1.Computational pathology in precision oncology: Evolution from task-specific models to foundation models.
Yuhao WANG ; Yunjie GU ; Xueyuan ZHANG ; Baizhi WANG ; Rundong WANG ; Xiaolong LI ; Yudong LIU ; Fengmei QU ; Fei REN ; Rui YAN ; S Kevin ZHOU
Chinese Medical Journal 2025;138(22):2868-2878
With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans
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Precision Medicine/methods*
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Medical Oncology/methods*
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Artificial Intelligence
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Neoplasms/pathology*
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Computational Biology/methods*
2.The role of tofacitinib in early atherosclerosis in mice with systemic lupus erythematosus
Qu CHEN ; Fengmei GE ; Zhao LI ; Qiushuang ZHANG ; Xue WU ; Qi CHEN ; Saiqi LI ; Xuebin WANG ; Xiuqing YAN
Chinese Journal of Rheumatology 2024;28(2):106-112
Objective:To investigate the effect of tofacitinib on early atherosclerosis of patients with systemic lupus erythematosus and explore the possible relationship between lupus nephritis and early atherosclerosis of systemic lupus erythematosus.Methods:Sixteen 8-week-old female MRL/lpr mice with a body weight of 20~25 g were selected and randomly divided into the treatment group and placebo group, with 8 mice in each group. The treatment group diluted tofacitinib by normal saline, and given at a dose of 10 mg·kg -1·d -1, and the placebo group (starch tablets) administered the medication in the same way as the treatment group for a total of 8 weeks. The ELISA method was applied to detect serum anti-dsDNA antibody levels in the two groups of mice. Bradford method protein concentration was used to determine the level of urine protein in mice. Automatic biochemical analyzer was used to detect blood lipids, urea nitrogen, serum creatinine, complement C3, complement C4 levels. Western blotting was used to determine the protein expression levels of monocyte chemoattractant protein-1 (MCP-1), non-receptor protein tyrosine kinase family 1 (JAK1), signal transducer and activator of transcription 1 (STAT1) and signal transducer and activator of transcription 2 (STAT2) in aortic and kidney tissues. After the aortic arch section were prepared, oil red O was used to stain the sections, and the vascular plaque area and intimal thickness were evaluated by ImageJ software. The kidneys were dissected and stained with HE, and the active lesions of lupus nephritis were evaluated using the glomerular activity scoring system. SPSS 23.0 software was used for statistical analysis, in which the between-group comparison was performed using two independent samples t-test, and the correlation analysis was performed using the Spearman method. Results:①The serum anti-dsDNA antibody expression level in the treatment group [(5.2±1.0) U/ml] was lower than that in the placebo group [(6.9±1.2) U/ml], ( Z=-3.07, P=0.008), and the levels of complement C3 and complement C4 were higher than those in the placebo group [(293±10) mg/L vs. (260±19) mg/L, Z=2.72, P=0.017]; (16±6) mg/L vs. (8±9) mg/L, Z=3.78, P=0.006]. There was no significant difference in serum BUN and Scr between the treatment group and the placebo group [(10.6±0.7) mmol/L vs. (11.5±1.1) mmol/L, Z=-1.96, P=0.071; (17±5) μmol/L vs. (22±6) μmol/L, Z=-1.79, P=0.095]. ② Compared with the placebo group, the levels of LDL, TC and TG in the treatment group decreased [(0.83±0.15) mmol/L vs. (1.08±1.05) mmol/L, Z=-3.95, P=0.001; (2.90±0.08) mmol/L vs. (1.81±0.97) mmol/L, Z=-5.17, P=0.001; (1.10±0.08) mmol/L vs. (1.60±0.42) mmol/L, Z=-3.23, P=0.013], and HDL level increased [(2.02±0.99) mmol/L vs. (1.81±0.97) mmol/L, Z=4.42, P=0.001]. ③ Compared with the placebo group, the levels of aortic MCP-1, JAK1, STAT1 and STAT2 in the treatment group were reduced [(0.17±0.30) vs. (0.23±0.05), Z=-3.06, P=0.009; (0.83±0.09) vs. (1.05±0.19), Z=-3.07, P=0.008; (0.77±0.07) vs. (0.94±0.13), Z=-2.83, P=0.014; (0.70±0.07) vs. (0.82±0.09), Z=-2.83, P=0.013], the aortic plaque area and aortic intimal thickness were lower than those in the placebo group [(12±31) μm 2vs. (1 242±1 101) μm 2, Z=-3.12, P=0.016; (63±7) μm vs. (82.10±8.06) μm, Z=-5.13, P<0.001]. ④ Compared with the placebo group, the urine protein level and glomerulonephritis activity score in the treatment group were decreased [(0.08±0.03) mg/mL vs. (0.20±0.11) mg/mL, Z=-3.08, P=0.015; (1.79±0.38) vs. (2.79±0.14) points, Z=-7.08, P<0.001)], and renal tissue MCP-1, JAK1, STAT1.Compared with the placebo group, STAT2 levels were reduced [(0.364±0.040) vs. (0.425±0.021), Z=-3.85, P=0.003; (0.689±0.074) vs. (0.838±0.068), Z=-4.19, P=0.001; (0.508±0.070) vs. (0.646±0.019), Z=-2.85, P=0.015; (0.618±0.062) vs. (0.740±0.101), Z=-2.94, P=0.013. ⑤ The glomerular mobility scores of the two groups were positively correlated with LDL, TCHO, TG, aortic plaque area and aortic intimal thickness ( r=0.51, P=0.043; r=0.79, P<0.001; r=0.64, P=0.008; r=0.82, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.53, P=0.036). The urine protein levels in the two groups were positively correlated with LDL, TC, TG, aortic plaque area and aortic intimal thickness ( r=0.67, P=0.004; r=0.68, P=0.004; r=0.53, P=0.033; r=0.80, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.57, P=0.021). Conclusion:The severity of lupus nephritis is correlated with atherosclerosis and dyslipidemia in the early stage of systemic lupus erythematosus. Tofacitinib may reduce the degree of early arteriosclerosis and lupus nephritis in MRL/LPR mice, and reduce blood lipid levels, which may be effective in improving the prognosis of SLE and improving the survival rate of patients.
3.Study on the correlation of integr in associated protein and disease activity and bone destruction in patients with rheumatoid arthritis
Xue WU ; Fang SHI ; Xiuqing YAN ; Fengmei GE ; Zhao LI ; Qiushuang ZHANG ; Qu CHEN ; Qi CHEN ; Xuebin WANG
Chinese Journal of Rheumatology 2022;26(9):603-607
Objective:To analyze the serum levels of integrin-associated proteins (CD47) in patients with rheumatoid arthritis (RA), and to explore its association with disease activity and bone destruction in RA.Methods:Serum and clinical data were collected from 65 RA patients and 25 healthy subjects. RA patients were grouped into low, moderate, and high bone erosion groups according to 7-joint ultrasonography score (US7). The levels of serum CD47, thrombospondin-1 (TSP-1) and receptor activator of nuclear factor-κB ligand (RANKL) were measured by enzyme-linked immunosorbnent assay (ELISA) in patients with RA and healthy subjects. The statistical analysis was carried out with independent t-test, analysis of variance, nonparametric rank sum test, pearson or Spearman correlation and logistic regression. Results:① The Serum levels of CD47, TSP-1, and RANKL were higher in the RA group than in the healthy controls ( P<0.01). ② In RA patients, serum CD47 level was positively correlated with disease course ( r=0.301, P<0.05), C-reactionprotein (CRP)( r=0.316, P<0.05), number of tender joints (TJC) ( r=0.254, P<0.05), number of swollen joints (SJC) ( r=0.316, P<0.05), disease activity score in 28 joints (DAS28) ( r=0.255, P<0.05), RANKL ( r=0.252, P<0.05) and TSP-1 ( r=0.260, P<0.05). Serum TSP-1 level was positively correlated with CRP ( r=0.299, P<0.05), TJC ( r=0.335, P<0.01), DAS28 ( r=0.315, P<0.05), RANKL ( r=0.305, P<0.05). ③ The disease course [ OR(95% CI)=1.048(1.033, 1.017)] and TSP-1 [ OR(95% CI)=1.013(1.000, 1.026)] were independently relevant factors affecting bone destruction. Conclusion:CD47 levels is significantly higher in RA patients than in healthy controls, and is associated with disease activity and bone destruction. CD47 may be involved in the bone destruction process of RA by acting on TSP-1.
4.Therapeutic effect and mechanism of sodium formononetin-3′-sulphonate on collagen-induced rheumatoid arthritis
Wenxing SHI ; Qing LYU ; Guiwu QU ; Ying ZHAO ; Fengmei ZHOU
Journal of China Pharmaceutical University 2021;52(5):579-585
To investigate the therapeutic effect and mechanism of sodium formononetin-3′-sulphonate (SFS) on collagen-induced rheumatoid arthritis in mice, C57 mice were induced with chicken type II collagen to establish a model of rheumatoid arthritis (collagen-induced arthritis, CIA), and were injected intraperitoneally with different doses of SFS (50,100,200 mg/kg). Body weight, food intake and foot swelling of all groups were observed during the experiment.After the treatment, TNF-α, IL-6, and IL-10 in the serum were detected with the CBA kit; NF-κB p65, p-NF-κB p65 (p-p65), TIPE2, PCNP and IκB-α in spleen tissue were determined by Western blot; the organ index, pathological changes of ankle joint cartilage tissue and the positive expression of NF-κB p65 in ankle joint tissue were also observed.The results showed that, compared with the model group, the body weight and food intake of mice in the treatment group increased, while the degree of foot swelling decreased; the expression levels of inflammatory factors TNF-α and IL-6 in serum decreased, while the expression of anti-inflammatory factor IL-10 increased; the expression levels of NF-κB p65, p-p65 and PCNP in spleen tissue decreased, while the expression of TIPE2 and IκB-α protein increased; the index of spleen and thymus of the CIA mice in the treatment group, the infiltration of inflammatory cells in the ankle joint, the destruction of synovial tissue and cartilage, and the positive expression of NF-κB p65 decreased.Among them, the high-dose group of SFS showed a better therapeutic effect.It is suggested that SFS has a therapeutic effect on CIA mice, and the mechanism may be achieved by regulating the NF-κB p65 signaling pathway and inhibiting the expression of inflammatory factors.
5.Evaluation of the clinic effects of perioperative psychological intervention combined appropriate sedation by target-controlled infusion of midazolam during operation via SCL-90 and OAA/S in patients undergoing thumb or finger reconstruction
Deming WANG ; Yuanxin ZHANG ; Yanqing CHEN ; Fengmei AN ; Yanliang QU
Journal of Chinese Physician 2013;15(11):1495-1498
Objective To evaluate the clinic effects of perioperative psychological intervention combined appropriate sedation by target-controlled infusion of midazolam during operation via symptom check List 90 (SCL-90) and observers assessment of alertness/sedation scale (OAA/S) in patients undergoing thumb or finger reconstruction.Methods Eighty patients undergoing thumb or finger reconstruction were randomly divided into group A,B,C,and D (n =20 cases per group).All patients were received brachial plexus block and spinal-epidural combined anesthesia.Patients in group A were given perioperative psychological intervention combined appropriate sedation by target-controlled infusion of midazolam during operation; patients in group B were received routine treatment; patients in group C were given perioperative psychological intervention; and patients in group D were sedated with midazolam during operation.The vital signs and the scores of OAA/S were observed during operation.The scores of visual analogue scale (VAS) and SCL-90 were recorded after operation.Results The OAA/S grade in groups A and D were stability than that in groups B and C (P < 0.05) ; the scores of VAS and the results of psychological status assessment by SCL-90 in group A were superior to groups B,C,and D (P < 0.05).Conclusions Perioperative psychological intervention combined appropriate sedation in operation on thumb or finger reconstruction is a excellence anaesthesia processing method.It might have beneficial effects on postoperative recovery profile,and strengthen the tolerance to pain and improve the patient's psychological status during operative period.

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