1.Progress in Disease-Syndrome-Integrated Mouse Models of Lung Cancer
Yulei ZHAO ; Bingbing HAN ; Xingxin WANG ; Guangjian YANG ; Yajie WANG ; Xiaoyong TANG
Laboratory Animal and Comparative Medicine 2026;46(4):531-540
Lung cancer has the highest mortality rate among malignant tumors worldwide, posing a severe threat to human health. Traditional Chinese medicine (TCM) offers unique advantages in treating lung cancer, with disease-syndrome-integrated animal models serving as a critical component of TCM lung cancer research. According to TCM pathogenesis, lung cancer is classified as a pattern of underlying deficiency with superficial excess. Clinically, it is often categorized into syndromes such as qi and yin deficiency, lung-spleen qi deficiency, lung yin deficiency, qi stagnation and blood stasis, and phlegm-heat obstructing the lungs. Treatment should fundamentally adhere to the principle of "strengthening the healthy qi and expelling pathogenic factors". This paper systematically reviews literature from 2005 to 2025 on disease-syndrome-integrated animal models for lung cancer. It summarizes the theoretical basis and establishment methods of four core disease-syndrome-integrated models: qi-yin deficiency pattern, spleen qi deficiency pattern, qi stagnation and blood stasis pattern, and kidney deficiency pattern. Further discussion covers their evaluation systems and limitations. Additionally, modeling approaches for other patterns including yang deficiency, spleen deficiency, and qi deficiency with blood stasis are summarized, with evaluation methods categorized by behavioral characteristics and biochemical indicators. Analysis reveals that current models predominantly use C57BL/6 mice, exhibiting issues such as insufficient clinical relevance, complex modeling procedures, numerous confounding factors, and a low degree of standardization. Future improvements to disease-syndrome-integrated lung cancer animal models could include using clustered regularly interspaced short palindromic repeats (CRISPR) technology to establish organoid–patient-derived xenograft models; developing controllable composite stress systems and standardized stimulus models, such as gradient-controlled alternating cold/heat chambers and programmed dietary regulation systems, to reduce nonspecific interference; and developing multidimensional dynamic modeling techniques by integrating clinical big data, including metabolomics and imaging features, to design dynamic intervention protocols, thereby providing more precise and reliable experimental tools for elucidating the mechanisms of TCM in lung cancer prevention and treatment.
2.Impact of metabolic risk factor control on mortality risk in patients with metabolic dysfunction-associated steatotic liver disease
Jingdan ZHANG ; Bingbing WANG ; Zeran WANG ; Fan FENG ; Ren NA ; Hongyan GE
Journal of Clinical Hepatology 2026;42(7):1576-1585
ObjectiveTo investigate the association of comprehensive control of multiple metabolic risk factors with the risk of all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and its quantitative effect. MethodsA retrospective cohort study was conducted based on the data from National Health and Nutrition Examination Survey (NHANES) in 2003—2018. A total of 29 458 participants were enrolled, including 12 528 patients with MASLD and 16 930 non-MASLD controls. The control status of nine risk factors was assessed, i.e., hypertension, diabetes, liver fibrosis (assessed by fibrosis-4 index [FIB-4]), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, serum albumin, renal function (assessed by serum creatinine), systemic inflammation (assessed by neutrophil count), smoking, and physical activity. According to the status of comprehensive risk factor control, the patients with MASLD were further divided into low-control group with 1 107 patients, moderate-control group with 7 042 patients, and high-control group with 4 379 patients. A total of 397 participants were enrolled in the external validation cohort, among whom there were 266 participants with MASLD and 131 participants without MASLD. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between groups. The Cox proportional hazards model incorporating complex sampling weights for NHANES data were used to investigate the association between the degree of risk factor control and all-cause mortality, and the Kaplan-Meier curve, the log-rank test, restricted mean survival time (RMST), and population attributable fraction (PAF) were used for further assessment. The robustness of the findings was validated in an independent clinical cohort (n=397). ResultsThe cohort study based on the NHANES database showed that during the median follow-up time of 6.7 years, 1 171 deaths occurred among the 12 528 patients with MASLD. There was a significant reduction in mortality risk with the increase in the number of risk factors controlled (trend test: χ2=65.06, P<0.001). Compared with the low-control group, the mortality risk decreased successively in the moderate-control group (hazard ratio [HR]=0.59, 95% confidence interval [CI]: 0.51 — 0.69) and the high-control group (HR=0.36, 95%CI: 0.27 — 0.48), and the mortality risk was reduced by 22% for each additional risk factor controlled (HR=0.78, 95%CI: 0.74 — 0.82). The PAF analysis showed that AST/ALT ratio control (PAF=19.2%) and physical activity (PAF=18.9%) were the largest contributors. The survival analysis of the sub-cohort constructed based on nearest neighbor matching (with a maximum follow-up time of 13.3 years) showed that there was a significant difference in cumulative survival rate between the MASLD groups with different control levels and the non-MASLD group (P<0.001). The RMST analysis further quantified the survival benefit of each group, and the high-control group had the longest 10-year RMST (9.88 years), which was superior to that of the non-MASLD group (9.43 years), the moderate-control group (9.33 years), and the low-control group (7.96 years). The multivariable-adjusted model analysis of the complete cohort showed that compared with the non-MASLD population, the MASLD patients in the low-control group had a significant increase in mortality risk, the moderate-control group had a comparable mortality risk, and the high-control group had a significantly lower mortality risk. The subgroup analysis showed a significant protective effect of comprehensive control in both male and female individuals (P<0.05), and the interaction analysis suggested a potentially stronger protective effect in female individuals (Pfor interaction=0.031). The protective effect was statistically significant in patients aged ≥60 years (P<0.05). There was a significant difference in protective effect across the groups stratified based on waist circumference (P<0.05), but there was no significant interaction between groups (Pfor interaction=0.821). In the external validation cohort, among the 397 participants, there were 72 cases of all-cause mortality (18.1%). The survival analysis showed a significant gradient increase in the survival rate of MASLD patients with the increase in the level of control (P=0.022). The RMST analysis showed that the moderate- and high-control groups had a better RMST than the non-MASLD group at 5 years (4.47 years vs 4.56 years vs 4.40 years), with a more significant survival advantage at 10 years (8.67 years vs 8.95 years vs 8.44 years). The Cox regression analysis showed that, with the low-control MASLD group as the reference, there was a significant reduction in mortality risk in the moderate-control group (HR=0.41, 95%CI: 0.21 — 0.81) and the high-control group (HR=0.32, 95%CI: 0.14 — 0.71); with the non-MASLD population as the reference, there was a significant increase in mortality risk in the low-control group (HR=2.02, 95%CI: 1.03 — 3.95), with a comparable mortality risk in the moderate-control group (HR=0.83, 95%CI: 0.48 — 1.44) and the high-control group (HR=0.66, 95%CI: 0.30 — 1.38), and the point estimates of the effects were highly consistent with the main study. ConclusionAmong MASLD patients, better control of metabolic risk factors is associated with a lower mortality risk. Achieving optimal control can eliminate the excess mortality risk associated with MASLD, thereby helping patients achieve a better survival prognosis than the general population.
3.miR-411-3p attenuates silica-induced pulmonary fibrosis in mice by suppressing alveolar type II epithelial-mesenchymal transition via targeting SMURF2 regulation
Siyi WANG ; Jiakun DU ; Siyuan SHAN ; Bingbing LI ; Xinyu WANG ; Zhongqiu WEI ; Hong XU ; Xuemin GAO
Journal of Environmental and Occupational Medicine 2025;42(12):1438-1445
Background Pneumoconiosis is the most serious occupational disease in China, among which silicosis accounts for more than 50%. microRNA (miRNA) plays an important role in the occurrence process of silicosis fibrosis, but the mechanism of it has not been fully clarified yet. Objective To explore the molecular mechanism by which miR-411-3p modulates the ubiquitination degradation of SMAD specific E3 ubiquitin protein ligase (SMURF) 2/Smad7, thereby suppressing epithelial-mesenchymal transition (EMT) in mouse alveolar type II epithelial cells and counteracting silica-induced pulmonary fibrosis. Methods Twenty-four 8-week-old SPF male C57BL/6J mice were randomly divided into four groups: Control group, silica group, silica +miR-411-3p agomir-NC group, and silica +miR-411-3p agomir group, with 6 mice in each group. Silicosis model was prepared by a one-time bronchial infusion of silicon dioxide (SiO2) (200 mg·mL-1, 50 μL). In vitro MLE-12 cells were divided into (1) control group and SiO2 group, (2) SiO2+negative control siRNA (siRNA-NC) group and SiO2+Smurf2 gene silencing (si-Smurf2) group, (3) SiO2+solvent (DMSO) group and SiO2+protease inhibitor (MG132) group, (4) mutant sequence plasmid (Mut)+miR-411-3p mimic control (miR-NC) group, Mut+miR-411-3p mimic group, wild sequence plasmid (Wt)+miR-NC group, and Wt+miR-411-3p mimic group, (5) SiO2+miR-NC group and SiO2+miR-411-3p mimic group. The pathological morphology and collagen deposition of lung tissue were observed after staining. Detection of miR-411-3p and proteins was conducted by real-time fluorescent quantitative PCR and Western blot. The binding of SMURF2 to Smad7 protein and Smad7 to ubiquitin (Ub) were detected by co-immunoprecipitation (Co-IP) method. Dual-luciferase reporter gene assay was adopted to verify the regulatory effect of miR-411-3p on Smurf2. Results In the SiO2-induced MLE-12 cells, compared to the control group, the SiO2-treated group showed significantly upregulated expressions of N-cadherin (N-Cad), collagen I (CoL I), SMURF2, transforming growth factor-β1 (TGF-β1), and phosphorylated Smad2/3 (p-Smad2/3). In contrast, the expressions of E-cadherin (E-Cad), Smad7, and miR-411-3p were significantly downregulated (P<0.05). The dual-luciferase reporter gene assay revealed a regulatory effect of miR-411-3p on Smurf2 (P<0.05). Meanwhile, in the MLE-12 cells induced by SiO2, the miR-411-3p mimic down-regulated the protein expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3, while up-regulated the protein expressions of E-Cad and Smad7 (P<0.05). The silenced Smurf2 gene inhibited the expressions of N-Cad, CoL I, and p-Smad2/3 proteins, while promoted the expressions of E-Cad and Smad7 proteins in the MLE-12 cells (P<0.05). The Co-IP results showed that the binding of SMURF2 to Smad7 was enhanced, and the ubiquitin binding ability of Smad7 was enhanced in the SiO2 group. In the lung tissue of mice, the results of pathological observation with hematoxylin-eosin (HE) and sirius red (VG) staining showed that compared with the agomir-NC, the lesion was relieved in the lung tissue of the miR-411-3p agomir group. Meanwhile, the expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3 were significantly down-regulated, while the expressions of E-Cad and Smad7 were significantly up-regulated (P<0.05). Conclusion MiR-411-3p alleviates the EMT of alveolar type II epithelial cells and antagonizes silicosis fibrosis progression in mice by inhibiting SMURF2-mediated ubiquitination and degradation of Smad7.
4.Application value of multi-phase left atrial appendage CTA imaging with pulmonary artery monitoring in preoperative evaluation of left atrial appendage closure
Bocheng WANG ; Yunting MEI ; Bingyi FANG ; Qiufang ZHU ; Haoqing PAN ; Haisheng LIANG ; Bingbing SUN ; Can WANG ; Jing ZHOU
Chongqing Medicine 2025;54(6):1356-1360
Objective To investigate the application value of 320-slice wide-detector multi-phase left at-rial appendage computed tomography angiography(LAA-CTA)with pulmonary artery(PA)monitoring in the preoperative evaluation of left atrial appendage closure.Methods A retrospective analysis was conducted on the clinical data of 110 patients who underwent LAA-CTA before left atrial appendage closure.Among them,47 patients underwent single-phase enhanced scanning with superior vena cava(SVC)monitoring(con-trol group),and 63 patients underwent multi-phase enhanced scanning with pulmonary artery monitoring(study group).The differences in imaging effects of the left atrial appendage under different monitoring points and phase imaging methods were compared,as well as the accuracy of comparing with the diagnostic results of transesophageal ultrasound(TEE),and the differences in the presentation of thrombus,perithrombus,and hypoperfusion areas in the left atrial appendage.Results The study group could comprehensively display the multi-phase CT value changes of different components(thrombus,peri-thrombotic viscosity,normal blood)within the left atrial appendage cavity,and its evaluation of lesion size and progression was superior to that of the control group.Using TEE as the gold standard,the study group demonstrated better diagnostic ac-curacy for different components and normal regions within the left atrial appendage cavity compared to the control group(P<0.001).Additionally,the study group improved the detection rate of peri-thrombotic vis-cosity,clearly delineated thrombus boundaries,and enhanced diagnostic accuracy(P<0.001).Conclusion Multi-phase LAA-CTA with pulmonary artery monitoring can effectively evaluate the morphological dimensions,thrombus,and peri-thrombotic CT manifestations of the left atrial appendage.It is simple to operate,with an accuracy rate close to the gold standard,providing reliable imaging evidence for preoperative evaluation of left atrial appendage closure.
5.The Impact of Basic Medical Insurance Outpatient Mutual Aid Policy on the Utilization of Medical Services based on Interrupted Time Series Analysis
Chunping HU ; Huoming WANG ; Bingbing TUO
Chinese Journal of Health Statistics 2025;42(5):685-688,693
Objective To analyze the impact of the basic medical insurance outpatient mutual aid policy on the utilization of medical services.Methods Data indicators related to the utilization of medical services from a tertiary hospital in Wuhan,Hubei Province,from January 2022 to December 2023 were collected.Interrupted time series analysis was used to examine the changing trends of outpatient visits,hospitalizations,and average cost per outpatient visit before and after the implementation of the outpatient mutual aid policy.The Granger causality test and vector autoregressive model were also used to analyze the association between outpatient and inpatient services.Results The outpatient mutual aid policy significantly increased the number of outpatient visits,hospitalizations,and day surgeries in the sample medical institutions(P<0.05),but had limited impact on the average cost per outpatient visit and hospitalization.Conclusion Outpatient mutual aid can effectively promote the utilization of outpatient services,but attention needs to be paid to potential moral hazard issues and strengthen the supervision of medical insurance funds.
6.Risk factors for postoperative SSI in neurosurgery department patients undergoing craniocerebral surgeries,establishment of Nomogram prediction model and its verification
Yinyin DENG ; Bingbing CHEN ; Yafang HONG ; Yubin WANG ; Xiaoqiang LIU ; Suling HUANG
Chinese Journal of Nosocomiology 2025;35(17):2630-2635
OBJECTIVE To explore the risk factors for postoperative surgical site infection(SSI)in the neurosur-gery department patients undergoing craniocerebral surgeries and establish Nomogram prediction model and verify it.METHODS A total of 1 265 patients who underwent craniocerebral surgeries in neurosurgery department of the First Hospital of Quanzhou City from Jan.2021 to Dec.2022 were recruited as the research subjects.The risk factors for the postoperative SSI were explored by logistic regression model.The Nomogram prediction model was established based on the independent risk factors that were screened by logistic regression analysis,and the model was verified.RESULTS Among 1 265 patients who underwent the craniocerebral surgeries,68 had SSI,with the infection rate of 5.38%.Diabetes mellitus,NNIS score no less than 2 points,NRS2002 score no less than 3 points,operation duration no less than 4.33 hours and drainage tube indwelling time more than 3 days were the independent risk factors for the postoperative SSI in the patients undergoing craniocerebral surgeries(P<0.05).The area under the receiver operating characteristic(ROC)curve(AUC)of the established Nomogram pre-diction model was 0.842 in the training group,0.863 in the verification group.the calibration curves were drawn,the goodness of fit of the established Nomogram risk prediction model was assessed by means of Hosmer-Leme-show test;the predicted probability of SSI was highly consistent with the actual probability of infection,with the modeling group(P=0.851),the validation group(P=0.893).CONCLUSIONS The postoperative SSI in the neurosurgery department patients undergoing craniocerebral surgeries is closely associated with the diabe-tes mellitus,NNIS score no less than 2 points,NRS2002 score no less than 3 points,operation duration no less than 4.33 hours and drainage tube indwelling time more than 3 days.The established Nomogram prediction model has high prediction capability and can accurately assess the risk of SSI in the patients.
7.Small-sized twin-nanoparticles normalize tumor vasculature to enhance tumor accumulation and penetration for potent eradication of cancer stem-like cells.
Changshun ZHAO ; Wei WANG ; Zhengchun HUANG ; Yuqing WAN ; Rui XU ; Junmei ZHANG ; Bingbing ZHAO ; Ke WANG ; Suchen WEN ; Yinan ZHONG ; Dechun HUANG ; Wei CHEN
Acta Pharmaceutica Sinica B 2025;15(10):5458-5473
Cancer stem cells (CSCs) are proposed to account for the progression, metastasis, and recurrence of diverse malignancies. However, the disorganized vasculars in tumors hinder the accumulation and penetration of nanomedicines, posing a challenge in eliminating CSCs located distantly from blood vessels. Herein, a pair of twin-like small-sized nanoparticles, sunitinib (St)-loaded ROS responsive micelles (RM@St) and salinomycin (SAL)-loaded GSH responsive micelles (GM@SAL), are developed to normalize disordered tumor vessels and eradicate CSCs. RM@St releases sunitinib in response to the abundant ROS in the tumor extracellular microenvironment for tumor vessel normalization, which improved intratumor accumulation and homogeneous distribution of small-sized GM@SAL. Sequentially, GM@SAL effectively accesses CSCs and achieves reduction-responsive drug release at high GSH concentrations within CSCs. More importantly, RM@St significantly extends the window of vessel normalization and enhances vessel integrity compared to free sunitinib, thus further amplifying the anti-tumor effect of GM@SAL. The combination therapy of RM@St plus GM@SAL produces considerable depression of tumor growth, drastically reducing CSCs fractions to 5.6% and resulting in 78.4% inhibition of lung metastasis. This study offers novel insights into rational nanomedicines designed for superior therapeutic effects by vascular normalization and anti-CSCs therapy.
8.Study on the Correlation of Traditional Chiense Medicine Syndrome Elements with Language Function and Activities of Daily Living in Patients Suffering Post-stroke Aphasia
Jinglei NI ; Linsong CHAI ; Mengxue WANG ; Yunshi HUANG ; Xiao XIONG ; Jia HUANG ; Bingbing LIN
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(6):1297-1305
Objective To explore the correlation of traditional Chinese medicine(TCM)syndrome elements with language function and activities of daily living(ADL)in patients suffering post-stroke aphasia(PSA).Methods Ninety-eight PSA patients hospitalized at the College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine from April 2023 to April 2024 were selected.The language function,TCM syndrome elements,and their correlations were analyzed.Results(1)Among PSA patients,males outnumbered females.PSA patients exhibited different performances on various aphasia-related scales,with language impairments mainly concentrated in naming and spontaneous speech.(2)The distribution of TCM syndrome elements varied in PSA patients with different age groups.In the age group<50 years old,qi obstruction(100.00%),phlegm syndrome(100.00%),and dampness syndrome(100.00%)were predominant.In the age group of 50-59 years old,phlegm syndrome(100.00%)and yang hyperactivity syndrome(96.30%)were predominant.In the age group of 60-69 years old,phlegm syndrome(100.00%)and yang hyperactivity syndrome(96.15%)were also predominant.In the age group of 70-79 years old,qi deficiency syndrome(100.00%)was predominant.In the age group of 80-89 years old,syndromes such as qi insecurity,qi obstruction,qi deficiency,phlegm,yang hyperactivity,blood stasis,wind stirring,and blood cold were concentrated(all 100.00%).However,there were no statistically significant differences in the distribution of TCM syndrome elements among various age groups(P>0.05).(3)The distribution of deficiency and excess syndrome elements varied in PSA patients with different genders.Among deficiency syndrome elements,yang hyperactivity,qi deficiency,and yin deficiency were predominant in males,while yang hyperactivity,qi deficiency,and blood deficiency were predominant in females.Among excess syndrome elements,phlegm syndrome,qi obstruction,and dampness syndrome were predominant in males,while phlegm syndrome,qi obstruction,and qi stagnation syndrome were predominant in females.However,there were no statistically significant differences in the distribution of deficiency and excess syndrome elements between genders(P>0.05).(4)After controlling the factors of age group and gender,partial correlation analysis of syndrome elements and language function showed that among the disease-location syndrome elements,spontaneous naming(r=-0.588,P=0.027)and sematic cued naming(r=-0.558,P=0.038)in the Boston Naming Test(BNT)were negatively correlated with the large intestine;among the disease-nature syndrome elements,BNT sematic cued naming(r=0.821,P<0.001)was positively correlated with qi sinking,while BNT spontaneous naming was negatively correlated with blood heat(r=-0.544,P=0.044)and was positively correlated with fluid depletion(r=0.860,P=0.028);BNT recognitive naming was positively correlated with external wind(r=0.966,P=0.034);errors in BNT sematic cued naming were negatively correlated with qi sinking(r=-0.540,P=0.005);the Modified Barthel Index(MBI)was positively correlated with essence deficiency(r=0.572,P=0.021).Conclusion The TCM syndrome elements of phlegm,qi block,yang hyperactivity,and qi deficiency are commonly seen in PSA patients.There is a certain correlation of language function and ADL with TCM syndrome elements in PSA patients.
9.Development of DUS Test Guidelines for New Pinellia ternata
Xinyao LI ; Mingxing WANG ; Bingbing LIAO ; Changjie CHEN ; Xiufu WAN ; Lanping GUO ; Yuhuan MIAO ; Dahui LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):225-233
Pinellia ternata, belonging to the Pinellia genus within the Araceae family, is a medicinal plant due to its tubers. There are severe issues with unclear germplasm and mixed varieties in its cultivation, necessitating urgent new variety protection efforts. The distinctness, uniformity, and stability (DUS) testing of the plant variety is the basis for protecting new plant varieties, and the DUS test guidelines are the technical basis for DUS testing. To develop the DUS test guidelines for P. ternata, agronomic traits of 229 germplasm of P. ternata were observed and measured during its two growth stages over the years, and each character was graded and described. A total of 38 traits were selected as the test traits of the DUS test guideline for P. ternata. There were three plant traits, 19 leaf traits, six flower traits, two fruit traits, two tuber traits, five bulbil traits, and one ploidy trait. These traits could be divided into 22 quality characters, 12 quantitative characters, and four pseudo-quantitative characters, as well as seven groups, including plants, leaves, flowers, fruit, tubers, bulbils, and ploidy. By searching for standard traits, 10 standard varieties were ultimately determined. Preparing these guidelines will have great significance for reviewing and protecting P. ternata varieties, safeguarding breeders' rights, and promoting the development of the P. ternata industry.
10.Correlation between cerebral perfusion and cognitive function in patients with minor stroke or transient ischemic attack caused by severe intracranial arterial stenosis or occlusion
Meiling SHANG ; Yanran CHEN ; Bingbing GUO ; Xiaotong CHI ; Lu QUAN ; Gezhi YAN ; Hui WANG ; Ling MA ; Fude LIU ; Jia YU ; Jianfeng HAN ; Ming ZHANG ; Wanghuan DUN ; Yujing WANG
Chinese Journal of Cerebrovascular Diseases 2025;22(10):701-711
Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate>0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P>0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P<0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P<0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P<0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P<0.016 7).No other statistically significant differences were found in pairwise comparisons(all P>0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P<0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P<0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.

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