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 ; Precision Medicine/methods* ; Medical Oncology/methods* ; Artificial Intelligence ; Neoplasms/pathology* ; Computational Biology/methods*

Objective:To explore the effects of aerobic exercise on learning and memory functions, hippocampal synaptic plasticity and the ADPN signaling pathway in diabetic rats.Methods:6-week-old male SD rats were randomly divided into a blank control group(NC group)and a high-fat diet group, and a rat model for diabetes was induced by feeding rats in the high-fat diet group with a high-fat diet combined with intraperitoneal instillation of low-dose streptozotocin(STZ)for 5 weeks.Rats in the high-fat diet group were further divided into a diabetic group(DC group)and a diabetic aerobic exercise group(DM group)after successful establishment of the model.Rats in the DM group were subjected to aerobic exercise for eight weeks and then the Morris water maze test was conducted to assess learning and memory functions, relevant serum markers were measured, Golgi staining was used to examine synaptic changes in the hippocampus, and Western blot was carried out to detect hippocampal protein expression levels of adiponectin(ADPN), AMP-activated protein kinase(AMPK), glucose transporter 4(GLUT4), synaptic plasticity-related protein synaptophysin(SYN)and postsynaptic density protein 95(PSD-95)for rats in each group.Results:Serum FBG and HBA1c in diabetic rats were markedly significantly decreased after 8 weeks of aerobic exercise( P<0.01), and serum ADPN and insulin were significantly increased after 8 weeks of aerobic exercise( P<0.05).When test results from the three groups of rats compared, the F value was 69.248 for FBG, 6.740 for INS, 7.017 for HBA1C and 14.315 for serum ADPN.The results of the water maze test and hippocampal Golgi staining showed that the escape latency of diabetic rats was highly significantly decreased after 8 weeks of aerobic exercise( P<0.01).The platform crossing times, the number of dendritic branches and the dendritic spine density in the hippocampal CA3 region of diabetic rats were significantly increased after 8 weeks of aerobic exercise( P<0.05).When results from the three groups of rats were compared, the F value was 13.934 for escape latency, 5.864 for platform crossing times, 9.307 and 6.734 for the number of dendritic branches and the density of dendritic spine in hippocampal CA3 region.Hippocampal PSD-95, SYN, ADPN, p-AMPK, and GLUT4 protein expression levels of diabetic rats were significantly increased( P<0.05)after 8 weeks of aerobic exercise.When results from the three groups of rats were compared, the F value was 15.137 for SYN, 5.415 for PSD-95, 9.687 for ADPN, 27.761 for GLUT4, and 9.298 for p-AMPK. Conclusions:Eight weeks of aerobic exercise can improve the learning and memory functions of diabetic rats, and the mechanisms may be related to exercise-induced hippocampal ADPN/AMPK/GLUT4 signaling activation in rats, leading to enhanced synaptic plasticity in the hippocampus.

Objective To explore prescription medication rules and potential mechanism of traditional Chinese medicine(TCM)in the treatment of alcoholic liver disease(ALD)based on the technology of data mining and network pharmacology.Methods The prescriptions related to the treatment of ALD were retrieved in Chinese National Knowledge Infrastructure,Wanfang,Chinese Biomedical Literature and VIP databases.After the data were collated according to the filter criteria,IBM SPSS Statistics 27.0 and IBM SPSS Modeler 18 software were used to analyze the prescription rules and association rules.Then,the medication rules of TCM in the treatment of ALD were summarized,and the core drug combinations were obtained.Active ingredients in the core drug combinations for ALD and their targets were screened by network pharmacology.GO and KEGG analysis were performed on the main targets,and molecular docking technique was used to verify the binding ability of active ingredients to main targets.Results A total of 143 prescription for ALD were screened,involving 222 Chinese medicine,among which 28 high-frequency Chinese medicine were used with a frequency≥25 times.Eight core drug combinations were obtained by associations rule analysis.It has been found that there are 215 intersection targets between"Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae"and ALD,including six core targets of AKT1,TNF,VEGFA,IL-1β,SRC,EGFR.One hundred and sixty-eight of signaling pathways are involved,including cancer pathways,PI3K/AKT signaling pathways,chemical carcinogenesis-reactive oxygen species,lipid and atherosclerosis,etc.Molecular docking results showed that the main active components including cerevisterol,genkwanin and demethoxycapillarisin had good binding ability to AKT1.Conclusion The main active ingredients in"Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae"can participate in the regulation of key signaling pathways such as PI3K/AKT by acting on key target proteins(AKT1,TNF,and VEGFA).Subsequently,they play a role in inhibiting inflammatory response and apoptosis,slowing down liver fibrosis,and promoting hepatocyte repair.This study provides data support and theoretical guidance for the study of TCM in the treatment of ALD.

OBJECTIVE: To assess the validity and effectiveness of parameter estimation using a time-dependent Weibull proportional hazards model for survival analysis containing partly interval censored data and explore the impact of different covariates on the results of analysis. METHODS: We established a time-dependent Weibull proportional hazards model using the Weibull distribution as the baseline hazard function of the model which incorporated time-varying covariates. Maximum likelihood estimation was employed to estimate the model parameters, which were obtained by optimization of the likelihood function. RESULTS AND CONCLUSION: Numerical simulation results showed that with higher proportions of precise observations across different sample sizes and parameter settings, the proposed model resulted in improved accuracy of parameter estimation with coverage probabilities approximating the theoretical expectation of 95%. As the sample sizes increased, the parameter biases of the model tended to decrease. Experiments with empirical data further validated the effectiveness of the model. Compared with the failure time data for each precisely observed individual, additional interval-censored data helped to obtain more effective estimates of the regression parameters. Comparison with the Cox model that included time-varying covariates further demonstrated the effectiveness of the time-dependent Weibull proportional hazards model for parameter estimation in survival analysis with partly interval censored data.
Proportional Hazards Models ; Survival Analysis ; Likelihood Functions ; Humans ; Computer Simulation ; Time Factors

Objective:To investigate the factors associated with delay in anticoagulant therapy in patients with cerebral venous sinus thrombosis (CVST) and its effect on outcome.Methods:Patients with CVST admitted to Changhai Hospital, Naval Medical University from January 2010 to August 2021 were retrospectively enrolled. Patients were divided into early anticoagulation group and late anticoagulation group by the median time interval from first symptom to initiation of anticoagulation. The modified Rankin Scale was used for outcome assessment at 90 d after onset. 0-2 scores were defined as good outcome and 3-6 were defined as poor outcome. Demographic and clinical data were compared for the early versus late anticoagulation group and for the good versus poor outcome groups. Multivariable logistic regression was used to identify independent influencing factors of delay in anticoagulation and the correlation of delay in anticoagulation with poor outcome. Results:A total of 131 patients were included, their age was 40.07±15.11 years old, and 68 (51.91%) were male. Of these, 65 patients (49.62%) were in the early anticoagulation group and 14 (10.69%) were in the poor outcome group. Compared with the late anticoagulation group, the early anticoagulation group had a significantly higher proportion of patients with seizures and brain parenchymal damage as well as higher D-dimer levels on admission, while the proportion of patients with visual impairment/papilloedema was significantly lower (all P<0.05). Compared with the good outcome group, the poor outcome group had significantly higher proportions of patients with seizures, dyskinesia, impaired consciousness, low Glasgow Coma Scale score, and brain parenchymal damage as well as higher D-dimer, total cholesterol and low density lipoprotein cholesterol levels, sites of thrombus involvement were more common in the superior sagittal and straight sinuses, and significantly lower proportions of patients with headache and lower albumin levels on admission (all P<0.05). Multivariate logistic regression analysis showed that visual impairment/papilloedema (odds ratio [ OR] 0.119, 95% confidence interval [ CI] 0.030-0.473; P=0.002) and brain parenchymal damage ( OR 1.341, 95% CI 1.042-1.727; P=0.023) were independently associated with a delay in anticoagulation treatment, and a delay in anticoagulation treatment ( OR 6.102, 95% CI 1.185-30.504; P=0.030) and D-dimer level on admission ( OR 1.299, 95% CI 1.141-1.480; P<0.001) were the independent predictors of poor outcome in patients with CVST. Conclusions:Visual impairment/papilloedema and absence of brain parenchymal damage on cranial imaging are the independent risk factors for delay in anticoagulation in patients with CVST. The delay in anticoagulation is strongly associated with the poor outcome in patients with CVST.

Objective:To investigate the current application of colonoscopy at hospitals in China.Methods:From November 2019 to January 2020, an online questionnaire survey was conducted among gastroenterologists and colonoscopists in hospitals of different levels. The contents of questionnaire survey included basic information of colonoscopy at the respondent′s hospital, protocols and patient education of bowel preparation, implementation of colonoscopy quality control, and colonoscopists′ understanding of polypectomy techniques and post-polypectomy follow-up.Results:A total of 236 valid questionnaires were collected, involving 187 hospitals, and 143 (76.5%) had an annual operation capacity of more than 5 000 cases. In terms of bowel preparation, split-dosed polyethylene glycol electrolyte powder (PEG) was the most commonly used (60.4%, 113/187) and the most common volume of PEG was 3 L (67.4%, 126/187). Verbal (90.9%, 170/187) and written (79.7%, 149/187) instructions were given more often than other methods for patient education of bowel preparation. Antifoaming agent was routinely used in 124 (66.3%) hospitals. In terms of quality control, only 11.5% (20/174) hospitals implemented all four measures. In terms of polypectomy techniques, 98.1% (203/207) colonoscopists chose hot snare polypectomy or endoscopic mucosal resection for lesions of diameter>1 cm, while options varied for lesions of diameter<1 cm. The interval of follow-up after polypectomy recommended by colonoscopists was shorter than that by guidelines.Conclusion:Several problems are found in the survey in the application of colonoscopy in China, i. e., patient education of bowel preparation is not diversified; quality control of colonoscopy still needs to be strengthened; polypectomy techniques and follow-up after polypectomy need to be further standardized.

Objective:To establish an artificial intelligence (AI)-assisted colorectal polyps classification system (AI polyps system) by using clinical big data, and to conduct the clinical verification.Methods:From June 2018 to June 2019, the colonoscopy images of polyps from 16 participating research centers were prospectively collected. The basic information of the polyps (location, size, shape and pathological biopsy results) in colonoscopy images of colorectal polyps were marked by senior colonoscopist, and the outline of the polyp was circled for the development of the AI polyps system. Taking pathological biopsy results of polyps as the gold standard, the sensitivity, specificity, and positivity predictive value (PPV), negative predictive value (NPV) and accuracy of white light model, narrow band imaging (NBI) model, the combination of white light and NBI model and colonoscopists′ identification of polyps were calculated respectively. Paired McNemar test and Kappa test were used for statistical analysis. Results:A total of 15 441 qualified colonoscopy images were collected, including 9 109 images in white light model and 6 332 images in NBI model. At laboratory level, the sensitivity, specificity, PPV, NPV and accuracy of white light model and NBI model in the identification of the polyps were 90.3%, 98.3%, 89.8%, 98.4%, 97.2%, and 90.5%, 92.5%, 92.3%, 90.6%, 91.5%, respectively. In clinical verification phase, a total of 78 polyps of 56 patients with colorectal polyps were enrolled. The sensitivity, specificity, PPV, NPV and accuracy of the white light model and NBI model in the identification of polyps were 70.3%, 82.1%, 78.8%, 74.4%, 76.3%, and 78.4%, 87.2%, 85.3%, 81.0%, 82.9%, respectively. There were no statistically significant differences between the diagnostic results of colonoscopists, the white light model, the NBI model and the results of pathological results (all McNemar test, all P>0.05), but the consistency were general and the Kappa values were 0.632, 0.525 and 0.657, respectively (all P<0.01). The Kappa value of combination of the white light and NBI model and the pathological results was 0.575, however the consistency was general, but the difterence was statistically significant (McNemar test, P=0.004). Conclusions:The established AI polyps system has a certain role in assisting diagnosis, but the accuracy still needs to be improved.

PURPOSE: The data on the differences between sputum autoantibodies (Sp-Abs) and serum autoantibodies (Se-Abs) in reflection of autoimmune responses to lungs is still lacking. METHODS: Ten types of Abs were investigated in matched Se and Sp samples collected from recruited subjects. Correlations between Ab levels and airway inflammatory parameters and measures of pulmonary function were assessed. The network-based and inter-correlated analysis was performed to explore the patterns of Sp- and Se-Ab profiles. RESULTS: Fifty stable asthmatic patients and 24 healthy volunteers were recruited for our study, 15 with mild asthma, 18 with moderate asthma and 17 with severe asthma. The concentrations of Sp-Ab against U1 small nuclear ribonucleoprotein (Sp-anti-U1-SnRNP), Sp-Ab against Smith antigen and Se-Ab against thyroid peroxidase (anti-TPO) in severe asthmatics and Sp-anti-U1-SnRNP in moderate asthmatics were significantly higher compared to healthy controls and mild asthmatic subjects (P < 0.05). Sp-anti-U1-SnRNP levels were positively correlated with the dose of inhaled corticosteroids, Sp eosinophil counts and fractional exhaled nitric oxide (r = 0.326, P = 0.022; r = 0.356, P = 0.012; r = 0.241, P = 0.025, respectively) and negatively correlated with Sp neutrophil counts (r = −0.308, P = 0.031) with adjustment for age. Spearman's correlation matrix showed multiple inter-correlations among Sp-Abs and Se-Abs (P < 0.05) while only the levels of Ab against DNA topoisomerase and anti-TPO in Se were correlated with those Sp-Ab counterparts (P < 0.05). The network-based analysis defined 2 clusters: clusters 1 and 2 contained 10 Sp-Abs and 10 Se-Abs, respectively. CONCLUSIONS: This study observes that Sp-Abs are more associated with clinical parameters and the severity of disease in asthma compared to Se-Abs. Targeting on Sp-Abs which are the hallmark of the localized autoimmune event might help us better understand the role of autoimmunity in the pathological mechanism of asthma.
Adrenal Cortex Hormones ; Asthma ; Autoantibodies ; Autoimmunity ; DNA Topoisomerases, Type I ; Eosinophils ; Healthy Volunteers ; Humans ; Iodide Peroxidase ; Lung ; Neutrophils ; Nitric Oxide ; Ribonucleoproteins, Small Nuclear ; Sputum

Objective: To evaluate the clinical value of a commercial low-residue diet (LRD) for bowel preparation of colonoscopy. Methods: This study was a prospective, endoscopist-blind, and randomized controlled trial. Participants were randomly assigned to two groups according to administration of LRD: the experimental group and the control group. Bowel preparation quality, compliance and tolerability of the two groups were compared. Results: A total of 61 patients were enrolled, with 32 in the experimental group and 29 in the control group. The outcomes were as follows: Boston Bowel Preparation Scale (BBPS) (7.8±1.0 VS 7.1±1.3, P=0.037), the rate of bowel preparation adequacy (87.5% VS 79.3%, P=0.388), compliance rate of dietary restriction (78.1% VS 55.2%, P=0.057), preparation completion rate (93.8% VS 93.1%, P=0.919), cecal intubation rate (both were 100.0%) and cecum arrival time (9.1±2.9 min VS 9.8±3.7 min, P=0.417), incidence of adverse (3.1% VS 3.4%, P=0.944), and hunger rate before colonoscopy (34.4% VS 48.3%, P=0.102). Conclusion The LRD for bowel preparation of colonoscopy significantly improves BBPS, but its effect on improving the bowel preparation adequacy, patient compliance and tolerability needs to be confirmed by further larger-scale trials.

Objective: To observe the difference in anti-inflammatory effect between living rhino horn and rhino horn by the method of comparative research to provide the experimental basis for the replacement of rhino horn by living rhino horn.Methods: The anti-inflammatory effects of living rhino horn and rhino horn were studied by the methods of paw edema in rats, cotton ball granuloma in mice, auricle swelling and peritoneal dye penetration.Results: Compared with that in the model control group, the foot metatarsus swelling degree at all time points in high (440 mg·kg-1) dose group and middle (220 mg·kg-1) dose group of living rhino horn and three doses groups of rhino horn showed statistical differences (P＜0.05 or P＜0.01).The high dose group (700 mg·kg-1) and middle dose group (350 mg·kg-1) of living rhino horn and rhino horn could significantly reduce the weight of cotton ball granuloma in mice (P＜0.05).Three doses groups (700, 350 and 175 mg·kg-1) of living rhino horn and rhino horn could significantly reduce auricle swelling in mice induced by xylene (P＜0.05 or P＜0.01).The absorbance of Evansan in the abdominal cavity in the middle dose group (350 mg·kg-1) of rhino horn and the high dose group (700 mg·kg-1) and middle (350 mg·kg-1) dose group of living rhino horn was significantly reduced (P＜0.05 or P＜0.01).There was no significant difference in the anti-inflammatory effect between living rhino horn and rhino horn at the same dose.Conclusion: Living rhino horn and rhino horn have a certain anti-inflammatory effect.The anti-inflammatory effect of living rhino horn is similar to those of the rhino horn, and living rhino horn can be used as a substitute of rhino horn.