ObjectiveTo compare the differences in fungal community composition between lesional and non-lesional scalp areas in patients suffering from severe alopecia areata （AA）， and compare these with healthy scalp areas in control subjects. Additionally， to preliminarily explore the changes in scalp fungal communities in severe AA patients and their potential underlying immunological mechanisms. MethodsA total of 20 severe AA patients and 18 healthy controls were enrolled. Skin swab samples were collected from lesional and non-lesional scalp areas of severe AA patients， as well as from the normal scalp of healthy controls. The fungal internal transcribed spacer （ITS） region was amplified and analyzed using high-throughput sequencing. ResultsThe lesional scalp areas of severe AA patients exhibited higher α-diversity and species richness in fungal communities. Notably， the relative abundance of Ascomycota， along with genera such as Mycosphaerella， Aspergillus， Penicillium， and Wallemia， significantly increased in the bald regions. In contrast， Acremonium and Schizophyllum were more predominant in the non-lesional areas of severe AA patients. ConclusionDistinct region-specific differences in scalp fungal microbiota in severe AA patients suggests that fungal dysbiosis may play a potential role in the pathogenesis of alopecia areata. These findings provide new insights into the disease characteristics of severe AA from the perspective of scalp microecology.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease （WD） through bioinformatics analysis and clinical validation，providing implications and directions for the diagnosis and treatment of WD. Methods（1） Screening of target genes： The differentially expressed genes （DEGs） between WD and healthy control were obtained from GeneCards，and the cuproptosis-related genes were obtained from Gene Expression Omnibus （GEO） and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses，the specific biological process，functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.（2）Validation of target genes： The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results（1） A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO，and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection，including three up-related genes（SQSTM1，MIF1，and TAX1BP1） and nine down-regulated genes（CP，SERPINE1，AOC3，GPX4，SLC27A5，VEGF-A，PDHB，PDK1，and ATP7B）.The common target genes were mainly enriched in monocarboxylic acid metabolism，oxidoreductase activity，negative regulation of molecular functions，which mainly involved HIF-1，ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1，SERPINE1，VEGFA，and AOC3 in WD.（2）A total of 30 blood samples were collected，including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers，WD patients had down-regulated mRNA levels of SERPINE1，GPX4，SLC27A5，and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1（P<0.05）. ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD，which can provide a new target for the diagnosis and treatment of WD.

Objective:To explore the clinical application value of artificial intelligence models in identifying bleeding events and hemorrhagic points during laparoscopic pancreatic surgery.Methods:This single-center retrospective cohort study collected surgical videos of 25 patients undergoing laparoscopic pancreatic surgery at the Department of General Surgery, Peking Union Medical College Hospital from January 2022 to December 2024. Videos within 5 seconds before and after representative bleeding events were captured at 30 frames/s, with 11 666 hemorrhagic-related video frames annotated. Two algorithm models were developed: a pigment-based model and a pigment+optical flow-based model for classification and target recognition of bleeding frames. The training and test sets for the pigment-based algorithm contained 4 692 hemorrhagic and 4 309 non-hemorrhagic frames, while those for the pigment+optical flow model included 1 339 hemorrhagic and 1 326 non-hemorrhagic frames. Performance evaluation was conducted using overlap thresholds, with accuracy and recall rates as key metrics.Results:The pigment-based model achieved 93.8% accuracy (134/143) and 43.3% recall (134/310) in hemorrhagic frame classification. At an overlap threshold of 0.3, the pigment-based model showed 84.1% accuracy (433/515) and 85.4% recall (433/507) in target recognition. When the threshold was increased to 0.5, the pigment+optical flow model demonstrated 88.1% accuracy (354/402) and 89.2% recall (354/397) in hemorrhagic target recognition.Conclusions:It is difficult to distinguish active bleeding from old bleeding completely by pigment information alone. The spatio-temporal features can be effectively extracted by combining pigment and optical flow information, and the bleeding can be accurately identified and located, which has potential clinical application value.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objectives:To investigate the predictive value of epicardial fat volume(EFV)and atrioventricular groove fat thickness(AVGT)—morphological biomarkers of epicardial adipose tissue—for major adverse cardiovascular events(MACE)in patients with dilated cardiomyopathy(DCM).Methods:This study enrolled 216 DCM patients.EFV and AVGT were obtained from cardiac magnetic resonance imaging(CMR).Patients were divided into event-free group(n=142)and event group(n=74)based on MACE occurrence during follow-up.Receiver operating characteristic(ROC)curve analysis was used to determine optimal cutoff values.Survival differences were assessed using Kaplan-Meier analysis,Cox proportional hazards regression analysis was used to identify independent risk factors,and restricted cubic spline(RCS)models were used to evaluate dose-response relationships.Results:AVGT and EFV were significantly higher in the event group than in event-free group(both P<0.05).ROC analysis identified optimal MACE-predicting cutoffs as follows:AVGT≥7.74 mm(area under the curve[AUC]=0.57)and EFV≥78.6 ml(AUC=0.62).Kaplan-Meier analysis revealed significantly lower MACE-free survival rates in patients with AVGT≥7.74 mm and EFV≥78.6 ml(both P<0.05).Cox regression analysis confirmed that AVGT(HR=2.18,95%CI:1.34-3.54)and EFV(HR=1.81,95%CI:1.11-2.96)were independent MACE risk factors(both P<0.05)in this patient cohort.RCS models demonstrated the significant linear associations between EFV/AVGT and MACE risk(bothoverall P<0.05).Conclusions:EFV and AVGT,the non-invasive imaging biomarkers quantifying and characterizing fat distribution,are independently correlated with elevated MACE risk in DCM patients.These metrics serve as potential prognostic indicators,enriching risk stratification indicators for early identification of high-risk patients and guiding personalized medication strategies.

A retrospective analysis was conducted on 26 patients with relapsed and refractory multiple myeloma (RRMM) who were treated with carfilzomib-based regimens at Beijing Chaoyang Integrative Medicine Rescue and First Aid Hospital from July 2021 to May 2024. The median number of treatment cycles was 5 (range, 2-8). The overall response rate was 53.8% (14/26). The median follow-up duration was 9.5 months, and the median progression-free survival (PFS) was 8.6 months (range, 1.7-25.2 months). Patients without plasmacytoma recurrence ( n=17) had a PFS of 12.3 months. In contrast, patients with plasmacytoma recurrence ( n=9) had a PFS of 6.2 months. The difference in PFS between these two groups was statistically significant ( P=0.013). Age (over 65 vs. 65 or younger), and treatment line (more than three vs. three or fewer) did not significantly affect treatment efficacy (all P>0.05). Common adverse reactions of grade 3 or higher included hematologic adverse reactions in 10 cases, which improved with symptomatic treatment. Non-hematologic adverse reactions included pulmonary infection (2 cases), renal failure (1 case), and heart failure (1 case). In conclusion, carfilzomib-based regimens demonstrate good clinical efficacy and manageable safety in the treatment of RRMM.

BACKGROUND:Linagliptin exhibits the capacity to regulate macrophage polarization,shifting them from the pro-inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This alteration results in a dampened release of inflammatory mediators,thereby mitigating local inflammation.OBJECTIVE:To explore the effects of linagliptin on macrophage polarization,osteoclast activation,and inflammatory osteolysis elicited by wear particles.METHODS:(1) Cell experiments:For macrophage polarization,RAW264.7 cells were cultured and divided into four groups:the control group received high-glucose culture medium;the M1-induced group received M1-inducing culture medium (high-glucose culture medium containing 100 ng/mL lipopolysaccharide and 20 ng/mL interferon-γ) to simulate an inflammatory environment;the low-and high-dose linagliptin groups were treated with 50 and 200 nmol/L linagliptin,respectively,for 4 hours before exposure to M1-inducing culture medium. After 24 hours of macrophage polarization induction,immunofluorescence staining and RT-PCR were performed. For osteoclast activation,RAW264.7 cells were cultured and divided into four groups:the control group was cultured with high-glucose culture medium,the osteoclast-induced group and low-and high-dose linagliptin groups were subjected to osteoclast induction. After osteoclast formation,cells were treated with linagliptin (50 and 200 nmol/L) for 3 days. Subsequently,cell tartrate-resistant acid phosphatase staining and RT-PCR were performed. (2) Animal experiments:Twenty-four male C57BL/6J mice were randomly divided into four groups:sham operation group,model group,low-dose linagliptin group,and high-dose linagliptin group. The model group,low-dose linagliptin group,and high-dose linagliptin group were induced to establish a cranial bone resorption model by injecting titanium particle suspension onto the surface of the skull. Starting from the 2nd day after modeling,the low-and high-dose linagliptin groups were orally administered linagliptin (2 and 10 mg/kg,respectively) once daily. After modeling for 3 weeks,serum macrophage polarization marker protein and inflammatory factor levels were detected;skull samples were collected for micro-CT scanning,bone parameter analysis,and hematoxylin-eosin staining to evaluate osteolysis and morphological changes.RESULTS AND CONCLUSION:(1) Cell experiments:Both low and high doses of linagliptin significantly suppressed M1 polarization while promoting M2 polarization compared to the M1-induced group (P<0.01). Notably,the high-dose group exhibited a more pronounced inhibitory effect (P<0.01). Inflammatory factor mRNA expression was elevated in the M1-induced group compared with the control group (P<0.01),whereas inflammatory factor mRNA expression was significantly lower in the low-and high-dose linagliptin groups compared with the M1-induced group (P<0.01). There was a significant upregulation of mRNA expression of osteoclast functional markers in the osteoclast-induced group compared with the control group (P<0.01). Conversely,both low and high doses of linagliptin led to a substantial downregulation of mRNA expression of these markers compared with the osteoclast-induced group (P<0.01),with the high-dose group exhibiting a more pronounced reduction. (2) Animal experiments:Titanium particle implantation induced cranial bone resorption damage in mice. Treatment with linagliptin effectively mitigated this bone resorption,with the high-dose group showing superior efficacy. To conclude,linagliptin has been shown to modulate macrophage polarization,inhibit osteoclast activation,and have a protective effect on the skeletal system.