2.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.
3.Experience of Using Charcoal-Processed Traditional Chinese Medicine in the Treatment of Gynecological Hemorrhagic Disorders
Xiaolan WU ; Zhaoling YOU ; Guiyun WANG ; Kailing WANG ; Xiaojuan YE ; Lingyu LIAO ; Yueheng LI ; Huiping LIU
Journal of Traditional Chinese Medicine 2025;66(3):308-311
Charcoal-processed traditional Chinese herbal medicine has various therapeutic effects, including astringing, hemostasis, anti-diarrhea, clearing heat, tonifying, and warming the interior. This paper summarizes the clinical application features, compatible experiences, dosages, and precautions for over 20 types of charcoal-processed herbal medicine in the treatment of gynecological bleeding disorders caused by dysfunctions such as dysfunctional uterine bleeding, endometriosis, uterine incision pseudocavity, and vaginal bleeding resulting from threatened miscarriage. The charcoal-processed herbal medicine include Huangqin (Scutellaria Baicalensis) Charcoal, Dahuang (Rheum Palmatum) Charcoal, Cebai (Platycladus Orientalis) Charcoal, Diyu (Sanguisorba Officinalis) Charcoal, Daji (Cirsium Setosum) Charcoal, Xiaoji (Cirsium Japonicum) Charcoal, Shengdi (Rehmannia Glutinosa) Charcoal, Aiye (Artemisia Argyi) Charcoal, Paojiang (Zingiber Officinale) Charcoal, Xuduan (Dipsacus Asper) Charcoal, Duzhong (Eucommia Ulmoides) Charcoal, Qiancao (Rubia Cordifolia) Charcoal, Puhuang (Typha Angustifolia) Charcoal, Shanzha (Crataegus Pinnatifida) Charcoal, Jingjie (Schizonepeta Tenuifolia) Charcoal, Xueyu (Carthamus Tinctorius) Charcoal, Zonglyu (Areca Catechu) Charcoal, Wumei (Prunus Mume) Charcoal, Shudahuang (Rheum Officinale) Charcoal, Lianfang (Nymphaea Alba) Charcoal, Mianmaguanzhong (Clematis Armandii) Charcoal, and Oujie (Nelumbo Nucifera) Charcoal.
4.YOD1 regulates microglial homeostasis by deubiquitinating MYH9 to promote the pathogenesis of Alzheimer's disease.
Jinfeng SUN ; Fan CHEN ; Lingyu SHE ; Yuqing ZENG ; Hao TANG ; Bozhi YE ; Wenhua ZHENG ; Li XIONG ; Liwei LI ; Luyao LI ; Qin YU ; Linjie CHEN ; Wei WANG ; Guang LIANG ; Xia ZHAO
Acta Pharmaceutica Sinica B 2025;15(1):331-348
Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.
5.Effect of unilateral or bilateral transcranial direct current stimulation on post-stroke dysphagia
Fei GAO ; Lixu LIU ; Xueyan HU ; Xiaoli WU ; Lingyu YANG ; Yuqi YANG ; Changqing YE ; Xiaoxia DU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(9):993-999
Objective To investigate the effect of unilateral or bilateral transcranial direct current stimulation(tDCS)on post-stroke dysphagia.Methods From February,2023 to March,2025,27 stroke patients with dysphagia and nasal feeding in Beijing Bo'ai Hos-pital were randomly divided into healthy side stimulation group,bilateral stimulation group and sham stimulation group,with nine cases in each group.All the groups received conventional swallowing training and tDCS,while the healthy side stimulation group stimulated on the healthy side of oropharyngeal cortex;and the bilateral stimu-lation group alternatively stimulated bilateral oropharyngeal cortex,with one hour interval between bilateral stim-ulation;the sham stimulation group stimulated the healthy side of oropharyngeal cortex for 30 seconds and then stop.The course lasted two weeks.The scores of Standard Swallowing Function Assessment Scale(SSA),Modi-fied Mann Assessment of Swallowing Ability(MMASA)and Rosenbek Penetration-Aspiration Scale(PAS)were compared before and after treatment.Results The intra-group effect(F=16.185,P<0.01)was significant in the scores of SSA,the intra-group effect(F=28.650,P<0.01)and interaction effect(F=3.453,P<0.01)were significant in the scores of MMASA,and there was no significant difference in the inter-group effect,intra-group effect and interaction effect in the scores of PAS(P>0.05).Post hoc test showed that there was no significant difference in the scores of SSA,MMASA and PAS among three groups(P>0.05).There was significant difference in the score difference of MMASA be-fore and after treatment among three groups(F=4.698,P<0.05).Post hoc test showed that the score difference of MMAS was more in the healthy side stimulation group than in the bilateral stimulation group and the sham stimulation group(P<0.05),with no significant difference between the bilateral stimulation group and the sham stimulation group(P>0.05).Conclusion tDCS can partly improve post-stroke dysphagia.The healthy side anode stimulation is superior to the alter-nating bilateral hemisphere anode stimulation.
6.Mechanism of CAPN4-mediated cancer stem cell stemness in cisplatin resistance in lung adenocarcinoma
Lingyu ZHANG ; Chunjiang LIU ; Qiumei LI ; Yunbin YE
Chinese Journal of Cancer Biotherapy 2025;32(7):681-688
Objective:To investigate the mechanisms by which calpain small subunit 1(CAPN4)regulates cisplatin resistance and cancer stem cell(CSC)stemness in lung adenocarcinoma,and to provide experimental evidence for reversing drug resistance through targeting CSC stemness.Methods:Tissue samples were collected from 10 lung adenocarcinoma patients who underwent surgical resection at Fujian Cancer Hospital from January 2023 to January 2024.Immunohistochemistry(IHC)stining was used to detect the differential expression of CAPN4 in five cisplatin-resistant and five cisplatin-sensitive lung adenocarcinoma tissues,followed with a histological scoring(H-score).CAPN4 gene expression-related survival analysis in lung cancer patients was conducted using The Cancer Genome Atlas(TCGA)database and Gene Expression Profiling Interactive Analysis(GEPIA)platform.Additionally,tissue samples from two cisplatin-resistant and two cisplatin-sensitive lung adenocarcinoma cases were collected to establish lung adenocarcinoma organoid(PDO)models.H-E and IHC staining were used to assess the morphological consistency between PDOs and the primary tumors.CAPN4 gene expression was silenced using lentivirus-mediated shRNA transduction.The expression levels of stem cell markers ALDH1A1,CD133,Nanog,and SOX9 were detected at both the gene and protein levels using quantitative polymerase chain reaction(qPCR)and Western blotting(WB),respectively.The sensitivity of CAPN4-knockdown PDOs to cisplatin was evaluated using the adenosine triphosphate(ATP)assay,and the apoptosis was assessed using the caspase-3 assay.Results:IHC results showed that CAPN4 protein expression was significantly upregulated in cisplatin-resistant lung adenocarcinoma tissues(P<0.05).TCGA cohort analysis revealed that high CAPN4 expression was significantly associated with poor prognosis(reduced OS)in lung adenocarcinoma patients(HR=1.4,P<0.05).PDOs derived from cisplatin-resistant patients exhibited significant upregulation in CAPN4 protein and stemness markers at both gene and protein levels(all P<0.05).Cisplatin sensitivity assays demonstrated that PDOs derived from cisplatin-resistant patients had significantly higher IC50 values than those from cisplatin-sensitive patients(P<0.05).After CAPN4 knockdown,the expression of stem cell makers in PDOs derived from cisplatin-resistant patients were significantly reduced,and their sensitivity to cisplatin was enhanced(P<0.05).Conclusion:Knockdown of CAPN4 reduces stem cell marker expression and enhances cisplatin sensitivity in lung adenocarcinoma PDOs,providing a potential therapeutic target for reversing cisplatin resistance in lung cancer.
7.Effect of unilateral or bilateral transcranial direct current stimulation on post-stroke dysphagia
Fei GAO ; Lixu LIU ; Xueyan HU ; Xiaoli WU ; Lingyu YANG ; Yuqi YANG ; Changqing YE ; Xiaoxia DU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(9):993-999
Objective To investigate the effect of unilateral or bilateral transcranial direct current stimulation(tDCS)on post-stroke dysphagia.Methods From February,2023 to March,2025,27 stroke patients with dysphagia and nasal feeding in Beijing Bo'ai Hos-pital were randomly divided into healthy side stimulation group,bilateral stimulation group and sham stimulation group,with nine cases in each group.All the groups received conventional swallowing training and tDCS,while the healthy side stimulation group stimulated on the healthy side of oropharyngeal cortex;and the bilateral stimu-lation group alternatively stimulated bilateral oropharyngeal cortex,with one hour interval between bilateral stim-ulation;the sham stimulation group stimulated the healthy side of oropharyngeal cortex for 30 seconds and then stop.The course lasted two weeks.The scores of Standard Swallowing Function Assessment Scale(SSA),Modi-fied Mann Assessment of Swallowing Ability(MMASA)and Rosenbek Penetration-Aspiration Scale(PAS)were compared before and after treatment.Results The intra-group effect(F=16.185,P<0.01)was significant in the scores of SSA,the intra-group effect(F=28.650,P<0.01)and interaction effect(F=3.453,P<0.01)were significant in the scores of MMASA,and there was no significant difference in the inter-group effect,intra-group effect and interaction effect in the scores of PAS(P>0.05).Post hoc test showed that there was no significant difference in the scores of SSA,MMASA and PAS among three groups(P>0.05).There was significant difference in the score difference of MMASA be-fore and after treatment among three groups(F=4.698,P<0.05).Post hoc test showed that the score difference of MMAS was more in the healthy side stimulation group than in the bilateral stimulation group and the sham stimulation group(P<0.05),with no significant difference between the bilateral stimulation group and the sham stimulation group(P>0.05).Conclusion tDCS can partly improve post-stroke dysphagia.The healthy side anode stimulation is superior to the alter-nating bilateral hemisphere anode stimulation.
8.Researchon the training model of innovative talents in traditional Chinese medicine with the integration of science and education in local high-level universities
Lanwen GAO ; Ye GAO ; Ronghua ZHANG ; Li YANG ; Huan WANG ; Xiaoyun LI ; Lingyu LI ; Yu CAI
Modern Hospital 2024;24(1):127-129
Traditional Chinese Medicine has a long history and plays a decisive role in the fields of modern medicine and pharmacy.It is an important part of our country's traditional medicine.With the progress of the times,people are paying more and more attention to the innovation and development of traditional Chinese medicine.However,the current traditional Chinese medicine talents trained by major universities cannot meet the needs and requirements of society.This is closely related to the current talent training model of universities.Local high-level universities have unique advantages and potential in cultivating inno-vative talents in traditional Chinese medicine.They can incorporate traditional Chinese medicine culture with local characteristics into the teaching content and practical links of training traditional Chinese medicine talents,and build innovative traditional Chi-nese medicine talents integrating science and education.The training model is more conducive to cultivating top innovative talents that meet the needs of society and and the development of traditional Chinese medicine.This article analyzes and discusses how local high-level universities can develop innovative talent training models that suit the needs of traditional Chinese medicine by combining local characteristics and disciplinary advantages,so as to provide useful reference and inspiration for local high-level u-niversities in cultivating talents in traditional Chinese medicine.
9.Mechanism of protopanaxatriol attenuating paclitaxel resistance in MDA-MB-231 cells
Lingyu LI ; Qianyun YE ; Yan LI ; Li HAN ; Panpan WANG ; Ronghua ZHANG
Chinese Journal of Pathophysiology 2024;40(5):796-805
AIM:To investigate the effect of protopanaxatriol(PPT)on the drug resistance of paclitaxel(PTX)-resistant human breast cancer MDA-MB-231 cells(MB231-PR cells).METHODS:The MB231-PR cells were constructed as cell models.They were treated with PPT,and incubated for a certain period of time according to the experi-mental settings.CellTiter-Glo was used to determine the viability of MB231-PR cells and MDA-MB-231 parental cells(MB231-PT cells).The change of sub-G1 phase was detected by flow cytometry.Western blot was used to evaluate the apoptosis-related proteins,such as cleaved caspase-3,cleaved poly(ADP-ribose)polymerase(PARP),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and survivin.The activity of nuclear factor-κB(NF-κB)was detected by lu-ciferase reporter assay and immunofluorescence assay.The mRNA expression levels of interleukin-6(IL-6),IL-8,chemo-kine CXC motif ligand 1(CXCL1),chemokine CC motif ligand 2(CCL2),CD44,NANOG,octamer-binding transcrip-tion factor 4(OCT4),sex-determining region Y-box 2(SOX2)and aldehyde dehydrogenase 1(ALDH1)were detected by qPCR.The protein levels of IL-6 and IL-8 were measured by ELISA.Tumor sphere formation assay was used to evaluate the characteristics of stem cells.RESULTS:(1)The viability of MB231-PR cells was suppressed by PPT treatment in a dose-dependent manner compared with MB231-PT cells(P<0.01).Besides,the viability of MB231-PR cells was de-creased after combined treatment with PPT and PTX(P<0.01),the accumulation of sub-G1 phase was induced(P<0.01),the ratio of Bax/Bcl-2 was elevated(P<0.01),and the protein levels of survivin,cleaved PARP and cleaved cas-pase-3 were increased(P<0.05).(2)After PPT treatment combined with PTX,the mRNA expression of inflammatory cy-tokines(IL-6,IL-8,CXCL1 and CCL2)and cancer stem cell-related markers(OCT4,SOX2,NANOG,ALDH1 and CD44)was reduced(P<0.05),and the protein levels of IL-6 and IL-8 were decreased(P<0.01).The activity of NF-κB in MB231-PR cells was suppressed(P<0.05),and the growth of tumor spheres from MB231-PR cells was damaged(P<0.05).(3)Immunofluorescence assay showed that PTX induced nuclear p-p65 expression,but this effect was attenuated by PPT.CONCLUSION:Combined treatment with PPT and PTX could attenuate PTX resistance of MB231-PR cells by inhibiting inflammatory cytokines and cancer stem cells.
10.Epidemiology and functional outcome of venous thromboembolism after stroke in rehabilitation wards
Xiaoli WU ; Xueyan HU ; Yuge ZHANG ; Changqing YE ; Yudong CHEN ; Hanzhi LI ; Lingyu YANG ; Fei GAO ; Yuqi YANG ; Lei SHAN ; Lixu LIU
Chinese Journal of Rehabilitation Theory and Practice 2022;28(1):44-49
Objective To explore the risk of venous thromboembolism (VTE), especially lower-extremity deep vein thrombosis (DVT) and pulmonary embolism (PE), for stroke patients in rehabilitating, and the functional outcome. Methods A total of 3 557 stroke patients in the neurological rehabilitation center of Beijing Bo'ai Hospital for stroke rehabilitation from January, 2015 to October, 2020 were reviewed through the electronic medical record system. Demographic characteristics, stroke characteristics (type and location), laboratory data (D-dimer polymer and arterial partial pressure of oxygen), motor function (Brunnstrom stage, Fugl-Meyer Assessment of motor and balance, modified Ashworth Scale score of triceps crus, and Holden Walking Ability Classification), activities of daily living (Barthel Index), and anticoagulant/antiplatelet treatment data were collected and analyzed. Results The incidence of DVT and PE was 28.5% and 1.29%, respectively. Most were found 30 days later after onset. The incidence of PE was higher after ischemic stroke (χ2 = 12.49, P < 0.001) rather than hemorrhagic stroke. The patients with hemispheric stroke, severe lower-extremity paralysis, and poor activities of daily living were more prone to complications associated with VTE. After rehabilitation, the function of stroke patients with PE could be improved (|t| > 4.302, P < 0.001). Conclusion The risk of DVT and PE in patients during stroke convalescence may not be negligible, and those with older age, previous history of thrombosis, severe stroke, and severe limb paralysis may be stratified in high-risk. Following anticoagulation treatment, early individualized comprehensive rehabilitation can be done for patients with PE to improve their function and activities of daily living.

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