1.Study on the role and mechanism of SPP1+ macrophages in the formation of chronic renal allograft fibrosis
Zexin YANG ; Zeping GUI ; Junqi ZHANG ; Gang ZHANG ; Hao CHEN ; Li SUN ; Shuang FEI ; Min GU ; Zijie WANG
Organ Transplantation 2026;17(3):413-421
Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)+ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1+ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1+ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1+ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1+ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1+ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.
2.Risk prediction models for delirium after adult cardiac surgery: A systematic review and meta-analysis
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(03):444-453
Objective To systematically evaluate the risk prediction models for postoperative delirium in adults with cardiac surgery. Methods The SinoMed, CNKI, Wanfang, VIP, PubMed, EMbase, Web of Science, and Cochrane Library databases were searched to collect studies on risk prediction models for postoperative delirium in cardiac surgery published up to January 29, 2025. Two researchers screened the literature according to inclusion and exclusion criteria, used the PROBAST bias tool to assess the quality of the literature, and conducted a meta-analysis of common predictors in the model using Stata 17.0 software. Results A total of 21 articles were included, establishing 45 models with 28733 patients. Age, cardiopulmonary bypass time, history of diabetes, history of cerebrovascular disease, and gender were the top five common predictors. The area under the curve (AUC) of the 45 models ranged from 0.544 to 0.98. Fourteen out of the 21 studies had good applicability, while the applicability of the remaining seven was unclear; 20 studies had a high risk of bias. Meta-analysis showed that the incidence of postoperative delirium in adults with cardiac surgery was 18.6% [95%CI (15.7%, 21.6%)], and age [OR=1.045 (1.036, 1.054), P<0.001], history of cerebrovascular disease [OR=1.758 (1.459, 2.057), P<0.001], gender [OR=1.732 (1.430, 2.034), P<0.001], mini-mental state examination score [OR=3.930 (1.859, 8.309), P<0.001], and length of ICU stay [OR=5.586 (4.289, 6.883), P<0.001] were independent influencing factors for postoperative delirium after cardiac surgery. Conclusion The risk prediction models for postoperative delirium after cardiac surgery have good predictive performance, but there is a high overall risk of bias. In the future, large-sample, multicenter, high-quality prospective clinical studies should be conducted to construct the optimal risk prediction model for postoperative delirium in adults with cardiac surgery, aiming to identify and prevent the occurrence of postoperative delirium as early as possible.
3.Mechanical Loading Improves Qi-Blood Nourishment in "Sinew Wei (痿)"via Mitochondrial Regulation
Xili CHANG ; Sipeng HUANG ; Wuquan SUN ; Mengni SHI ; Chengheng YOU ; Min FANG ; Qingguang ZHU
Journal of Traditional Chinese Medicine 2026;67(7):725-729
This study focuses on the core pathology of sinew wei (痿), which is mainly characterized by the fai-lure of qi and blood to nourish the sinews. A mechanical-biological response framework is constructed with mitochondria as a key component, explaining the modern interpretation of the disease location of sinew transmitting to qi and blood pathology. Mechanical loading, as a physical stress stimulus applied to the body, manifests primarily as passive loading formed by external forces such as massage, and active loading resulting from voluntary muscle contractions, such as dao yin (导引). Mechanical loading can regulate mitochondrial function through two pathways, mechanical signal transduction and metabolic demand-driven regulation. Skeletal muscle mitochondrial dysfunction is regarded as the core microscopic basis of qi imbalance in sinew wei, highlighting the intrinsic connection between qi and mitochondrial energy metabolism, as well as between blood and microcirculatory efficiency. Accordingly, distinct regulatory patterns of mechanical loading are identified. Wei associated with qi stagnation may correspond to mitochondrial network fragmentation and can be treated by regulating qi through passive loading, such as tuina, to restore mitochondrial dynamics. In contrast, wei caused by qi deficiency is attributed to insufficient mitochondrial biogenesis and may be treated by tonifying qi through active loading, such as dao yin, to promote mitochondrial biogenesis. This framework reveals the biological differences in mitochondrial regulation induced by distinct mechanical loading modalities and provides a microscopic mechanism-based explanation for the principle of "treating the same disease with different methods" in sinew wei.
4.Analysis of Rheumatoid Arthritis and Periodontitis Multimorbidity from Perspective of Abnormal Collateral Theory
Xiaojing GUO ; Jiuli DING ; Hongyuan SUN ; Lei ZHANG ; Min LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):280-287
The multimorbidity of rheumatoid arthritis (RA) and periodontitis (PD) has drawn increasing attention, as both conditions are characterized by chronic inflammation, immune dysregulation, and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development, and their coexistence mutually exacerbates disease progression. However, traditional Chinese medicine (TCM) currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study, based on the TCM theory of abnormal collateral, thoroughly examines the intrinsic connection between RA and PD multimorbidity, proposing "abnormal collateral as the pivot, with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral", where its pathogens act as toxic factors that invade the joints through collaterals, triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows: the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation, leading to collateral malnutrition; heat-toxins traversing collaterals induce collateral hyperactivity, resulting in pathological angiogenesis; ultimately, toxin accumulation at the pivotal abnormal collateral site erodes bone, activating the receptor activator of nuclear factor kappa-B ligand (RANKL)-receptor activator of nuclear factor kappa-B (RANK) signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology, immune-inflammation, and bone metabolism, offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity, the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs", along with TCM therapeutic principles such as "unblocking, clearing, and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration, thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.
5.Analysis of Rheumatoid Arthritis and Periodontitis Multimorbidity from Perspective of Abnormal Collateral Theory
Xiaojing GUO ; Jiuli DING ; Hongyuan SUN ; Lei ZHANG ; Min LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):280-287
The multimorbidity of rheumatoid arthritis (RA) and periodontitis (PD) has drawn increasing attention, as both conditions are characterized by chronic inflammation, immune dysregulation, and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development, and their coexistence mutually exacerbates disease progression. However, traditional Chinese medicine (TCM) currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study, based on the TCM theory of abnormal collateral, thoroughly examines the intrinsic connection between RA and PD multimorbidity, proposing "abnormal collateral as the pivot, with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral", where its pathogens act as toxic factors that invade the joints through collaterals, triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows: the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation, leading to collateral malnutrition; heat-toxins traversing collaterals induce collateral hyperactivity, resulting in pathological angiogenesis; ultimately, toxin accumulation at the pivotal abnormal collateral site erodes bone, activating the receptor activator of nuclear factor kappa-B ligand (RANKL)-receptor activator of nuclear factor kappa-B (RANK) signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology, immune-inflammation, and bone metabolism, offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity, the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs", along with TCM therapeutic principles such as "unblocking, clearing, and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration, thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.
6.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
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.
7.Analysis of Incidence and Risk Factors for Periprosthetic Fracture after Total Knee Arthroplasty in South Korea from 2010 to 2020Based on National Registry Data
Jisu PARK ; Tae Woo KIM ; Min Ki KIM ; Jiyu SUN ; Kee Jeong BAE ; Moon Jong CHANG ; Chong Bum CHANG ; Seung-Baik KANG
Clinics in Orthopedic Surgery 2025;17(3):408-416
Background:
Periprosthetic fracture (PPF) is a troublesome complication as it utilizes substantial healthcare resources. Recent studies about the epidemiology of PPF after total knee arthroplasty (TKA) are still lacking, and there is limited national-level analysis focusing on the comorbid chronic conditions as risk factors of PPF. This study used national registry data from South Korea and aimed to investigate the epidemiology of PPF following TKA between 2010 and 2020 and identify which comorbidities contributed to the risk of PPF.
Methods:
Using Health Insurance Review and Assessment (HIRA) service data in South Korea, the incidence of PPF after TKA between 2010 and 2020 was evaluated and stratified by age and sex. Medical comorbidities were evaluated as possible risk factors for PPF using Cox regression analysis.
Results:
PPF occurred in 14,429 patients, accounting for 2.37% of total TKA patients. The prevalence of PPF by sex was 2.50% in women and 1.64% in men. The PPF rate was 2.82% in under 60 years, 2.25% in 60 to 69 years, 2.42% in 70 to 79 years, 2.29% in 80 to 89 years, and 2.12% in over 90 years. Among 17 analyzed comorbidities, 11 were found to be associated with PPF after TKA. Severe liver disease (hazard ratio [HR], 1.303), hemiplegia (HR, 1.244), and dementia (HR, 1.206) were the top 3 risk factors.Although osteoporosis, pulmonary disease, peptic ulcer, and diabetes showed relatively low HRs than these top 3 factors, the incidence rates were higher.
Conclusions
PPF occurred in 2.37% of TKA patients in South Korea from 2010 to 2020. PPF rate was higher in women. To prevent PPF after TKA, proper patient management and education should be emphasized, particularly in patients with severe liver disease, hemiplegia, and dementia.
8.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
Background:
and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia.
Methods:
Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Results:
Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.
Conclusions
This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.
9.Asparaginase-Associated Pancreatitis and Pancreatic Pseudocyst Managed with Endoscopic Cystogastrostomy in Adult Acute Lymphoblastic Leukemia
Gyewon PARK ; Eun Sun KIM ; Hyuk Soon CHOI ; Bora KEUM ; Yoon Tae JEEN ; Hoon Jai CHUN ; Hong Sik LEE ; Jae Min LEE
Korean Journal of Pancreas and Biliary Tract 2025;30(1):31-35
Anticancer treatment for acute lymphocytic leukemia is based on drugs such as methotrexate, 6-mercaptopurine, vincristine, and asparaginase. Asparaginase-related pancreatitis is known to have an incidence of up to 18%, and is a major cause of discontinuation of anticancer treatment for leukemia due to acute onset and chronic complications. There were various cases of treatment of peripancreatic fluid retention caused by anticancer drugs in leukemia patients. Use of lumen-apposing metal stents (LAMS) for walled-off necrosis (WON) drainage has recently increased. The electrocautery-enhanced delivery system allowed simpler and faster stent placement, streamlining the overall procedure and potentially reducing procedure time. Therefore, favorable outcomes have been reported with the use of LAMS for endoscopic drainage of various conditions. In this paper, we discuss a case in which hot-system LAMS was performed to treat L-asparaginase-induced acute pancreatitis and pancreatic pseudocyst in an adult patient with acute lymphoblastic leukemia.
10.Performance of Digital Mammography-Based Artificial Intelligence Computer-Aided Diagnosis on Synthetic Mammography From Digital Breast Tomosynthesis
Kyung Eun LEE ; Sung Eun SONG ; Kyu Ran CHO ; Min Sun BAE ; Bo Kyoung SEO ; Soo-Yeon KIM ; Ok Hee WOO
Korean Journal of Radiology 2025;26(3):217-229
Objective:
To test the performance of an artificial intelligence-based computer-aided diagnosis (AI-CAD) designed for fullfield digital mammography (FFDM) when applied to synthetic mammography (SM).
Materials and Methods:
We analyzed 501 women (mean age, 57 ± 11 years) who underwent preoperative mammography and breast cancer surgery. This cohort consisted of 1002 breasts, comprising 517 with cancer and 485 without. All patients underwent digital breast tomosynthesis (DBT) and FFDM during the preoperative workup. The SM is routinely reconstructed using DBT. Commercial AI-CAD (Lunit Insight MMG, version 1.1.7.2) was retrospectively applied to SM and FFDM to calculate the abnormality scores for each breast. The median abnormality scores were compared for the 517 breasts with cancer using the Wilcoxon signed-rank test. Calibration curves of abnormality scores were evaluated. The discrimination performance was analyzed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity using a 10% preset threshold. Sensitivity and specificity were further analyzed according to the mammographic and pathological characteristics.The results of SM and FFDM were compared.
Results:
AI-CAD demonstrated a significantly lower median abnormality score (71% vs. 96%, P < 0.001) and poorer calibration performance for SM than for FFDM. SM exhibited lower sensitivity (76.2% vs. 82.8%, P < 0.001), higher specificity (95.5% vs.91.8%, P < 0.001), and comparable AUC (0.86 vs. 0.87, P = 0.127) than FFDM. SM showed lower sensitivity than FFDM in asymptomatic breasts, dense breasts, ductal carcinoma in situ, T1, N0, and hormone receptor-positive/human epidermal growth factor receptor 2-negative cancers but showed higher specificity in non-cancerous dense breasts.
Conclusion
AI-CAD showed lower abnormality scores and reduced calibration performance for SM than for FFDM.Furthermore, the 10% preset threshold resulted in different discrimination performances for the SM. Given these limitations, off-label application of the current AI-CAD to SM should be avoided.

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