1.Interventional Effect of Active Ingredients of Chinese Medicine and Compound Formulas on Epithelial-mesenchymal Transition in Lung Cancer: A Review
Shanshan SONG ; Min JIANG ; Xinxin LIU ; Bozhen HUANG ; Siyi MA ; Guoyu WANG ; Wanqing WANG ; Luyao WANG ; Liang WANG ; Ruiqing BO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):336-346
Lung cancer is the leading cause of cancer-related deaths worldwide, and tumor metastasis is a key factor contributing to the mortality of most lung cancer patients. Aberrant activation of epithelial-mesenchymal transition (EMT) is a major driver of lung cancer progression and metastasis. EMT is characterized by the loss of apical-basal polarity and intercellular adhesion in highly differentiated, polarized, and organized epithelial cells, which acquire motility, migratory potential, and invasive properties. During this process, cells undergo cytoskeletal remodeling and transform into a mesenchymal phenotype, accompanied by associated changes in cellular markers. The EMT process is highly complex and is tightly regulated by intricate networks involving multiple transcription factors, post-translational controls, epigenetic modifications, and non-coding RNAs. Therefore, therapies targeting the mechanisms of malignant transformation and their associated pathways in lung cancer are of significant clinical importance. In recent years, EMT has attracted increasing attention as a potential target for cancer therapy. Chinese medicine, with its characteristics of multi-target action, low side effects, and good therapeutic efficacy, has demonstrated an important role in anticancer treatment. A series of studies have investigated the role of Chinese medicine in inhibiting EMT in lung cancer. Active ingredients of Chinese medicine, including flavonoids, glycosides, phenols, terpenoids, saccharides, and alkaloids, as well as Chinese medicine compound formulas, have shown significant regulatory effects on EMT. Their mechanisms mainly involve multiple pathways, targets, and links, including signaling pathways, exosomes, microRNAs (miRNAs), and the tumor-associated immune microenvironment. This article summarizes the mechanisms by which EMT promotes malignant tumor progression and reviews the current research on how Chinese medicine active ingredients, monomers, and compound formulas inhibit EMT and suppress lung cancer cell migration and invasion. This study is expected to provide comprehensive theoretical information for basic and translational research on lung cancer.
2.Intervention of Exercise Combined with Shenghui Tang in M1AChR Regulation of Mitochondrial Autophagy Improves Learning and Memory Ability of Alzheimer's Disease Model Rats
Xiaoxue TAO ; Min XIAO ; Kunyang TANG ; Bo WANG ; Chunchun ZHAO ; Rongxiang LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):120-130
ObjectiveTo make clear exercise combined with Shenghui Tang interferes in acetylcholine receptor (M1AChR) to improve mitochondrial autophagy and enhance cognition of Alzheimer's disease (AD) model rats through the adenylate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsForty-eight male SD rats of SPF grade were randomly divided into a blank group, a model group, a Shenghui Tang group (9.3 g·kg-1), an exercise group, an exercise + Shenghui Tang group (9.3 g·kg-1), and a rapamycin group (1.5 mg·kg-1). Except for the blank group, the rat model of AD was constructed by injecting amyloid beta (Aβ1-42) into hippocampus stereotaxically. The exercise group received treadmill exercise for 4 weeks, while the Shenghui Tang group received intragastric administration for 4 weeks, and the exercise + Shenghui Tang group received treadmill exercise and intragastric administration of Shenghui Tang for 4 weeks simultaneously. After the intervention, the Morris water maze test was used to detect the learning and memory ability. Spontaneous behavior was observed in the open field test. The pathological structure of hippocampal neurons was observed by NISSl staining. The expression level of M1AChR in hippocampus was detected by immunohistochemistry (IHC). The autophagy ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The apoptosis rate was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of Beclin1 and microtubule-associated protein light chain 3β (LC3β) was detected by immunofluorescence (IF). The protein expression of M1AChR, AMPK, p-AMPK, mTOR, Beclin1, LC3β, and chelate 1 (SQSTM1/p62) in hippocampus was detected by Western blot. ResultsCompared with the blank group, the model group exhibited significantly increased platform escape latency on the fifth day (P<0.01) and significantly decreased activity distance in the target quadrant and times of crossing the platform (P<0.01). The total movement distance in the open field, the time of movement in the central area, and the average speed obviously decreased (P<0.05). The arrangement of nerve cells in hippocampus CA1 region was dispersed, and the numbers of Nissl bodies and M1AChR positive cells significantly decreased (P<0.01). The expression of TUNEL positive cells was significantly increased (P<0.01). The typical autophagic lysosomal structure decreased. The protein expression of M1AChR, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, LC3Ⅱ/Ⅰ in hippocampus was significantly decreased (P<0.01), and the protein expression of p62 was significantly increased (P<0.01). Compared with the model group, the exercise + Shenghui Tang group exhibited obviously improved space exploration and positioning navigation ability (P<0.05, P<0.01). The total movement distance in the open field, the time of movement in the central area, and the average speed of movement significantly increased (P<0.01). The number of Nissl bodies significantly increased (P<0.01). The number of M1AChR positive cells in hippocampus was significantly increased (P<0.01). The expression of TUNEL positive cells was significantly decreased (P<0.01). The protein expression of M1AChR, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, LC3Ⅱ/Ⅰ in hippocampus was significantly increased (P<0.01), while the protein expression of p62 was significantly decreased (P<0.01). Compared with the exercise + Shenghui Tang group, the Shenghui Tang group and the exercise group showed significantly increased platform escape latency on the fifth day (P<0.01) and obviously decreased activity distance in the target quadrant and times of crossing the platform (P<0.05, P<0.01). The total movement distance in the open field, the time of movement in the central area, and the average speed of movement significantly decreased (P<0.01). The number of Nissl bodies and the number of M1AChR positive cells significantly decreased (P<0.01). The expression of TUNEL positive cells was obviously increased (P<0.05). Ultrastructure of the hippocampal region showed decreased autophagy level. The protein expression of M1AChR, p-AMPK/AMPK, p-mTOR/mTOR, LC3Ⅱ/Ⅰ in the hippocampus was obviously decreased in the Shenghui Tang group (P<0.05, P<0.01), while the protein expression of p62 was significantly increased (P<0.01). In the exercise group, the protein expression of M1AChR, p-AMPK/AMPK, Beclin1, and LC3Ⅱ/Ⅰ was obviously decreased (P<0.05, P<0.01), while the protein expression of p-mTOR/mTOR and p62 was significantly increased (P<0.01). ConclusionExercise combined with traditional Chinese medicine can enhance the expression of M1AChR in the hippocampus of AD model rats, induce autophagy through the AMPK/mTOR signaling pathway, and improve the learning and memory ability of AD rats.
3.Genetic Correlation and Mendelian Randomization Analysis Revealed an Unidirectional Causal Relationship Between Left Caudal Middle Frontal Surface Area and Cigarette Consumption
Hongcheng XIE ; Anlin WANG ; Minglan YU ; Tingting WANG ; Xuemei LIANG ; Rongfang HE ; Chaohua HUANG ; Wei LEI ; Jing CHEN ; Youguo TAN ; Kezhi LIU ; Bo XIANG
Psychiatry Investigation 2025;22(3):279-286
Objective:
Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them.
Methods:
To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted.
Results:
The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4).
Conclusion
Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.
4.Effectiveness of the integrated schistosomiasis control programme in Sichuan Province from 2015 to 2023
Chen PU ; Yu ZHANG ; Jiajia WAN ; Nannan WANG ; Jingye SHANG ; Liang XU ; Ling CHEN ; Lin CHEN ; Zisong WU ; Bo ZHONG ; Yang LIU
Chinese Journal of Schistosomiasis Control 2025;37(3):284-288
Objective To investigate the effectiveness of the integrated schistosomiasis control programme in Sichuan Province during the stage moving from transmission interruption to elimination (2015—2023), so as to provide insights into formulation of the schistosomiasis control measures during the post-elimination stage. Methods Schistosomiasis control data were retrospectively collected from departments of health, agriculture and rural affairs, forestry and grassland, water resources, and natural resources in Sichuan Province from 2015 to 2023, and a database was created to document examinations and treatments of human and livestock schistosomiasis, and snail survey and control, conversion of paddy fields to dry fields, ditch hardening, rivers and lakes management and building of forests for snail control and schistosomiasis prevention. The completion of schistosomiasis control measures was investigated, and the effectiveness was evaluated. Results A total of 20 545 155 person-times received human schistosomiasis examinations in Sichuan Province during the period from 2015 to 2023, and 232 157 person-times were seropositive, with a reduction in the seroprevalence from 2.10% (44 299/2 107 003) in 2015 to 1.12% (9 361/837 896) in 2023 (χ2 = 7.68, P < 0.001). The seroprevalence of human schistosomiasis appeared a tendency towards a decline in Sichuan Province over years from 2015 to 2023 (b = −8.375, t = −10.052, P < 0.001); however, no egg positive individuals were identified during the period from 2018 to 2023, with the prevalence of human Schistosoma japonicum infections maintained at 0. Expanded chemotherapy was administered to 2 754 515 person-times, and medical assistance of advanced schistosomiasis was given to 6 436 persontimes, with the treatment coverage increasing from 46.80% (827/1 767) in 2015 to 64.87% (868/1 338) in 2023. Parasitological tests for livestock schistosomiasis were performed in 35 113 herd-times, and expanded chemotherapy was administered to 513 043 herd-times, while the number of fenced livestock decreased from 121 631 in 2015 to 103 489 in 2023, with a reduction of 14.92%. Snail survey covered 433 621.80 hm2 in Sichuan Province from 2015 to 2023, with 204 602.81 hm2 treated by chemical control and 4 637.74 hm2 by environmental modifications. The area of snail habitats decreased from the peak of 5 029.80 hm2 in 2016 to 3 709.72 hm2 in 2023, and the actual area of snail habitats decreased from the peak of 8 585.48 hm2 in 2016 to 473.09 hm2 in 2023. The mean density of living snails remained low across the study period except in 2017 (0.62 snails/0.1 m2). Schistosomiasis control efforts by departments of agriculture and rural affairs in Sichuan Province included conversion of paddy fields to dry fields covering 153 346.93 hm2, hardening of 6 110.31 km ditches, building of 70 356 biogas digesters, replacement of cattle with 227 161 sets of machines, and captive breeding of 21 161 070 livestock from 2015 to 2023, and the control efforts by departments of water resources included rivers and lakes management measuring 5 676.92 km and renovation of 2 331 irrigation areas, while the control efforts by departments of forestry and grassland included building of forests for snail control and schistosomiasis prevention covering 23 913.33 hm2, renovation of snail control forests covering 8 720 hm2 and newly building of shelterbelts covering 764 686.67 hm2. All 63 endemic counties (cities and districts) had achieved the criterion for schistosomiasis elimination criteria in Sichuan Province by the end of 2023. Conclusion Following the integrated control efforts from 2015 to 2023, remarkable achievements have been obtained in the schistosomiasis control programme in Sichuan Province, with all endemic counties successfully attaining the schistosomiasis elimination target at the county level.
5.Genetic Correlation and Mendelian Randomization Analysis Revealed an Unidirectional Causal Relationship Between Left Caudal Middle Frontal Surface Area and Cigarette Consumption
Hongcheng XIE ; Anlin WANG ; Minglan YU ; Tingting WANG ; Xuemei LIANG ; Rongfang HE ; Chaohua HUANG ; Wei LEI ; Jing CHEN ; Youguo TAN ; Kezhi LIU ; Bo XIANG
Psychiatry Investigation 2025;22(3):279-286
Objective:
Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them.
Methods:
To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted.
Results:
The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4).
Conclusion
Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.
6.Correlation between differences in starch gelatinization, water distribution, and terpenoid content during steaming process of Curcuma kwangsiensis root tubers by multivariate statistical analysis.
Yan LIANG ; Meng-Na YANG ; Xiao-Li QIN ; Zhi-Yong ZHANG ; Zhong-Nan SU ; Hou-Kang CAO ; Ke-Feng ZHANG ; Ming-Wei WANG ; Bo LI ; Shuo LI
China Journal of Chinese Materia Medica 2025;50(10):2684-2694
To elucidate the mechanism by which steaming affects the quality of Curcuma kwangsiensis root tubers, methods such as LSCM, RVA, dual-wavelength spectrophotometry, LF-NMR, and LC-MS were employed to qualitatively and quantitatively detect changes in starch gelatinization characteristics, water distribution, and material composition of C. kwangsiensis root tubers under different steaming durations. Based on multivariate statistical analysis, the correlation between differences in gelatinization parameters, water distribution, and terpenoid material composition was investigated. The results indicate that steaming affects both starch gelatinization and water distribution in C. kwangsiensis. During the steaming process, transformations occur between amylose and amylopectin, as well as between semi-bound water and free water. After 60 min of steaming, starch gelatinization and water distribution reached an equilibrium state. The content of amylopectin, the amylose-to-amylopectin ratio, and parameters such as gelatinization temperature, viscosity, breakdown value, and setback value were significantly correlated(P≤0.05). Additionally, the amylose-to-amylopectin ratio was significantly correlated with total free water and total water content(P≤0.05). Steaming induced differences in the material composition of C. kwangsiensis root tubers. Clustering of primary metabolites in the OPLS-DA model was distinct, while secondary metabolites were classified into 9 clusters using the K-means clustering algorithm. Differential terpenoid metabolites such as(-)-α-curcumene were significantly correlated with zerumbone, retinal, and all-trans-retinoic acid(P<0.05). Curcumenol was significantly correlated with isoalantolactone and ursolic acid(P<0.05), while all-trans-retinoic acid was significantly correlated with both zerumbone and retinal(P<0.05). Alpha-tocotrienol exhibited a significant correlation with retinal and all-trans-retinoic acid(P<0.05). Amylose was extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and α-tocotrienol(P<0.05). Amylopectin was significantly correlated with zerumbone(P<0.05) and extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and 9-cis-retinoic acid(P<0.01). The results provide scientific evidence for elucidating the mechanism of quality formation of steamed C. kwangsiensis root tubers as a medicinal material.
Curcuma/chemistry*
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Starch/chemistry*
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Multivariate Analysis
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Water/chemistry*
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Terpenes/analysis*
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Plant Roots/chemistry*
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Plant Tubers/chemistry*
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Drugs, Chinese Herbal/chemistry*
7.Rapid characterization and identification of non-volatile components in Rhododendron tomentosum by UHPLC-Q-TOF-MS method.
Su-Ping XIAO ; Long-Mei LI ; Bin XIE ; Hong LIANG ; Qiong YIN ; Jian-Hui LI ; Jie DU ; Ji-Yong WANG ; Run-Huai ZHAO ; Yan-Qin XU ; Yun-Bo SUN ; Zong-Yuan LU ; Peng-Fei TU
China Journal of Chinese Materia Medica 2025;50(11):3054-3069
This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry*
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Chromatography, High Pressure Liquid/methods*
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Drugs, Chinese Herbal/chemistry*
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Mass Spectrometry/methods*
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Plant Leaves/chemistry*
8.Liquiritin improves macrophage degradation of engulfed tumour cells by promoting the formation of phagolysosomes via NOX2/gp91phox.
Caiyi YANG ; Kehan CHEN ; Yunliang CHEN ; Xuting XIE ; Pengcheng LI ; Meng ZHAO ; Junjie LIANG ; Xueqian XIE ; Xiaoyun CHEN ; Yanping CAI ; Bo XU ; Qing WANG ; Lian ZHOU ; Xia LUO
Journal of Pharmaceutical Analysis 2025;15(5):101093-101093
The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.
9.Meta-analysis of anterior cervical decompression and fusion ROI-CTM self-locking system in treatment of degenerative cervical spondylosis
Yanjie ZHOU ; Chunfeng CAO ; Zhongzu ZHANG ; Xiong NIU ; Xin WANG ; Zaihai YANG ; Liang ZHOU ; Bo LI
Chinese Journal of Tissue Engineering Research 2025;29(3):617-627
OBJECTIVE:Anterior cervical decompression and fusion is a classic surgical method for the treatment of degenerative cervical spondylosis.The use of nail plates increases the fusion rate and stability and indirectly leads to adjacent vertebral degeneration and postoperative dysphagia.In this paper,the clinical results and complications of ROI-CTM self-locking system and traditional cage combined with screw-plate internal fixation in the treatment of degenerative cervical spondylosis were compared by meta-analysis to provide evidence-based support for the selection of internal fixation methods in anterior cervical decompression and fusion. METHODS:CNKI,WanFang,VIP,PubMed,Cochrane Library,Web of Science,and Embase databases were searched for Chinese and English literature on the application of ROI-CTM self-locking system and fusion cage combined with screw plate internal fixation in the treatment of degenerative cervical spondylosis.The retrieval time range was from inception to July 2023.Two researchers selected the literature strictly according to the inclusion and exclusion criteria.The Cochrane bias risk tool was used to evaluate the quality of randomized controlled trials.Newcastle-Ottawa Scale was used to assess the quality of cohort studies.Meta-analysis was performed using RevMan 5.4 software.Outcome indicators included operation time,intraoperative blood loss,Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,incidence of adjacent vertebral degeneration,cage subsidence rate,and incidence of dysphagia. RESULTS:Thirteen articles were included,including eleven retrospective cohort studies and two randomized controlled trials,with 1 136 patients,569 in the ROI-C group,and 567 in the cage combined with the nail plate group.Meta-analysis results showed that the operation time(MD=-15.52,95%CI:-18.62 to-12.42,P<0.000 01)and intraoperative blood loss(MD=-24.53,95%CI:-32.46 to-16.61,P<0.000 01)in the ROI-C group and the fusion device combined with nail plate group.Postoperative adjacent segment degeneration rate(RR=0.40,95%CI:0.27-0.60,P<0.000 01)and postoperative total dysphagia rate(RR=0.18,95%CI:0.13-0.26),P<0.000 01)were statistically different.The two groups had no significant difference in Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,or cage subsidence rate(P≥0.05). CONCLUSION:Applying an ROI-CTM self-locking system and traditional cage combined with plate internal fixation in anterior cervical decompression and fusion can achieve satisfactory clinical results in treating degenerative cervical spondylosis.The operation of the ROI-CTM self-locking system is more straightforward.Compared with a cage combined with plate internal fixation,the ROI-CTM self-locking system can significantly reduce the operation time and intraoperative blood loss and has obvious advantages in reducing the incidence of postoperative dysphagia and adjacent segment degeneration.The ROI-CTM self-locking system is recommended for patients with skip cervical spondylosis and adjacent vertebral disease.However,given its possible high settlement rate,using a fusion cage combined with screw-plate internal fixation is still recommended for patients with degenerative cervical spondylosis with multiple segments and high-risk factors of fusion cage settlement,such as osteoporosis and vertebral endplate damage.
10.Genetic Correlation and Mendelian Randomization Analysis Revealed an Unidirectional Causal Relationship Between Left Caudal Middle Frontal Surface Area and Cigarette Consumption
Hongcheng XIE ; Anlin WANG ; Minglan YU ; Tingting WANG ; Xuemei LIANG ; Rongfang HE ; Chaohua HUANG ; Wei LEI ; Jing CHEN ; Youguo TAN ; Kezhi LIU ; Bo XIANG
Psychiatry Investigation 2025;22(3):279-286
Objective:
Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them.
Methods:
To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted.
Results:
The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4).
Conclusion
Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

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