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*

With the widespread application of information technology in the field of Traditional Chinese Medicine(TCM),the data in the TCM domain is becoming increasingly rich.The emergence of data-driven research in TCM has utilized knowledge graphs for the management,analysis,and presentation of TCM data,becoming a crucial method for the inheritance and innovation of Traditional Chinese Medicine.Therefore,reasoning based on TCM knowledge graphs has become a hot topic in contemporary TCM research.In order to better utilize knowledge graph reasoning technology to promote innovation and development in TCM,this article,after providing an overview of TCM knowledge graph reasoning,focuses on the development of knowledge graph reasoning in TCM and its applications from three perspectives:logic rule-based,distributed representation,and neural network-based methods.Finally,the article summarizes the advantages and disadvantages of knowledge reasoning methods and provides prospects for research and applications in TCM knowledge graph reasoning,including studies on interpretability,temporal knowledge graphs,and the fusion of multimodal information.

With the widespread application of information technology in the field of Traditional Chinese Medicine(TCM),the data in the TCM domain is becoming increasingly rich.The emergence of data-driven research in TCM has utilized knowledge graphs for the management,analysis,and presentation of TCM data,becoming a crucial method for the inheritance and innovation of Traditional Chinese Medicine.Therefore,reasoning based on TCM knowledge graphs has become a hot topic in contemporary TCM research.In order to better utilize knowledge graph reasoning technology to promote innovation and development in TCM,this article,after providing an overview of TCM knowledge graph reasoning,focuses on the development of knowledge graph reasoning in TCM and its applications from three perspectives:logic rule-based,distributed representation,and neural network-based methods.Finally,the article summarizes the advantages and disadvantages of knowledge reasoning methods and provides prospects for research and applications in TCM knowledge graph reasoning,including studies on interpretability,temporal knowledge graphs,and the fusion of multimodal information.

Objective To explore the correlation of occurrence of major adverse cardiovascular events(MACE)with QRS-T angle,N-terminal pro-B-type natriuretic peptide(NT-proBNP)and fibrinogen(FIB)levels and platelet/lymphocyte ratio(PLR)in patients with acute myocardial in-farction(AMI)after percutaneous coronary intervention(PCI).Methods A retrospectively analy-sis was conducted on 98 AMI patients undergoing PCI in our department from May 2020 to June 2022.According to the occurrence of MACE or not,they were divided into MACE group(25 cases)and non-MACE group(73 cases).The general data and QRS-T angle,PLR,and Fib and NT-proBNP levels were compared between the two groups.Univariate logistic regression analysis and ROC curve analysis were used to analyze the influencing factors and predictive efficacy for MACE occurrence in AMI patients after PCI.Results Significantly larger QRS-T angle and PLR,and higher FIB and NT-proBNP levels were observed in the MACE group than the non-MACE group(P＜0.05,P＜0.01).Univariate logistic regression analysis showed that RS-T angle(OR=1.086,95％CI:1.043-1.131,P=0.000),PLR(OR=1.184,95％CI:1.102-1.272,P=0.000)and NT-proBNP level(OR=1.009,95％CI:1.004-1.014,P=0.000)were influencing factors for MACE occurrence in AMI patients after PCI.ROC curve analysis indicated that the AUC value of QRS-T angle,PLR and NT-proBNP level in predicting MACE after PCI in AMI patients was 0.822,0.870 and 0.907,with a sensitivity of 76.00％,76.00％and 84.00％,and a specificity of 72.60％,89.04％and 94.52％,respectively.Conclusion QRS-T angle,PLR and NT-proBNP are the influencing factors of MACE in AMI patients after PCI,and they have good predictive value.

Objective To explore the correlation of occurrence of major adverse cardiovascular events(MACE)with QRS-T angle,N-terminal pro-B-type natriuretic peptide(NT-proBNP)and fibrinogen(FIB)levels and platelet/lymphocyte ratio(PLR)in patients with acute myocardial in-farction(AMI)after percutaneous coronary intervention(PCI).Methods A retrospectively analy-sis was conducted on 98 AMI patients undergoing PCI in our department from May 2020 to June 2022.According to the occurrence of MACE or not,they were divided into MACE group(25 cases)and non-MACE group(73 cases).The general data and QRS-T angle,PLR,and Fib and NT-proBNP levels were compared between the two groups.Univariate logistic regression analysis and ROC curve analysis were used to analyze the influencing factors and predictive efficacy for MACE occurrence in AMI patients after PCI.Results Significantly larger QRS-T angle and PLR,and higher FIB and NT-proBNP levels were observed in the MACE group than the non-MACE group(P＜0.05,P＜0.01).Univariate logistic regression analysis showed that RS-T angle(OR=1.086,95％CI:1.043-1.131,P=0.000),PLR(OR=1.184,95％CI:1.102-1.272,P=0.000)and NT-proBNP level(OR=1.009,95％CI:1.004-1.014,P=0.000)were influencing factors for MACE occurrence in AMI patients after PCI.ROC curve analysis indicated that the AUC value of QRS-T angle,PLR and NT-proBNP level in predicting MACE after PCI in AMI patients was 0.822,0.870 and 0.907,with a sensitivity of 76.00％,76.00％and 84.00％,and a specificity of 72.60％,89.04％and 94.52％,respectively.Conclusion QRS-T angle,PLR and NT-proBNP are the influencing factors of MACE in AMI patients after PCI,and they have good predictive value.

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

OBJECTIVE To study the pharmacological basis of Schisandra chinensis in the treatment of allergic asthma. METHODS The common components of 10 batches of S. chinensis from different habitats were analyzed by UPLC-Q-TOF-MS/MS. Furthermore， the allergic asthma model was established by intraperitoneal injection of ovalbumin （OVA） and aluminum hydroxide for stimulation combined with atomization exitation； general behavioral observation and the contents of interferon γ （IFN-γ）， interleukin-4 （IL-4） and immunoglobulin E （IgE） in serum were taken as criteria for evaluating the therapeutic effect of S. chinensis from different habitats in the treatment of allergic asthma. Correlation coefficients between common peak area and efficacy evaluation index of each batch of medicinal material were analyzed through grey correlation degree and Pearson correlation analysis. RESULTS A total of 21 common components were identified in 10 batches of S. chinensis from different habitats. After administration of S. chinensis， symptoms such as shortness of breath， sneezing and curling of rats were alleviated. In addition， the content of IFN-γ was significantly increased while the contents of IL-4 and IgE in serum were distinctly decreased （P＜0.01）. Grey correlation analysis showed that 11 common components had high correlation coefficients with IFN-γ， IL-4 and IgE （rˉ＞0.8）. Pearson correlation analysis showed that 8 components were significantly positively correlated with the content of IFN-γ （P＜ 0.05）， and 9， 8 components were significantly negatively correlated with the content of IL-4 and IgE （P＜0.05）. Based on the results of grey correlation degree and Pearson correlation analysis， 7 components such as peak 3， 4， 6， 7， 9， 19 and 20， were highly related to S. chinensis in the treatment of allergic asthma. CONCLUSIONS Schisandrol A， schisandrin B， schisandrin C， gomisin M2， gomisin J， pregomisin and angeloylgomisin H are the potential pharmacodynamic substance basis of S. chinensis in the treatment of allergic asthma.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.