Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective:To analyze the changes and structural variations in hospitalization costs for patients with lung malignancies after the implementation of diagnosis-intervention packet (DIP) payment system, and to evaluate its effectiveness.Methods:Data from the first page of medical records and hospitalization cost data from the hospital information system of a tertiary general hospital in Henan Province were extracted for patients diagnosed with lung malignancies from 2020 to 2023. The data were divided into pre-implementation group (2020—2021) and post-implementation group (2022—2023) based on the implementation time of DIP. Chi-square test, t test, and Wilcoxon rank-sum test were used to analyze the differences in basic characteristics and hospitalization costs of patients with lung malignancies before and after the implementation of DIP. Grey relational analysis was employed to examine the internal associations between total hospitalization costs and various cost components. Structural variation analysis was used to assess the changes in the structure of hospitalization costs after the implementation of DIP. Results:A total of 14 587 hospitalized patients with lung malignancies were included, with 6 807 cases in the pre-implementation group and 7 780 cases in the post-implementation group. The average length of hospital stay decreased from (13.17±6.74) days before implementation to (12.02±6.49) days after implementation ( P<0.05). The proportion of level-four surgeries increased from 46.4% to 57.0% ( P<0.05). The average hospitalization cost per patient with lung malignancies decreased from 56 952 yuan before DIP implementation to 55 560 yuan after implementation ( P<0.05). For patients with lung malignancies diagnosed as C34.1, C34.2, C34.3, and C34.8, the top four cost components most strongly associated with total hospitalization costs were treatment costs, material costs, comprehensive medical service costs, and diagnostic costs, with correlation coefficients all>0.80. For patients with C34.9, the top four cost components most strongly associated with total hospitalization costs were treatment costs, comprehensive medical service costs, diagnostic costs, and Western medicine costs, with correlation coefficients>0.95. For patients diagnosed as C34.1, C34.2, C34.3, and C34.9, diagnostic costs, Western medicine costs, and material costs contributed significantly to the structural variation of hospitalization costs, with contribution rate of structure variation all exceeding 75%, among which Western medicine costs and material costs showed negative variation. For patients diagnosed as C34.8, treatment costs, Western medicine costs, and material costs contributed significantly to the structural variation of hospitalization costs, with contribution rate of structure variation all exceeding 80%, among which Western medicine costs showed negative variation. Conclusions:The implementation of DIP reduced the hospitalization costs for patients with lung malignancies, optimized the structure of hospitalization costs, improved the efficiency of medical services, and promoted the rational allocation of medical resources.

Objective To investigate the effect of lateral wedge insoles (LWI) with different heights on lower limb biomechanical characteristics during single-leg landing in patients with chronic ankle in? stability (CAI). Methods Thirty CAI undergraduates (15 males and 15 females) were recruited. All participants were required to perform a single-leg landing task from a height of 30 cm. They first un? derwent the test with flat insoles (FI),followed by tests with 3 mm and 6 mm LWI in a randomized order. A Qualisys 3D motion capture system and Kistler force platform were used to synchronously col? lect data. Kinematic and kinetic data of the lower limb tri-joints (hip,knee and ankle) were ana? lyzed from the moment of ground contact to the body stabilization phase. Results(1) Kinematically,compared with the FI group,the 3 mm and 6 mm LWI groups showed greater hip and knee flexion angles (P<0.001),smaller hip adduction (P<0.05,P<0.01),ankle plantarflexion (P<0.05,P<0.001),and knee valgus angles (P<0.05,P<0.001) at the moment of ground contact. The 6 mm LWI group had larger hip/knee flexion angles (P<0.001) and smaller ankle plantarflexion angles (P<0.001) at contact than the 3 mm LWI group. Additionally,compared with the FI group,the 6 mm LWI group showed significantly smaller ankle eversion angles (P<0.05). The 6 mm LWI group showed larger peak knee flexion angle (P<0.05) and peak ankle eversion angle (P<0.01) than the FI group,while the 3 mm LWI group also had a greater peak ankle eversion angle (P<0.05) than the FI group. Meanwhile,the 3 mm and 6 mm LWI groups had a larger knee flexion-extension range of motion (ROM)(P<0.05,P<0.01) but smaller ankle flexion-extension ROM (P<0.001) than the FI group. The 6 mm LWI group showed a significantly greater hip adduction-abduction ROM (P<0.001,P<0.05) than the other groups,with a smaller ankle plantar flexion-extension ROM (P<0.05) than the 3 mm LWI group. (2) The peak vertical ground reaction force (peak vGRF) of the LWI groups was signifi? cantly lower than the FI group (P<0.01),with that of the 6 mm LWI group significantly lower than the 3 mm LWI group (P<0.001). Moreover,there were significantly greater peak hip flexion moment (P<0.01) and smaller peak ankle plantarflexion moment of the LWI groups than the FI group (P<0.001),with a smaller peak ankle plantarflexion moment of the 6 mm LWI group than the 3 mm LWI group (P<0.05). (3) Significantly greater subjective comfort was observed in the 6 mm LWI group than the FI group (P<0.01). Conclusion LWI can improve landing patterns in CAI patients,re? duce their ground reaction forces,and lower the risk of ankle sprain. The 6 mm LWI outperforms the 3 mm LWI in improving flexion angles of the lower limb tri-joints at ground contact,ankle flexion-ex? tension ROM,peak vGRF,and peak ankle plantarflexion moment during single-leg landing tasks. Therefore,LWI can be used as a wearable protective device during rehabilitation to prevent recurrent ankle sprains among such patients.

Objective:To analyze the lower limb muscle synergy patterns during the jump landing/cutting in patients with functional ankle instability(FAI),those who have experienced an ankle sprain without instability(Coper),and healthy controls(CON).Method:Twelve populations were recruited for each of the FAI,Coper,and CON groups(male/female ratio and whether the injured side was the favorable side were matched among groups).Kinematic,kinetic and sur-face electromyography(sEMG)data were collected from the unilateral lower limb during the jumping landing/cutting maneuver.Muscle synergy analysis was conducted using a non-negative matrix decomposition algorithm to extract parameters including the number of synergies,variance accounted for(VAF),synergy vectors,and activation coefficients.Result:Four synergy patterns existed in all three groups.Synergy l mainly activated the hip and knee exten-sors,contributing to impact absorption during landing.Synergy 2 mainly activated the knee extensors and ankle plantarflexors,functioning during both landing absorption and force generation in the lateral cut.Synergy 3 mainly activated the knee flexors and ankle plantarflexors,playing a role in the lateral cut force phase.Syner-gy 4 mainly activated the tibialis anterior muscle,contributing during the early landing phase and at the end of the lateral cut force generation phase,with a primary role in ankle stabilization.There was no significant difference in the number of synergies among the three groups,but the VAF-l(the VAF value when the num-ber of synergy is 1)of FAI group was significantly higher than the other two groups(P＜0.05).In the synergy vectors,the FAI and Coper groups showed increased activation weights for the periprosthetic muscles,reduced activation weights for the ankle plantarflexors and extensor digitorum brevis,and greater activation weights for the tibialis anterior muscles(P＜0.05).In terms of activation coefficients,the Coper group exhibited an earlier peak activation of synergy 2 and synergy 3(P＜0.05).Conclusion:Differences in ankle stabilization did not affect the number of muscle synergies in the lower ex-tremity,but muscle contributions within each synergy were altered in patients with FAI,indicating a compensa-tory strategy that relied more on proximal muscle while reducing the functional contributions of foot muscles to impact absorption and force generation.In the Coper group,reduced ankle muscle activation was compen-sated for by central adjustment of activation coefficient.

Objective:To analyze the lower limb muscle synergy patterns during the jump landing/cutting in patients with functional ankle instability(FAI),those who have experienced an ankle sprain without instability(Coper),and healthy controls(CON).Method:Twelve populations were recruited for each of the FAI,Coper,and CON groups(male/female ratio and whether the injured side was the favorable side were matched among groups).Kinematic,kinetic and sur-face electromyography(sEMG)data were collected from the unilateral lower limb during the jumping landing/cutting maneuver.Muscle synergy analysis was conducted using a non-negative matrix decomposition algorithm to extract parameters including the number of synergies,variance accounted for(VAF),synergy vectors,and activation coefficients.Result:Four synergy patterns existed in all three groups.Synergy l mainly activated the hip and knee exten-sors,contributing to impact absorption during landing.Synergy 2 mainly activated the knee extensors and ankle plantarflexors,functioning during both landing absorption and force generation in the lateral cut.Synergy 3 mainly activated the knee flexors and ankle plantarflexors,playing a role in the lateral cut force phase.Syner-gy 4 mainly activated the tibialis anterior muscle,contributing during the early landing phase and at the end of the lateral cut force generation phase,with a primary role in ankle stabilization.There was no significant difference in the number of synergies among the three groups,but the VAF-l(the VAF value when the num-ber of synergy is 1)of FAI group was significantly higher than the other two groups(P＜0.05).In the synergy vectors,the FAI and Coper groups showed increased activation weights for the periprosthetic muscles,reduced activation weights for the ankle plantarflexors and extensor digitorum brevis,and greater activation weights for the tibialis anterior muscles(P＜0.05).In terms of activation coefficients,the Coper group exhibited an earlier peak activation of synergy 2 and synergy 3(P＜0.05).Conclusion:Differences in ankle stabilization did not affect the number of muscle synergies in the lower ex-tremity,but muscle contributions within each synergy were altered in patients with FAI,indicating a compensa-tory strategy that relied more on proximal muscle while reducing the functional contributions of foot muscles to impact absorption and force generation.In the Coper group,reduced ankle muscle activation was compen-sated for by central adjustment of activation coefficient.

Objective To investigate the effect of lateral wedge insoles (LWI) with different heights on lower limb biomechanical characteristics during single-leg landing in patients with chronic ankle in? stability (CAI). Methods Thirty CAI undergraduates (15 males and 15 females) were recruited. All participants were required to perform a single-leg landing task from a height of 30 cm. They first un? derwent the test with flat insoles (FI),followed by tests with 3 mm and 6 mm LWI in a randomized order. A Qualisys 3D motion capture system and Kistler force platform were used to synchronously col? lect data. Kinematic and kinetic data of the lower limb tri-joints (hip,knee and ankle) were ana? lyzed from the moment of ground contact to the body stabilization phase. Results(1) Kinematically,compared with the FI group,the 3 mm and 6 mm LWI groups showed greater hip and knee flexion angles (P<0.001),smaller hip adduction (P<0.05,P<0.01),ankle plantarflexion (P<0.05,P<0.001),and knee valgus angles (P<0.05,P<0.001) at the moment of ground contact. The 6 mm LWI group had larger hip/knee flexion angles (P<0.001) and smaller ankle plantarflexion angles (P<0.001) at contact than the 3 mm LWI group. Additionally,compared with the FI group,the 6 mm LWI group showed significantly smaller ankle eversion angles (P<0.05). The 6 mm LWI group showed larger peak knee flexion angle (P<0.05) and peak ankle eversion angle (P<0.01) than the FI group,while the 3 mm LWI group also had a greater peak ankle eversion angle (P<0.05) than the FI group. Meanwhile,the 3 mm and 6 mm LWI groups had a larger knee flexion-extension range of motion (ROM)(P<0.05,P<0.01) but smaller ankle flexion-extension ROM (P<0.001) than the FI group. The 6 mm LWI group showed a significantly greater hip adduction-abduction ROM (P<0.001,P<0.05) than the other groups,with a smaller ankle plantar flexion-extension ROM (P<0.05) than the 3 mm LWI group. (2) The peak vertical ground reaction force (peak vGRF) of the LWI groups was signifi? cantly lower than the FI group (P<0.01),with that of the 6 mm LWI group significantly lower than the 3 mm LWI group (P<0.001). Moreover,there were significantly greater peak hip flexion moment (P<0.01) and smaller peak ankle plantarflexion moment of the LWI groups than the FI group (P<0.001),with a smaller peak ankle plantarflexion moment of the 6 mm LWI group than the 3 mm LWI group (P<0.05). (3) Significantly greater subjective comfort was observed in the 6 mm LWI group than the FI group (P<0.01). Conclusion LWI can improve landing patterns in CAI patients,re? duce their ground reaction forces,and lower the risk of ankle sprain. The 6 mm LWI outperforms the 3 mm LWI in improving flexion angles of the lower limb tri-joints at ground contact,ankle flexion-ex? tension ROM,peak vGRF,and peak ankle plantarflexion moment during single-leg landing tasks. Therefore,LWI can be used as a wearable protective device during rehabilitation to prevent recurrent ankle sprains among such patients.

Objective:To analyze the changes and structural variations in hospitalization costs for patients with lung malignancies after the implementation of diagnosis-intervention packet (DIP) payment system, and to evaluate its effectiveness.Methods:Data from the first page of medical records and hospitalization cost data from the hospital information system of a tertiary general hospital in Henan Province were extracted for patients diagnosed with lung malignancies from 2020 to 2023. The data were divided into pre-implementation group (2020—2021) and post-implementation group (2022—2023) based on the implementation time of DIP. Chi-square test, t test, and Wilcoxon rank-sum test were used to analyze the differences in basic characteristics and hospitalization costs of patients with lung malignancies before and after the implementation of DIP. Grey relational analysis was employed to examine the internal associations between total hospitalization costs and various cost components. Structural variation analysis was used to assess the changes in the structure of hospitalization costs after the implementation of DIP. Results:A total of 14 587 hospitalized patients with lung malignancies were included, with 6 807 cases in the pre-implementation group and 7 780 cases in the post-implementation group. The average length of hospital stay decreased from (13.17±6.74) days before implementation to (12.02±6.49) days after implementation ( P<0.05). The proportion of level-four surgeries increased from 46.4% to 57.0% ( P<0.05). The average hospitalization cost per patient with lung malignancies decreased from 56 952 yuan before DIP implementation to 55 560 yuan after implementation ( P<0.05). For patients with lung malignancies diagnosed as C34.1, C34.2, C34.3, and C34.8, the top four cost components most strongly associated with total hospitalization costs were treatment costs, material costs, comprehensive medical service costs, and diagnostic costs, with correlation coefficients all>0.80. For patients with C34.9, the top four cost components most strongly associated with total hospitalization costs were treatment costs, comprehensive medical service costs, diagnostic costs, and Western medicine costs, with correlation coefficients>0.95. For patients diagnosed as C34.1, C34.2, C34.3, and C34.9, diagnostic costs, Western medicine costs, and material costs contributed significantly to the structural variation of hospitalization costs, with contribution rate of structure variation all exceeding 75%, among which Western medicine costs and material costs showed negative variation. For patients diagnosed as C34.8, treatment costs, Western medicine costs, and material costs contributed significantly to the structural variation of hospitalization costs, with contribution rate of structure variation all exceeding 80%, among which Western medicine costs showed negative variation. Conclusions:The implementation of DIP reduced the hospitalization costs for patients with lung malignancies, optimized the structure of hospitalization costs, improved the efficiency of medical services, and promoted the rational allocation of medical resources.

The automatic detection of tuberculosis lesions based on medical imaging has become a research hotspot in medical image processing.A comprehensive review of relevant researches and applications pertaining to deep learning in tuberculosis lesion detection is provided,which elucidates the experimental benchmarks in tuberculosis analysis,covering public datasets of pulmonary medical images and recent research advancements in tuberculosis detection and classification competitions,introduces emerging trends in deep learning methods and applications in tuberculosis detection,and analyzes the challenges existing in tuberculosis diagnosis using deep learning.The review summarizes and provides insights into the research advances and challenges of these technologies from the aspects of technical characteristics,performance advantages,and application prospects.

Demoralization syndrome is a common psychological problem in patients with chronic diseases, which seriously affects their prognosis and quality of life. This article reviews the concept and assessment tools of demoralization syndrome, current status, influencing factors, and intervention measures of demoralization syndrome in chronic disease patients, so as to provide reference for clinical medical and nursing staff to develop targeted intervention measures to reduce the level of demoralization syndrome in chronic disease patients.

Toxoplasma gondii is a worldwide parasite that can infect almost all kinds of mammals and cause fatal toxoplasmosis in immunocompromised patients. Apoptosis is one of the principal strategies of host cells to clear pathogens and maintain organismal homeostasis, but the mechanism of cell apoptosis induced by T. gondii remains obscure. To explore the apoptosis influenced by T. gondii, Vero cells infected or uninfected with the parasite were subjected to apoptosis detection and subsequent dual RNA sequencing (RNA-seq). Using high-throughput Illumina sequencing and bioinformatics analysis, we found that pro-apoptosis genes such as DNA damage-inducible transcript 3 (DDIT3), growth arrest and DNA damage-inducible α (GADD45A), caspase-3 (CASP3), and high-temperature requirement protease A2 (HtrA2) were upregulated, and anti-apoptosis genes such as poly(adenosine diphosphate (ADP)-ribose) polymerase family member 3 (PARP3), B-cell lymphoma 2 (Bcl-2), and baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5) were downregulated. Besides, tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1), TRAF2, TNF receptor superfamily member 10b (TNFRSF10b), disabled homolog 2 (DAB2)-interacting protein (DAB2IP), and inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) were enriched in the upstream of TNF, TNF-related apoptosis-inducing ligand (TRAIL), and endoplasmic reticulum (ER) stress pathways, and TRAIL-receptor 2 (TRAIL-R2) was regarded as an important membrane receptor influenced by T. gondii that had not been previously considered. In conclusion, the T. gondii RH strain could promote and mediate apoptosis through multiple pathways mentioned above in Vero cells. Our findings improve the understanding of the T. gondii infection process through providing new insights into the related cellular apoptosis mechanisms.