The retrospective cross-sectional study was conducted. The clinical data of 567 patients undergoing abdominal surgery in 6 medical centers, including 445 cases in the Zhengzhou Central Hospital Affiliated to Zhengzhou University, 54 cases in the the First Affiliated Hospital of Zhengzhou University, 49 cases in the Shangqiu First People's Hospital, 10 cases in the Luoyang Central Hospital, 5 cases in the First Affiliated Hospital of Henan University of Science and Technology and 4 cases in the Henan Provincial People's Hospital, from June 1 to June 30, 2020 were collected. There were 284 males and 283 females, aged (51±18)years. Observation indicators: (1) incidence of SSI after surgery; (2) influencing factors of SSI. Follow-up was conducted using outpatient examination and telephone interview to detect the incidence of SSI. Patients without implant were followed up within postoperative 30 days, and patients with implant were followed up within postoperative 1 year. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measure-ment data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Univariate analysis was performed using the corresponding statistical methods. Multivariate analysis was performed using the Logistic stepwise regression model advance method. Results:(1) Incidence of SSI after surgery. All the 567 patients were followed up after surgery as planned. There were 27 cases with SSI after surgery including 9 cases with superficial incision infection, 9 cases with deep incision infection, 9 cases with organ/gap infection. Of the 27 cases with SSI after surgery, 18 cases with positive results of incisional microbial culture including 8 cases with positive results of Escherichia coli, 6 cases with positive results of Klebsiella pneumonia, 3 cases with positive results of Enterococcus faecium and 1 case with positive result of Pseudomonas aeruginosa. (2) Influencing factors of SSI. Results of univariate analysis showed that age, preoperative hemoglo-bin, preoperative albumin, preoperative fasting blood glucose, preoperative intestinal preparation, surgical type, surgical site, surgical incision type, duration of intensive cure unite, duration of post-operative hospital stay, duration of total hospital stay, operation time, hospital expense were related factors affecting the incidence of SSI of patients undergoing abdominal surgery ( χ2=40.12, Z=?4.22, ?2.21, ?4.75, χ2=7.07, 16.43, 38.06, 17.50, Z=?4.43, ?4.42, ?7.14, ?7.15, ?5.90, P<0.05) and the American Association of Anesthesiologists Classification, preoperative oral antibiotics, surgical methods and postoperative intensive care unit stay were related factors affecting the incidence of SSI of patients undergoing abdominal surgery ( P<0.05). Results of multivariate analysis showed that age, preopera-tive fasting blood glucose, preoperative intestinal preparation, surgical type, surgical site as appendix and rectum, surgical methods, surgical incision type as infective incision and polluted incision, operation time were independent factors affecting the incidence of SSI of patients undergoing abdo-minal surgery ( odds ratio=7.69, 1.21, 0.27, 5.82, 5.19, 19.08, 0.23, 27.76, 4.97, 1.01, 95% confidence intervals as 2.04?28.95, 1.04?1.41, 0.08?0.94, 1.36?24.85, 1.10?24.43, 4.48?81.25, 0.06?0.87, 2.54?303.53, 1.12?22.14, 1.01?1.02, P<0.05). Conclusion:Age, preoperative fasting blood glucose, preoperative intestinal preparation, surgical type, surgical site as appendix and rectum, surgical methods, surgical incision type as infective incision and polluted incision, operation time are independent factors affecting the incidence of SSI of patients undergoing abdominal surgery.

Background Arsenic can be toxic to human by triggering oxidative stress, which is companied by epigenetic modifications. Objective To investigate the modification of N⁶-methyladenosine (m⁶A) in human embryonic lung fibroblasts (HELF) during oxidative stress induced by sodium arsenite (NaAsO₂). Methods HELF cells were treated by designed concentrations of NaAsO₂ (0, 2.5, 5, 10, and 20 μmol·L⁻¹) for 48 h. Cell viability was detected by 3-(4,5-dimethylthia zol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium (MTS) method; the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) as well as the content of malondialdehyde (MDA) were detected with corresponding kits; the level of m⁶A methylation in total RNA was detected by enzyme-linked immunosorbent assay; the mRNA expressions of m⁶A modified enzymes were detected by real-time fluorescence quantitative PCR, including methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), Wilms' tumor 1-associated protein (WTAP), fat mass and obesity-associated protein (FTO), alkB family of Fe(II)/α-ketoglutarate-dependent dioxygenases 5 (ALKBH5), YTH domain containing protein 2 (YTHDC2), YTH domain family protein 2 (YTHDF2), and YTH domain family protein 3 (YTHDF3); the protein expressions of METTL3, FTO, YTHDC2, YTHDF3, and nuclear factor erythroid 2-related factor 2 (NRF2) were detected by Western blotting. The enrichment of m⁶A in NRF2 mRNA was detected by RNA methylated immunoprecipitation combined with real-time fluorescence quantitative PCR (MeRIP-qPCR). Results After the 0, 2.5, 5, 10, and 20 μmol·L⁻¹ NaAsO₂ treatment, the MTS results showed that compared with the control group, the cell viability of the 20 μmol·L⁻¹ group decreased to 84% (P<0.05). The colorimetry results showed that compared with the control group, the activities of T-SOD in the 10 and 20 μmol·L⁻¹ groups decreased (P<0.05); the activities of GSH-Px in the 2.5 and 10 μmol·L⁻¹ groups decreased (P<0.05); the contents of MDA in the 10 and 20 μmol·L⁻¹ groups increased. The results of enzyme-linked immunosorbent assay showed that the overall m⁶A methylation levels in the 0, 2.5, 5, 10, and 20 μmol·L⁻¹ groups were (0.193 ± 0.023)%, (0.247 ± 0.021)%, (0.253 ± 0.006)%, (0.233 ± 0.006)%, and (0.262 ± 0.010)%, respectively, and compared with the control group, the m⁶A methylation levels in all the NaAsO₂ treated groups increased (P<0.05). The real-time fluorescence quantitative PCR results showed that compared with the control group, the mRNA relative expression level of METTL3 decreased in the 2.5, 10, and 20 μmol·L⁻¹ groups (P<0.05); the mRNA relative expression level of FTO decreased in the 20 μmol·L⁻¹ group; the mRNA relative expression level of YTHDC2 increased in the 10 and 20 μmol·L⁻¹ groups (P<0.05); the mRNA relative expression level of YTHDF3 increased in the 2.5, 10, and 20 μmol·L⁻¹ groups (P<0.05). The Western blotting results showed that compared with the control group, the relative protein expression of METTL3 decreased in the 10 and 20 μmol·L⁻¹ groups; the relative protein expression of FTO decreased in the 5 and 20 μmol·L⁻¹ groups; the relative protein expression of YTHDC2 decreased in the 20 μmol·L⁻¹ group (P<0.05); the relative nuclear protein expression of NRF2 decreased in the 10 and 20 μmol·L⁻¹ groups (P<0.05). The MeRIP-qPCR results showed that m⁶A enrichment was significantly increased in the 20 μmol·L⁻¹ NaAsO₂ exposure group compared with the control group (P<0.05). After over-expression of FTO, the mRNA and protein relative expression levels of FTO and the relative expression level of nuclear protein of NRF2 in the FTO group were higher than those in the control group (P<0.05); the mRNA and protein relative expression levels of FTO in the NaAsO₂ + FTO group and the nuclear protein expression level of NRF2 were higher than those in the NaAsO₂ group (P<0.05). Conclusion In the process of oxidative stress induced by NaAsO₂, m⁶A methylation level, m⁶A modified enzymes, m⁶A modification of NRF2 mRNA, and NRF2 expression could change in HELF cells.