1.Mechanism of Ferroptosis in Cerebral Ischemia-reperfusion and Interventional Mechanism of Huoxue Huayu Jiedu Prescription Based on "Blood Stasis and Toxin" Pathogenesis
Jiayue HAN ; Danyi PAN ; Jiaxuan XIAO ; Yuchen LIU ; Jiyong LIU ; Yidi ZENG ; Jinxia LI ; Caixing ZHENG ; Hua LI ; Wanghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):51-60
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 1st, 3rd, 5th, and 7th 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 3rd and 5th 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.
2.Research progress on H-E stained whole slide image analysis by artificial intelligence in lung cancer
Mengqi JIANG ; Yuchen HAN ; Xiaolong FU
China Oncology 2024;34(3):306-315
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.
3.Preliminary study on predicting hepatic artery thrombosis formation and evaluating treatment efficacy with ultrasound hemodynamic parameters in transplanted liver
Yuchen YANG ; Yuli ZHU ; Wen SHEN ; Wenping WANG ; Huixiong XU ; Hong HAN
Chinese Journal of Ultrasonography 2024;33(2):106-111
Objective:To clarify the changes of intrahepatic ultrasound hemodynamics before and after hepatic artery thrombosis (HAT) after liver transplantation (LT), providing early warning and anticoagulation guidance to clinicians.Methods:The clinical data of patients who underwent liver transplantation at Zhongshan Hospital of Fudan University between June 2006 and October 2022 were retrospectively analyzed, 47 patients with a diagnosis of HAT confirmed by DSA (digital subtraction angiography) were included in the HAT group, and 71 patients without vascular complications were included in the non-HAT group. Differences in peak flow velocity (PSV), resistance index (RI), and portal vein velocity (PVV) were compared between the two groups. Logistic regression analysis was used to determine the relationship between postoperative PSV decline and HAT occurrence, while ROC curve were used to determine the critical value and evaluate the diagnostic efficacy. Patients with HAT were divided into well-treatment group and poor-treatment group according to whether the blood flow was restored after multiple surgeries or thrombolytic treatments. The changes of early intrahepatic hemodynamics after surgical or thrombolytic therapy were compared between the two groups.Results:①A decrease in PSV of the transplanted hepatic artery was measured 1 d before HAT, and PSV<0.39 m/s predicted thrombus formation with a sensitivity of 0.70, specificity of 0.86, and the AUC was 0.83. ②After treatment, PSV in the HAT group increased immediately, approaching the normal level on the 2nd day. In the well-treatment group, PSV and PVV reached normal levels on the first day after treatment, which were significantly higher than the corresponding values in the poor-treatment group ( P=0.030, 0.021). Conclusions:In the early stage after liver transplantation, a PSV<0.39 m/s is related to the occurrence of HAT thrombosis 1 d later. A significant increase in PSV on the first day after treatment indicates a good treatment response, and there is no need for further DSA re-examination or increasing the number of thrombolysis.
4.Study on the clinical characteristics of Chinese and Western medicine in 474 children with genetically-related tic disorder
Yuchen HU ; Simeng WANG ; Zilin CHEN ; Fei HAN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(7):961-970
Objective This study aimed to analyze the impact of genetic factors on the clinical presentation of tic disorder and investigate the pathogenesis of tic disorder considering different sources of genetic influence and generations,along with the distribution characteristics of evidence from Chinese medicine.Methods Inclusion of 474 cases of tic disorder was assembled(from October,2020 to October,2023),and clinical data on the children,including gender,age of onset,disease duration,initial symptoms,severity,comorbidities,and family history,and TCM patterns were collected.Firstly,the children were divided into genetic and nongenetic groups based on family history,and their clinical manifestations were observed.Secondly,the age of peak incidence of tic disorder in China(6 or 9 years)was used as the age segmentation point to explore the influence of heredity on clinical manifestations at different ages and the distribution of TCM patterns.Finally,children with genetically-related tic disorder were selected as probands to carry out family studies.The morbidity of the first-degree,second-degree and third-degree relatives of the probands were investigated to analyze the morbidity characteristics and distribution of TCM patterns of children with tic disorder under different genetic types.Results Out of 474 children,226 cases(47.7%)belonged to the genetic group,and 248 cases(52.3%)to the nongenetic group.Compared with the non-genetic group,the genetic group had a younger age of onset(P=0.013),a longer duration of illness(P=0.011),a higher degree of severity(P<0.01),and more comorbid conditions(P=0.016).Children in the genetic group with an age of onset under 6 years accounted for a larger proportion of the liver-hyperactive and wind-driven pattern(26.5%)and a smaller proportion of the qi depression transforming into fire pattern(17.1%),which were significantly different from those in the non-genetic group(P=0.016).In the genetic group,146 cases(64.6%)were inherited from the father,80 cases(35.4%)from the mother,and there was no significant difference in the developmental characteristics of children with tic disorder from different sources of genetic influence.Furthermore,183 cases(81.0%)were inherited from the parent-child generation,26 cases(11.5%)from the second generation,and 17 cases(7.5%)from the third generation;the difference in initial symptoms between different genetic generations was statistically significant(P=0.042).Conclusion Children with genetically related tic disorder have a younger age of onset,their condition is more severe,and they are more likely to be comorbid with other psychiatric disorders.The variation in the distribution of Chinese medicine patterns among children with tic disorder of different ages of onset.
5.The ninth edition of TNM staging for lung cancer: precise staging for precise diagnosis and treatment
Hanyue LI ; Yiyang WANG ; Hui LIU ; Hongxu LIU ; Liyan JIANG ; Yuchen HAN ; Wenyong ZHOU ; Teng MAO ; Wentao FANG
Chinese Journal of Surgery 2024;62(6):537-542
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.
6.Progress on structural abnormalities in the cerebral cortex in children with attention deficit/hyperactivity disorder
Haixia YUAN ; Xinmin HAN ; Tianyi CHEN ; Yuchen SONG
The Journal of Practical Medicine 2024;40(10):1455-1459
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.
7.Efficacy of color Doppler ultrasound-guided percutaneous nephrostomy in the treatment of anastomotic leakage after laparoscopic pyeloplasty in children
Xiangyang CHU ; Luping LI ; Junjie ZHANG ; Shengli ZHANG ; Xiaojiang HAN ; Xiang ZHAO ; Pengpeng LIU ; Bin YU ; Chunyu CHEN ; Yuchen LIU ; Nuoxian LI ; Yingzhong FAN
Chinese Journal of Urology 2024;45(8):587-591
Objective:To investigate the efficacy of color Doppler ultrasound-guided percutaneous nephrostomy in the treatment of anastomotic leakage after laparoscopic pyeloplasty.Methods:A retrospective analysis was performed for the data of 15 children with peritoneal irritation after LP who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to January 2023, of which 10 cases were anastomotic leaks and 5 cases were with renal pelvic blood clots. There were 12 males and 3 females. Age (4.2±2.7) years. The lesions were located on the left side of 11 cases and on the right side of 4 cases. All 15 cases had varying degrees of nausea, vomiting, abdominal pain and other symptoms. Physical examination: the children all showed painful faces and tense abdominal muscles. 15 patients had a preoperative pain score of 9.5 (8, 10). Ultrasound examination showed that the anterior and posterior diameters of renal pelvis separation were (34.93±4.86) mm, the anterior and posterior diameter/renal parenchymal thickness of renal pelvis separation was 15.66±1.02, renal dynamic nuclear imaging shows the renal function of the affected side was (29.69±1.71)%. Thirteen cases had the above symptoms before the abdominal drainage tube was removed, and the time of symptom onset was (3.3±1.1) days after surgery, of which 8 cases had a large increase in abdominal drainage, and color Doppler ultrasonography showed a large amount of fluid in the intra-abdominal intestinal space (about 500 ml). In 5 cases, the intraperitoneal drainage volume did not increase, and color Doppler ultrasonography showed strong echo in the renal pelvis, and blood clots were considered. All 13 patients were placed in the prone position under local anesthesia and underwent color Doppler ultrasound-guided percutaneous nephrostomy. The remaining 2 cases had abdominal drainage tube removed on the 3rd day after surgery, and peritoneal irritation signs appeared on the 4th and 6th days after surgery, respectively. Color Doppler ultrasonography showed that there was a large amount of fluid in the intra-abdominal intestinal space, and color Doppler ultrasound-guided peritoneal puncture and drainage + prone percutaneous nephrostomy was performed in the supine position under local anesthesia, and the biochemical analysis of the peritoneal puncture drainage fluid was confirmed to be anastomotic urine leakage. The drainage volume and urine output of 15 cases of peritoneal puncture drainage and pyelostomy were recorded, and the relief of nausea and vomiting symptoms and the score of postoperative pain after percutaneous nephrostomy were recorded. The changes of hydronephrosis and renal function before and after percutaneous nephrostomy were compared.Results:In this study, 15 patients underwent percutaneous nephrostomy with a duration of (16.8±1.9) min. The symptoms of nausea and vomiting disappeared after operation, and the pain scores were 3.2(2, 4) and 0.4(0, 2) at 2 h and 12 h after operation, respectively, which were statistically significant compared with those before operation ( P<0.01). In 13 children with simple percutaneous nephrostomy, the abdominal drainage tube was removed on (3.6±0.8) days and (8.6±1.0) days after percutaneous nephrostomy. In 2 children with peritoneal puncture and drainage plus percutaneous nephrostomy, the abdominal drainage tube was removed 3 days after the fistula operation, and the pyelostomy tube was removed 8 days after the fistula operation. The anterior and posterior diameters of renal pelvis separation were (10.87±4.05), (10.13±3.50) and (9.13±3.11) mm by color Doppler ultrasound at 3, 6 and 12 months after LP operation, respectively, and there were statistically significant differences compared with preoperative comparisons ( P<0.01).The diameter before and after renal pelvis separation was (7.60±2.86) mm, the diameter before and after renal pelvic separation/renal parenchymal thickness was 1.97±0.22, and the renal function was (39.23±2.66)% at 24 months after operation, which was statistically significant compared with that before operation ( P<0.01). Conclusions:Color Doppler ultrasound-guided percutaneous nephrostomy can effectively alleviate symptoms in the early stage, which could help to the healing of ureteral anastomosis, and has less trauma and short operation course.
8.Effects of sodium selenite on migration and angiogenesis of lung cancer cells and its mechanism
Yuchen HAN ; Weiwei CHEN ; Yu BAI ; Jing DU ; Fei WANG ; Jiajia AN
Chinese Journal of Pathophysiology 2024;40(9):1598-1605
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.
9.Progress in the application of absolute ethanol in interventional embolization treatment of peripheral arteriovenous malformations
Qianyun HAN ; Yuchen SHEN ; Deming WANG ; Lixin SU ; Xiao LI ; Xindong FAN
Journal of Interventional Radiology 2024;33(11):1244-1252
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.
10.Effect of MEIS1 expression on survival in patients after radical gastrectomy and its value in prognostic evaluation
Jiaxin YI ; Yangyu ZHANG ; Yingli FU ; Yuchen PAN ; Yongjie HAN ; Jing JIANG ; Yanhua WU
Journal of Jilin University(Medicine Edition) 2024;50(5):1358-1364
Objective:To discuss the postoperative survival of the gastric cancer patients with different expression levels of myeloid ecotropic viral integration site 1(MEIS1),and to analyze the predictive value of MEIS1 expression in the prognosis evaluation of gastric cancer.Methods:In a gastric cancer survival cohort,215 patients who underwent radical gastrectomy were selected.Immunohistochemical staining was used to detect the expression levels of MEIS1 in both gastric cancer and adjacent normal tissues.The relationship between expression level of MEIS1 and the clinicopathological characteristics of the patients were analyzed by x2 test or Fisher's exact probability method;survival curves were plotted by Kaplan-Meier method;the differences in survival of the patients between MEIS1 high expression group and MEIS1 low expression group were compared by Log-rank test;multivariate Cox proportional hazards regression model was used to calculate the hazard ratios(HR)and 95%confidence intervals(CI)to assess the relationship between MEIS1 expression level and the survival of the gastric cancer patients.Results:The immunohistochemical staining result showed that the expression level of MEIS1 in gastric cancer tissue was decreased.The univariate analysis results showed that the patients with high MEIS1 expression had a longer overall survival than those with low expression(P=0.049),and had a better prognosis.The multivariate Cox proprotional hazards regression analysis results showed that the low MEIS1 expression and high TNM stage were the independent risk factors for poor prognosis of the patients with gastric cancer(HR=1.577,95%CI:1.011-2.460,P=0.045;HR=2.709,95%CI:1.708-4.297,P<0.001).Conclusion:The gastric cancer patients with low expression of ME1S1 have a shorter postoperative overall survival;MEIS1 is a promising biomarker for prognosis assessment of the patients after radical gastrectomy.

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