OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

Mechanical thrombectomy can improve the clinical outcome of patients with acute anterior circulation larger vessel occlusive stroke.However,a remarkable proportion of patients,even they have achieved a successful recanalization,still develop adverse outcomes,such as futile recanalization(FR).According to relevant literature reports,there are many factors that can affect futile recanalization.In this paper,a series of factors such as age,recanalization time,infarct volume,baseline severity,blood pressure that may affect futile recanalization of mechanical thrombectomy in patients with inanterior circulation large vessel occlusion will be comprehensively described and analyzed.(J Intervent Radiol,2024,33:321-324)

Objective To explore the risk factors and countermeasures of the perfusionist-related near-miss event (NME) in cardiopulmonary bypass (CPB). Methods The clinical data of the patients who underwent cardiac surgery in the Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University from March 2020 to July 2021 were retrospectively analyzed. According to whether NME occurred during the operation, the patients were divided into an NME group and a non-NME group. The clinical data of the two groups were compared, and the risk factors for NME were analyzed. Results A total of 702 patients were enrolled, including 424 males and 278 females with a median age of 56.0 years. There were 125 patients in the NME group and 577 patients in the non-NME group. The occurrence rate of NME was 17.81%. Univariate analysis showed that there were statistical differences between the two groups in the gender, body surface area, CPB time, European system for cardiac operative risk evaluation score, emergency surgery, type of surgery, night CPB initiation, modified ultrafiltration use, multi-device control, average operation time, et al. (all P<0.05). The above variables were dimensionality reduction processed by least absolute shrinkage and selection operator regression, and the λ of minimum mean square error of 10-fold cross validation was 0.014. The variables of the corresponding model were selected as follows: multi-device control, night CPB initiation, minimum hematocrit, modified ultrafiltration use, CPB time. The results of multivariate logistic regression showed that night CPB initiation [OR=9.658, 95%CI (4.735. 19.701), P<0.01] and CPB time [OR=1.003, 95%CI (1.001, 1.006), P=0.014] were independent risk factors for NME. Conclusion Night CPB initiation and CPB time are independent risk factors for NME during CPB, which should be recognized and early warned in clinical work.

AIM:To investigate the effect of vaccarin(VAC)on endothelial dysfunction in type 2 diabetes mellitus(T2DM),and to uncover the underlying mechanisms.METHODS:(1)C57BL/6 mice received intraperitoneal injection of streptozotocin and were fed with a high-fat diet(21.8 kJ/kg,60%of the energy source was fat)to construct a T2DM mouse model.Thirty mice were randomly divided into control,T2DM and T2DM+VAC groups,with 10 mice in each group.The mice in T2DM+VAC group were given 1 mg/kg VAC via oral gavage for 6 weeks,while those in control and T2DM groups were given the same volume of PBS.The mRNA and protein expression levels of BCL2-interacting pro-tein 3(BNIP3),PTEN-induced kinase 1(PINK1)and parkin in the thoracic aorta were detected by RT-qPCR and West-ern blot.(2)Human umbilical vein endothelial cells(HUVECs)were stimulated by high glucose(HG;35 mmol/L glu-cose).Mitochondrial membrane potential,autophagy and mitochondrial superoxide levels were detected using JC-1,acri-dine orange(AO)and MitoSOX staining,respectively.RESULTS:Compared with control group,the mRNA and protein levels of BNIP3,PINK1 and parkin were significantly increased in the thoracic aorta of T2DM mice(P<0.05).Compared with T2DM group,the mRNA and protein levels of BNIP3,PINK1 and parkin in the thoracic aorta were significantly re-duced in T2DM+VAC group(P<0.05).The results of JC-1,AO and MitoSOX staining showed that VAC attenuated the decrease in mitochondrial membrane potential and the increase in autophagy and mitochondrial superoxide levels in HG-in-duced HUVECs.Treatment with VAC also inhibited HG-mediated mitochondrial damage in HUVECs after BNIP3 overex-pression.The effect of miR-570-3p mimic on mitochondrial damage was similar to VAC.RT-qPCR and Western blot showed that both miR-570-3p mimic and VAC significantly reduced the mRNA and protein levels of BNIP3,PINK1 and parkin.In contrast,inhibition of miR-570-3p exhibited the opposite effects.CONCLUSION:Treatment with VAC alle-viated endothelial dysfunction in T2DM by inhibiting HG-induced mitochondrial dysfunction through miR-570-3p/BNIP3.

Objective To explore the changes in macrophage infiltration behavior during the dynamic evolution of thrombi following the formation of acute carotid artery thrombosis occlusion(ACTO).Methods 15 healthy male New Zealand rabbits were selected to establish an ACTO model by causing injury to the rabbit carotid artery using surgical sutures treated with ferric chloride.All rabbits were randomly divided into 5 groups according to the end-point time using the random number table method,namely 24-hour group,1 week group,4week group,8 week group,and 12week group postoperatively,with 3 rabbits in each group.At 24 hours post-operation,the ACTO model was examined by DS A.At 24 hours,1 week,4 weeks,8 weeks,and 12 weeks post-operation,samples were taken from the thrombotic arterial segment of the 3 rabbits in each group and embedded in paraffin.The thrombus samples were stained with hematoxylin-eosin(HE)and Martius scarlet blue(MSB)to analyze changes in thrombus morphology and composition(including red blood cells,fibrin and collagen fibers).Orbit Imaging Analysis software was used for semi-quantitative analysis of the thrombus composition components.Using immunohistochemistry to detect the distribution of MO and M2 macrophages in thrombi,aimed to summarize the dynamic evolution of thrombus morphology,composition,and macrophage infiltration behavior at different stages following ACTO occurrence.Results The 24-hour DSA results indicated that all experimental rabbits successfully established the ACTO model.(1)HE staining showed a continuous increase in thrombus size from 24 hours to 1 week.By 4 weeks,signs of thrombus dissolution appeared,and at 8 weeks,neovascularization was observed within the thrombus.By 12 weeks,signs of fibrosis were evident in the thrombus.(2)MSB staining revealed that during the acute phase of thrombus formation(within 24 hours after surgery),red blood cells were the predominant component initially,but after this period,fibrin and collagen fibers became the main components.(3)The detection results of MO macrophages showed that 24 hours after surgery,MO macrophages in the thrombus were not evenly distributed throughout the thrombus,but mainly gathered at the thrombus edge;at 1 week after surgery,the positive area percentage of MO macrophage in the thrombus increased compared with 24 hours after surgery(thrombus edge:[41.7±27.0]％vs.[24.6±16.7]％,thrombus core:[35.7±19.6]％vs.[11.1±10.4]％,all P＜0.001),and evenly distributed within the thrombus;at 4 weeks after surgery,MO macrophages in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.7±6.1]％vs.[41.7±27.0]％,thrombus core:[12.1±8.5]％vs.[35.7±19.6]％,all P＜0.001),the differences were statistically significant.At 4,8,and 12 weeks after surgery,MO macrophages within the thrombus did not change significantly with time(thrombus edge:[10.7±6.1]％,[8.0±7.7]％,and[8.9±5.3]％;thrombus core:[12.1±8.5]％,[9.5±4.2]％,and[15.7±11.0]％),and the differences were not statistically significant(all P＞0.05).In addition,at 12 weeks after surgery,MO macrophages at the thrombus edge was less than the thrombus core([8.9+5.3]％vs.[15.7±11.0]％,P＜0.01).The detection results of M2 macrophages showed that 24 hours after surgery,M2 macrophages in the thrombus were widely distributed throughout the thrombus;at 1 week after surgery,the positive area percentage of M2 macrophages in the thrombus increased compared with 24 hours after surgery(thrombus edge:[22.1±11.3]％vs.[11.4±8.7]％,P＜0.001;thrombus core:[24.5±9.8]％vs.[7.6±6.0]％,P＜0.001);at 4 weeks after surgery,M2 macrophage in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.6±3.7]％vs.[22.1±11.3]％,P＜0.001;thrombus core:[9.2±4.3]％vs.[24.5±9.8]％,P＜0.001);at 8 weeks after surgery,M2 macrophages in the thrombus increased compared with 4 weeks after surgery([17.9±8.8]％vs.[9.2±4.3]％,P＜0.001),and the differences were statistically significant.However,M2 macrophages in the thrombus did not change significantly from 8 weeks to 12 weeks after surgery(thrombus edge:[9.4±6.3]％vs.[8.5±5.3]％,P＞0.05;thrombus core:[17.9±8.8]％vs.[14.4±10.0]％,P＞0.05).In addition,at 8 and 12 weeks after surgery,M2 macrophages in the thrombus core was greater than the thrombus edge(8 weeks after surgery:[17.9±8.8]％vs.[9.4±6.3]％,P＜0.001;12weeks after surgery:[14.4±10.0]％vs.[8.5±5.3]％,P＜0.001).Conclusions This study successfully established an ACTO animal model and demonstrated for the first time the dynamic evolution of macrophages within 12 weeks post-thrombus formation.Macrophages may played a significant role in both thrombus formation and fibrinolysis,as well as in the promotion of thrombus dissolution and the formation of new blood vessels within the thrombus which may potentially promote the spontaneous reperfusion of the occluded vessels.The results of this study need further verification.

Objective:To explore the factors associated with vascular luminal dilatational remodeling (VLDR) following balloon angioplasty for intracranial atherosclerotic stenosis (ICAS).Methods:A case-control study was conducted to analyze the data of symptomatic severe ICAS patients who received either paclitaxel-coated balloon angioplasty (PCBA) or plain balloon angioplasty (POBA) at our center from January 2019 to January 2022 and completed the six-month follow-up. The patients were divided into VLDR group and non-VLDR group according to whether VLDR occurred on follow-up digital subtraction angiography (DSA). The baseline data, preoperative and postoperative lesion characteristics (DSA), and perioperative related information were collected. The definition of VLDR was a decrease in luminal stenosis rate by more than 10% at the time of follow-up compared to the immediate postoperative period. Multivariate logistic regression was performed to analyze possible factors affecting VLDR such as balloon type, balloon length, and expansion time.Results:A total of 88 patients were included in this study, with 16 in the VLDR group and 72 in the non-VLDR group. The follow-up time for all included patients was 6.00 (5.00, 7.00) months. VLDR occurred in 18.2% (16/88) of cases, with a VLDR incidence of 30.4% (14/46) after PCBA and 4.8% (2/42) after POBA. Univariate logistic regression analysis revealed that treatment balloon type, balloon length, inflated time, immediate postoperative stenosis rate, follow-up time and Mori classification may affect the occurrence of VLDR. Multivariate logistic regression analysis showed that the use of paclitaxel-coated balloon (PCB) ( OR=9.82, 95% CI 1.99-48.49, P=0.005) and postoperative immediate stenosis rate ( OR=1.07, 95% CI 1.00-1.14, P=0.042) were independently associated with VLDR. Conclusion:The occurrence of VLDR following balloon angioplasty in ICAS was associated with the use of PCB and immediate postoperative stenosis rates, which will provide guidance for the clinical application of PCB.

Objective:To report single-center clinical experience with endovascular recanalization for non-acute symptomatic intracranial vertebral artery occlusion, to assess the feasibility and safety of endovascular recanalization and to propose the benefit group for selected patients.Methods:From January 2019 to December 2021, 92 patients with non-acute symptomatic intracranial vertebral artery occlusion who underwent endovascular recanalization were retrospectively analyzed. The patients were divided into three groups (low, medium and high-risk group) according to occlusion length, occlusion duration, occlusion nature, calcification of the occlusion segment, and occlusion angulation, and the indicators of patients in each group were analyzed, including the general baseline data of the patients, surgical status and follow-up results. The technical success and perioperative complication rates of low, medium and high-risk groups were calculated. Meanwhile, the differences between three groups were evaluated using the χ2 test for trend or ANOVA analysis. Results:The overall technical success rate of endovascular recanalization was 83.7% (77/92), and the perioperative complication rate was 10.9% (10/92). Among the 3 classification groups, the recanalization success rate from the low-risk group to the high-risk group was 100%, 93.3%, 27.8%( P=0.047), and gradually decreased; while the overall perioperative complication rate was 0, 10.0%, 38.9% ( P=0.001), and gradually increased; the proportion of 90-day mRS score 0-2 was 100%, 83.3%, 22.2% ( P=0.026), and progressively decreased; 77 patients with successful recanalization were followed up, the rate of restenosis/reocclusion was 0, 17.9%, 80.0%( P=0.001), and progressively increased. Patients in the low-and intermediate-risk groups performed well with endovascular recanalization. In 88 patients (4 patients lost to follow-up), a median clinical follow-up of 13 (7, 16) months, stroke or death beyond 30 days was 17.4% (16/92). Conclusions:Endovascular recanalization is safe and feasible for reasonably selected patients with non-acute symptomatic intracranial vertebral artery occlusion, especially in low-and medium-risk groups, and it also provides an alternative to conservative therapy for patients with non-acute symptomatic intracranial vertebral artery occlusion.

A large number of non-specific immune cells, such as macrophages, neutrophils and natural killer cells, as well as specific immune cells, such as B cells and T cells, are presented in the atherosclerotic plaques and arterial blood. In addition, immune-related regulatory molecules such as interferon-γ, interleukin-17, and interleukin-1β highly express in atherosclerotic lesion tissues, which is similar to the tumor immune microenvironment and influence the atherosclerosis progression. In this paper, the research progress of immune cells and related factors involved in the immune microenvironment around cerebral atherosclerotic lesions is reviewed to provide idea and basis for its clinical diagnosis and treatment.

Objective:To evaluate the safety and efficacy of drug-coated balloon (DCB) in the treatment of symptomatic intracranial atherosclerotic stenosis.Methods:Forty-nine patients with symptomatic intracranial atherosclerotic stenosis treated with DCB in the People′s Hospital of Zhengzhou University from January 2018 to August 2021 were retrospectively included. The location and number of lesions were as follows: 21 cases of the middle cerebral artery, 11 cases of the intracranial segment of vertebral artery, 12 cases of the basilar artery, and 5 cases of the intracranial segment of internal carotid artery. Pre-dilatation of the lesion with a normal balloon followed by DCB angioplasty. Clinical follow-up (outpatient or telephone) was carried out at 30 days, 3 months, 6 months, and 1 year after the operation. Imaging follow-up was carried out at 6 months postoperatively. The surgical success rate (defined as the proportion of patients with residual stenosis<50% after balloon dilatation), perioperative safety (any strokes, TIA, and deaths within 1 month), stroke recurrence, and restenosis were analyzed.Results:The operation was performed in all patients successfully. The median stenosis level was 80% (75%, 85%) preoperatively and 20% (15%, 30%) at the time after the operation. The success rate of the operation was 91.8% (45/49). Stenting was given in 11 cases (22.4%, 11/49) for severe flow-limiting vascular entrapment, or non-flow-limiting entrapment, owing to the concern of subsequent progression of the entrapment. Three cases (6.1%, 3/49) had significant vascular elastic retraction and implement stent implantation. One patient (2.0%, 1/49) developed symptomatic cerebral infarction during perioperative period, and the symptoms improved after treatment. No fatal or disabling stroke occurred. All patients were followed-up successfully. The median follow-up time was 12 months. Two patients (4.1%, 2/49) had a stroke in the responsible vascular area, and 1 (2.0%, 1/49) patient had a stroke in the non-responsible vascular area. Thirty-eight patients (77.6%, 38/49) had followed-up images. The median follow-up time of postoperative imaging was 6 months. Restenosis occurred in two cases (1 case had symptomatic restenosis), and the incidence of restenosis was 5.3% (2/38).Conclusions:DCB in the treatment of symptomatic intracranial atherosclerotic stenosis has a high technical success rate, good perioperative safety, and low stroke recurrence rate in short-term follow-up, demonstrating the good feasibility, safety, and efficacy of DCB.

Objective:To investigate the variations and related influencing factors of the volumes, positions, and morphologies of geometries formed by surgical clips in intensity-modulated radiation therapy (IMRT) for whole breasts after breast-conserving surgery.Methods:A retrospective analysis was conducted on 18 patients treated with IMRT from October 2021 to September 2022 after breast-conserving surgery. Set-up errors were obtained by reading the coordinate information of tumor bed surgical clips according to the cone beam CT (CBCT) images at 0, 10, 20, 30, 40, and 50 Gy sequentially. Geometries were constructed using the convex hull program, and the volumes ( Vct and V0-5) of geometries were then calculated based on the localization CT images and the six CBCT images, respectively. The centroid displacements ( D0-5) and degrees of inclusion ( DI0-5) of these geometries were compared. The t-test or rank-sum test was used to analyze the effects of radiation doses on V0-5, D0-5, and DI0-5. The Pearson correlation analysis was conducted to analyze the correlations between D0-5 and corresponding set-up errors in three-dimensional directions, and the correlations of average V0-5 variation ( AV), average D0-5 ( AD), and average DI0-5 ( ADI) with the body mass index (BMI), the volume of a breast ( VB), the breast axial height ( H), and the time interval from surgery to radiotherapy ( T) each. The influences of quadrants ( Q) where geometries are located and states ( S) of geometries adhering to or away from the chest walls on AV, AD, and ADI were analyzed through one-way ANOVA. Results:The differences between D5 and D0, between D5 and D1, and between D5 and D2 were statistically significant ( t = -3.27, -4.52, -3.38, P < 0.05), respectively. The differences between DI5 and DI0, between DI5 and DI1, between DI5 and DI2 were statistically significant ( t = 2.53, 2.70, 2.64, P < 0.05), respectively. D1 and D4 correlated with the set-up errors in the superior-inferior dimension, and D3 correlated with the set-up errors in the left-right dimension ( r = 0.50, 0.56, 0.53, P < 0.05). The AD was related to BMI, VB, and H ( r = 0.54, 0.48, 0.50, P < 0.05). There were statistically significant differences in AV and ADI of geometries away from ( S3) and near ( S2) chest walls ( F = 2.66, 3.83, P < 0.05). The AD differences of geometries between S3 and the state adhering to chest walls ( S1) and between S3 and S2 were statistically significant ( F = 7.46, P < 0.05), respectively. Conclusions:The geometries are relatively constant volumes during whole-breast radiotherapy. However, their positions and morphologies vary greatly in the late course. The volume variation ratios, centroid displacements, and degrees of inclusion of geometries are all affected by the states of their attachments to the chest walls. The centroid displacements correlate with breast morphologies and BMI. The radiotherapy plan modification can be individualized.