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.

BACKGROUND:Cervical rotation-traction manipulation is effective and safe in the treatment of cervical spondylotic radiculopathy,and has been widely used in clinical work.However,its effects on the biomechanics of cervical vertebra and intervertebral disc and the area of intervertebral foramen have not been systematically clarified. OBJECTIVE:Based on the finite element analysis technique,a relevant research and analysis were carried out to provide digital evidence for the mechanism of effect of cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy. METHODS:The CT image data of a volunteer with no neck diseases were selected as the finite element model material at its left-handed physiological limit position.The initial construction of the finite element model was completed by Mimics 19.0 software,Geomagic Studio 2013 software,Hypermash 14.0 software,and ANSYS Workbench 2020 R2 software,respectively.Based on the literature,the grid division of cervical structure and the assignment of elastic modulus and elastic coefficient were completed.Based on the previous work of the team,the mechanical effects of cervical rotation-traction manipulation were simulated on the model.Effects of cervical rotation-traction manipulation on the mechanical parameters of each vertebral body and intervertebral disc in C3-T1 segment and on the cervical lateral foramen area were analyzed. RESULTS AND CONCLUSION:(1)During cervical rotation-traction manipulation,the stress of bone structure was significantly higher than that of soft tissue such as intervertebral disc.(2)When operating the technique,the stress at the top of each cervical vertebra was higher,the stress at the bottom was lower,and the stress at the facet joint and transverse process was lower.The stress at the top of the intervertebral disc was lower,the stress at the bottom was higher,but the highest point of the intervertebral disc stress was outside the top.(3)In addition,after loading the lifting force,the projected area of the C6/C7 intervertebral foramen increased significantly compared with that before loading.(4)It is indicated that the cervical rotation-traction manipulation has the mechanical characteristics of changing the stress structure of the cervical spine itself,and can expand the C6/7 intervertebral cervical foramen area on the opposite side of the patient's cervical rotation,so as to achieve the purpose of treating cervical spondylotic radiculopathy.

BACKGROUND:The evaluation and management of cervical vascular pathologies before orthopedic manual therapy have great significance for reducing risks,ensuring patients'interests and promoting optimal clinical decision-making.However,the research and exploration of this field in China are still in its infancy.In 2020,the International Federation of Orthopaedic Manipulative Physical Therapists(IFOMPT)released the International Framework for Examination of the Cervical Region for potential of vascular pathologies of the neck prior to Orthopaedic Manual Therapy(OMT)Intervention:International IFOMPT Cervical Framework(2020).This framework has important references and guiding values for the clinical practice of cervical manipulation in China. OBJECTIVE:To integrate and interpret the core content of the framework,to provide a reference for the clinical practice of cervical manual therapy in China. METHODS:On the basis of a full study of the framework,the authors interpret the core content of the framework from eight aspects including clinical reasoning,patient history,planning the physical examination,physical examination,risk and benefit.Meanwhile,seven databases including PubMed,EMbase,Cochrane Library,CNKI,WanFang,VIP and China Biomedical Literature Service System databases were searched by computer to screen clinical practice guidelines and expert consensus on neck pain.Through longitudinal comparison of multiple high-quality guidelines and consensus,the authors combine with the clinical practice in China to carry out discussion and analysis. RESULTS AND CONCLUSION:This framework expounds the management strategy and implementation path of cervical vascular disease evaluation before cervical manipulation from multiple dimensions,suggesting that we should improve clinicians'attention to cervical vascular disease evaluation before manipulation,and construct evaluation criteria and implementation path with Chinese clinical characteristics.Meanwhile,we should further carry out basic scientific research with multidisciplinary techniques and promote shared decision-making and teaching model innovation to achieve the best clinical decision.

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 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.

Objective:Based on single-center clinical results of endovascular recanalization for symptomatic non-acute internal carotid artery occlusion (ICAO), a new patient classification method is proposed to distinguish the most suitable ICAO patient subgroups for endovascular recanalization.Methods:A total of 140 patients with symptomatic non-acute ICAO accepted endovascular recanalization in Department of Cerebrovascular Intervention, He'nan Provincial People's Hospital from January 2019 to December 2021 were selected. These patients were divided into low risk group ( n=57), medium risk group ( n=54) and high risk group ( n=29) according to the occlusion segments, occlusion times, plaque features, calcification at the occlusion site and occlusion segment angulation. The immediate postoperative recanalization rate, perioperative complications, perioperative death, and prognoses 90 d after endovascular recanalization (modified Rankin scale scores of 0-2 as good prognosis) were evaluated in the 3 groups. Results:The immediate postoperative recanalization rate was 82.9% (114/140), perioperative complication rate was 11.4% (16/140), and perioperative mortality was 0.7% (1/140). The success recanalization rate decreased gradually from the low risk group to the high risk group (100%, 85.2%, and 37.9%), while the perioperative complication rate was the opposite (0%, 11.1%, and 34.5%), with significant differences ( P<0.05). Ninety d after endovascular recanalization, 109 patients had good prognosis and 27 had poor prognosis; the good prognosis rate in low risk group, medium risk group and high risk group was 98.2%, 79.6% and 34.5%, respectively, with significant differences ( P<0.05). The vascular restenosis rate in low risk group, medium risk group and high risk group was 0%, 8.7% and 18.2%, and re-occlusion rate was 0%, 6.5% and 27.2%, respectively, 90 d after endovascular recanalization, with significant differences ( P<0.05). Conclusion:Endovascular recanalization is technically feasible for patients with symptomatic non-acute ICAO, especially those met the criterions of low and medium risk groups in our study.

Objective To analyze the changes in morphology of intervertebral foramina in patients with cervical spondylotic radiculopathy (CSR) treated with fixedpoint lateral flexion and rotation manipulation based on three-dimensional (3D) reconstruction technology, so as to provide references for the effectiveness of manipulation treatment. MethodsForty patients with CSR were treated with fixed point lateral flexion and rotation manipulation once every other day for a total of 7 times and 2 weeks as a course of treatment. CT data of the patients before and after treatment were analyzed by using multifunctional CT, Mimics 21.0, Geomagic and SolidWorks 2017. The area of the intervertebral foramen, anterior and posterior diameter of the intervertebral foramen, upper and lower diameter of the intervertebral foramen were measured before and after treatment, as well as the infrared thermal imaging temperature differences of the bilateral neck and shoulder, front and back of the upper limb, and the VAS scores of the patients were observed before treatment, 7 d after treatment, 14 d after treatment and 1 month follow-up. Results Foraminal area, anterior and posterior diameters, upper and lower diameters of 40 patients were improved after treatment, and the temperature differences of infrared thermal imaging of patients before and after treatment were statistically significant. The VAS score of the patients decreased progressively. Conclusions Fixed point lateral flexion manipulation can significantly improve the shape of the intervertebral foramen in patients with CSR, so as to achieve the treatment purpose of relieving nerve compression.

Objective:To explore the relationship between neutrophil to lymphocyte ratio(NLR) and first pass effect (FPE) during mechanical thrombectomy in patients with acute anterior circulation large vessel occlusive stroke.Methods:Four hundred and six patients with acute anterior circulation large vessel occlusive stroke, admitted to and received mechanical thrombectomy in our hospital from January 2018 to June 2021, were chosen in our study. They were divided into FPE group ( n=186) and non-FPE group ( n=220) according to whether the occluded vessels were successfully or completely re-canalized after the first mechanical thrombectomy. The baseline data, clinical characteristics and operation related data were recorded and compared. The factors with P<0.05 in univariate analysis were included in multivariate Logistic regression analysis to identify the independent factors for FPE. The receiver operating characteristic (ROC) curve was plotted to compare the effectiveness of various factors in predicting FPE. Results:Univariate analysis showed that there were significant differences in gender, proportion of different collateral circulation grading, neutrophil count, lymphocyte count, platelet to lymphocyte ratio (PLR), and NLR between the two groups ( P<0.05). As compared with non-FPE group, FPE group had significantly higher ASPECTS scores at admission, significantly shorter time from femoral artery puncture to recanalization, significantly higher proportion of vascular recanalization, statistically higher proportion of patients using balloon guiding catheter, significantly lower ratio of contrast extravasation, significantly lower incidences of spontaneous intracerebral hemorrhage and mortality, and statistically higher rate of good prognosis 90 d after surgery ( P<0.05). The results of multivariate Logistics regression analysis showed that gender ( OR=0.686, 95%CI: 1.131-3.491, P=0.017), ASPECTS scores ( OR=0.143, 95%CI: 0.094-0.220, P<0.001), NLR ( OR=1.722, 95%CI: 1.413-2.098, P<0.001), and PLR ( OR=1.007, 95%CI: 1.003-1.014, P<0.001) were independent factors for FPE. ROC curve results showed that the areas under the curve predicted by gender, ASPECTS scores, PLR, NLR and combination of multiple factors (gender+ASPECTS scores+PLR+NLR) were 0.60, 0.17, 0.71, 0.77 and 0.91, respectively; among them, NLR had the highest efficacy in single-factor prediction for FPE, with cut-off value of 5.86, specificity of 83.3%, and sensitivity of 62.3%. Conclusion:High NLR at admission in patients with acute anterior circulation large vessel occlusive stroke is likely to have FPE failure during mechanical thrombectomy.

Objective:To investigate the effect of thrombus burden on the clinical outcome of endovascular recanalization in large vessel occlusive stroke.Methods:Patients with acute anterior circulation occlusion who underwent endovascular treatment within 24 hours after onset in Zhengzhou University People′s Hospital from January 2018 to December 2019 were retrospectively collected. According to the clot burden score (CBS) of DSA, total objectives were divided into CBS≥6 group (24 cases) and CBS<6 group (38 cases). Clinical data of the two groups were collected and the modified Rankin scale (mRS) was used to evaluate the clinical outcome at 90 days after surgery. Independent sample t-test, Wilcoxon rank sum test and χ 2 test were used to compare the clinical data between the two groups. Independent risk factors affecting the clinical outcome were analyzed by binary logistic regression. Results:There were no statistically significant differences in basic demographic data, stroke risk factors and other factors between the CBS≥6 group and CBS<6 group ( P>0.05).The proportion of using tirofiban after surgery in the CBS≥6 group (63.2%, 24/38) was lower than that in the CBS<6 group (87.5%, 21/24) (χ2=4.380, P=0.044). The discharge NIHSS score of the CBS≥6 group was [5.0 (3.3, 7.8) points] lower than CBS<6 group [8.5 (1.8, 14.5) points] ( Z=5.221, P=0.022). The proportion of postoperative mRS 0-2 was (91.7%, 22/24) in the CBS≥6 group higher than CBS<6 group(39.5%, 15/38) (χ2=20.486, P=0.001), there were no statistically significant differences between the two groups ( P<0.05). The results of binary logistics regression analysis showed the CBS groups (OR=0.042, 95%CI 0.007-0.244 , P=0.001) was an independent risk factor affecting good outcome. Subgroup analysis of whether tirofiban was used or not showed there was no statistically significant difference in clinical prognosis between the two groups ( P>0.05). Conclusions:The clinical outcome of CBS≥6 group is significantly better than that of CBS<6 group, and patients with small thrombus burden are more likely to get a good clinical outcome of 90 days.

Objective:To investigate the safety and efficacy of endovascular treatment in acute anterior circulation massive cerebral infarction and its prognostic factors.Methods:A retrospective analysis was performed on clinical data of 34 patients with acute anterior circulatory massive cerebral infarction who received intravascular treatment in our hospital from February 2018 to December 2019. The perioperative hemorrhage rate and mortality rate were analyzed in these patients. Modified Rankin scale (mRS) scores were taken as the evaluation standard in the prognoses of these patients during the 90 d of follow up, and the influencing factors affecting the prognoses of patients with massive cerebral infarction were analyzed.Results:The operation was successful in 30 patients (88.2%); the operation time was (97.41±54.58) min, and the number of thrombolysis was (1.91±0.75) times. Distal embolization occurred in 4 patients (11.8%); there were 3 patients with non-symptomatic hemorrhage (8.8%) and 3 patients with symptomatic hemorrhage (8.8%). Cerebral hernia occurred in 7 patients (20.6%); there were 5 deaths (14.4%). During the 90 d of follow up, 13 patients (38.2%) had good prognosis, and 21 (61.8%) had poor prognosis; there were statistically significant differences in NIHSS scores at admission, infarction locations in diffusion weighted imaging, vascular occlusion locations in DSA, pecentages of patients accepted preoperative intravenous thrombolysis and patients with cerebral hernia between the two groups ( P<0.05). NIHSS scores at admission ( OR=0.817, 95% CI: 0.682-0.980, P=0.029), thrombus load scale scores ( OR=5.981, 95%CI: 1.827-19.575, P=0.003), vascular occlusion locations in DSA ( OR=0.031, 95% CI: 0.003-0.311, P=0.003) and pecentage of patients accepted preoperative intravenous thrombolysis ( OR=0.092, 95% CI: 0.010-0.838, P=0.034) were independent factors influencing the prognoses of emergency intravascular treatment. Conclusions:Endovascular recanalization can achieve a relatively good prognosis in patients with massive cerebral infarction. Patients with low NIHSS scores, high thrombotic load scale scores, and middle cerebral artery occlusion, and patients accepted direct intravascular treatment have relatively good prognosis.