Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Objective:To establish a predictive model of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer based on magnetic resonance imaging (MRI) parameters and multimodal ultrasound.Methods:The medical records of 279 patients with HER2 positive breast cancer admitted to Linyi People’s Hospital, Tai’an Central Hospital Affiliated to Qingdao University and Shandong First Medical University affiliated Provincial Hospital from Mar. 2021 to Nov. 2023 were retrospectively analyzed, and randomly divided into a training set ( n=223) and a validation set ( n=56) according to the 8∶2 law. All patients received neoadjuvant chemotherapy combined with targeted therapy and were divided into non-pathologic complete response (NpCR) and pathologic complete response (pCR) groups according to chemotherapy effect. By comparing MRI parameters and multimodal ultrasound parameters of the two groups, and the pCR risk model after neoadjuvant chemotherapy for HER2 positive breast cancer patients was constructed and verified. Results:After 3 cycles of chemotherapy, the incidence of pCR in 223 patients in the training set was 42.15%. Among 56 patients in the validation set, the incidence of pCR was 42.86%. The apparent diffusion coefficient (ADC) of pCR group was higher than NpCR group ( P<0.05). The peak systolic flow velocity (PSV), resistance index (RI), maximum radial change rate, area under the curve (AUC) and peak intensity (PI) in pCR group were higher than NpCR group ( P<0.05), and the ultrasound elastic score in pCR group was lower than NpCR group ( P<0.05). ΔADC ( OR=4.141, 95% CI: 1.820-9.421), maximum diameter change rate ( OR=5.212, 95% CI: 2.291-11.857), PI ( OR=4.802, 95% CI: 2.111-10.923) and ultrasonic elasticity score ( OR=6.629, 95% CI: 1.595-8.256) were the influencing factors of pCR after neoadjuvant chemotherapy for HER2 positive breast cancer ( P<0.05). The sensitivity and specificity of pCR predicted by the training set model after neoadjuvant chemotherapy for HER2 positive breast cancer were 90.43% (95% CI: 82.15%-95.26%), 91.47% (95% CI: 84.91%-95.45%), and the AUC was 0.904 (95% CI: 0.834-0.968). Validation set model predicted the pCR sensitivity after neoadjuvant chemotherapy for HER2 positive breast cancer was 87.50% (95% CI: 66.54%-96.71), specificity was 90.63% (95% CI: 73.83%-97.55%), and AUC was 0.897 (95% CI: 0.821-0.954) . Conclusion:The histogram model based on ΔADC, maximum radial rate of lesion change, PI and ultrasonic elasticity score can be used to evaluate the risk of pCR after neoadjuvant chemotherapy for HER2 positive breast cancer.

Objective:To establish a predictive model of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer based on magnetic resonance imaging (MRI) parameters and multimodal ultrasound.Methods:The medical records of 279 patients with HER2 positive breast cancer admitted to Linyi People’s Hospital, Tai’an Central Hospital Affiliated to Qingdao University and Shandong First Medical University affiliated Provincial Hospital from Mar. 2021 to Nov. 2023 were retrospectively analyzed, and randomly divided into a training set ( n=223) and a validation set ( n=56) according to the 8∶2 law. All patients received neoadjuvant chemotherapy combined with targeted therapy and were divided into non-pathologic complete response (NpCR) and pathologic complete response (pCR) groups according to chemotherapy effect. By comparing MRI parameters and multimodal ultrasound parameters of the two groups, and the pCR risk model after neoadjuvant chemotherapy for HER2 positive breast cancer patients was constructed and verified. Results:After 3 cycles of chemotherapy, the incidence of pCR in 223 patients in the training set was 42.15%. Among 56 patients in the validation set, the incidence of pCR was 42.86%. The apparent diffusion coefficient (ADC) of pCR group was higher than NpCR group ( P<0.05). The peak systolic flow velocity (PSV), resistance index (RI), maximum radial change rate, area under the curve (AUC) and peak intensity (PI) in pCR group were higher than NpCR group ( P<0.05), and the ultrasound elastic score in pCR group was lower than NpCR group ( P<0.05). ΔADC ( OR=4.141, 95% CI: 1.820-9.421), maximum diameter change rate ( OR=5.212, 95% CI: 2.291-11.857), PI ( OR=4.802, 95% CI: 2.111-10.923) and ultrasonic elasticity score ( OR=6.629, 95% CI: 1.595-8.256) were the influencing factors of pCR after neoadjuvant chemotherapy for HER2 positive breast cancer ( P<0.05). The sensitivity and specificity of pCR predicted by the training set model after neoadjuvant chemotherapy for HER2 positive breast cancer were 90.43% (95% CI: 82.15%-95.26%), 91.47% (95% CI: 84.91%-95.45%), and the AUC was 0.904 (95% CI: 0.834-0.968). Validation set model predicted the pCR sensitivity after neoadjuvant chemotherapy for HER2 positive breast cancer was 87.50% (95% CI: 66.54%-96.71), specificity was 90.63% (95% CI: 73.83%-97.55%), and AUC was 0.897 (95% CI: 0.821-0.954) . Conclusion:The histogram model based on ΔADC, maximum radial rate of lesion change, PI and ultrasonic elasticity score can be used to evaluate the risk of pCR after neoadjuvant chemotherapy for HER2 positive breast cancer.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Purpose/Significance To deeply analyze the research progress on the application of medical knowledge graph in the field of stroke,to discuss the problems of the development of stroke knowledge graph in China,and to put forward suggestions for the construc-tion of stroke knowledge graph.Method/Process By reviewing and analyzing the relevant literature,the application of medical knowledge graph in the field of stroke is sorted out and summarized.Result/Conclusion There are still many deficiencies in the development of stroke knowledge graph in China,and in the future,in-depth research can be carried out from four aspects,namely,expanding the ap-plication scope of knowledge graph,promoting the fusion of knowledge graph,developing more efficient algorithms,and upgrading to cog-nitive graph by joint artificial intelligence(AI).

Humans ; Vaccines, Inactivated ; COVID-19/prevention & control* ; Vaccination ; Viral Vaccines ; Immunity ; Antibodies, Viral

ObjectiveTo screen and establish animal models of combined stasis and toxin syndrome based on the comparison of three modeling methods， i.e.， carrageenan （Ca）， Ca combined with dried yeast （Ca+Yeast）， and Ca combined with lipopolysaccharide （Ca+LPS）. MethodForty SPF male SD rats were randomly divided into normal group， Ca group， Ca+Yeast group， and Ca+LPS group， with 10 rats in each group. The Ca group， Ca+Yeast group， and Ca+LPS group received an intraperitoneal injection of Ca （10 mg·kg^-1） on the first day. The Ca+LPS group received an intraperitoneal injection of LPS （50 μg·kg^-1） on the second day， and the Ca+Yeast group received a subcutaneous injection of dry yeast suspension （2 mg·kg^-1） on the back on the second day. The rectal temperature of each group was dynamically observed after modeling. After 24 hours of modeling， the macroscopic evaluation indexes， including tongue manifestation， pulse， and black tail length in each group were observed. The PeriCam PSI imaging system was used to detect the blood flow perfusion of the rat tail. The automatic hemorheology analyzer was used to measure the whole blood viscosity and plasma viscosity of each group. The PL platelet function analyzer was used to detect the platelet aggregation rate of the rats. The enzyme-linked immunosorbent assay （ELISA） was used to detect the interleukin-6 （IL-6） level in the rat plasma. The myocardial tissue， brain tissue， and lung tissue of each group of rats were observed by hematoxylin-eosin （HE） staining. ResultCompared with the normal group， all three model groups showed varying degrees of black tail （P<0.05， P<0.01）， reduced blood flow perfusion at the tail end （P<0.05， P<0.01）， decreased R， G， and B values of tongue manifestation （P<0.05， P<0.01）， and increased maximum platelet aggregation rate （P<0.05， P<0.01）. The pulse amplitudes of the Ca+Yeast group and the Ca+LPS group were lower than that of the normal group （P<0.05， P<0.01）. In addition， the average rectal temperature of the Ca+Yeast group increased after 24 hours of modeling （P<0.01）， and the low-， medium-， and high-shear whole blood viscosity and plasma viscosity increased （P<0.05， P<0.01） as compared with those in the normal group. Additionally， the expression level of the plasma inflammatory factor IL-6 was significantly up-regulated （P<0.05）. Pathological morphology results showed that the Ca+Yeast group had the most severe pathological changes， with small foci of myocardial fiber dissolution， inflammatory cell infiltration， and fibroblast proliferation observed. In the hippocampal area， the neurons were sparse and had undergone red degeneration. In the small focus of the lung interstitium， lymphocytes and neutrophils were infiltrated. ConclusionThe animal model of combined stasis and toxin syndrome was properly established using Ca+Yeast. The systematic evaluation system of the model， which includes traditional Chinese medicine four diagnostic information， western medicine microscopic indicators， and tissue pathological morphology， is worthy of consideration and reference by researchers.

Objective     To exploring the effectiveness of perioperative application of new surgical clinical classification and staging for myasthenia gravis (MG) in reducing the incidence of postoperative myasthenic crisis (MC). Methods     The clinical data of patients with generalized MG admitted to the Comprehensive Treatment Center for Myasthenia Gravis of Henan Provincial People’s Hospital from January 2018 to June 2022 were retrospectively analyzed, who were scored with myasthenia gravis-activities of daily living (MG-ADL) score and quantification of the myasthenia gravis (QMG) score at the first visit, 1 day before surgery, and 3 days after surgery. The patients were divided into a group A (typeⅡ) and a group B (typeⅢ+Ⅳ+Ⅴ) by the new surgical clinical classification and staging of MG according to the disease progression process, and all patients underwent expanded thoracoscopic thymus (tumor) resection after medication and other interventions to control symptoms in remission or stability. The incidence of MC and the efficiency rate after surgery were analyzed. The normal distribution method and percentile method were used to calculate the unilateral 95% reference range of the QMG score and MG-ADL score. Results     Finally 126 patients were enrolled, including 62 males and 64 females, aged 13-71 years, with an average age of 46.00±13.00 years. There were 95 patients in the group A and 31 patients in the group B, and the differences of the preoperative baseline data between the two groups were not statistically significant (P>0.05). The incidence of postoperative MC was 1.05% (1/95) in the group A and 3.23%(1/31) in the group B (P>0.05). The effective one-sided 95% reference range of the QMG score and MG-ADL score 1 day before surgery was 0-7.75 and 0-5.00, and there was no postoperative death in both groups. Conclusion     The new surgical clinical classification and staging of MG can guide the timing of surgery, which can benefit patients undergoing surgery for MG and greatly reduce the incidence of postoperative MC.

OBJECTIVE To investigate whether electroacupuncture(EA)ameliorates abnormal trigeminal neuralgia(TN)orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1.METHODS A mouse infraorbital nerve transection model(pT-ION)of neuropathic pain was established,and EA or sham EA was used to treat ipsilateral acu-puncture points(GV20-Baihui and ST7-Xia-guan).Golgi-Cox staining and transmission elec-tron microscopy(TEM)were administrated to observe the changes of synaptic plasticity in the hippocampus CA1.RESULTS Stable and per-sistent orofacial allodynia and anxiety-like behav-iors induced by pT-ION were related to changes in hippocampal synaptic plasticity.Golgi stain-ings showed a decrease in the density of dendritic spines,especially mushroom-type dendritic spines,in hippocampal CA1 neurons of pT-ION mice.TEM results showed that the density of synapses,membrane thickness of the postsynap-tic density,and length of the synaptic active zone were decreased,whereas the width of the synap-tic cleft was increased in pTION mice.EA attenu-ated pT-ION-induced orofacial allodynia and anx-iety-like behaviors and effectively reversed the abnormal changes in dendritic spines and syn-apse of the hippocampal CA1 region.CONCLU-SION EA modulates synaptic plasticity of hippo-campal CA1 neurons,and reduces abnormal oro-facial pain and anxiety-like behavior,providing evidence for a TN treatment strategy.