With the rapid advancement of artificial intelligence technology, computational pathology has evolved from task-specific models to foundation models capable of supporting multiple organs, diseases, and downstream tasks. However, existing methods remain limited to single-pass inference on images and are unable to fully emulate the complex diagnostic processes encountered in real-world clinical settings. In recent years, large language models have driven the development of agent-based paradigms. By leveraging capabilities such as navigation, reasoning, and tool use, these frameworks offer a novel approach for modeling complex diagnostic workflows. Framed within the context of clinical pathology diagnostic processes, this article systematically reviews the key challenges and advances in computational pathology research across three stages: preliminary overview, diagnostic analysis, and report writing, and discusses the current functional roles and implementation approaches of agent-based technologies at each stage. Although validation scenarios in existing studies remain limited, the core modules and methods required to construct a pathology diagnostic agent system are largely in place. Agent-related technologies are expected to facilitate the development of a clinically deployable intelligent assistance platform for pathology diagnosis.

Pathology diagnosis is the "gold standard" for clinical disease diagnosis and treatment. Intelligent pathology image analysis has significant clinical value in improving diagnostic efficiency and ensuring consistency. This paper systematically reviews the core multiple instance learning paradigm for whole slide image analysis, and elaborates the pretraining system, core functional branches and latest advances of pathology foundation models. Taking clinical usability as the core evaluation dimension, it establishes a multi-dimensional evaluation framework, analyzes the clinical translation potential of different technical routes, and points out the core contradiction of "excellent laboratory performance but insufficient clinical usability" in current pathology foundation models. It further dissects the key clinical translation bottlenecks of pathology foundation models, outlines future application and development directions, and provides a reference for technological research and development as well as clinical translation in computational pathology.

Objective To investigate the correlation between c-MYC expression and mitochondrial metabolism in malignant duct epithelial cells of pancreatic cancer patients.Methods GEPIA database was used to analyze the correlation between c-MYC expression and overall survival.The expression of c-MYC in tumor tissues was detected by immunohistochemical staining.The difference of DLAT and DLST gene expression between tumor and normal tis-sues was compared in GEPIA database.HP A database was used to analyze the correlation between c-MYC and DLAT,DLST expression in tumor tissues.The expression level of DLAT and DLST in tumor tissues was evaluated by immunofluorescence staining.Results The high expression of c-MYC gene was negatively correlated with overall survival(P＜0.01).The level of c-MYC protein was positively correlated with the pathological grade of PanIN.Compared with normal tissues,the expression of DLAT and DLST genes in pancreatic cancer cells was increased(P＜0.01).The protein level of c-MYC was positively correlated with those of DLAT and DLST(P＜0.01,P＜0.001).Conclusions The high expression of mitochondrial metabolic enzymes DLAT and DLST in pancreatic ductal adenocarcinoma cells is significantly correlated with the expression level of c-MYC,which increases with the progression of pancreatic cancer.

Objective:To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer.Methods:A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate.Results:Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side ( P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion:For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

Objective To evaluate the correction rate,accuracy of pedicle screw fixation and overall clinical efficacy of intravertebral osteotomy and internal fixation surgery with the assistance of 3D printing guide plates in treatment of severe kyphosis.Methods A single-center nonrandomized clinical pilot study was conducted on 19 patients(8 males and 11 females)with severe kyphosis undergoing intravertebral osteotomy between December 2018 and June 2023.Seven of them(CAD group)had preoperative planning with computer-aided design(CAD)and intraoperative guidance of individualized 3D printing guide plates.And another 12 patients(control group)were corrected with conventional pedicle screw placement.Postoperative evaluation included assessment of posterior Cobb angle,spinal angular correction rate,accuracy of pedicle screw placement and Oswestry Dysfunction Index(ODI)questionnaire.Results The 19 patients were at a mean age of 48.0 years,and followed up for 26.4(9～54)months.All of them achieved relatively satisfactory corrective results,with those of the CAD group having a correction rate of 96.83％and those of the control group of 86.61％.There were no statistical differences in average intraoperative blood loss(857 vs 1 045 mL)and average operative time(344 vs 402 min),but significant difference was observed in average length of hospital stay(11 vs 18 d,P＜0.05)between the 2 groups.A total of 278 nails were placed in this study,including 70 guide-assisted pedicle screws,97.1％of which were grade A or B.In the control group,208 pedicle screws were placed,93.8％of which were grade A or B.Postoperative CT/X-ray scanning displayed that both groups achieved certain correction for kyphosis.No obvious difference was found in the average spinal angular correction(43.37° vs 36.10°),and significantly higher correction rate was seen in the CAD group than the control group(96.83％vs 86.61％,P＜0.01).The ODI value was notably lower in the CAD group than the control group(P＜0.05).Conclusion CAD-assisted preoperative planning,surgical simulation and individualized 3D printing guide plates can promote surgical correction and accuracy of pedicle screw placement and improves the quality of life of patients with severe kyphotic deformity.

Cytochrome P450 enzyme 1A1 (CYP 1A1) is one of the main members of CYP1A subfamily, which participates in metabolizing and activating a variety of indirect carcinogens. CYP1A1 can induce carcinogenesis by participating in activating exogenous compounds to produce intermediates or active metabolites that bind to specific biomolecules. CYP1A1 plays a critical role in the metabolic activation of benzo(a)pyrene e ［B(a)P］, and plays a key role in activating the toxic and carcinogenic effects of B(a)P. CYP1A1 involves in the metabolic activation of 7,12-dimethyl benzanthracene and 2-amino-1-methyl-6-phenylimidazo［4,5-b］pyridine (PhIP), and plays an important role in PhIP-induced genotoxicity. CYP1A1 is the main enzyme to metabolize and activate 7H-dibenzo［c,g］carbazole (DBC), a key factor in the carcinogenic effect of DBC. CYP1A1 is also associated with metabolic activation of indirect carcinogens such as aflatoxin B1, 3-nitrobenzene, and naphthalene. Inhibition of the catalytic activity of CYP1A1 can decrease the CYP1A1-mediated activity of carcinogens, thus playing a role in the prevention and treatment of malignant tumors.

Objective:To evaluate the diagnostic value of multiparametric cardiac magnetic resonance(CMR)or detecting the occurrence of acute rejection(AR)after heart transplantation(HT).Methods:From 2019 to 2021, 44 HT recipients are prospectively recruited from Guangdong Provincial People's Hospital.Another 51 healthy volunteers are recruited from a local community as healthy controls.CMR studies are performed for obtaining baseline parameters.According to the clinicopathological diagnostic criteria of AR by the consensus of International Society for Heart and Lung Transplantation, 81 CMR studies of 44 HT recipients are further divided into two groups of AR (18 cases)and non-AR(71 cases). CMR parameters includ global ventricular structure/function, T2, T1, extracellular volume(ECV)and late gadolinium enhancement(LGE). A combined model is established by binary Logistic regression and receiver operator characteristic curve(ROC)constructed.Results:The age range is(41.8±16.8)years in 44 HT recipients and(41.8±9.7)years in 51 healthy controls.T1 mapping indicated that myocardial global ECV of left ventricle is significantly higher in AR patients than non-AR controls(32.4%±6.0% vs 28.5%±2.4%; P<0.001 9). Global native T1 is higher in AR group than that in non-AR group(49.8±3.1 vs 47.5±2.8 ms, P=0.009)and the difference is statistically significant.The cutoff value of global ECV is 30.62% with a sensitivity of 61% and a specificity of 86% for detecting AR.And T2 mapping reveale that T2 value of global left ventricle is significantly higher in AR group than that in non-AR group(49.8±3.1 vs 47.5±2.8 ms, P=0.009). LGE extent is significantly higher in AR group than those in non-AR group( P=0.004). Through including global native T1 and ECV into a logistic regression model, multiparametric CMR can yield an area under curve(AUC)of 0.794.It hints at the potential of CMR for detecting AR. Conclusions:Multiparametric cardiac magnetic resonance offers an excellent predictive capacity for a noninvasive detection of AR.

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

Objective:To analyze the microsatellite instability (MSI) status in endometrioid endometrial carcinoma (EEC) with deficient mismatch repair (dMMR) and to explore the concordance between MSI next generation sequencing (NGS)/PCR and MMR immunohistochemistry (IHC) results.Methods:Sixty dMMR EEC cases by IHC from November 2017 to February 2019 were selected in the Department of Pathology, Peking Union Medical College Hospital. Two pathologists reviewed the IHC results. The MSI status and the germline/somatic mutational status of MMR genes were analyzed by NGS. MLH1 promoter methylation status was determined by methylation-specific PCR (MSP) in cases with MLH1 protein deficiency. In cases with discrepant results between MMR IHC and MSI NGS, the MSI status was detected again by PCR, and the reasons for the discrepancy were discussed with gene mutation and MLH1 promoter methylation results.Results:Among 60 dMMR EEC specimens, 3 samples were re-assigned as proficient mismatch repair (pMMR) after pathological review, and identified as MSS by NGS. Another 3 dMMR cases showed MSI-uncertainty (MSI-U) by NGS due to insufficient tumor content. In the remaining 54 cases, the concordance between MMR IHC and MSI NGS was 87% (47/54). The seven discrepant cases was further analyzed: in 5 discrepant cases with MLH1/PMS2 protein loss, one case did not have enough samples for detection, one case was MSI-H, and the remaining three cases were MSS by PCR. All these 5 cases with MLH1/PMS2 protein loss showed the MLH1 promoter hypermethylation, two of which also had a somatic mutation in the MSH2 gene. The two discrepant cases with MSH6 protein loss were both MSS by PCR, one of which was considered to have Lynch syndrome with germline mutation in MSH6 gene.Conclusions:Although the overwhelming majority of dMMR EEC cases by IHC shows MSI-H by NGS/PCR, there are uncommon discrepant dMMR EEC cases with MSS. They are mostly found in cases with MLH1/PMS2 protein loss caused by MLH1 promoter hypermethylation and rarely related to Lynch syndrome. Both MMR IHC and MSI NGS/PCR tests have their advantages and disadvantages, complimentary to each other.

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.