1.Phenomics of traditional Chinese medicine 2.0: the integration with digital medicine
Min Xu ; Xinyi Shao ; Donggeng Guo ; Xiaojing Yan ; Lei Wang ; Tao Yang ; Hao LIANG ; Qinghua PENG ; Lingyu Linda Ye ; Haibo Cheng ; Dayue Darrel Duan
Digital Chinese Medicine 2025;8(3):282-299
Abstract
Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.
2.A new furan α -butenolactones from Alisma orientale and their potential antifibrotic activities
Deng-hui ZHU ; Peng-li GUO ; Si-qi TAO ; Jing-ke ZHANG ; Meng-nan ZENG ; Xiao-ke ZHENG ; Wei-sheng FENG
Acta Pharmaceutica Sinica 2024;59(7):2058-2061
Four furan
3.Super-thin free anterolateral thigh flap harvested at the junction plane of superficial and deep fat of superficial fascia to repair soft tissue defect of foot
Tao GUO ; Hongjun LIU ; Qiaochu ZHANG ; Yang WANG ; Peng JIN ; Wenzhong ZHANG ; Tao XU ; Chaoqun YUAN ; Jiaxiang GU
Chinese Journal of Plastic Surgery 2024;40(9):954-962
Objective:To investigate the clinical effect of super-thin free anterolateral thigh (ALT) flap at the junction plane of superficial and deep fat of superficial fascia to repair the soft tissue defects of the foot.Methods:The clinical data of patients with foot soft tissue defects admitted to Northern Jiangsu People’s Hospital Affiliated to Yangzhou University from June 2017 to December 2022 were retrospectively analyzed. During the operation, the super-thin free ALT flap on the affected side was harvested at the junction of superficial and deep fat of superficial fascia to repair the foot wound. The donor site wound was sutured directly or repaired with full-thickness skin graft. The flap survival and complications were observed after the operation, and the operation effect was evaluated from the following five aspects. (1) The Maryland foot function score was used to evaluate the recovery of foot function. The full score was 100 points, of which 90-100 points were excellent, 75-89 points were good, 50-74 points were fair, and < 50 points were poor. (2) The Vancouver scar scale (VSS) was used to evaluate the scar condition of the foot. The total score was 0-15 points. The higher the score, the more serious the scar. (3) The cold intolerance symptom severity (CISS) scale was used to evaluate the cold tolerance of the affected foot. The total score was 4-100 points. The higher the score, the more serious the symptoms. (4) Measuring static two-point discrimination to evaluate foot sensation, the smaller the measured value, the better the sensory recovery. (5) The satisfaction of patients with foot appearance was investigated, which was divided into five grades: very satisfied, satisfied, general, dissatisfied and very dissatisfied. Descriptive analysis of the data was performed using SPSS 26.0 software.Results:A total of 13 patients with foot soft tissue defects were enrolled, including 8 males and 5 females. The mean age was 54.7 years (range, 39-70 years). There were 10 cases of left foot and 3 cases of right foot. The wound area after thorough debridement ranged from 5.5 cm ×5.0 cm to 22.0 cm ×18.0 cm. The operation time was (145.1 ± 30.6) min. The area of the flap was 6.0 cm×5.5 cm to 23.5 cm×19.0 cm, and the thickness was (5.2 ± 1.1) mm (range, 3.0- 6.5 mm). The wound at the donor site was sutured directly in 9 cases, and coverd with the abdominal full-thickness skin graft in 4 cases. After the operation, 1 patient had partial epidermal necrosis at the distal end of the flap, 1 patient had venous crisis.The flaps survived after symptomatic treatment. The remaining 11 flaps survived smoothly. The patients were followed up for 12 to 20 months, with an average of 16 months. The foot flaps were soft and free of damage, and no secondary fat reduction or plastic surgery was required. There were no complications such as wound dehiscence, skin graft necrosis, muscle hernia, and quadriceps weakness in 13 cases of donor site except for hypoesthesia caused by scar hyperplasia in 4 cases with skin graft. At the last follow-up, the Maryland foot function score was (87.4±7.3) points, of which 7 cases were excellent, 4 cases were good, and 2 cases were fair. The excellent and good rate was 11/13. The foot scar was not obvious, the VSS score was (3.2±1.2) points. The foot was more tolerant to cold and the sensory recovery was better, the CISS score was (37.5±7.1) points and the static two-point discrimination was (13.9±1.0) mm. One month after the operation, the results of patients’ satisfaction with foot appearance were as follows: 11 cases were very satisfied and 2 cases were satisfied.Conclusion:The super-thin free ALT flap is obtained at the junction plane of superficial and deep fat of superficial fascia to repair the soft tissue defect of the foot, which can optimize the operation time. The appearance and function of the foot recover well after the operation, avoiding the secondary shaping operation, reducing the damage to the donor site, and the patients are satisfied.
4.Clinical efficacy of repeated transcranial magnetic stimulation combined with acupuncture for chronic insomnia
Fenfen YAO ; Tao XU ; Hongling HU ; Jian CHEN ; Xiaoyan YOU ; Qing GUO ; Junyan CHEN ; Peng YU
China Modern Doctor 2024;62(27):12-16
Objective To explore the clinical efficacy of repeated transcranial magnetic stimulation(rTMS)and acupuncture therapy in the treatment of chronic insomnia disorder(CID)patients.Methods A total of 80 patients with CID,who were treated at Nanchang First Hospital from January 2022 to December 2023,were selected for the study.The patients were randomly divided into control group and treatment group,with 40 cases in each group.The control group patients were treated with dexmedetomidine,while the treatment group patients received rTMS and acupuncture therapy in addition to control group.The treatment course was 4 weeks,and the sleep quality,sleep related indicators,and psychological condition improvement of both groups of patients were observed before and after treatment.Results After treatment,the Pittsburgh sleep quality index scores of both groups of patients decreased(P<0.05);The sleep latency and number of awakenings were lower than before treatment(P<0.05),and the total sleep time,sleep efficiency,and proportion of rapid eye movement sleep were higher than before treatment,treatment group showed more significant improvement than control group(P<0.05).After treatment,the Hamilton anxiety and depression scale scores of both groups of patients decreased compared to before treatment,but there was no statistically significant difference in control group before and after treatment(P>0.05).However,there was a statistically significant difference in treatment group before and after treatment(P<0.05).Conclusion The combination of rTMS and acupuncture treatment can significantly improve the sleep quality of CID patients,while also reducing the accompanying symptoms of anxiety and depression.
5.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
6.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.
7.Diagnostic concordance and influencing factors of quantitative flow fraction and fractional flow reserve
Rui-Tao ZHANG ; Peng-Xin XIE ; Zhen-Yu TIAN ; Lin MI ; Ji-Sheng ZHOU ; Ben-Zhen WU ; Li-Yun HE ; Li-Jun GUO
Chinese Journal of Interventional Cardiology 2024;32(9):481-488
Objective This study aimed to explore the diagnostic concordance of fractional flow reserve(FFR)and quantitative flow ratio(QFR)and the characteristics affecting this concordance.Methods Patients with non-acute myocardial infarction admitted to the Department of Cardiology,Peking University Third Hospital between January 2019 and December 2021 were enrolled.The patients were divided into four groups:FFR+/QFR+and FFR-/QFR-,FFR+/QFR-and FFR-/QFR+with FFR or QFR≤0.80 as positive and>0.80 as negative.Using FFR as the gold standard,the diagnostic value of QFR was analyzed,and differences in clinical features and pathological characteristics among the groups were compared.Results A total of 236 patients were included.The mean age was(64.48±9.63)years,and 67.8%were male.All patients had 30%-70%coronary stenosis.The consistency rate of QFR and FFR was 78.0%(n=184),and the Person correlation coefficient was 0.557(P<0.001).Among FFR+patients,the minimum lumen diameter was larger[(1.56±0.34)mm vs.(1.39±0.31)mm,P=0.019],lesion length was shorter[(21.37±11.73)mm vs.(36.86±18.09)mm,P<0.001],and coronary angiography-based index of microcirculartory resistance(AMR)was higher[(277.50±28.87)mmHg·s/m vs.(178.02±49.13)mmHg·s/m,P<0.001]in the disconcordance group.Multivariate regression analysis suggested that AMR[OR 0.93,95%CI 0.88-0.99,P=0.030]and lesion length[OR 1.27,95%CI 1.01-1.60,P=0.045]were independent predictors of disconcordance.In the FFR-group,the lesion length was longer[(33.08±16.05)mm vs.(21.40±13.36)mm,P=0.020],and AMR[(169.66±24.01)mmHg·s/m vs.(265.95±44.78)mmHg·s/m,P<0.001]and low-density lipoprotein-C[1.57(1.10,1.97)mmol/L vs.2.15(1.79,2.74)mmol/L,P=0.031]were lower in the disconcordance group.No statistically significant variables were identified by multivariate regression.Conclusions QFR had high diagnostic value compared with FFR.In the FFR+group,AMR and lesion length may have affected the diagnostic consistency of QFR and FFR.The study provided more evidence for the clinical application of QFR.
8.Functional Studies on the Regulation of Flowering by PfFT3,a Member of the Perilla PEBP Gene Family
Qi-Feng WANG ; Xiao-Yan FENG ; Hui LI ; Fu-Peng HOU ; Xi GUO ; Jun-Xing LU ; Jian HU ; Tao ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2024;40(8):1173-1184
Perilla frutescens,a short-day plant,is rich in biologically active substances and nutrients.Current research on Perilla frutescens focuses on agronomic traits such as yield and fatty acid accumula-tion,with limited exploration of the flowering process and floral organ development.The molecular regu-latory mechanisms underlying these aspects remain unclear.FLOWERING LOUC T(FT)is a florigen in Arabidopsis,plays critical roles in floral transition.PfFT3 is unannotated by genome but annotated by transcriptomics data to the FT-like subfamily.Its function in controlling flowering is yet to be explored.Here subcellular localization analysis showed that PfFT3 is localized in the nucleus and cytoplasm.The plant over-expression vector pCAMBIAI1303-PfFT3 was constructed and transformed into wild-type(Col-0)and mutant fd-2,fd-3,and ft-10 plants by agrobacterium-mediated inflorescence infiltration as a means of obtaining genetically stable and pure overexpression and backfill transgenic lines in Arabidopsis,respectively.Analysis of the results showed that overexpression of PfFT3 significantly promoted early flowering in Arabidopsis and rescued the late-flowering phenotype of the mutants fd-2,fd-3,and ft-10,and that expression of the exogenous PfFT3 promoted the expression of the downstream endogenous flow-ering genes AtSOC1,AtAP1,AtFUL,and AtLFY.This study demonstrates the positive role of PfFT3 in promoting flowering,providing a foundation for further investigation of PfPEBP function and advancing the breeding of early-flowering Perilla frrutescens cultivars.
9.Associations of short-term ambient particulate matter exposure and MTNR1B gene with triglyceride-glucose index:A family-based study
Huangda GUO ; Hexiang PENG ; Siyue WANG ; Tianjiao HOU ; Yixin LI ; Hanyu ZHANG ; Mengying WANG ; Yiqun WU ; Xueying QIN ; Xun TANG ; Jing LI ; Dafang CHEN ; Yonghua HU ; Tao WU
Journal of Peking University(Health Sciences) 2024;56(3):375-383
Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90%females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95%CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95%CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95%CI:0.004-0.076).The TyG index was 0.079(95%CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.
10.Gene-gene/gene-environment interaction of transforming growth factor-β signaling pathway and the risk of non-syndromic oral clefts
Tianjiao HOU ; Zhibo ZHOU ; Zhuqing WANG ; Mengying WANG ; Siyue WANG ; Hexiang PENG ; Huangda GUO ; Yixin LI ; Hanyu ZHANG ; Xueying QIN ; Yiqun WU ; Hongchen ZHENG ; Jing LI ; Tao WU ; Hongping ZHU
Journal of Peking University(Health Sciences) 2024;56(3):384-389
Objective:To explore the association between polymorphisms of transforming growth factor-β(TGF-β)signaling pathway and non-syndromic cleft lip with or without cleft palate(NSCL/P)among Asian populations,while considering gene-gene interaction and gene-environment interaction.Methods:A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium,which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P.After stringent quality control measures,343 single nucleotide polymorphism(SNP)spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS)dataset for further analysis.The transmission disequilibrium test(TDT)was used to test for SNP effects.The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction.Environmental factors collected for the study in-cluded smoking during pregnancy,passive smoking during pregnancy,alcohol intake during pregnancy,and vitamin use during pregnancy.Due to the low rates of exposure to smoking during pregnancy and al-cohol consumption during pregnancy(<3%),only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed.The threshold for statistical significance was rigorously set at P=1.46 × 10-4,applying Bonferroni correction to account for multiple testing.Results:A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P(P<0.05),but none of these associations was statistically significant after Bonferroni's multiple test correction.How-ever,there were 6 pairs of SNPs rs4939874(SMAD2)and rs1864615(TGFBR2),rs2796813(TGFB2)and rs2132298(TGFBR2),rs4147358(SMAD3)and rs1346907(TGFBR2),rs4939874(SMAD2)and rs1019855(TGFBR2),rs4939874(SMAD2)and rs12490466(TGFBR2),rs2009112(TGFB2)and rs4075748(TGFBR2)showed statistically significant SNP-SNP interaction(P<1.46 × 10-4).In contrast,the analysis of gene-environment interactions did not yield any significant results after being cor-rected by multiple testing.Conclusion:The comprehensive evaluation of SNP associations and interac-tions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations.However,the significant gene-gene interactions identified suggest that the genetic architec-ture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling path-way.These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

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