Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Objective:To investigate the application value of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in evaluating flow diverter (FD) apposition and endothelialization in aneurysm animal models, and analyze the effect of incomplete stent apposition (ISA) on aneurysm lumen healing and stent endothelialization.Methods:Lateral common carotid artery aneurysm models in swines were established by surgical method and then FD was implanted. Immediately after surgery, OCT and IVUS were used to evaluate the locations and degrees of ISA, and difference between these 2 methods in evaluating FD apposition was compared. DSA was performed at 12 weeks after surgery to evaluate the aneurysm occlusion (Kamran grading) and stent patency. OCT and IVUS were used again to observe the stent endothelial situation; by comparing with histopathologic results, effect of ISA on aneurysm healing and stent endothelialization was analyzed.Results:Lateral common carotid artery aneurysm models in 6 swines were established, and 6 Tubridge FDs were successfully implanted. Compared with IVUS (3 stents, 4 locus), OCT could detect more ISA (6 stents, 14 locus); and the vascular diameter change area (7 locus), aneurysm neck area (4 locus) and the head and tail of FD (3 locus) were the main sites of FD malapposition; average distance between stent wire and vessel wall was (560.14±101.48) μm. At 12 weeks after surgery, DSA showed that 1 patient had a little residual contrast agent at the aneurysm neck (Kamran grading 3), and the remaining 5 had complete aneurysm occlusion (Kamran grading 4). One FD had moderate lumen stenosis, and the other 5 FDs had lumen patency. OCT indicated mostly disappeared acute ISA; ISA proportion decreased to 21.4 % (3/14), including 2 in the aneurysm neck and 1 in the partial stent. Histopathological results showed bare stent woven silk, without obvious endothelial coverage; in one FD with luminal stenosis, intimal hyperplasia was mainly composed of vascular smooth muscle cells.Conclusion:In carotid artery aneurysm model with FD implantation, OCT can detect more ISA than IVUS; most acute ISA have good outcome at 12 th week of follow-up, while severe ISA can cause delayed FD endothelialization and delayed aneurysm occlusion.

Objective     To analyze the effects of systematic lymph node dissection (SLND) and lobe-specific lymph node dissection (L-SND) on perioperative and long-term outcomes of patients with clinicalⅠA (cⅠA) stage lung adenocarcinoma. Methods     A retrospective analysis was done on the patients with cⅠA stage lung adenocarcinoma who received thoracoscopic radical resection admitted to the Affiliated Hospital of Qingdao University from January 2013 to August 2016. Propensity score matching was conducted to eliminate the biases. The recurrence-free survival was compared between the two groups after matching. Perioperative parameters and postoperative complications were also analyzed. Results     A total of 725 patients were enrolled, including 252 males and 473 females, with a median age of 62.0 (31.0-69.0) years. There were 228 patients in the L-SND group and 497 patients in the SLND group. After matching, there were 211 patients in each group and no statistical difference in the incidence of postoperative complications (10.9% vs. 13.7%, P=0.374), identification of metastatic positive lymph nodes (12.3% vs. 9.0%, P=0.270), or recurrence-free survival (P=0.492) were found between two groups, whereas the operation time (163.9±39.4 min vs. 135.4±32.4 min, P<0.001), intraoperative blood loss [100.0 (20.0-800.0) mL vs. 100.0 (10.0-400.0) mL, P<0.001], intubation time [4.0 (1.0-18.0) d vs. 4.0 (1.0-9.0) d, P<0.001] and hospital stay (12.3±3.3 d vs. 10.8±2.4 d, P=0.003) in the SLND group were found to be significantly higher or longer than those in the L-SND group. Conclusion     L-SND has a similar efficiency to SLND in terms of postoperative complications, pathological lymph node metastasis, and recurrence-free survival, as well as significant advantages in reducing intraoperative blood loss, and shortening operation time, intubation time and length of hospital stay. Therefore, L-SND can be recommended to replace SLND as a method for lymph node resection in patients with cⅠA stage lung adenocarcinoma.

Objective : To study the resistance pattern of streptomycin and ethambutol in Mycobacterium tuberculosis in Luoyang area , guide clinical medication and supplement epidemiological data on local drug⁃resistant tuberculosis . Methods : The positive results of high⁃resolution melting curve (HRM) in 2 941 cases in Luoyang area were analyzed to assess the risk factors associated with streptomycin and ethambutol resistance . Results : Of the 2 941 HRM⁃positive patients , 18 . 4% were resistant to streptomycin and 8. 0% were ethambutol . Both streptomycin and ethambutol and resistance rates were higher in men than those in women ( 19. 0% vs 16. 9% , P = 0. 129 ; 8. 0% vs 7. 9% , P = 0. 987) . The resistance rates to streptomycin and ethambutol were higher in urban than those in rural areas (21 . 3% vs 16. 6% , P = 0. 002 ; 9. 8% vs 6. 9% , P = 0. 004) . The resistance rate was much higher in previously treated patients than those newly diagnosed for MTB infection (25 . 8% vs 17. 3% , P < 0. 001 ; 12. 1% vs 7. 4% , P = 0. 002) . The resistance rates to streptomycin were higher in the < 51 years than those in the > 50 years group (21 . 1% vs 16. 1% , P < 0. 001) . According to age , the highest resistance rates to streptomycin and ethambutol occurred in the age range of 31 - 35 years and 56 - 60 years in men , respectively , while in the age range of 21 - 25 years and 56 - 60 years in women , respectively . In multivariate models , prior treatment history , age less than 51 years , and urban area were positively associated with streptomycin and ethambutol resistance after adjusting for smear results and year testing . Conclusion Men , prior treatment history , age less than 51 years , and urban residents are key monitoring targets for streptomycin and ethambutol resistant tuberculosis .

Objective:To establish the common carotid artery aneurysm models of Wallstent double stent overlapping implantation in miniature pigs, and evaluate the safety and effectiveness of this procedure by observing the imaging and pathological changes.Methods:Sidewall aneurysm and fusiform aneurysm models in Bama miniature pigs were established surgically and 2 Wallstent stents were overlapped and implanted in situ. Aneurysm healing immediately after surgery and during 8 weeks of follow-up were evaluated according to 2D-DSA by O'Kelly-Marotta (OKM) grading scale and Kamran scale; degrees of stent adhesion immediately after surgery and status of stent endothelialization and aneurysm healing at 2, 4, and 8 weeks after surgery were observed by high resolution C-arm CT(HR-CBCT) and optical coherence tomography (OCT); and the changes of stent endothelialization were evaluated by comparing the HR-CBCT and OCT results with histopathology at 8 weeks after surgery. Perioperative adverse events were recorded.Results:After successful establishment of common carotid artery aneurysm models (including 4 sidewall aneurysms and 4 fusiform aneurysms with average diameter of [11.0±2.8] mm) in 8 miniature pigs, a total of 16 Wallstent stents (2 in each aneurysm) were implanted across the aneurysmal neck, with a technical success rate of 100%. No serious complications such as acute stent thrombosis, or aneurysm rupture and bleeding were observed in the perioperative period. The 2D-DSA immediately after surgery showed obvious intracranial contrast agent retention in 6 patients (1 patient in grading 1, 3 in grading 2, and 2 in grading 3) and aneurysm occlusion in 2 patients (grading 4). Eight weeks after follow-up, all 8 aneurysms had complete occlusions (grading 4); and 2 experimental pigs had in-stent restenosis, with stenosis rates of 52% and 67%, respectively. HR-CBCT and OCT immediately after surgery and during follow-up indicated that the stent metal braid was gradually covered by proliferating intima, with disappeared aneurysm. The cause of in-stent restenosis in 2 experimental pigs was local intima hyperplasia resulted from poor stent adhesion, and pathological findings indicated that the intima hyperplasia was mainly composed of smooth muscle cells and fibrous connective tissues.Conclusion:In animal models, Wallstent stent overlapping implantation is safe and effective in common carotid aneurysms, but intraoperative adverse adhesion of overlapping stent should be avoided.

Objective:To explore the application value of artificial intelligence-assisted diagnosis model based on convolutional neural network (CNN) in the differential diagnosis of benign and malignant breast masses.Methods:A total of 10 490 images of 2 098 patients with breast lumps (including 1 132 cases of benign tumor, 779 cases of malignant tumor, 32 cases of inflammation, 155 cases of adenosis) were collected from January 2016 to January 2018 in Beijing Tiantan Hospital Affiliated to the Capital University of Medical Sciences. They were divided into training set and test set and the auxiliary artificial intelligence diagnosis model was used for training and testing. Two sets of data training models were compared by two-dimensional imaging (2D) and two-dimensional and color Doppler flow imaging (2D-CDFI). The ROC curves of benign breast tumors, malignant tumors, inflammation and adenopathy were analyzed, and the area under the ROC curve (AUC) were calculated.Results:The accuracies of 2D-CDFI ultrasonic model for training group and testing group were significantly improved. ①For benign tumors, the result from training set with 2D image was: sensitivity 92%, specificity 95%, AUC 0.93; the result from training set with 2D-CDFI images was: sensitivity 93%, specificity 95%, AUC 0.93; the result for test set with 2D images was: sensitivity 91%, specificity 96%, AUC 0.94; the result for test set with 2D-CDFI images was: sensitivity 93%, specificity: 94%, AUC 0.94. ② For malignancies, the result for training set with 2D images was: sensitivity 93%, specificity 97%, AUC 0.94; the result for training set with 2D-CDFI images was: sensitivity 93%, specificity 96%, AUC 0.94; the result for test set with 2D images was: sensitivity 93%, specificity 96%, AUC 0.94; the result for test set with 2D-CDFI images was: sensitivity 93%, specificity 96%, AUC 0.94. ③For inflammation, the result for training set with 2D images was: sensitivity 81%, specificity 99%, AUC 0.91; the result for training set with 2D-CDFI images was: sensitivity 86%, specificity 99%, AUC 0.89; the result for test set with 2D images was: sensitivity 100%, specificity 98%, AUC 0.98; the result for test set with 2D-CDFI images was: sensitivity 100%, specificity 99%, AUC 0.96. ④For adenopathy, the result for training set with 2D images was: sensitivity 88%, specificity 97%, AUC 0.94; the result for training set with 2D-CDFI images was: sensitivity 93%, specificity 98%, AUC 0.94; the result for test set with 2D images was: sensitivity 94%, specificity 98%, AUC 0.93; the result for test set with 2D-CDFI images was: sensitivity 88%, specificity 99%, AUC 0.90. Its diastolic accuracy was not affected even if the maximum diameter of the tumor was less than 1 cm.Conclusions:Through the deep learning of artificial intelligence based on CNN for breast masses, it can be more finely classified and the diagnosis rate can be improved. It has potential guiding value for the treatment of breast cancer patients.

Objective:To evaluate the mechanical parameters of the carotid artery plaques using velocity vector imaging(VVI), and to investigate the correlations between the mechanical parameters and the histological components in the plaques.Methods:Fifty-three patients undergoing carotid endarterectomy (CEA) from April to December, 2019 in Beijing Tiantan Hospital were selected and underwent VVI examination before operation. The plaques were divided into 5 parts along the long axis and named as R1, R2, R3, R4, R5, respectively. The mechanical parameters of the plaques in each region of interest were measured(longitudinal strain and strain rate). After operation, plaques were collected in 49 cases and the specimens were divided into five sections corresponding to preoperative images for HE staining and CD68 immunohistochemical analysis. According to the pathological diagnostic criteria of unstable plaques in previous studies, all plaques were divided into stable group and unstable group. Image-pro Plus 6.0 analysis software was used to measure the number of macrophages and the percentage of lipid core in plaques and the mean integral optical density of CD68 positive reaction area.Results:Among 49 cases, 33 cases were for unstable group, 16 cases were stable group. The longitudinal strain and strain rate of two groups of patients were R1>R2>R5>R4>R3, the number of macrophages, mean integral optical density, and percentage of lipid core were R2>R3>R1>R4>R5, differences were statistically significant ( P<0.05), the above indexes in unstable group were higher than in stable group, but there was no statistically significant difference ( P>0.05). The longitudinal strain was positively correlated with the number of macrophages, mean integral optical density and lipid core content in the plaque( r=0.300, 0.255, 0.394 respectively, P<0.05), and the strain rate was positively correlated with the number of macrophages and lipid core content in the plaque( r=0.199, 0.214 respectively, P<0.05) and r values in R1-R2 were higher than in R1-R5(longitudinal strain: r=0.480, 0.418, 0.582; strain rate: r=0.292, 0.319, P<0.05). Conclusions:The longitudinal strain and strain rate of the plaques are positively correlated with the macrophage and lipid core content of the plaques, and the r values of the upstream of plaques are higher. Therefore, VVI technique is valuable in detecting the stability of the plaques.

Objective:To investigate the value of tumor hemodynamics and morphological features from conventional dynamic contrast-enhanced MRI (DCE-MRI) scan before surgery in predicting postoperative recurrence time in breast cancer patients.Methods:A retrospective analysis of 58 patients with breast cancer who had recurred after operation from November 2012 to December 2014 in Liaoning Cancer Hospital was performed. According to the recurrence time, the patients were divided into early recurrence group (≤2 years after surgery, 33 cases) and late recurrence group (>2 years after surgery, 25 cases). All patients underwent routine DCE-MRI scans before surgery, and hemodynamic features of the three-dimensional volume of the tumor and the morphological and textural features of the tumor in each phase were extracted by computer. The counts and measurement data of patients in early recurrence group and late recurrence group were compared by Fisher′s exact probability method and Mann-Whitney U test, and receiver operating characteristic (ROC) curves were drawn. The multivariate logistic regression was used to calculate the combined efficacy in predicting early recurrence and late recurrence. Kaplan-Meier method was used to analyze the survival prognosis, and Log-Rank test was used to compare the differences in survival curves between groups. Results:There was no significant difference in background parenchymal enhancement, lesion margin, lesion internal enhancement characteristics, lesion morphology, time-signal intensity curve type and the degree of whole-breast vascularity increase between early recurrence and late recurrence groups ( P>0.05).There were significant differences in the maximum concentration of contrast (Max Conc), the area under the time signal curve (AUC) and the maximum slope value of the time signal curve (Max Slope) ( P<0.05). Comparative analysis of the radiomics parameters of 8 phases DCE-MRI found that the sphericity of morphological characteristic parameters in the phase 3 was statistically different between the early recurrence and late recurrence groups ( P=0.03). Area under the ROC curve of AUC, Max Conc, Max Slope and parameter sphericity of phase 3 morphological characteristics for predicting early and late recurrence were 0.664, 0.659, 0.684 and 0.670, respectively. The area under the ROC combined with the above four parameters for prediction was 0.765, with a specificity of 63.6% and a sensitivity of 84.0%; the predictive efficacy was higher than that of univariate. Fifty-eight patients were followed up for 17 to 64 months with a median follow-up of 47 months. The disease-free survival and overall survival in the early recurrence group were significantly lower than those in the late recurrence group, and the difference was statistically significant ( P<0.05). Conclusion:It is of certain value to predict the postoperative recurrence time of breast cancer based on the tumor hemodynamic characteristics combined with morphological characteristics from preoperative non-invasive conventional DCE-MRI.

Objective: To clarify the status of proliferation and differentiation of RCJ3.1C5.18 cells in chondrogenesis and explore insulin-like growth factor binding proteins (Igfbps) gene expression profile during the process. The results provided a research foundation for understanding the role of Igfbps in chondrogenesis. Methods: Fetal rat derived mesenchymal chondrogenic cell line RCJ3.1C5.18 was used, which progresses spontaneously to differentiated growth plate chondrocytes. The proliferation and differentiation status of cells were determined by cell staining, real-time PCR and Muse™ Cell Analyzer at days 1, 4, 7 and 10 of culture respectively. Igfbps gene expression was assessed by real-time PCR. Results: In the early period (1-4 days), cells proliferated rapidly and the expression of chondrocytes marker genes, such as typeⅡ collagen, SRY-box 9 and aggrecan increased gradually. Igfbp4 and Igfbp6 gene expression paralleled the expression of chondrocytes marker genes. On days 7-10 of culture, cells viability decreased and gradually developed hypertrophic-like and osteogenic-like characteristics, which was confirmed by specific staining and gene expression of alkaline phosphatase, matrix metallopeptidase 13.Igfbp1, Igfbp3 and Igfbp5 mRNA levels were up regulated gradually at this stage. Conclusions The status of proliferation and differentiation of cells are different in the process of chondrogenesis. Changes in Igfbp gene expression are associated with chondrocyte differentiation, suggesting that they have different role during chondrocyte proliferation and differentiation.

Objective To investigate the influence of the purging fire and removing toxin method on chemokines and adhesion factors related to vascular endothelialitis injury induced by toxin of trimeresurus stejnegeri bite.Methods ① Animal experiment:50 healthy New Zealand white rabbits were chosen.According to random numbers generated by statistical software,they were divided into normal control group,model group,low,middle and high dose Sheshang capsule groups,10 in each group.Trimeresurus stejnegeri bite model was replicated by injecting 0.75 mL/kg snake venom into subcutaneous tissues of rabbits' right hind legs.And the same volume of normal saline was injected into the rabbit in the normal control group.After the model was established for 6 hours,the rabbits in low,middle and high dose Sheshang capsule groups received 174,348 and 522 mg· kg-1 · d-1 of Sheshang capsule solution respectively (the content of capsules was dissolved in normal saline to make liquid with 17.4,34.8 and 52.2 g/L Sheshang solution respectively,so the volume of gavage of each group was 10 mL· kg-1 · d-1);in the model and normal control groups,the same amount of normal saline was given by gavage,once daily for consecutive one week.24 hours after the last gavage,the blood of the rabbits was collected through an auricular border vein and the serum was separated by centrifuge ready for use.Meanwhile,the whole abdominal aorta segment of the rabbit was harvested and kept them in liquid nitrogen ready for use.② Cell experiment:human umbilical vascular endothelial cell (HUVEC) was cultured with MEM for 24 hours.The solution was replaced and according to the random number generated by statistical software,the cells were divided into blank control group,model group and low,middle,high dose Sheshang capsule medicinal serum groups,10 wells in each group.Trimeresurus stejnegeri toxin cell model was reproduced by addition of 5 mg/L snake venom into the cell culture medium.After 6-hour culture,the cells of model group and blank control group received 10％ normal rabbit serum,and the cells of low,middle and high dose Sheshang medicinal serum capsule groups received serum containing 5％,10％ and 15％ drug,respectively.After culture for 72 hours,the cells were collected and the total RNA was extracted.The real-time fluorescent quantitative polymerase chain reaction (qPCR) was used to detect the levels of mRNA of interleukin-8 (IL-8),monocyte chemoattractant protein-1 (MCP-1),intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial cell adhesion molecule-1 (VCAM-1) in the vascular endothelial cells of rabbit aorta abdominalis and human umbilical vein,and the content of serum E-select element (CD62E) was measured by enzyme linked immunosorbent assay (ELISA).Results In model group,the expression levels of mRNA in IL-8,MCP-1,ICAM-1,VCAM-1 and the content of CD62E were all increased significantly in the endothelial cells of rabbit aorta abdominalis and HUVEC compared with those in control group [when the mRNA expression levels of IL-8,MCP-1,ICAM-1 and VCAM-1 in normal and blank control group were all being 1,the mRNA expression levels (2-△ △Ct) of the above mentioned inflammatory factors and adhesion molecule in animal model group were 3.96 ± 0.39,3.07 ± 0.27,3.71 ± 0.26,3.94 ± 0.26,and the mRNA expression levels (2-△ △Ct) of the above mentioned inflammatory factors and adhesion molecule in HUVEC model group were 3.53±0.70,2.24±0.48,3.13±0.44,2.80±0.13,respectively,all P ＜ 0.01].The content of CD62E in serum was increased significantly in model group compared with that in normal control group (μg/L:1.31 ± 0.22 vs.0.82 ± 0.13,P ＜ 0.01),the mRNA expression levels of IL-8,MCP-1,ICAM-1 and VCAM-1 were decreased significantly in low,middle,high dose Sheshang capsule groups compared with those in model group in endothelial cells of aorta abdominalis of rabbits and HUVEC [abdominal aorta:IL-8 mRNA (2-△ △Ct) were 1.13 ± 0.19,1.26 ± 0.16,1.27 ± 0.17 vs.3.96 ± 0.39,MCP-1 mRNA (2-△ △ Ct) were 1.79 ± 0.24,2.22 ± 0.38,1.76±0.19 vs.3.07±0.27,ICAM-1 mRNA (2 △△Ct) were 2.05±0.11,1.68±0.09,2.37±0.48 vs.3.71±0.26,VCAM-1 mRNA (2-△△Ct) were 1.59±0.08,1.40±0.11,1.84±0.11 vs.3.94±0.26;HUVEC:IL-8 mRNA (2-△△Ct) were 2.33±0.59,2.82±0.82,2.51±0.77 vs.3.53±0.70,MCP-1 mRNA (2-△△Ct) were 1.59±0.35,1.48±0.36,1.54±0.29 vs.2.24±0.48,ICAM-1 mRNA (2-△△Ct) were 1.46±0.38,1.77±0.65,1.73±0.50 vs.3.13±0.44,VCAM-1 mRNA (2-△△Ct) were 2.49±0.24,2.18±0.19,2.45±0.24 vs.2.80±0.13,all P ＜ 0.05].The contents of CD62E were decreased significantly in middle,high dose Sheshang capsule groups compared with the content in model group (μg/L:1.01 ±0.14,1.04±0.13 vs.1.31 ±0.22,all P ＜ 0.01),but there were no statistical significant differences among the three drug group (all P ＞ 0.05).Conclusion The therapy of purging fire and removing toxin can treat vascular endothelial injury by inhibiting the inflammatory response induced by Trimeresurus stejnegeri bites.