1.Research progress of nano drug delivery system based on metal-polyphenol network for the diagnosis and treatment of inflammatory diseases
Meng-jie ZHAO ; Xia-li ZHU ; Yi-jing LI ; Zi-ang WANG ; Yun-long ZHAO ; Gao-jian WEI ; Yu CHEN ; Sheng-nan HUANG
Acta Pharmaceutica Sinica 2025;60(2):323-336
Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.
2.Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression
Kepu ZHENG ; Leiyang DAI ; Shengning ZHANG ; Yingpeng ZHAO ; Wang LI ; Yang GAO ; Yuanyi MANG ; Lingfeng JIAO ; Yu TANG ; Jianghua RAN
Gut and Liver 2025;19(3):410-426
Background/Aims:
Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear.
Methods:
This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis.
Results:
Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer.
Conclusions
In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.
3.Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression
Kepu ZHENG ; Leiyang DAI ; Shengning ZHANG ; Yingpeng ZHAO ; Wang LI ; Yang GAO ; Yuanyi MANG ; Lingfeng JIAO ; Yu TANG ; Jianghua RAN
Gut and Liver 2025;19(3):410-426
Background/Aims:
Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear.
Methods:
This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis.
Results:
Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer.
Conclusions
In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.
4.Modified Sini Powder in treating mild to moderate generalized anxiety disorder in patients with syndrome of liver depression transforming into fire: a single-center, randomized, double-blind, dose-controlled trial.
Jia-Xin XU ; Hong-Jun YANG ; Hong-Wei WU ; Li-Jun MAO ; Jian-Xin WANG ; Zong-Liang YU ; Yang ZHAO ; Xiao-Nan HAO ; Rui GAO
China Journal of Chinese Materia Medica 2025;50(14):4063-4070
A single-center, randomized, double-blind, dose-controlled trial of modified Sini Powder in treating mild to moderate generalized anxiety disorder(GAD) in the patients with syndrome of liver depression transforming into fire was conducted at Xiyuan Hospital, China Academy of Chinese Medical Sciences. A total of 80 patients with mild to moderate GAD and the syndrome of liver depression transforming into fire were included. Patients were assigned by the central randomization system at a ratio of 3∶1 into an observation group(n=60, receiving a conventional-dose of granules of modified Sini Powder) and a control group(n=20, receiving low-dose granules with the active ingredients being 50% of that in observation group). Assessments were conducted before treatment(baseline), after 2 weeks of introduction, after 2/4/8 weeks of treatment, and after 4 weeks of follow-up. The results were summarized as follows. In terms of primary outcome indicators, the observation group(62.2%) showed higher total response rate than the control group(26.6%)(P<0.05), and greater Hamilton anxiety scale(HAMA) score reduction after 8 weeks of treatment(P<0.05). In terms of secondary outcome indicators, the HAMA score(somatic anxiety score), traditional Chinese medicine(TCM) syndrome scores, Pittsburgh sleep quality index(PSQI) scale, and clinical global impression(CGI) scale score in the observation group showed a significant compared to the control group at each visit points(P<0.05). Adverse events occurred in 10 cases, including 9(16.9%) cases in the observation group and 1(6.6%) case in the control group. No adverse reaction was observed. In conclusion, conventional-dose modified Sini Powder demonstrated superior efficacy and favorable safety for mild and moderate GAD in the patients with the syndrome of liver depression transforming into fire over low-dose treatment.
Humans
;
Male
;
Female
;
Adult
;
Middle Aged
;
Double-Blind Method
;
Drugs, Chinese Herbal/administration & dosage*
;
Anxiety Disorders/drug therapy*
;
Treatment Outcome
;
Young Adult
;
Powders
;
Aged
;
Liver/drug effects*
;
Generalized Anxiety Disorder
5.Mechanisms of tumor immune microenvironment remodeling in current cancer therapies and the research progress.
Yuanzhen YANG ; Zhaoyang ZHANG ; Shiyu MIAO ; Jiaqi WANG ; Shanshan LU ; Yu LUO ; Feifei GAO ; Jiayue ZHAO ; Yiru WANG ; Zhifang XU
Chinese Journal of Cellular and Molecular Immunology 2025;41(4):372-377
The cellular and molecular components of the tumor immune microenvironment (TIME) and their information exchange processes significantly influence the trends of anti-tumor immunity. In recent years, numerous studies have begun to evaluate TIME in the context of previous cancer treatment strategies. This review will systematically summarize the compositional characteristics of TIME and, based on this foundation, explore the impact of current cancer therapies on the remodeling of TIME, aiming to provide new insights for the development of innovative immune combination therapies that can convert TIME into an anti-tumor profile.
Tumor Microenvironment/immunology*
;
Humans
;
Neoplasms/therapy*
;
Immunotherapy/methods*
;
Animals
6.Prognostic Significance of Endothelial Activation and Stress Index in Mantle Cell Lymphoma.
Xin-Yue ZHOU ; Zhi-Qin YANG ; Jin HU ; Feng-Yi LU ; Qian-Nan HAN ; Huan-Huan ZHAO ; Wen-Xia GAO ; Yu-Han MA ; Hu-Jun LI ; Zhen-Yu LI ; Kai-Lin XU ; Wei CHEN
Journal of Experimental Hematology 2025;33(4):1051-1056
OBJECTIVE:
To investigate the predictive value of endothelial activation and stress index (EASIX) for the prognosis of patients with mantle cell lymphoma (MCL).
METHODS:
A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023, had therapeutic indications and received standard treatment.
RESULTS:
A total of 66 patients were included and divided into high EASIX group and low EASIX group, according to a cutoff value of 0.97 determined by the receiver operating characteristic (ROC) curve. Multivariate Cox regression analysis showed that prealbumin <0.2 g/L, high EASIX, and ECOG PS score ≥2 were independent risk factors influencing overall survival (OS) in MCL patients. The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months, and the median progression-free survival was 8.8 and 26.0 months, respectively. The proportions of patients with ECOG PS score ≥2 and prealbumin <0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.
CONCLUSION
At the time of initial diagnosis, EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL. Furthermore, patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.
Humans
;
Lymphoma, Mantle-Cell/pathology*
;
Prognosis
;
Retrospective Studies
;
Male
;
Female
;
Middle Aged
;
Aged
;
ROC Curve
7.Analysis of Hormone Levels in Patients with Hematological Diseases Before and After Hematopoietic Stem Cell Tansplantation.
Fen LI ; Yu-Jin LI ; Jie ZHAO ; Zhi-Xiang LU ; Xiao-Li GAO ; Hai-Tao HE ; Xue-Zhong GU ; Feng-Yu CHEN ; Hui-Yuan LI ; Qi SA ; Lin ZHANG ; Peng HU
Journal of Experimental Hematology 2025;33(5):1443-1452
OBJECTIVE:
By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage.
METHODS:
The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed.
RESULTS:
After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same.
CONCLUSION
HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans
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Hematopoietic Stem Cell Transplantation
;
Female
;
Male
;
Hematologic Diseases/blood*
;
Follicle Stimulating Hormone/blood*
;
Triiodothyronine/blood*
;
Luteinizing Hormone/blood*
;
Thyroid Gland/metabolism*
;
Estradiol/blood*
;
Thyrotropin/blood*
;
Gonads/metabolism*
;
Adult
;
Middle Aged
;
Adrenocorticotropic Hormone/blood*
;
Hormones/metabolism*
;
Adrenal Cortex/metabolism*
;
Prolactin
8.Mechanism of Reactive Oxygen/Nitrogen Species in Liver Ischemia-Reperfusion Injury and Preventive Effect of Chinese Medicine.
Lei GAO ; Yun-Jia LI ; Jia-Min ZHAO ; Yu-Xin LIAO ; Meng-Chen QIN ; Jun-Jie LI ; Hao SHI ; Nai-Kei WONG ; Zhi-Ping LYU ; Jian-Gang SHEN
Chinese journal of integrative medicine 2025;31(5):462-473
Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy*
;
Reactive Oxygen Species/metabolism*
;
Reactive Nitrogen Species/metabolism*
;
Humans
;
Liver/drug effects*
;
Animals
;
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal/pharmacology*
9.Zedoarondiol Inhibits Neovascularization in Atherosclerotic Plaques of ApoE-/- Mice by Reducing Platelet Exosomes-Derived MiR-let-7a.
Bei-Li XIE ; Bo-Ce SONG ; Ming-Wang LIU ; Wei WEN ; Yu-Xin YAN ; Meng-Jie GAO ; Lu-Lian JIANG ; Zhi-Die JIN ; Lin YANG ; Jian-Gang LIU ; Da-Zhuo SHI ; Fu-Hai ZHAO
Chinese journal of integrative medicine 2025;31(3):228-239
OBJECTIVE:
To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment.
METHODS:
ApoE-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation.
RESULTS:
Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36.
CONCLUSION
Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals
;
MicroRNAs/genetics*
;
Exosomes/drug effects*
;
Plaque, Atherosclerotic/genetics*
;
Neovascularization, Pathologic/genetics*
;
Human Umbilical Vein Endothelial Cells/metabolism*
;
Humans
;
Blood Platelets/drug effects*
;
Apolipoproteins E/deficiency*
;
Thrombospondin 1/metabolism*
;
CD36 Antigens/metabolism*
;
Platelet Activation/drug effects*
;
Male
;
Mice
;
Mice, Inbred C57BL
10.Shexiang Tongxin Dropping Pill Improves Stable Angina Patients with Phlegm-Heat and Blood-Stasis Syndrome: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.
Ying-Qiang ZHAO ; Yong-Fa XING ; Ke-Yong ZOU ; Wei-Dong JIANG ; Ting-Hai DU ; Bo CHEN ; Bao-Ping YANG ; Bai-Ming QU ; Li-Yue WANG ; Gui-Hong GONG ; Yan-Ling SUN ; Li-Qi WANG ; Gao-Feng ZHOU ; Yu-Gang DONG ; Min CHEN ; Xue-Juan ZHANG ; Tian-Lun YANG ; Min-Zhou ZHANG ; Ming-Jun ZHAO ; Yue DENG ; Chang-Jiang XIAO ; Lin WANG ; Bao-He WANG
Chinese journal of integrative medicine 2025;31(8):685-693
OBJECTIVE:
To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents.
METHODS:
This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs).
RESULTS:
This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed.
CONCLUSION
STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans
;
Double-Blind Method
;
Drugs, Chinese Herbal/adverse effects*
;
Male
;
Female
;
Middle Aged
;
Angina, Stable/physiopathology*
;
Aged
;
Syndrome
;
Treatment Outcome
;
Placebos
;
Tablets

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