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.

ObjectiveTo examine the impact of Toll-like receptor 4 （TLR4）-mediated neutrophil extracellular traps （NETs） formation on isoproterenol （ISO）-induced heart failure （HF） in aged mice. MethodsThe mice were randomly divided into Control group， Model group， TAK-242 （TLR4 inhibitor） group， LPS （TLR4 agonist） group and LPS+DNaseⅠ （NETs inhibitor） group， with 8 mice in each group. The HF model was established by continuous infusion of ISO through an osmotic pump， and TAK-242， LPS， and LPS+DNaseⅠ interventions were administered during the last week of infusion for 7 consecutive days. ELISA was used to detect the N-terminal pro-B-type natriuretic peptide （NT-pro BNP）， cardiac troponin I （cTnI）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and serum and myocardial tissue myeloperoxidase-DNA （MPO-DNA） and neutrophil elastase-DNA （NE-DNA） levels. HE staining was used to observe the pathological changes of myocardial tissue. Masson staining was used to observe the deposition of collagen fibers in myocardial tissue. Immunofluorescence was used to observe the colocalization of Ly6G and MPO in myocardial tissue. The protein expressions of TLR4， MPO， NE and cit-H3 in myocardial tissue were detected by Western blot. ResultsCompared with the Control group， the end-diastolic interventricular septal thickness （IVSD）， left ventricular end-diastolic diameter （LVEDD） and left ventricular end-systolic diameter （LVESD） in the Mode group significantly increased （P<0.01）， fractional shortening （FS） and ejection fraction （EF） significantly decreased （P<0.01）， and the myocardial structure was significantly damaged. The myocardial collagen fiber precipitation， serum NT-pro BNP， cTnI， IL-1β， IL-6 and TNF-α contents， MPO-DNA and NE-DNA contents in serum and myocardial tissue significantly increased （P<0.01）. The co-localization of Ly6G and MPO and the expression of TLR4， MPO， NE and cit-H3 proteins in myocardial tissue significantly increased （P<0.01）. After TAK-242 intervention， the above indicators were significantly reversed， while the injury was further aggravated in LPS group. DNaseⅠ treatment could partially alleviate the deterioration of myocardial structure and function induced by LPS. ConclusionTLR4 and NETs are abnormally elevated in the myocardial tissue of aged HF mice. Treatment with the TLR4 inhibitor TAK-242 effectively suppresses NET formation， attenuates inflammatory responses， and enhances cardiac function in aged HF mice.

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.

Objective To evaluate the effects of thoracoscopic intercostal nerve block and incision infiltration block on postoperative recovery quality and analgesia in patients with partial pulmonary resection.Methods From July 2023 to December 2023,60 patients scheduled for elective thoracoscopic partial lung resection were divided into two groups by random number table method,with 30 cases in each group.The observation group underwent thoracoscopic vision intercostal nerve block,and the control group underwent incision local infiltration block.Intravenous patient-controlled analgesia was adopted in all cases after the operation.The 15-item Recovery Quality Scale(QOR-15)score was recorded 1 day before surgery,24 hours and 48 hours after surgery.The visual analogue pain scores(VAS)at rest and cough at 2,4,8,24,and 48 hours after surgery,consumption of sufentanil within 24 hours and 48 hours after surgery,remedial analgesia and related adverse reactions were recorded.Results The QOR-15 scores of the observation group at 24 hours and 48 hours after operation were(103.4±14.2)and(111.2±6.9),which were higher than those of the control group(91.3±21.4)and(101.8±14.8),and the differences were statistically significant(P＜0.05).At rest,the VAS scores of the observation group at 2,4,8 and 24 hours after surgery were(2.0±0.9),(2.1±0.9),(2.5±1.2)and(2.4±1.2).Compared with the control group(3.1±1.2),(3.4±1.7),(3.5±1.7)and(3.2±1.3),the differences were statistically significant(P＜0.05).When coughing,the VAS scores of the observation group at 2,4 and 8 hours after operation were(2.4±0.6),(2.5±0.6)and(3.0±1.2),which were lower than(3.2±1.2),(3.7±1.7)and(4.0±2.1)of the control group.The difference was statistically significant(P＜0.05).The consumption of sufentanil within 24 hours and 48 hours after surgery in the observation group was(58.1±7.5)μg and(116.5±14.9)μg,respectively,which were lower than those in the control group(63.2±8.5)μg and(125.0±16.7)μg,and the difference was statistically significant(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Compared with incision infiltration block,thoracoscopic intercostal nerve block has better postoperative analgesic effect and higher postoperative recovery quality.

Objective Focusing on gynecological surgery,we constructed a prediction model for surgical duration by extracting features from unstructured surgical planning texts and integrating multimodal data via artificial intelligence technology.Methods The clinical data of 34 614 patients who underwent gynecologic surgeries at West China Second University Hospital,Sichuan University between January 2022 and October 2024 were collected.An embedding-transformer model was constructed to convert surgical planning texts into a one-dimensional numerical feature,referred to as the step feature.The predictive value of the step feature was assessed by comparing the performance improvements of linear regression,random forest,eXtreme Gradient Boosting(XGBoost),support vector regression,K-nearest neighbor regression,and artificial neural network algorithms in two scenarios—with and without the step feature as an input.The out-of-sample prediction accuracy of the models was assessed using mean absolute error(MAE),root mean squared error(RMSE),and R-squared(R2).Furthermore,the model interpretability was examined using SHapley Additive exPlanations(SHAP)values.Results SHAP results showed that the step feature had the highest predictive contribution.Temporal factors in surgical scheduling also influenced gynecological surgery duration.The XGBoost model demonstrated optimal performance on the test set,significantly improving prediction accuracy with a 40.43%increase in R2,while reducing MAE and RMSE by 21.27%and 20.13%,respectively,compared to the baseline model without the step feature.Conclusion The embedding-transformer model developed in this study effectively extracts features from surgical planning texts and enhances the predictive performance of machine learning models.The XGBoost prediction model can assist hospital administrators in implementing more refined management of gynecological surgeries and improving the utilization efficiency of surgical resources.

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 explore the impact of a staged trauma integrated treatment model based on information network platforms on the emergency treatment outcomes of patients with severe cranial injury.Methods:A convenience sampling method was used to select 80 patients with severe cranial injury treated at Yiwu Central Hospital from June 2023 to June 2024. Patients admitted from June to December 2023 were assigned to the control group ( n=37), while patients admitted from January to June 2024 were assigned to the intervention group ( n=43). The control group received conventional emergency treatment for cranial injury, while the intervention group received the staged trauma integrated treatment model based on an information network platform. The emergency response time (response time, triage time, emergency room treatment time, and handover time to the ward), National Institutes of Health Stroke Scale (NIHSS) score, Glasgow Coma Scale (GCS) score, incidence of complications, and family satisfaction were compared between the two groups. Results:After intervention, the intervention group had shorter emergency response time, triage time, emergency room treatment time, and handover time to the ward compared to the control group, with statistically significant differences ( P<0.01). The NIHSS score in the intervention group was lower, and the GCS score was higher, with statistically significant differences ( P<0.05). The incidence of complications in the intervention group was lower, and family satisfaction was higher compared to the control group, with statistically significant differences ( P<0.05) . Conclusions:The staged trauma integrated treatment model based on an information network platform can optimize the emergency treatment process for severe cranial injury, shorten treatment times, improve hospital-to-hospital and interdepartmental coordination, reduce neurological damage and complication rates, and increase family satisfaction. It is worth promoting for clinical use.

Objective To evaluate the effects of thoracoscopic intercostal nerve block and incision infiltration block on postoperative recovery quality and analgesia in patients with partial pulmonary resection.Methods From July 2023 to December 2023,60 patients scheduled for elective thoracoscopic partial lung resection were divided into two groups by random number table method,with 30 cases in each group.The observation group underwent thoracoscopic vision intercostal nerve block,and the control group underwent incision local infiltration block.Intravenous patient-controlled analgesia was adopted in all cases after the operation.The 15-item Recovery Quality Scale(QOR-15)score was recorded 1 day before surgery,24 hours and 48 hours after surgery.The visual analogue pain scores(VAS)at rest and cough at 2,4,8,24,and 48 hours after surgery,consumption of sufentanil within 24 hours and 48 hours after surgery,remedial analgesia and related adverse reactions were recorded.Results The QOR-15 scores of the observation group at 24 hours and 48 hours after operation were(103.4±14.2)and(111.2±6.9),which were higher than those of the control group(91.3±21.4)and(101.8±14.8),and the differences were statistically significant(P＜0.05).At rest,the VAS scores of the observation group at 2,4,8 and 24 hours after surgery were(2.0±0.9),(2.1±0.9),(2.5±1.2)and(2.4±1.2).Compared with the control group(3.1±1.2),(3.4±1.7),(3.5±1.7)and(3.2±1.3),the differences were statistically significant(P＜0.05).When coughing,the VAS scores of the observation group at 2,4 and 8 hours after operation were(2.4±0.6),(2.5±0.6)and(3.0±1.2),which were lower than(3.2±1.2),(3.7±1.7)and(4.0±2.1)of the control group.The difference was statistically significant(P＜0.05).The consumption of sufentanil within 24 hours and 48 hours after surgery in the observation group was(58.1±7.5)μg and(116.5±14.9)μg,respectively,which were lower than those in the control group(63.2±8.5)μg and(125.0±16.7)μg,and the difference was statistically significant(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Compared with incision infiltration block,thoracoscopic intercostal nerve block has better postoperative analgesic effect and higher postoperative recovery quality.

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.