1.Low disease activity and remission status of systemic lupus erythematosus in a real-world study
Limin REN ; Chuchu ZHAO ; Yi ZHAO ; Huiqiong ZHOU ; Liyun ZHANG ; Youlian WANG ; Lingxun SHEN ; Wenqiang FAN ; Yang LI ; Xiaomei LI ; Jibo WANG ; Yongjing CHENG ; Jiajing PENG ; Xiaozhen ZHAO ; Miao SHAO ; Ru LI
Journal of Peking University(Health Sciences) 2024;56(2):273-278
Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7%of patients met the criteria of LLDAS,while 10.4%of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.
2.Mechanism of Xiyanping injection in treatment of acute lung injury using network pharmacology and molecular docking analysis
Shao-Yan NIE ; Su-Su FAN ; Yu-Shan ZHU ; Xue-Rong PENG ; Ying-Xia WANG ; Xuan ZHANG
Chinese Pharmacological Bulletin 2024;40(6):1165-1171
Aim To explore the protective effects of Xiyanping injection against lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice,and investi-gate the underlying mechanism.Methods In the LPS-induced ALI mouse model,the protective effect of Xiyanping injection against ALI was evaluated by ob-serving the pathological indicators of lung tissue.Net-work pharmacology and molecular docking were used to explore its mechanism.Western blot method was used to validate the predicted target proteins.Results Xiy-anping injection significantly improved the pathological injury and alleviated inflammatory reactions in lungs of ALI mice.Four active ingredients were identified in Xiyanping injection,namely,14-deoxy-11-oxo-an-drographolide,14-deoxyandrographolide,14-deoxy-12-methoxyandrographolide,and andrographolide-19-β-D-glucoside.A total of 288 corresponding drug targets and 4 960 ALI-related targets were obtained,with 192 genes overlapping.The ten core targets associated with Xiyanping injection were identified as STAT3,EGFR,PIK3R1,MAPK1,PIK3CA,NFKB1,ESR1,MAPK8,JAK2,and FYN.GO enrichment analysis re-vealed 310 biological processes(BP),65 cellular components(CC),and 80 molecular functions(MF)associated with the overlapping genes.KEGG pathway enrichment analysis identified 141 pathways related to ALI,with the top 20 pathways including MAPK,TNF-α,VEGF,cAMP,mTOR,AMPK,NOD,JAK-STAT,IL-17,and NF-κB.Molecular docking results demonstrated strong binding affinity between core tar-gets(MAPK1,MAPK8,NFKB1)and active ingredi-ents(14-deoxy-12-methoxyandrographolide and 14-de-oxyandrographolide).Western blotting showed that medium and high doses of Xiyanping injection signifi-cantly downregulated p38,JNK,ERKl/2,NF-κB p65 protein expression in lung tissue of ALI mice(P<0.01).Conclusions Xiyanping injection has a cer-tain protective effect against ALI,and the mechanism is related to regulating MAPK and NF-κB signaling pathways.
3.Dynamic evaluation of inflammation in infarct area after acute myocardial infarction and its relationship with left ventricular remodeling by 18F-FDG PET imaging
Feifei ZHANG ; Xiaoliang SHAO ; Jianfeng WANG ; Xiaoyu YANG ; Min XU ; Peng WAN ; Shengdeng FAN ; Yunmei SHI ; Wenji YU ; Bao LIU ; Xiaoxia LI ; Xiaoyun WANG ; Baosheng MENG ; Yong WANG ; Yuetao WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(11):661-667
Objective:To evaluate inflammation early in the infarct zone and its dynamic changes after acute myocardial infarction (AMI) using 18F-FDG PET imaging, and analyze its relationship with left ventricular remodeling progression (LVRP). Methods:Sixteen Bama miniature pigs (4-6 months old, 8 females) were selected. AMI models were established by balloon occlusion of the left anterior descending artery. 18F-FDG PET imaging was performed before AMI and at days 1, 5, 8, and 14 post-AMI to evaluate the regional inflammation response. 18F-FDG SUV ratio (SUVR) and the percentage of uptake area of left ventricle (F-extent) in the infarct zone, and the SUVRs of the spleen and bone marrow, were measured. Echocardiography and 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT myocardial perfusion imaging (MPI) were performed at the above time points and on day 28 post-AMI to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and myocardial perfusion defect extent. The degree of LVRP at day 28 post-AMI was defined as ΔLVESV(%)=(LVESV AMI 28 d-LVESV AMI 1 d)/LVESV AMI 1 d×100%. Data were analyzed using repeated measures analysis of variance, Kruskal-Wallis rank sum test and Pearson correlation analysis. Results:Twelve pigs were successfully modeled and completed the study. Inflammation in the infarct zone persisted until day 14 post-AMI. The SUVR of the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 1.03±0.08, 3.49±1.06, 2.93±0.90, 2.38±0.76, and 1.63±0.62, respectively ( F=49.31, P<0.001). The F-extent values in the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 0, (40.08±12.46)%, (40.00±12.76)%, (31.08±12.82)%, and 16.50%(7.25%, 22.00%), respectively ( H=37.61, P=0.001). There were no significant differences in the SUVRs of bone marrow and spleen before and after AMI ( F values: 0.69 and 0.77, both P>0.05). At day 1 post-AMI, both SUVR and F-extent in the infarct zone were significantly correlated with LVRP ( r values: 0.82 and 0.70, P values: 0.001 and 0.035). Conclusions:18F-FDG PET imaging can be used to evaluate inflammation in the infarct area and its dynamic changes after AMI. Inflammation in the infarct area is severe at day 1, and then gradually decreases. The extent and severity of inflammation visible on 18F-FDG PET imaging 1 d after AMI are closely related to LVRP.
4.Development and validation of a stromal-immune signature to predict prognosis in intrahepatic cholangiocarcinoma
Yu-Hang YE ; Hao-Yang XIN ; Jia-Li LI ; Ning LI ; Si-Yuan PAN ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Peng-Cheng WANG ; Chu-Bin LUO ; Rong-Qi SUN ; Jia FAN ; Jian ZHOU ; Zheng-Jun ZHOU ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2024;30(4):914-928
Background:
Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC.
Patients and methods:
We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time.
Results:
We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort.
Conclusion
We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.
5.Application of "eliminating stagnation and bloodletting/fire needling" in treatment of jingjin diseases.
Jun YANG ; Hui-Lin LIU ; Bin LI ; Ying CHANG ; Lu LIU ; Peng CHEN ; Wei YOU ; Shao-Song WANG ; Fan ZHANG ; Yuan-Bo FU ; Jia WEI
Chinese Acupuncture & Moxibustion 2023;43(8):889-893
Based on the development of conditions, the etiology and pathogenesis of jingjin (muscle region of meridian) diseases are summarized as 3 stages, i.e. stagnation due to over-exertion at early stage, manifested by tendon-muscle contracture and tenderness; cold condition due to stagnation, interaction of stasis and cold, resulting in clustered nodules at the middle stage; prolonged illness and missed/delayed treatment, leading to tendon-muscle contracture and impairment of joint function at the late stage. It is proposed that the treatment of jingjin diseases should be combined with the characteristic advantages of fire needling and bloodletting technique, on the base of "eliminating stagnation and bloodletting/fire needling". This combined therapy warming yang to resolve stasis and dispels cold to remove nodules, in which, eliminating the stagnation is conductive to the tissue regeneration, and the staging treatment is delivered in terms of the condition development at different phases.
Acupuncture Therapy/methods*
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Bloodletting
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Medicine, Chinese Traditional
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Muscular Diseases/therapy*
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Humans
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Hot Temperature/therapeutic use*
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Contracture/therapy*
6.Effect of continuous renal replacement therapy on plasma concentration, clinical efficacy and safety of colistin sulfate
Danyang PENG ; Fan ZHANG ; Zhaozhen LI ; Pin LYU ; Ziqi GUO ; Yinyin CHEN ; Jingge ZHAO ; Jingjing NIU ; Bo GUO ; Wenqing JIA ; Xiaofeng JIANG ; Xiaozhao LI ; Shaoyan QI ; Bingyu QIN ; Huanzhang SHAO
Chinese Critical Care Medicine 2023;35(1):88-92
Objective:To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate.Methods:Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups.Results:A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. ① There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE Ⅱ: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [μmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. ② Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). ③ Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. ④ Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. Conclusions:CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.
7.Chinese expert consensus on emergency surgery for severe trauma and infection prevention during corona virus disease 2019 epidemic (version 2023)
Yang LI ; Yuchang WANG ; Haiwen PENG ; Xijie DONG ; Guodong LIU ; Wei WANG ; Hong YAN ; Fan YANG ; Ding LIU ; Huidan JING ; Yu XIE ; Manli TANG ; Xian CHEN ; Wei GAO ; Qingshan GUO ; Zhaohui TANG ; Hao TANG ; Bingling HE ; Qingxiang MAO ; Zhen WANG ; Xiangjun BAI ; Daqing CHEN ; Haiming CHEN ; Min DAO ; Dingyuan DU ; Haoyu FENG ; Ke FENG ; Xiang GAO ; Wubing HE ; Peiyang HU ; Xi HU ; Gang HUANG ; Guangbin HUANG ; Wei JIANG ; Hongxu JIN ; Laifa KONG ; He LI ; Lianxin LI ; Xiangmin LI ; Xinzhi LI ; Yifei LI ; Zilong LI ; Huimin LIU ; Changjian LIU ; Xiaogang MA ; Chunqiu PAN ; Xiaohua PAN ; Lei PENG ; Jifu QU ; Qiangui REN ; Xiguang SANG ; Biao SHAO ; Yin SHEN ; Mingwei SUN ; Fang WANG ; Juan WANG ; Jun WANG ; Wenlou WANG ; Zhihua WANG ; Xu WU ; Renju XIAO ; Yang XIE ; Feng XU ; Xinwen YANG ; Yuetao YANG ; Yongkun YAO ; Changlin YIN ; Yigang YU ; Ke ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Gang ZHAO ; Xiaogang ZHAO ; Xiaosong ZHU ; Yan′an ZHU ; Changju ZHU ; Zhanfei LI ; Lianyang ZHANG
Chinese Journal of Trauma 2023;39(2):97-106
During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.
8.Assessment of left ventricular diastolic dyssynchrony and its influencing factors early after acute myocardial infarction by SPECT gated myocardial perfusion imaging: an experimental study
Feifei ZHANG ; Jianfeng WANG ; Xiaoliang SHAO ; Xiaoyu YANG ; Min XU ; Peng WAN ; Shengdeng FAN ; Yunmei SHI ; Wenji YU ; Bao LIU ; Xiaoxia LI ; Mei XU ; Jiatian CHEN ; Yuetao WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(3):154-159
Objective:To evaluate the left ventricular diastolic dyssynchrony (LVDD) and its influencing factors early after acute myocardial infarction (AMI) using phase analysis of SPECT gated myocardial perfusion imaging (GMPI).Methods:Bama miniature swines ( n=16) were subjected to establish AMI models. GMPI was performed before and 1 d after AMI to obtain the extent of myocardial perfusion defect (Extent, %) and left ventricular systolic dyssynchrony (LVSD)/LVDD parameters, namely the phase histogram bandwidth (PBW) and phase standard deviation (PSD). Meanwhile, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early to late peak mitral diastolic flow (E/A) were obtained by echocardiography. Independent-sample t test, paired t test and Pearson correlation analysis were used to analyze the data. Results:Sixteen AMI swines were successfully created. Compared to baseline, Extent, LVEDV and LVESV significantly increased on 1 d after AMI ( t values: -11.14, -4.55, -6.12, all P<0.001), while LVEF and E/A significantly decreased ( t values: 10.16, 2.18, P<0.001, P=0.046). GMPI showed that the LVDD parameters PBW and PSD increased significantly on 1 d after AMI when compared to those at baseline((142.25±72.06)° vs (33.06±8.98)°, (56.15±26.71)° vs (12.51±5.13)°; t values: -6.11, -6.60, both P<0.001). There were significant differences between LVSD parameters and LVDD parameters (PBW: (109.06±62.40)° vs (142.25±72.06)°, PSD: (44.40±25.61)° vs (56.15±26.71)°; t values: -2.73, -2.20, P values: 0.016, 0.044). LVDD parameters PBW, PSD were negatively correlated with E/A after AMI ( r values: -0.569, -0.566, P values: 0.021, 0.022), and positively correlated with the Extent ( r values: 0.717, 0.634, P values: 0.002, 0.008). The phase analysis of SPECT GMPI to evaluate LVDD showed good intra-observer and inter-observe reproducibility (intraclass correlation coefficient (ICC): 0.953-0.984, all P<0.001). Conclusions:LVDD occurs early on 1 d after AMI, and can reflect left ventricular diastolic dysfunction. The Extent is correlated with LVDD significantly. Phase analysis of SPECT GMPI is an accurate method to evaluate LVDD and left ventricular diastolic function.
9.Topoisomerase Ⅱα Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis.
Lu JIN ; An SHAO-GUANG ; Ma JUN-JIE ; Yang YUE ; Zhang LEI ; Yu PENG ; Tao HENG ; Chen YUN-FAN ; Zhang HAO-XUAN
Chinese Medical Sciences Journal 2022;37(4):331-339
Objective To investigate the expression of topoisomeraseⅡα (TOP2α) in hepatocellular carcinoma (HCC) and its role in predicting prognosis of HCC patients. Methods We used HCC-related datasets in UALCAN, HCCDB, and cBioPortal databases to analyze the expression and mutation of TOP2α and its co-expressed genes in HCC tissues. GO function and KEGG pathway enrichment of TOP2α and its co-expressed genes were identified. The TIMER database was used to analyze infiltration levels of immune cells in HCC. The impacts of TOP2α and its co-expression genes and the infiltrated immune cells on the survival of HCC patients were assayed by Kaplan-Meier plotter analysis. Results TOP2α and its co-expression genes were highly expressed in HCC (P< 0.001) and detrimental to overall survival of HCC patients (P< 0.001). TOP2α and its co-expression genes were mainly involved in cell mitosis and proliferation, and cell cycle pathway (ID: hsa04110, P = 0.001945). TOP2α and its co-expression genes were mutated in HCC and the mutations were significantly detrimental to overall survival (P = 0.0247) and disease-free survival (P = 0.0265) of HCC patients. High TOP2α expression was positively correlated with the infiltration of B cell (r = 0.459, P< 0.01), CD8+ T cell (r = 0.312, P< 0.01), CD4+ T cell (r = 0.370, P< 0.01), macrophage (r = 0.459, P< 0.01), neutrophil (r = 0.405, P< 0.01), and dendritic cell (r = 0.473, P< 0.01) in HCC. The CD8+ T cell infiltration significantly prolonged the 3- and 5-year survival of HCC patients (all P< 0.05), and CD4+ T cell infiltration significantly shortened the 3-, 5-, and 10-year survival of HCC patients (all P< 0.05). ConclusionTOP2α may be an oncogene, which was associated with poor prognosis of HCC patients and could be used as a biomarker for the prognostic prediction of HCC.
Humans
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Biomarkers, Tumor/genetics*
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Carcinoma, Hepatocellular/genetics*
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CD8-Positive T-Lymphocytes
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Computational Biology
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Liver Neoplasms/genetics*
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Prognosis
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DNA Topoisomerases, Type II/genetics*
10.Modern research on Chinese medicine based on single-cell omics: technologies and strategies.
Peng-Hui YANG ; Li-Jun JIN ; Jie LIAO ; Xin SHAO ; Jun-Yun CHENG ; Lu LI ; Xiao-Yan LU ; Xiao-Hui FAN
China Journal of Chinese Materia Medica 2022;47(15):3977-3985
As one of the most advanced technologies, single-cell omics technology develops rapidly in recent years. Based on different technical strategies, it enables unbiased and high-throughput access to multiple omics information at single-cell resolution. So far, single-cell omics technology, by virtue of its great powder in resolving tissue heterogeneity, has become a revolutionary tool to deeply understand the functional structure of tissues, reveal complex disease processes, and elucidate drug mechanisms of action. In view of the technical challenges in deconstructing the complexity of Chinese medicine and clarifying the modern scientific connotation of traditional Chinese medicine(TCM) theory, single-cell omics technology has huge application potential in the discovery of pharmacodynamic substances, construction of action networks, and elucidation of integrated regulatory mechanisms, which brings new opportunities for modern research in TCM. The present study briefly introduced three representative single-cell omics technologies, i.e., single-cell transcriptome sequencing, spatial transcriptomics, and single-cell multimodal omics, and their main application patterns. On this basis, an outlook was proposed on the strategies and applications for modern research in TCM using single-cell omics technology.
Drugs, Chinese Herbal/pharmacology*
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Medicine, Chinese Traditional
;
Technology

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