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.

Based on the concept of "blood exhaustion" from The Inner Canon of Yellow Emperor （《黄帝内经》）， a three-stage syndrome differentiation and treatment strategy for cancer-related anorexia-cachexia syndrome is proposeed. In the cancer-induced anorexia stage， the pathogenesis is characterized by cancer consuming the spleen and stomach， leading to stagnation of transportation and transformation in the middle jiao （焦）. Treatment should focus on strengthening the spleen， promoting appetite， dispersing accumulation， and aiding digestion， with modified Zisheng Pills （资生丸） in Extensive Notes on Medicine from Xian Xing Studio （《先醒斋医学广笔记》） or Zisheng Decoction （资生汤） in Records of Chinese Medicine with Reference to Western Medicine （《医学衷中参西录》）. In the pre-cachectic stage of malnutrition， the pathogenesis involves insufficient nourishment of blood and qi with essence depletion hindering production. Treatment should focus on nourishing blood and harmonizing ying （营）， warming yang and supplementing qi， and modified Huangqi Jianzhong Decoction （黄芪建中汤） can be used. In the cachectic stage， the pathogenesis involves blood deficiency and essence exhaustion， with blood stasis obstructing the collaterals. The therapeutic approach should focus on tonifying deficiency and replenishing essence， unblocking collaterals， and removing stasis， and modified Buzhong Yiqi Decoction （补中益气汤） and Zuo Gui Beverage （左归饮） are suggested.

ObjectiveTo enhance teaching in postoperative cancer rehabilitation, this study developed an integrative Chinese-Western medicine postoperative oncology rehabilitation system, termed the medical oncology generative pre-trained transformer (MedOncoGPT). By introducing MedOncoGPT as an intelligent assistant, an integrated teaching model combining Chinese and Western medicine was established. The study evaluated its impact on students’ integrative clinical reasoning and practical abilities, providing support for instructional reform in related courses. MethodsUsing teaching resources as the knowledge base, MedOncoGPT was built upon the open-source ChatGLM model and incorporated Low-Rank Adaptation (LoRA) fine-tuning and retrieval-augmented generation (RAG) techniques to address postoperative integrative oncology scenarios. The system was applied in courses and clinical clerkships related to integrative oncology. In alignment with course objectives, a five-stage instructional process—pre-class preparation, in-class inquiry, simulated multidisciplinary consultation, clinical reinforcement, and teaching reflection—was designed to guide students in completing syndrome differentiation, comprehensive assessment, and follow-up planning within real or simulated case contexts. Comparative analyses of student engagement, syndrome differentiation thinking, evidence-based awareness, and interdisciplinary integration skills before and after the teaching reform were conducted using questionnaires, course assessments, classroom observations, and semi-structured interviews. ResultsFollowing the implementation of MedOncoGPT, students demonstrated improved performance in case analysis, prescription formulation, and integrative Chinese-Western medical evaluation compared with those receiving traditional instruction. Classroom participation and the relevance of student inquiries also increased. Self-assessment results indicated high levels of satisfaction with respect to clarity of integrative clinical reasoning, ability to retrieve and apply guideline-based evidence, and awareness of appropriate use of intelligent tools in clinical decision-making. More than 92% of students reported that the system facilitated understanding of abstract theoretical concepts presented in textbooks. Instructors noted that the system helped reduce lesson preparation time, enriched typical case materials and discussion scenarios, and promoted the translation of research findings into classroom teaching. Pilot data showed that, with MedOncoGPT assistance, the mean time for initial syndrome differentiation decreased from 18.4 min to 12.1 min, and the agreement rate increased from 68.3% to 82.5%. In the teaching pilot, the experimental group achieved a higher mean score on the final case analysis assessment than the control group (82.6 vs. 74.3). ConclusionThe integration of MedOncoGPT into teaching on postoperative integrative cancer rehabilitation enabled the establishment of a stable instructional process within existing curricula and enhanced students’ integrative clinical reasoning and evidence-based practice capabilities. The approach demonstrates positive potential for advancing the integration of research, clinical practice, and education and represents a valuable exploratory strategy for instructional reform in courses on integrative Chinese-Western medicine.

ObjectiveTo enhance teaching in postoperative cancer rehabilitation, this study developed an integrative Chinese-Western medicine postoperative oncology rehabilitation system, termed the medical oncology generative pre-trained transformer (MedOncoGPT). By introducing MedOncoGPT as an intelligent assistant, an integrated teaching model combining Chinese and Western medicine was established. The study evaluated its impact on students’ integrative clinical reasoning and practical abilities, providing support for instructional reform in related courses. MethodsUsing teaching resources as the knowledge base, MedOncoGPT was built upon the open-source ChatGLM model and incorporated Low-Rank Adaptation (LoRA) fine-tuning and retrieval-augmented generation (RAG) techniques to address postoperative integrative oncology scenarios. The system was applied in courses and clinical clerkships related to integrative oncology. In alignment with course objectives, a five-stage instructional process—pre-class preparation, in-class inquiry, simulated multidisciplinary consultation, clinical reinforcement, and teaching reflection—was designed to guide students in completing syndrome differentiation, comprehensive assessment, and follow-up planning within real or simulated case contexts. Comparative analyses of student engagement, syndrome differentiation thinking, evidence-based awareness, and interdisciplinary integration skills before and after the teaching reform were conducted using questionnaires, course assessments, classroom observations, and semi-structured interviews. ResultsFollowing the implementation of MedOncoGPT, students demonstrated improved performance in case analysis, prescription formulation, and integrative Chinese-Western medical evaluation compared with those receiving traditional instruction. Classroom participation and the relevance of student inquiries also increased. Self-assessment results indicated high levels of satisfaction with respect to clarity of integrative clinical reasoning, ability to retrieve and apply guideline-based evidence, and awareness of appropriate use of intelligent tools in clinical decision-making. More than 92% of students reported that the system facilitated understanding of abstract theoretical concepts presented in textbooks. Instructors noted that the system helped reduce lesson preparation time, enriched typical case materials and discussion scenarios, and promoted the translation of research findings into classroom teaching. Pilot data showed that, with MedOncoGPT assistance, the mean time for initial syndrome differentiation decreased from 18.4 min to 12.1 min, and the agreement rate increased from 68.3% to 82.5%. In the teaching pilot, the experimental group achieved a higher mean score on the final case analysis assessment than the control group (82.6 vs. 74.3). ConclusionThe integration of MedOncoGPT into teaching on postoperative integrative cancer rehabilitation enabled the establishment of a stable instructional process within existing curricula and enhanced students’ integrative clinical reasoning and evidence-based practice capabilities. The approach demonstrates positive potential for advancing the integration of research, clinical practice, and education and represents a valuable exploratory strategy for instructional reform in courses on integrative Chinese-Western medicine.

Background/Aims: Data from Asia regarding the short-term and long-term outcomes for acute severe ulcerative colitis (ASUC) are limited. We assessed the outcomes of ASUC, identified the risk factors for colectomy, and compared colectomy rates between the pre-biologics and post-biologics eras in Taiwan. Methods: The patients with an ASUC diagnosis between January 2013 and March 2022 at 5 tertiary medical centers were retrospectively analyzed. Results: In total, 98 patients were enrolled, with 68.4% diagnosed in the post-biologics era. In 78.6% of the ASUC patients initially received intravenous steroid therapy, for which the success rate was 74.1%. As for rescue therapy, 15 patients (93.8%) received biologics and 1 (6.3%) received cyclosporin. Biologics rescue therapy had a 93.3% success rate. One (1%) mortality due to septic shock occurred. The colectomy rate for index ASUC admission was 11.2%. Patients receiving colectomy were predominantly male (P= 0.012) and at older age (P= 0.016). Higher C-reactive protein (P= 0.035), lower albumin (P= 0.017), and hemoglobin (P= 0.023) levels were associated with colectomy risk. During a median follow-up of 24 months, 13 patients (15.1%) had recurrent ASUC and 23.1% of patients received colectomy. The accumulated colectomy rate at 3 years did not differ between the pre- and post-biologics eras (16.1% vs. 13.4%, P= 0.270). Conclusions This is the first Asian study on ASUC to compare colectomy rates between the prebiologics and post-biologics eras, revealing no significant difference. The recurrent ASUC had a higher colectomy rate than the index ASUC.

ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway to improve neuronal function in vascular dementia （VaD） rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries （CCA） combined with bilateral vascular occlusion （2-VO）. Eighty-four SD rats were randomly divided into a blank group， sham group， model group， piracetam group （0.2 g·kg^-1）， and low-， medium-， and high-dose Yifei Xuanfei Jiangzhuo prescription groups （6.09， 12.18， and 24.36 g·kg^-1）. Drug administration began on day 7 after surgery， once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin （HE） staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen （NeuN）. Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase （IKK）， NF-κB p65， NLRP3， Caspase-1， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β）. ResultsCompared with the blank group， the model group showed a significant reduction in platform-crossing frequency （P0.01）， aggravated hippocampal injury， a significant increase in neuronal apoptosis （P0.05）， decreased NeuN positivity in the CA1 region （P0.05）， increased nuclear expression of NF-κB p65 （P0.05）， and significantly elevated expression of p-IKK， p-NF-κB p65， NLRP3， cleaved Caspase-1， ASC， and cleaved IL-1β （P0.05）. Compared with the model group， all drug-treated groups improved learning and spatial memory in VaD rats， alleviated hippocampal pathological injury and neuronal apoptosis， and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg^-1 reduced hippocampal expression levels of p-IKK， p-NF-κB p65， NLRP3， Caspase-1， ASC， and cleaved IL-1β in VaD rats （P0.05）， showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway， thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.

ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway to improve neuronal function in vascular dementia （VaD） rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries （CCA） combined with bilateral vascular occlusion （2-VO）. Eighty-four SD rats were randomly divided into a blank group， sham group， model group， piracetam group （0.2 g·kg^-1）， and low-， medium-， and high-dose Yifei Xuanfei Jiangzhuo prescription groups （6.09， 12.18， and 24.36 g·kg^-1）. Drug administration began on day 7 after surgery， once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin （HE） staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen （NeuN）. Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase （IKK）， NF-κB p65， NLRP3， Caspase-1， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β）. ResultsCompared with the blank group， the model group showed a significant reduction in platform-crossing frequency （P0.01）， aggravated hippocampal injury， a significant increase in neuronal apoptosis （P0.05）， decreased NeuN positivity in the CA1 region （P0.05）， increased nuclear expression of NF-κB p65 （P0.05）， and significantly elevated expression of p-IKK， p-NF-κB p65， NLRP3， cleaved Caspase-1， ASC， and cleaved IL-1β （P0.05）. Compared with the model group， all drug-treated groups improved learning and spatial memory in VaD rats， alleviated hippocampal pathological injury and neuronal apoptosis， and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg^-1 reduced hippocampal expression levels of p-IKK， p-NF-κB p65， NLRP3， Caspase-1， ASC， and cleaved IL-1β in VaD rats （P0.05）， showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway， thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.

Objective: To investigate the epidemiological characteristics and spatial-temporal clustering of varicella in Changchun City from 2020 to 2024, so as to provide the evidence for formulating local varicella prevention and control measures. Methods: The individual case data of varicella were collected through the Surveillance and Reporting Management System of the Chinese Disease Prevention and Control Information System in Changchun City from 2020 to 2024. Descriptive epidemiological methods were used to analyze the population ,regional, and temporal distribution. Spatial autocorrelation and spatio-temporal scanning analyses were used to identify the spatial-temporal clustering characteristics. Results: A total of 8 850 varicella cases were reported in Changchun City from 2020 to 2024, with an average annual incidence of 19.64/105. There were 4 929 male cases and 3 921 female cases, with a male-to-female ratio of 1.26∶1. The age was mainly 0-<20 years (6 649 cases, 75.13%), and students were the predominant occupation (6 036 cases, 68.20%). The top three counties (cities, districts) with the highest number of cases were Chaoyang District (1 944 cases), Gongzhuling City (1 054 cases) and Nanguan District (987 cases), accounting for 45.03%. The peak incidence periods were from April to June and from October to December, with 2 166 and 4 226 cases, accounting for 24.47% and 47.75%, respectively. Spatial autocorrelation analysis showed that spatial clustering existed from 2020 to 2024. The high-high clustering areas were mainly some townships (streets) in Chaoyang District, Nanguan District, Changchun New District and Jingyue District. Spatio-temporal scanning analysis identified 6 high-risk clustering areas. The class Ⅰ clustering area was Nanhu Street in Chaoyang District, with the clustering period from September 2020 to February 2022. Conclusions Varicella cases in Changchun City were mainly males and students aged 0-<20 years from 2020 to 2024. The peak incidence was mainly in winter. Chaoyang District was a high-risk area, with obvious spatial-temporal clustering.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.