1.Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagen.
Chuanjing CHENG ; Kaixin LIU ; Jinling ZHANG ; Yanqi HAN ; Tiejun ZHANG ; Yuanyuan HOU ; Gang BAI
Acta Pharmaceutica Sinica B 2025;15(3):1497-1513
Platelets are indispensable for physiological hemostasis and pathological thrombus formation, and platelet adhesion to endothelial collagen is a critical initial step in thrombus formation, often overlooked in current antiplatelet therapies. This study aims to elucidate how ginsenoside CK enhances hemodynamic circulation, alleviates stasis, and proposes therapeutic mechanisms. Inspired by the effects on improving microcirculatory disturbances in an acute soft tissue injury model, CK was identified as a PHD2 inhibitor, effectively suppressing platelet adhesion to collagen. It was proposed that targeting PHD2 regulates collagen hydroxylation modification, thereby influencing the formation of its three-dimensional structure, reducing the binding affinity between VWF and collagen, and ultimately suppressing thrombotic events. The efficacy of this mechanism was subsequently confirmed through a mouse DIC model, demonstrating the feasibility of CK in alleviating circulatory disorders. It is worth noting that when Phd2 was knocked down in mice's lungs, pulmonary embolism was significantly reduced. Additionally, PHD2 inhibitors approved for other diseases have exhibited similar anti-thrombotic effects. Moreover, when PHD2 inhibitors were combined with aspirin, they more effectively inhibited arterial thrombosis in rats. The findings offer valuable insights into potential targets for developing antiplatelet drugs or expanding therapeutic applications for existing PHD2 inhibitors in treating thrombotic diseases.
2.Innovation theory, technical methods and industrial application of quality marker of traditional Chinese medicine.
Tiejun ZHANG ; Gang BAI ; Changxiao LIU
Chinese Herbal Medicines 2025;17(1):84-86
Quality marker (Q-Marker) of traditional Chinese medicine (TCM) is a new concept of TCM quality research. Since it was proposed in 2016, it has aroused wide response from the industry and has become an innovative theory and technical method leading the quality research and quality control of TCM. This paper summarized the core connotation, theoretical basis and innovative value of Q-Marker, proposed the technical strategies and paths of the Q-Marker research, and showed the prospect of its application in the TCM industry. The paper provides references for TCM quality research, quality evaluation, quality control and scientific supervision and has important significance for promoting the quality standard and quality control level of TCM.
3.Exploring the Mechanism of Shaoyao Decoction in Treating Ulcerative Colitis Based on Network Pharmacology,Molecular Docking,and Experimental Studies
Tonghui JIN ; Chaoyue LIU ; Ying WANG ; Han WANG ; Tiejun LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(8):2373-2389
Objective To explore the active components,therapeutic targets,and molecular mechanisms of Shaoyao Decoction in the treatment of ulcerative colitis(UC)using network pharmacology techniques,bioinformatics methods,and experimental approaches.Methods Screening active components of Shaoyao Decoction and predicting their targets using databases such as PubChem,screening HCC-related disease targets through the NCBI database,constructing a PPI network,conducting GO functional enrichment and KEGG pathway analysis to identify potential biological processes and signaling pathways involved,and validating with molecular docking using AutoDock Tools.Forty male C57BL/6J mice were randomly divided into normal,model,Mesalazine,and Shaoyao Tang groups based on body weight.Except for the normal group,all other groups were induced with ulcerative colitis(UC)by providing 2.5%dextran sulfate sodium(DSS)in drinking water for 5 days.After continuous intragastric administration for 7 days,the mice were sacrificed.The levels of cytokines such as IL-2,IL-1β,IL-6,and TNF-α in colon tissues were measured by ELISA,and pathological sections of colon tissue samples were observed.Results The study identified 20 active components and 945 targets of Shaoyao Tang,among which 609 were related to UC.Through PPI network analysis,22 key targets including VEGFA,AKT1,PTGS2,and STAT3 were determined.GO analysis revealed 409 enriched terms,involving negative regulation of inflammatory response to antigenic stimulus,positive regulation of inflammatory response,etc.KEGG analysis discovered 136 significantly enriched pathways,including the NF-κB signaling pathway,Toll-like receptor signaling pathway(related to inflammation and immunity),VEGF signaling pathway,and ErbB signaling pathway(related to cell proliferation and apoptosis).Molecular docking revealed that the active ingredients exhibited strong affinity with target proteins such as IL-6,TNF,TLR4,IL-2,IL-1B,and PTGS2,forming stable conformations.The final ELISA results demonstrated that the levels of multiple inflammatory cytokines in the colon tissue of DSS-induced ulcerative colitis(UC)mouse models were significantly elevated,with notable upregulation of IL-2,IL-1β,IL-6,and TNF-α compared to the normal group(P<0.05).Following drug intervention,both the Mesalazine group and the Shaoyao Decoction group exhibited significant anti-inflammatory effects,effectively reducing the expression levels of the aforementioned inflammatory cytokines in the colon tissue(P<0.05).Notably,compared to the Mesalazine group,Shaoyao Decoction demonstrated a more pronounced regulatory effect on inflammatory cytokines(P<0.05).Conclusion In this study,the innovative integration of network pharmacology prediction,molecular docking validation and key inflammatory factor assay systematically elucidated the"multi-component-multi-target-multi-pathway"anti-inflammatory mode of Paeonia lactiflora broth in the treatment of UC.The experiments demonstrated that Paeonia lactiflora broth could regulate the release of pro-inflammatory cytokines by regulating the levels of IL-2,IL-1β,IL-6,TNF-α cytokines and other related cytokines to reduce the inflammation of the colon and improve the damage of colon tissues in mice with UC.
4.Prone-position MRI of lumbar spine for diagnosing pediatric occult tethered cord syndrome
Jie LI ; Yurong MA ; Wanjun HU ; Na HAN ; Songhong YUE ; Tiejun GAN ; Guangyao LIU ; Shuai YUAN ; Jing ZHANG
Chinese Journal of Medical Imaging Technology 2025;41(10):1641-1645
Objective To investigate the value of prone-position MRI of lumbar spine for diagnosing pediatric occult tethered cord syndrome(OTCS).Methods A total of 67 children with suspected tethered cord syndrome(TCS)and confirmed OTCS by surgery were prospectively enrolled as OTCS group,while 73 healthy subjects were recruited as control group.Supine-and prone-position lumbar MR examinations were performed in both groups.The position of filum terminale on prone axial T2WI and the presence or absence of"sunset sign"(i.e.filum terminale located within the dorsal 1/2 of spinal canal on prone axial T2WI)were observed,spinal cord conus mobility was calculated.The efficacy of"sunset sign"for diagnosing OTCS in children was calculated through comparison between groups.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the diagnostic efficacy of spinal cord conus mobility.Results On prone-position axial T2WI,"sunset sign"was found in 58 cases(58/67,86.57%)but not in 9 cases(9/67,13.43%)in OTCS group,which was not even observed in control group.The sensitivity of"sunset sign"for diagnosing pediatric OTCS was 86.57%(58/67),with specificity of 100%(73/73),positive predictive value of 100%(58/58)and negative predictive value of 89.02%(73/82).The spinal cord conus mobility was(19.30±5.89)%in OTCS group and(31.71±6.58)%in control group,being statistically different between groups(t=-11.722,P<0.001).The sensitivity,specificity and AUC of spinal cord conus mobility for diagnosing pediatric OTCS was 80.60%,90.41%and 0.920,respectively.Conclusion Prone-position MRI of lumbar spine could be used in diagnosing pediatric OTCS.
5.Differences in clinical and laboratory features and survival between Chinese and Western patients with myelodysplastic neoplasm
Linlin LIU ; Bing LI ; Tiejun QIN ; Zefeng XU ; Shiqiang QU ; Lijuan PAN ; Qingyan GAO ; Meng JIAO ; Yujiao JA ; Chenwen LI ; Qi SUN ; Huijun WANG ; Zhijian XIAO
Chinese Journal of Hematology 2025;46(3):223-230
Objective:To compare the clinical and laboratory characteristics and survival between Chinese and Western patients with myelodysplastic neoplasms (MDS) .Methods:Clinical and laboratory data were collected from 1,464 primary adult patients diagnosed with MDS at the Institute of Hematology & Blood Diseases Hospital from August 2016 to June 2024. Collected data were retrospectively analyzed and compared with 2,191 patients from the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM) .Results:Chinese patients were significantly younger (median age: 56 years vs. 72 years, P<0.001) and experienced more severe hematopenia ( P<0.001) compared with patients from the IWG-PM. Further, Chinese patients exhibited a higher percentage of isolated del (20q), +8, and complex karyotypes as well as a lower percentage of normal karyotypes, del (5q), and -Y ( P<0.001). Higher U2AF1, NRAS, and NPM1 mutation rates and lower ASXL1, SF3B1, and RUNX1 mutation rates were observed in Chinese patients than in participants from the IWG-PM ( P<0.05). No significant difference in overall survival (OS) was found between the two groups (median OS: 48 [95% CI: 40 - 56]months, vs. 45[95% CI: 40 - 49] months; P=0.449). Among participants aged ≤45 years, Chinese patients demonstrated more trisomy 8 ( P=0.070) and U2AF1 mutation ( P<0.001) and higher 4-year OS rate compared with those from the IWG-PM (75.5% vs. 62.1%, P=0.001). Among participants aged ≥70 years, Chinese patients exhibited more complex karyotypes but fewer del (5q) as well as more NPM1 but less SF3B1 and TET2 compared with those from the IWG-PM ( P<0.05). Chinese patients demonstrated shorter survival (median OS: 20 [95% CI: 13 - 27] months vs. 37 [95% CI: 32 - 42] months, P<0.001) . Conclusion:Chinese and Western MDS patients differ in age of onset, clinical features, and cytogenetic or molecular genetic abnormalities, with significant differences persisting in age-matched groups. Although the OS is similar, disparities exist in survival for younger and older patients between the two populations.
6.Efficacy and survival outcomes of patients with lymphocytic variant hypereosinophilic syndrome
Shiqiang QU ; Ningning LIU ; Tiejun QIN ; Zefeng XU ; Bing LI ; Lijuan PAN ; Meng JIAO ; Qingyan GAO ; Huijun WANG ; Xiaofei AI ; Zhijian XIAO
Chinese Journal of Hematology 2025;46(7):611-617
Objective:To analyze the clinical characteristics, therapeutic responses, and survival outcomes of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) .Methods:We retrospectively reviewed clinical data from 16 consecutive patients diagnosed with L-HES at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, between July 2019 and October 2024. A control group of 65 patients with idiopathic hypereosinophilic syndrome (iHES), diagnosed during the same period, was used for comparison. Clinical and laboratory characteristics, therapeutic responses, and survival outcomes were compared between the two groups.Results:The most frequently involved organs at presentation in patients with L-HES were the skin (75.0%), gastrointestinal tract (25.0%), respiratory tract (18.8%), lymph nodes (18.8%), heart (12.5%), and spleen (6.3%). Compared with iHES patients, patients with L-HES had a significantly higher incidence of skin involvement ( P=0.016), with no statistically significant differences observed in the involvement of other organs. No statistically significant differences were found in complete blood count parameters between the two groups. Multiparameter flow cytometry revealed that the median percentage of CD3 -CD4 + T cells in the peripheral blood of patients with L-HES was 4.08% ( IQR: 1.64%-32.78%), with a median absolute count of 0.10 (0.05-0.55) ×10 9/L. Serum immunoglobulin E (IgE) levels were significantly higher in the L-HES group than in the iHES group ( P<0.001). Clonal rearrangement of T-cell receptor genes was detected in 75.0% of patients with L-HES. After diagnosis, 14 patients with L-HES received glucocorticoids as first-line therapy, yielding an overall response rate of 92.9%. During glucocorticoid tapering, 11 patients experienced recurrent eosinophilia or worsening of clinical symptoms. Three patients received interferon-alpha as a second-line therapy, with two achieving complete remission. After a median follow-up of 16 months ( IQR: 8-28 months), one patient died of cardiac insufficiency 8 months after diagnosis, and no cases of lymphoma transformation were observed. The 2-year overall survival rate was (91.7±8.0) %, which did not significantly differ from that of the iHES group (96.2±2.6) % ( P=0.746) . Conclusions:Patients with L-HES generally have a favorable prognosis and are often characterized by skin involvement and significantly elevated serum IgE levels at diagnosis. They typically respond well to glucocorticoid therapy, although relapse is common during dose tapering. Interferon-alpha may serve as an effective second-line therapeutic option.
7.Prognostic value of the FS-15 frailty score in patients with myelodysplastic syndromes
Xin WANG ; Tiejun QIN ; Zefeng XU ; Shiqiang QU ; Bing LI ; Lijuan PAN ; Qingyan GAO ; Meng JIAO ; Yue ZHONG ; Binhan JIANG ; Linlin LIU ; Jinying ZHAO ; Wenjun XIE ; Zhijian XIAO
Chinese Journal of Hematology 2025;46(9):806-814
Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.
8.Myelodysplastic neoplasms with acute myeloid leukemia-like mutations: clinical features, molecular profiles, and prognosis
Zefei BAO ; Linlin LIU ; Bing LI ; Tiejun QIN ; Zefeng XU ; Shiqiang QU ; Lijuan PAN ; Qingyan GAO ; Meng JIAO ; Yujiao JIA ; Chengwen LI ; Qi SUN ; Huijun WANG ; Zhijian XIAO
Chinese Journal of Hematology 2025;46(11):997-1004
Objective:To investigate the clinical, laboratory, and prognostic features of myelodysplastic neoplasm (MDS) patients harboring acute myeloid leukemia (AML) -like mutations.Methods:We retrospectively analyzed clinical, molecular, and outcome data from 1 464 adults with primary MDS diagnosed at the Institute of Hematology and Blood Diseases Hospital from August 2016 to June 2024.Results:AML-like mutations were detected in 64 patients (4.4% ). Compared with patients without AML-like mutations, those with AML-like mutations were younger [median 50 ( IQR 39–60) vs 56 (45, 65) years; P=0.001], more often female (51.6% vs 35.4% ; P=0.009), had higher bone marrow blast percentage [6.5% (3.0%, 10.5% ) vs 2.5% (1.0%, 7.0% ) ; P<0.001], a higher rate of normal karyotype (75.0% vs 48.1% ; P<0.001), and lower hemoglobin levels [73 (67, 82) g/L vs 80 (66, 98) g/L; P=0.006]. The AML-like group had a higher number of gene mutations than the non-AML-like group [3 ( IQR 2–4) vs 2 (1, 3) ; P<0.001). It was enriched for mutations in NPM1, DNMT3A, WT1, PTPN11, NRAS, BCOR, FLT3, CEBPA, and MYC (all P<0.05) and had lower rates of U2AF1, ASXL1, and TP53 mutations (all P<0.05). Overall survival (OS) did not differ between groups ( P=0.730) ; however, the AML-like group had significantly shorter leukemia-free survival (LFS) [19 months (95% CI: 13–25) vs 46 months (95% CI: 38–54) ; P=0.012] and a higher 2-year cumulative incidence of AML transformation [ (41.7±9.1) % vs (10.4±1.1) % ; P<0.001]. Within the AML-like group, OS, LFS, and cumulative incidence of AML transformation did not differ between patients with low blasts and those with excess blasts (IB). Multivariable Cox regression identified age ≥60 years and PTPN11 mutations as independent adverse prognostic factors for OS, while DNMT3A, PTPN11, and FLT3 mutations independently predicted leukemic transformation. Conclusions:MDS patients harboring AML-like mutations exhibit distinct clinical and molecular features and a higher risk of progression to AML.
9.Xiao Chaihutang Intervention in Digestive System Tumors: A Review
Ying WANG ; Tonghui JIN ; Yanting SUN ; Tiejun LIU ; Weipeng YANG ; Han WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):257-268
Xiao Chaihutang, originating from the Treatise on Typhoid and Miscellaneous Diseases, is a classic formula for harmonizing the Shaoyang. It excels in regulating the pivotal mechanism and unblocking the triple energizer, corresponding to the pathogenesis of digestive system tumors characterized by the interlocking of deficiency, stasis, phlegm, and toxicity, as well as disharmony between Yin and Yang. This paper systematically reviews research findings from China and abroad over the past decade, exploring the anti-tumor effects of Xiao Chaihutang on digestive system tumors from three dimensions: theoretical rationale, clinical efficacy, and molecular mechanisms. At the level of principle and method, Xiao Chaihutang takes "harmonization" as its core therapeutic guideline. By reconciling the exterior and interior to restore the Shaoyang pivot, harmonizing Yin and Yang to improve the tumor microenvironment, and regulating the liver and spleen to consolidate and protect the foundation of postnatal essence, it promotes the restoration of the body's dynamic balance of Yin and Yang. Clinical studies have demonstrated that Xiao Chaihutang, used alone or in combination with modern medical therapies, shows definite efficacy against digestive system tumors such as hepatocellular carcinoma, pancreatic carcinoma, and gastrointestinal carcinoma. It can significantly improve patients' quality of life, inhibit tumor progression, effectively relieve concomitant symptoms such a s cancer-related fever, anxiety, depression, and insomnia, and alleviate postoperative embolic syndromes as well as adverse reactions to radiotherapy and chemotherapy. Experimental studies have revealed that Xiao Chaihutang can inhibit tumor cell proliferation, induce apoptosis, arrest the cell cycle, suppress tumor cell invasion and metastasis, and improve the tumor microenvironment. Through the above analysis, this study elucidates the current clinical and experimental research status of Xiao Chaihutang in the treatment of digestive system tumors, aiming to provide theoretical support for its precise clinical application. On this basis, it further explores key issues in the identification of pharmacodynamic substances and the accumulation of evidence in evidence-based medicine, thereby offering a new perspective for the innovative development of integrative Chinese and Western medicine in synergistic cancer therapy.
10.Exploring the Mechanism of Shaoyao Decoction in Treating Ulcerative Colitis Based on Network Pharmacology,Molecular Docking,and Experimental Studies
Tonghui JIN ; Chaoyue LIU ; Ying WANG ; Han WANG ; Tiejun LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(8):2373-2389
Objective To explore the active components,therapeutic targets,and molecular mechanisms of Shaoyao Decoction in the treatment of ulcerative colitis(UC)using network pharmacology techniques,bioinformatics methods,and experimental approaches.Methods Screening active components of Shaoyao Decoction and predicting their targets using databases such as PubChem,screening HCC-related disease targets through the NCBI database,constructing a PPI network,conducting GO functional enrichment and KEGG pathway analysis to identify potential biological processes and signaling pathways involved,and validating with molecular docking using AutoDock Tools.Forty male C57BL/6J mice were randomly divided into normal,model,Mesalazine,and Shaoyao Tang groups based on body weight.Except for the normal group,all other groups were induced with ulcerative colitis(UC)by providing 2.5%dextran sulfate sodium(DSS)in drinking water for 5 days.After continuous intragastric administration for 7 days,the mice were sacrificed.The levels of cytokines such as IL-2,IL-1β,IL-6,and TNF-α in colon tissues were measured by ELISA,and pathological sections of colon tissue samples were observed.Results The study identified 20 active components and 945 targets of Shaoyao Tang,among which 609 were related to UC.Through PPI network analysis,22 key targets including VEGFA,AKT1,PTGS2,and STAT3 were determined.GO analysis revealed 409 enriched terms,involving negative regulation of inflammatory response to antigenic stimulus,positive regulation of inflammatory response,etc.KEGG analysis discovered 136 significantly enriched pathways,including the NF-κB signaling pathway,Toll-like receptor signaling pathway(related to inflammation and immunity),VEGF signaling pathway,and ErbB signaling pathway(related to cell proliferation and apoptosis).Molecular docking revealed that the active ingredients exhibited strong affinity with target proteins such as IL-6,TNF,TLR4,IL-2,IL-1B,and PTGS2,forming stable conformations.The final ELISA results demonstrated that the levels of multiple inflammatory cytokines in the colon tissue of DSS-induced ulcerative colitis(UC)mouse models were significantly elevated,with notable upregulation of IL-2,IL-1β,IL-6,and TNF-α compared to the normal group(P<0.05).Following drug intervention,both the Mesalazine group and the Shaoyao Decoction group exhibited significant anti-inflammatory effects,effectively reducing the expression levels of the aforementioned inflammatory cytokines in the colon tissue(P<0.05).Notably,compared to the Mesalazine group,Shaoyao Decoction demonstrated a more pronounced regulatory effect on inflammatory cytokines(P<0.05).Conclusion In this study,the innovative integration of network pharmacology prediction,molecular docking validation and key inflammatory factor assay systematically elucidated the"multi-component-multi-target-multi-pathway"anti-inflammatory mode of Paeonia lactiflora broth in the treatment of UC.The experiments demonstrated that Paeonia lactiflora broth could regulate the release of pro-inflammatory cytokines by regulating the levels of IL-2,IL-1β,IL-6,TNF-α cytokines and other related cytokines to reduce the inflammation of the colon and improve the damage of colon tissues in mice with UC.

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