BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

Objective To explore the value of pulmonary perfusion SPECT/CT imaging for diagnosing pulmonary embolism(PE)and combining with clinical and laboratory indicators for predicting prognosis.Methods Totally 260 patients with suspected PE were retrospectively collected,and PE was clinically confirmed in 237 cases.The diagnostic efficacy of pulmonary perfusion SPECT/CT imaging and CT pulmonary angiography(CTPA)were compared.Among 237 patients with clinically confirmed PE,160 cases were initially diagnosed who underwent standard anticoagulant therapy and were regularly followed up to 3 months after discharge,and their prognosis were analyzed.Logistic regression was used to analyze clinical data,laboratory indicators and pulmonary perfusion defect scores based on pulmonary perfusion SPECT/CT imaging to screen the independent predictors of poor prognosis of PE of the above patients,and a prediction model was then constructed.Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the predictive efficacy of this model for predicting prognosis of PE.Results The positive rate of PE diagnosed with pulmonary perfusion SPECT/CT was higher than that with CTPA(66.54％[173/260]vs.59.62％[155/260],x2=4.765,P=0.038).Among 160 cases of clinically confirmed PE,poor prognosis was observed in 51 cases,while good prognosis was noticed in 109 cases.Patients' age,blood urea nitrogen,serum creatinine,uric acid,D-dimer level and pulmonary perfusion defect score were all independent predictors for poor prognosis of PE(all P＜0.05),and AUC of the established combined model was 0.731.Conclusion Pulmonary perfusion SPECT/CT imaging could be used for diagnosing PE,and combining with clinical and laboratory indicators could effectively predict prognosis of PE.

Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.

Objective To analyze the clinical characteristics and interventional treatment effects of pa-tients with renal arteriovenous fistula in this hospital over the past 10 years.Methods A retrospective analy-sis was conducted on the clinical and imaging data of 40 patients with renal arteriovenous fistula who were treated in this hospital from October 2012 to October 2022.After classifying the fistula type using digital sub-traction angiography(DSA),an individualized embolization plan was developed by a vascular surgery team.Postoperatively,the embolization materials,embolization success rate,clinical success rate,perioperative renal function changes and complications were analyzed.Results A total of 29 cases(72.5%)had acquired renal arteriovenous fistula,while 11 cases(27.5%)had non-acquired renal arteriovenous fistula.Forty-three super-selective transcatheter arterial embolization(TAE)procedures were performed,achieving a technical success rate of 100.0%(40/40)and a clinical success rate of 95.0%(38/40).The mean serum creatinine levels after TAE were(91.39±23.72)mmol/L in the non-acquired group and(105.94±35.51)mmol/L in the acquired group.No statistically significant difference was observed in perioperative serum creatinine changes between the two groups(P=0.095).No severe complications such as renal function deterioration occurred postopera-tively in any patient.Conclusion Gross hematuria serves as the primary clinical manifestation of renal arterio-venous fistula,with abdominal pain being more prevalent in non-acquired renal arteriovenous fistula.The em-bolization approach combining coils with polyvinyl alcohol particles demonstrates favorable safety and efficacy in treating renal arteriovenous fistula.

Objective:To investigate and analyze basic status of radiotherapy units in Hebei Province in 2024.Methods:Led by the Fourth Hospital of Hebei Medical University, the Radiation Oncology Branch of the Hebei Medical Association, and the Radiation Oncology Expert Committee of the Hebei Society of Clinical Oncology, a province-wide survey was conducted using structured questionnaires. The survey covered key aspects such as basic information of radiotherapy institutions, personnel allocation, equipment configuration, and implementation of radiotherapy techniques. Collected data were summarized and descriptively analyzed comparing with a 2013 survey of radiotherapy in Hebei Province.Results:All 158 radiotherapy institutions across Hebei Province participated in the survey. A total of 2273 radiotherapy professionals were reported, including 1317 radiation oncologists (57.94%), 332 medical physicists (14.61%), 71 radiotherapy engineers (3.12%), and 553 radiotherapy technologists (24.33%). The number of radiotherapy devices significantly increased from 121 in 2013 to 237 in 2024, including 68 domestic radiotherapy equipment. The current inventory includes 195 medical linear accelerators (2.61 units per million population), 2 cobalt-60 units, 27 afterloading machines, 9 tomotherapy (TOMO) systems, 3 CyberKnife units, and 1 proton therapy system. Three-dimensional conformal radiotherapy and stati intensity-modulated radiotherapy have been widely adopted across the province, while advanced techniques such as volumetric-modulated arc therapy, stereotactic body radiotherapy, and respiration-gated technology, and respiratory gating are gradually being implemented.Conclusions:In recent years, the configuration of radiotherapy personnel in Hebei Province has become more balanced, and the availability of precision radiotherapy equipment has significantly improved. There is a growing trend in the adoption of domestically manufactured radiotherapy equipment, marking substantial progress in the development of radiation oncology services in the region.

Network analysis serves as a critical methodological approach for enhancing the efficiency of health management in elderly patients with chronic diseases,demonstrating unique advantages in precisely identifying intervention targets.This article comprehensively reviews recent advancements in the application of network analysis for managing chronic conditions in older adults,systematically organizing research findings across 3 analytical dimensions:cross-sectional networks,dynamic networks,and individualized networks.The review aims to provide healthcare professionals with a robust theoretical foundation and methodological support for developing personalized health management strategies.

Objective To propose a novel method based on three-dimensional depthwise separable convolution network(3D DSN)for the separation of PET images with dual tracers of 18F-FDG and 18F-FAPI.Methods A total of 120 pairs of 18F-FDG and 18F-FAPI PET images of the same patient scanned separately at different time points were collected,and the dual-tracer PET image was generated through simulation.After the image registration of PET images of two tracers for ensuring spatial position matching,the registered PET images were forward-projected to generate sinogram data,and the sinogram data of two tracers were accumulated to obtain mixed sinogram data.Subsequently,the dual-tracer PET image was reconstructed using maximum likelihood expectation maximization and input into a 3D DSN based network for image separation,thereby obtaining PET images of two single tracers.Results Compared with 3D CNN method,the proposed method increased the structure similarity index measure(SSIM)of the separated 18F-FDG images to the real 18F-FDG images by 0.87%,increased the peak signal-to-noise ratio(PSNR)by 11.8%,and reduced the normalized root mean square error(NRMSE)by 52%.The SSIM of the separated 18F-FAPI images to the real 18F-FAPI images increased by 1.1%,PSNR increased by 17.0%,and NRMSE decreased by 51%.Conclusion The proposed method can be effectively applied to simultaneous PET imaging with dual PET tracers,reducing the number of scans and costs in time and money,and providing clinical doctors more accurate and abundant diagnostic information.

Objective:To investigate the changes in iodine intake and iodine nutrition trends of pregnant women in a certain district of Beijing, as well as their related influencing factors, to provide a basis for formulating iodine supplementation strategies for pregnant women.Methods:According to the National Monitoring Program for Iodine Deficiency Disorders, a stratified random sampling method was used to select 100 pregnant women (balanced in early, middle, and late pregnancy) for monitoring each year from 2021 to 2024. Based on the salt iodine and urinary iodine levels of pregnant women, combined with their intake of iodine supplements and other medications, a generalized linear model (GLM) was used to analyze the annual trends in salt iodine and urinary iodine levels. Generalized linear mixed-effects models (GLMMs) were employed to evaluate the variations in salt iodine and urinary iodine levels of pregnant women during different pregnancy periods.Results:From 2021 to 2024, a total of 400 pregnant women were enrolled, with salt iodine levels of (19.23 ± 6.18), (21.31 ± 6.41), (22.38 ± 6.86), and (15.87 ± 9.43) mg/kg, respectively. There was a statistically significant differences between different years ( F = 15.21, P < 0.001). By 2024, the proportion of non-iodized salt consumed reached 25.0% (25/100). The median urinary iodine levels in each year were 136.02, 151.27, 117.83, and 122.94 μg/L, respectively, and the differences between different years were statistically significant ( H = 31.89, P < 0.001). The GLM results showed that compared with 2021, the salt iodine level increased by 2.21 mg/kg (β = 2.21, P = 0.038) in 2022, increased by 3.24 mg/kg (β = 3.24, P = 0.002) in 2023, and decreased by 3.28 mg/kg (β = - 3.28, P = 0.002) in 2024. The urinary iodine level decreased by 24.53 μg/L (β = - 24.53, P = 0.030) in 2024. The GLMMs results showed that compared with early pregnancy, urinary iodine levels increased by 33.68 μg/L (β = 33.68, P = 0.008) in middle pregnancy and 43.17 μg/L (β = 43.17, P = 0.001) in late pregnancy. Conclusions:From 2021 to 2024, the iodine intake of pregnant women in a certain district of Beijing shows an overall trend of first increasing and then decreasing, especially with an increase in the proportion of non iodized salt consumption in 2024. And the iodine nutrition status varies during different pregnancy periods. It is necessary to strengthen the promotion of iodized salt and the publicity of iodine deficiency disorders prevention and control, to ensure that pregnant women can obtain sufficient iodine nutrition through other means when their intake of iodized salt is reduced.

Objective:To investigate the changes in iodine intake and iodine nutrition trends of pregnant women in a certain district of Beijing, as well as their related influencing factors, to provide a basis for formulating iodine supplementation strategies for pregnant women.Methods:According to the National Monitoring Program for Iodine Deficiency Disorders, a stratified random sampling method was used to select 100 pregnant women (balanced in early, middle, and late pregnancy) for monitoring each year from 2021 to 2024. Based on the salt iodine and urinary iodine levels of pregnant women, combined with their intake of iodine supplements and other medications, a generalized linear model (GLM) was used to analyze the annual trends in salt iodine and urinary iodine levels. Generalized linear mixed-effects models (GLMMs) were employed to evaluate the variations in salt iodine and urinary iodine levels of pregnant women during different pregnancy periods.Results:From 2021 to 2024, a total of 400 pregnant women were enrolled, with salt iodine levels of (19.23 ± 6.18), (21.31 ± 6.41), (22.38 ± 6.86), and (15.87 ± 9.43) mg/kg, respectively. There was a statistically significant differences between different years ( F = 15.21, P < 0.001). By 2024, the proportion of non-iodized salt consumed reached 25.0% (25/100). The median urinary iodine levels in each year were 136.02, 151.27, 117.83, and 122.94 μg/L, respectively, and the differences between different years were statistically significant ( H = 31.89, P < 0.001). The GLM results showed that compared with 2021, the salt iodine level increased by 2.21 mg/kg (β = 2.21, P = 0.038) in 2022, increased by 3.24 mg/kg (β = 3.24, P = 0.002) in 2023, and decreased by 3.28 mg/kg (β = - 3.28, P = 0.002) in 2024. The urinary iodine level decreased by 24.53 μg/L (β = - 24.53, P = 0.030) in 2024. The GLMMs results showed that compared with early pregnancy, urinary iodine levels increased by 33.68 μg/L (β = 33.68, P = 0.008) in middle pregnancy and 43.17 μg/L (β = 43.17, P = 0.001) in late pregnancy. Conclusions:From 2021 to 2024, the iodine intake of pregnant women in a certain district of Beijing shows an overall trend of first increasing and then decreasing, especially with an increase in the proportion of non iodized salt consumption in 2024. And the iodine nutrition status varies during different pregnancy periods. It is necessary to strengthen the promotion of iodized salt and the publicity of iodine deficiency disorders prevention and control, to ensure that pregnant women can obtain sufficient iodine nutrition through other means when their intake of iodized salt is reduced.