ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury， as well as the protective role of Huoxue Huayu Jiedu prescription （HXHYJDF） against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups： sham group， model group， deferoxamine （DFO） group （100 mg·kg^-1）， low-dose HXHYJDF group （4.52 g·kg^-1）， medium-dose HXHYJDF group （9.04 g·kg^-1）， and high-dose HXHYJDF group （18.07 g·kg^-1）， with ten rats in each group. Except for the sham group， the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1^st， 3^rd， 5^th， and 7^th days post-reperfusion using the modified neurological severity scores （m-NSS）. Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin （HE） staining and transmission electron microscopy. The contents of malondialdehyde （MDA）， glutathione （GSH）， divalent iron ions （Fe²⁺）， and reactive oxygen species （ROS） in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot （WB） were used to detect the expression of iron death marker proteins glutathione peroxidase 4 （GPX4）， ferroportin-1 （FPN1）， transferrin receptor protein 1 （TfR1）， and ferritin mitochondrial （FtMt） in brain tissue. ResultsCompared with the sham group， the mNSS score of the model group was significantly increased （P<0.01）. HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced， and the intercellular space was widened. The nucleus was fragmented， and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded， and the mitochondrial cristae decreased. The matrix was lost and vacuolated， and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS increased significantly （P<0.01）. The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased （P<0.01）， and the expression of FtMt and TfR1 proteins was significantly increased （P<0.01）. Compared with those of the model group， the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3^rd and 5^th days， respectively （P<0.05， P<0.01）. The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS decreased significantly （P<0.05， P<0.01）. The content of GSH in the low-dose HXHYJDF group increased significantly （P<0.01）， and the contents of MDA and ROS decreased significantly （P<0.01）. The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly （P<0.01）， and the expression of FtMt and TfR1 decreased significantly （P<0.01）. The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly （P<0.05）， and the expression of TfR1 decreased significantly （P<0.01）. WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose， medium-dose， and low-dose HXHYJDF groups were significantly up-regulated （P<0.01）， and the expression levels of FtMt and TfR1 proteins were significantly down-regulated （P<0.01）. ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury， improve the pathological morphology of the infarcted brain tissue， and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury， with increased levels of MDA， Fe²⁺， ROS， and TfR1 and decreased levels of FtMt， FPN1， GPX4， and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins， promoting the discharge of free iron， reducing brain iron deposition， alleviating oxidative stress， and inhibiting ferroptosis.

Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

Arteriovenous malformations(AVMs)are a kind of high-flow vascular malformation.AVMs can be classified in many ways,including histo-embryological classification,hemodynamic classification,etc.At present,the two mainstream classification systems used to guide the embolization treatment of peripheral AVMs are proposed by Cho and Yakes respectively based on the angiographic morphology of the lesions.Interventional embolization is the first-line treatment for AVMs.Among the many embolization agents,absolute ethanol is a permanent liquid embolization agent.Absolute ethanol can directly destroy the vascular endothelial cells to achieve a good curative efficacy,therefore,it has been wildly used in the treatment of peripheral AVMs.Yakes classification combines the angiographic classification with absolute ethanol embolization therapy.During absolute ethanol treatment,close attention should be paid to the occurrence of complications such as elevated pulmonary artery pressure.Although there are challenges remaining in the treatment of AVMs,the rapid development of molecular genetics has made targeted drug adjunctive treatment for AVMs possible.Perhaps,the novel therapeutic mode of combination use of traditional therapy targeted drug may be able to make a breakthrough in the treatment of AVMs.

With the development of chest CT screening, surgically resected lung tumors have shifted from predominantly large masses to predominantly small nodules. The intraoperative frozen diagnosis of pulmonary small nodules faces many challenges, such as the accurate understanding about the concepts of adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic adenocarcinoma, as well as their differential diagnosis with small size invasive adenocarcinoma, benign tumors (such as bronchiolar adenoma, sclerosing pneumocytoma, etc.), metastatic tumors and so on. This study summarizes some common problems encountered in the intraoperative frozen diagnosis of small pulmonary nodules in daily practice, focusing on the diagnosis and differential diagnosis of adenocarcinoma, in order to make the accurate intraoperative frozen diagnosis of small pulmonary nodules and diminish misdiagnosis.

Objective:To investigate the clinicopathological features and differential diagnosis of primary pulmonary hyalinizing clear cell carcinoma (HCCC), as well as its diagnostic pitfalls in assessing biopsy specimens.Methods:Five cases of primary pulmonary HCCC diagnosed in the Department of Pathology, Shanghai Chest Hospital, Shanghai, China from August 2019 to December 2023 were collected. The clinicopathological characteristics, immunohistochemistry, and the EWSR1 gene related translocation and fusion were summarized, and relevant literature was reviewed.Results:Among the five cases of HCCC, two were males and three were females, with ages ranging 36-74 years. The tumors were located in the lumen of the bronchus or trachea and showed an exophytic polypoid growth pattern. The maximum diameter of the tumors ranged from 1.3 to 5.0 cm. Histologically, the tumor cells showed transparent cytoplasm and slight cellular atypia, with medium-sized round cells arranged in cords, nests, and trabecula. Small nucleoli were noted, while mitotic figures were rare. The interstitial bands of the tumor in various thickness were anastomosed with hyalining and sclerosing fibrous tissues. All the tumor cells were positive for CKpan, CK7, p40, p63 and CK5/6, but negative for S-100, SMA, Calponin, TTF1 and Napsin A; Ki-67 proliferation index was less than 10% (1%-10%). FISH testing showed EWSR1 gene translocation in all cases, three of which were confirmed by next generation sequencing to have EWSR1::ATF1 gene fusion.Conclusions:Biopsy specimens of primary HCCC in the lungs are prone to misdiagnosis due to the expression of squamous cell carcinoma biomarkers, which poses a unique challenge. A complete understanding of the morphological characteristics of primary pulmonary HCCC, combined with immunohistochemistry and molecular testing, is helpful to reach accurate diagnosis.

AIM:To investigate the effects of sodium selenite(SS)on viability,migration and angiogenesis of human non-small-cell lung cancer(NSCLC)H520 and A549 cells.METHODS:The H520 cells,A549 cells,and hu-man umbilical vein endothelial cells(HUVEC)were divided into control group(0 μmol/L SS),low dose group(5 μmol/L SS),middle dose group(10 μmol/L SS),and high dose group(20 μmol/L SS).Cell viability was assessed using the CCK-8 assay,and the half-maximal inhibitory concentration(IC50)was calculated.Cell migration and invasion abilities were determined through wound healing and Transwell assays.The regulatory effects of SS on angiogenesis,vasculogenic mimicry and"mosaic"vascular formation between HUVEC and NSCLC cells were detected using vessel forming assays.The expression of vascular endothelial growth factor(VEGF)in the supernatant of lung cancer cells in each group was de-tected using chemiluminescence.RT-qPCR was used to assess the mRNA expression of VEGF,vascular endothelial growth factor receptor 2(VEGFR2)and angiotensin II(Ang II).Western blot was used to examine the protein levels of VEGF,p-PI3K,and p-Akt in H520 and A549 cells.RESULTS:The IC50 values of SS to HUVEC,A549 cells and H520 cells for 48 h were 6.762,9.003 and 7.356 μmol/L,respectively.Compared with control group,the wound healing rate was significantly decreased in each group treated with SS for 48 h(P<0.01).In HUVEC,the number of migrating cells in middle dose and high dose groups decreased(P<0.01),whereas in lung cancer cells,the number of migrating cells in each group decreased after SS treatment(P<0.01).The mRNA expression levels of VEGF,VEGFR2 and Ang II were lower in high-dose SS group than those in control group(P<0.05 or P<0.01).In H520 cells,compared with control group,the protein levels of VEGF,p-PI3K and p-Akt in SS treatment groups were significantly decreased(P<0.05 or P<0.01).CONCLUSION:Sodium selenite inhibits the viability and migration of HUVEC,H520 cells and A549 cells,and inhibits the formation of vasculogenic mimicry and mosaic vessels in NSCLC cells.This mechanism may be related to the inhibition of PI3K-Akt signaling pathway activation and regulation of VEGF.

Neuroimaging is increasingly widely used in the field of ADHD research,and more and more studies have shown that ADHD patients have structural abnormalities such as reduced cortical volume,thinning thickness,and reduced surface area,which are related to complex clinical symptoms and abnormal brain function in patients.However,the use of neuroimaging to identify biomarkers as an objective diagnostic tool for ADHD still faces many challenges.Multimodal studies can be used to explore the relationship between the structure and function of different brain regions in ADHD patients,and to use neuroimaging to reveal the mechanism of the evolution of clinical symptoms in the whole life cycle of ADHD patients.

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

Pathology is the gold standard for diagnosis of neoplastic diseases.Whole slide imaging turns traditional slides into digital images,and artificial intelligence has shown great potential in pathological image analysis,especially deep learning models.The application of artificial intelligence in whole slide imaging of lung cancer involves many aspects such as histopathological classification,tumor microenvironment analysis,efficacy and survival prediction,etc.,which is expected to assist clinical decision-making of accurate treatment.Limitations in this field include the lack of precisely annotated data and slide quality varying among institutions.Here we summarized recent research in lung cancer pathology image analysis leveraging artificial intelligence and proposed several future directions.