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: Intrathyroid thymic carcinoma（ITTC） is a rare thyroid tumor that lacks typical clinical manifestations and imaging features, making preoperative diagnosis challenging.The primary treatment for ITTC is radical surgery; however, the effectiveness of adjuvant radiotherapy and chemotherapy post-surgery is not well-established. This paper presents a case of ITTC , analyzing the clinical data and correlating it with the literature to explore the clinical manifestations, diagnostic approach, treatment, and prognosis of ITTC.
Humans ; Prognosis ; Thymoma ; Thymus Neoplasms/diagnosis* ; Thyroid Neoplasms/pathology*

OBJECTIVES: We propose a multi-scale jaw cyst segmentation model, AConvLSTM U-Net, which is based on bidirectional dense connections and attention mechanisms to achieve accurate automatic segmentation of mandibular cyst images. METHODS: A dataset consisting of 2592 jaw cyst images was used. AConvLSTM U-Net designs a MBC on the encoding path to enhance feature extraction capabilities. A DPD was used to connect the encoder and decoder, and a bidirectional ConvLSTM was introduced in the jump connection to obtain rich semantic information. A decoding block based on scSE was then used on the decoding path to enhance the focus on important information. Finally, a DS was designed, and the model was optimized by integrating a joint loss function to further improve the segmentation accuracy. RESULTS: The experiment with AConvLSTM U-Net for jaw cyst lesion segmentation showed a MCC of 93.8443%, a DSC of 93.9067%, and a JSC of 88.5133%, outperforming all the other comparison segmentation models. CONCLUSIONS The proposed algorithm shows a high accuracy and robustness on the jaw cyst dataset, demonstrating its superior performance over many existing methods for automatic segmentation of jaw cyst images and its potential to assist clinical diagnosis.
Humans ; Jaw Cysts/diagnostic imaging* ; Algorithms ; Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer

Objective To compare the efficacy and tolerability of the novel bowel-cleansing agent TCIC-001 and the traditional polyethylene glycol (PEG) regimen for bowel preparation prior to colonoscopy. Methods Prospective inclusion of 62 patients who were scheduled to undergo colonoscopy at Zhongshan Hospital, Fudan University from July 2021 to July 2022. They were randomly divided into TCIC-001 group (n=31) and PEG group (n=31) using a random number table method. The TCIC-001 group took TCIC-001 orally, drinking water in stages, with a total liquid intake of 1 500 mL; the PEG group took PEG orally, taking it in 4 doses, with a total liquid intake of 3 000 mL. The primary endpoint indicator is the quality of intestinal hygiene evaluated by the Boston Bowel Preparation Scale (BBPS), the secondary endpoint indicators were medication adherence, medication duration, frequency of bowel movements, duration of bowel movements, and incidence of adverse events between two groups. Results No significant differences were observed in sex, age, or defecation frequency between the two groups. For efficacy, both groups achieved equivalent bowel cleanliness, with a “good preparation” rate of 93.55% and comparable BBPS score of each intestinal segment and total scores. For tolerability, the TCIC-001 group had a shorter medication duration compared to the PEG group ([48.8±25.9] min vs [82.8±28.4] min, P<0.001), a longer defecation duration ([288.6±74.0] min vs [236.5±74.3] min, P<0.001), and a lower incidence of first defecation before medication completion (9.68% vs 41.94%, P=0.004). Regarding safety, no significant differences were observed between the TCIC-001 group and the PEG group in incidences of chloride disturbances (0% vs 9.68%) and calcium disturbances (3.23% vs 6.45%), and no other adverse events. Conclusions TCIC-001 demonstrated comparable bowel-cleansing efficacy to PEG while significantly improving tolerability (reduced medication time and lower risk of premature defecation) and maintaining favorable safety.

Objective:To evaluate the effects of heparin on focal adhesion kinase (FAK)/Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil-containing protein kinase (ROCK) signaling pathways during acute lung injury (ALI) in septic mice.Methods:Thirty SPF healthy adult male C57BL/6J mice, aged 6-8 weeks, weighing 20-23 g, were assigned into 3 groups ( n=10 each) using a random number table method: control group (group C), ALI group, and heparin group (group H). Septic ALI model was prepared by intraperitoneal injection of lipopolysaccharide 15 mg/kg, while group C received the equal volume of normal saline. In group H, heparin sodium solution 10 U was injected via the tail vein at 30 min before developing the model. The equal volume of normal saline was injected in C and ALI groups. Venous blood samples were collected from the eyeballs under deep anesthesia at 24 h after lipopolysaccharide injection. The mice were subsequently sacrificed and lung tissues were obtained for determination of the serum concentrations of interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) (using enzyme-linked immunosorbent assay), wet/dry lung weight (W/D) ratio, expression of vascular endothelial adhesion factor 1 (VCAM-1) (by immunohistochemical staining) and expression of FAK, phosphorylated FAK (p-FAK), RhoA, GTP-bound RhoA (RhoA-GTP) and ROCK (by Western blot) and for examination of the pathological changes. The lung injury was assessed and scored. Results:Comparison with group C, the serum concentrations of IL-1β, IL-6 and TNF-α, W/D ratio and lung injury scores were significantly increased, and the expression of VCAM-1, p-FAK, RhoA-GTP and ROCK was up-regulated in ALI group ( P<0.05). Compared with ALI group, the serum concentrations of IL-1β, IL-6 and TNF-α, W/D ratio and lung injury scores were significantly decreased, and the expression of VCAM-1, p-FAK, RhoA-GTP and ROCK was down-regulated in H group ( P<0.05). Conclusions:The mechanism through which heparin mitigates ALI is associated with the inhibition of the FAK/RhoA/ROCK signaling pathway in septic mice.

Objective:To analyze the prognostic outcomes of 1 147 patients who underwent liver transplantation at Qingdao University Affiliated Hospital and to summarize measures to enhance the efficacy of liver transplantation.Methods:A retrospective analysis was conducted on the clinical and follow-up data of 1 147 liver transplant patients at Qingdao University Affiliated Hospital.Results:The overall postoperative 1-, 3-, and 5-year survival rates for the 1 147 liver transplant patients were 87.20%, 73.40%, and 65.60%, respectively. The survival rates for benign disease liver transplant recipients were 88.01%, 84.98%, and 81.39% at 1, 3, and 5 years post-transplant, respectively, compared to recipients transplanted for malignancies of 78.11%, 64.41%, and 60.06% (all P<0.001). Among the mid vs more recent period, patients' 1-year and 3-year postoperative survival rates were 84.20%, 70.80% vs 90.50%, 71.70%, respectively,significantly in favor of recently enrolled patients ( P=0.022). In the complex surgery group, patients' 1-, 3-, and 5-year survival rates were 82.70%, 65.50%, 56.70%, while in less complicated group, it was 89.00%, 76.50%, 69.20% ( P<0.001). The primary causes of death for benign disease recipients were multi-organ failure (4.1%), while in recipients with malignant disease primary cause of death was tumor recurrence (23.7%). Postoperative complications included primary graft dysfunction, delayed graft function recovery, portal vein thrombosis, hepatic artery thrombosis, biliary stricture, post-transplant lymphoproliferative disorder, and graft-versus-host disease, with occurrence rates of 1.05%, 6.89%, 1.92%, 0.44%, 2.00%, 0.61%, and 0.44%, respectively. Conclusions:With the continuous improvement in surgical techniques and perioperative care levels, the 3-year survival rate of recipients at our center has increased. Malignant diseases and complex liver transplantation remain crucial factors affecting recipient prognosis, highlighting the need to further enhance comprehensive treatment capabilities for patients with malignant diseases and complex surgeries.

Objective:To evaluate the effect of imatinib on the endotoxemia-induced acute lung injury in mice.Methods:Sixty SPF male, 8-12 weeks, C57BL/6 mice were randomly (random) divided into 4 groups ( n=15 each): control group (group C), imatinib group (groupⅠ), endotoxemia group (group LPS) and imatinib + endotoxemia group (group I+LPS). The endotoxemia model of acute lung injury was established. After 24 hours, the mice were sacrificed. The pathological changes of lung tissues were evaluated, the lung injury scores were calculated, and the wet/dry ratios of lung tissues were measured. ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. Detection kits were used to analyze the levels of malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in lung tissues; The expression levels of phosphorylated nuclear factor-kappa B (p-NF-κB), nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues were analyzed by western blotting. Results:Compared with the group C, the wet/dry (W/D) ratio of lungs [(3.47±0.41) vs. (5.58±0.47)], lung injury scores [(1.25±0.89) vs. (10.25±1.75)], and the levels of TNF-α and IL-6 in serum increased in the group LPS ( P<0.05). The levels of SOD, CAT, GSH and GSH/GSSG decreased, the level of MDA increased, and the expression of p-NF-κB, Nrf2 and HO-1 protein up-regulated ( P<0.05). Compared with the LPS group, the W/D ratio of lungs [(5.58±0.47) vs.(4.62±0.38)] and lung injury scores [(10.25±1.75) vs. (7.00±1.31)] in the I+LPS group decreased ( P<0.05), and the levels of TNF-α and IL-6 in the serum decreased ( P<0.05). In lung tissues, the levels of SOD, CAT, GSH and GSH/GSSG increased (all P<0.05), the level of MDA decreased (all P<0.05), the expression of p-NF-κB protein decreased, and the expression of Nrf2 and HO-1 protein increased ( P<0.05). Conclusions:Imatinib improves sepsis-induced acute lung injury in mice, and the mechanism of actions behind may be related to the inhibition of oxidative stress.

Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

Objective To investigate the effect of dihydroartemisinin(DHA)for enhancing the inhibitory effect of cisplatin(DDP)on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism.Methods CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA(0,5,10,20,40,80,and 160 μmol/L)and DDP(0,4,8,16,32,64,128 μmol/L)for 24 or 48 h,and the combination index of DHA and DDP was calculated using Compusyn software.HNE1/DDP cells treated with DHA,DDP,or their combination for 24 h were examined for cell viability,proliferation and colony formation ability using CCK-8,EdU and colony-forming assays.Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species(ROS).The expression levels of apoptosis-related proteins cleaved PARP,cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting.The effects of N-acetyl-cysteine(a ROS inhibitor)on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed.Results Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells.The combination index of DHA(5 μmol/L)combined with DDP(8,16,32,64,128 μmol/L)were all below 1.Compared with DHA or DDP alone,their combined treatment more potently decreased the cell viability,colony-forming ability and the number of EdU-positive cells,and significantly increased the apoptotic rate,intracellular ROS level,and the expression levels of cleaved PARP,cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells.N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells(P<0.01).Conclusion DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.