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 and summarize the imaging and pathological features of non-acute occlusion following flow diverter (FD) implantation in animal models.Methods:Four experimental pigs (experimental group) that experienced non-acute occlusion (occlusion time exceeding 24 hours) within the FD stent implanted in the common carotid artery, and 19 pigs (control group) that did not experience stent occlusion during the same period were involved. Using an interventional approach under digital subtraction angiography (DSA), the 4 occluded FD lumens were mechanically opened. Optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histopathological examinations were performed to evaluate the intraluminal composition and characteristics of the occlusive tissues. These findings were compared with non-occluded FD stents to summarize the imaging and pathological changes within the occluded FD lumen.Results:The occlusion times of the FD stents in the 4 experimental pigs were 16 weeks, 20 weeks, 20 weeks, and 24 weeks postoperatively. All occluded stents were successfully recanalized under DSA, with a technical success rate of 4/4. Among the 19 non-occluded FD stents, OCT and IVUS revealed uniform (16 stents) or non-uniform (3 stents) neointimal coverage of the stent struts, presenting as homogeneous high/slightly high signal intensity or medium echogenicity. Histopathological examination indicated that the neointima was primarily composed of smooth muscle cells and a small amount of fibrous connective tissues. In contrast, the 4 occluded FD stents demonstrated excessive neointimal proliferation and plaque formation, leading to luminal loss, as shown by OCT and IVUS. The occlusion tissues predominantly presented as homogeneous high signal intensity with weak attenuation (fibrous plaques) on OCT, with some regions showing blurred low signal intensity and strong attenuation (lipid plaques). IVUS presented homogeneous echogenicity (fibrous plaques) and hypoechogenic zones (lipid plaques). Histopathological examination showed that the occlusion tissues mainly consisted of smooth muscle cells, fibrous connective tissues, and lipids, accompanied by numerous foam cells and a minor presence of inflammatory cells.Conclusions:Histopathological examinations confirm that non-acute occlusion of FD is mainly caused by excessive hyperplasia of intima along with the formation of fibrous plaques and lipid plaques. OCT and IVUS have typical finding in imaging that can assist in determining the cause of stent occlusion as well as the lesion's nature, thereby providing crucial guidance for subsequent clinical treatment and drug selection.

Objective:To investigate and summarize the imaging and pathological features of non-acute occlusion following flow diverter (FD) implantation in animal models.Methods:Four experimental pigs (experimental group) that experienced non-acute occlusion (occlusion time exceeding 24 hours) within the FD stent implanted in the common carotid artery, and 19 pigs (control group) that did not experience stent occlusion during the same period were involved. Using an interventional approach under digital subtraction angiography (DSA), the 4 occluded FD lumens were mechanically opened. Optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histopathological examinations were performed to evaluate the intraluminal composition and characteristics of the occlusive tissues. These findings were compared with non-occluded FD stents to summarize the imaging and pathological changes within the occluded FD lumen.Results:The occlusion times of the FD stents in the 4 experimental pigs were 16 weeks, 20 weeks, 20 weeks, and 24 weeks postoperatively. All occluded stents were successfully recanalized under DSA, with a technical success rate of 4/4. Among the 19 non-occluded FD stents, OCT and IVUS revealed uniform (16 stents) or non-uniform (3 stents) neointimal coverage of the stent struts, presenting as homogeneous high/slightly high signal intensity or medium echogenicity. Histopathological examination indicated that the neointima was primarily composed of smooth muscle cells and a small amount of fibrous connective tissues. In contrast, the 4 occluded FD stents demonstrated excessive neointimal proliferation and plaque formation, leading to luminal loss, as shown by OCT and IVUS. The occlusion tissues predominantly presented as homogeneous high signal intensity with weak attenuation (fibrous plaques) on OCT, with some regions showing blurred low signal intensity and strong attenuation (lipid plaques). IVUS presented homogeneous echogenicity (fibrous plaques) and hypoechogenic zones (lipid plaques). Histopathological examination showed that the occlusion tissues mainly consisted of smooth muscle cells, fibrous connective tissues, and lipids, accompanied by numerous foam cells and a minor presence of inflammatory cells.Conclusions:Histopathological examinations confirm that non-acute occlusion of FD is mainly caused by excessive hyperplasia of intima along with the formation of fibrous plaques and lipid plaques. OCT and IVUS have typical finding in imaging that can assist in determining the cause of stent occlusion as well as the lesion's nature, thereby providing crucial guidance for subsequent clinical treatment and drug selection.

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 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 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 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 investigate pouch function, quality of life, and their influencing factors after ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) .Methods:Clinical data of 111 patients undergoing IPAA in the UC database at Department of General Surgery, Jinling Hospital from 2014 to 2020 were retrospectively analyzed. Through the questionnaire, pouch functional score (PFS) and Cleveland global quality of life (CGQL) were obtained. These patients were diveided into two groups according to the PFS score. Univariate and multivariate analysis were used to compare the clinical features and reveal the risk factors of PFS.Results:A total of 111 patients were enrolled in this study, including 65 males and 38 females. 63 patients were in the good pouch function group, and 48 in the poor pouch function group. The median score of PFS was 7 (3.0-10.0) . Univariate analysis showed that compared with the good pouch function group, the poor pouch function group had a longer duration of disease before operation[44.5 (21.0-86.0) months vs. 14.0 (5.0-70.0) months, P = 0.005], a shorter follow-up time[16.0 (7.0-28.8) months vs. 26.0 (15.0-39.0) months, P = 0.020], and a higher proportion of pouchitis (29.1% vs. 12.9%, P = 0. 031) . The multivariate logistic regression analysis showed duration of disease before operation ( OR = 0.974, 95% CI: 0.951-0.997, P = 0.030) and pouchitis ( OR = 3.251, 95% CI: 1.168-9.045, P = 0.024) were the independent risk factor of PFS in UC patients.The median CGQL was 0.77 (0.67-0.87) . The median surgical satisfaction score was 9.0 (8.0-10.0) . There was a correlation between CGQL and PFS ( rs = -0.376, P<0.001) . Conclusions:Most patients recover well after IPAA, and are highly satisfied with the operation. A good pouch function has a positive influence on the quality of life.

Objective:To investigate pouch function, quality of life, and their influencing factors after ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) .Methods:Clinical data of 111 patients undergoing IPAA in the UC database at Department of General Surgery, Jinling Hospital from 2014 to 2020 were retrospectively analyzed. Through the questionnaire, pouch functional score (PFS) and Cleveland global quality of life (CGQL) were obtained. These patients were diveided into two groups according to the PFS score. Univariate and multivariate analysis were used to compare the clinical features and reveal the risk factors of PFS.Results:A total of 111 patients were enrolled in this study, including 65 males and 38 females. 63 patients were in the good pouch function group, and 48 in the poor pouch function group. The median score of PFS was 7 (3.0-10.0) . Univariate analysis showed that compared with the good pouch function group, the poor pouch function group had a longer duration of disease before operation[44.5 (21.0-86.0) months vs. 14.0 (5.0-70.0) months, P = 0.005], a shorter follow-up time[16.0 (7.0-28.8) months vs. 26.0 (15.0-39.0) months, P = 0.020], and a higher proportion of pouchitis (29.1% vs. 12.9%, P = 0. 031) . The multivariate logistic regression analysis showed duration of disease before operation ( OR = 0.974, 95% CI: 0.951-0.997, P = 0.030) and pouchitis ( OR = 3.251, 95% CI: 1.168-9.045, P = 0.024) were the independent risk factor of PFS in UC patients.The median CGQL was 0.77 (0.67-0.87) . The median surgical satisfaction score was 9.0 (8.0-10.0) . There was a correlation between CGQL and PFS ( rs = -0.376, P<0.001) . Conclusions:Most patients recover well after IPAA, and are highly satisfied with the operation. A good pouch function has a positive influence on the quality of life.

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.