1.Rho/ROCK:key Mediator of Pulmonary Fibrosis and New Target of TCM for IPF Prevention and Treatment
Yuanyuan WU ; Kangchen LI ; Mingyan LI ; Xiling PENG ; Feifan ZHANG ; Han LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):256-265
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by dyspnea and progressive deterioration of lung function, which significantly impacts patients' quality of life and imposes a major burden on society. Although modern medicine has increasingly enriched the treatment options for pulmonary fibrosis, unfavorable factors such as high costs and significant side effects contribute to the persistently low survival rate of patients. Studies have shown that the occurrence and development of pulmonary fibrosis are closely related to abnormalities in multiple pathways. Among these, Rho/Rho-associated coiled-coil protein kinase (ROCK) plays a key role in the disease progression of IPF by regulating the cytoskeleton. This pathway not only transmits biochemical molecular signals that promote the progress of fibrosis but also responds to the biomechanical environment, such as the increased lung tissue stiffness caused by the deposition of extracellular matrix (ECM) during the process of pulmonary fibrosis. Therefore, research on this pathway is of great significance for the prevention and treatment of IPF. In recent years, traditional Chinese medicine (TCM) has shown remarkable effects in preventing and treating IPF. Many TCM compounds and active components can reduce the production of α-smooth muscle actin (α-SMA), CollagenⅠ (ColⅠ), ColⅢ, and inflammatory factors in lung tissue by regulating the Rho/ROCK signaling pathway. These compounds inhibit the transformation of fibroblasts (FBs) into myofibroblasts (MyoFBs), intervening in the process of pulmonary fibrosis. Based on this, the article briefly reviews relevant research from recent years, discusses the key role of the Rho/ROCK pathway in pulmonary fibrosis from an interdisciplinary perspective, and summarizes the mechanisms through which TCM regulates Rho/ROCK to prevent and treat IPF, based on resources from PubMed, CNKI, and other databases, in order to provide important references for the broader clinical application of TCM in the prevention and treatment of IPF.
2.Neutrophil activation is correlated with acute kidney injury after cardiac surgery under cardiopulmonary bypass
Tingting WANG ; Yuanyuan YAO ; Jiayi SUN ; Juan WU ; Xinyi LIAO ; Wentong MENG ; Min YAN ; Lei DU ; Jiyue XIONG
Chinese Journal of Blood Transfusion 2025;38(3):358-367
[Objective] To explore the relationship between neutrophil activation under cardiopulmonary bypass (CPB) and the incidence of cardiac surgery-associated acute kidney injury (CS-AKI). [Methods] This prospective cohort study enrolled adult patients who scheduled for cardiac surgery under CPB at West China Hospital between May 1, 2022 and March 31, 2023. The primary outcome was acute kidney injury (AKI). Blood samples (5 mL) were obtained from the central vein before surgery, at rewarming, at the end of CPB, and 24 hours after surgery. Neutrophils were labeled with CD11b, CD54 and other markers. To assess the effect of neutrophils activation on AKI, propensity score matching (PSM) was employed to equilibrate covariates between the groups. [Results] A total of 120 patients included into the study, and 17 (14.2%) developed AKI. Both CD11b+ and CD54+ neutrophils significantly increased during the rewarming phase and the increases were kept until 24 hours after surgery. During rewarming, the numbers of CD11b+ neutrophils were significantly higher in AKI compared to non-AKI (4.71×109/L vs 3.31×109/L, Z=-2.14, P<0.05). Similarly, the CD54+ neutrophils counts were also significantly higher in AKI than in non-AKI before surgery (2.75×109/L vs 1.79×109/L, Z=-2.99, P<0.05), during rewarming (3.12×109/L vs 1.62×109/L, Z=-4.34, P<0.05), and at the end of CPB (4.28×109/L vs 2.14×109/L, Z=-3.91, P<0.05). An analysis of 32 matched patients (16 in each group) revealed that CD11b+ and CD54+ neutrophil levels of AKI were 1.74 folds (4.83×109/L vs 2.77×109/L, Z=-2.72, P<0.05) and 2.34 folds (3.32×109/L vs 1.42×109/L, Z=-4.12, P<0.05), respectively, of non-AKI at rewarming phase. [Conclusion] Neutrophils are activated during CPB, and they can be identified by CD11b/CD54 markers. The activated neutrophils of AKI patients are approximately 2 folds of non-AKI during the rewarming phase, with disparity reached peak between groups during rewarming. These findings suggest the removal of 50% of activated neutrophils during the rewarming phase may be effective to reduce the risk of AKI.
3.Clinical observation on Jiu-Wei-Yong-An granule combined with cetirizine in the treatment of eczema with damp-heat accumulation of skin syndrome
Yuanyuan MENG ; Yunyang WU ; Tingru CHEN ; Qinwufeng GU ; Yanlong YANG
Journal of Pharmaceutical Practice and Service 2025;43(6):298-302
Objective To observe the clinical effect of Jiu-Wei-Yong-An granule combined with cetirizine in the treatment of damp-heat accumulation syndrome of eczema. Methods 108 eczema patients with syndrome of damp-heat accumulated in the skin, treated in the Department of Traditional Chinese Surgery in the First Affiliated Hospital of Naval Medical University from December 2021 to March 2023, were selected. They were randomly divided into an observation group and a control group, 54 cases in each. Both groups took cetirizine tablets orally for basic treatment. The observation group was given Jiu-Wei-Yong-An granules, and the control group was given placebos of the same. The clinical efficacy before and after treatment in the two groups was observed and compared, including TCM syndrome scores, eczema area and severity index (EASI), visual analogue scale (VAS), and adverse reactions. Results After treatment, the total effective rate of the observation group (88.9%) was higher than that of the control group (77.8%), and the difference was statistically significant (P<0.05). After treatment, the TCM syndrome score, EASI and VAS in the observation group were significantly lower than those in the control group (P<0.05), and the difference was statistically significant. There was no significant difference in the total rate of adverse reactions between the two groups (P>0.05). Conclusion The combination of Jiu-Wei-Yong-An granules and cetirizine tablets in the treatment of damp-heat eczema showed significantly better clinical outcomes in the observation group compared to the control. It effectively improved patient conditions, reduced skin lesion areas, and alleviated itching, with both safety and efficacy that merit clinical promotion.
4.Meta-analysis of external treatment by Traditional Chinese Medicine for skin pruritus induced by eczema
Tingru CHEN ; Qinwufeng GU ; Yunyang WU ; Yuanyuan MENG ; Yanlong YANG ; Ruimin LI
Journal of Pharmaceutical Practice and Service 2025;43(8):383-389
Objective To evaluate the clinical efficacy of Traditional Chinese Medicine (TCM)external treatment methods in alleviating skin pruritus caused by eczema through a Meta-analysis. Methods Randomized clinical trials investigating the use of TCM external treatment methods for skin pruritus caused by eczema were searched in databases including China National Knowledge Infrastructure (CNKI), VIP, Wanfang, Sinomed, PubMed, Embase, LILACS, and Cochrane, up to December 2024. Two reviewers independently screened and entered the statistical data, conducted bias risk assessment by the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0, and performed Meta-analysis using RevMan 5.4.1. Results Ultimately, 14 studies involving 1 788 patients were included. Compared to the control group, TCM external treatment methods (treatment group)showed better improvement in pruritus scores (Z=11.88, P<0.000 01), better improvement in Eczema Area and Severity Index (EASI) scores (Z=23.15, P<0.000 01), higher overall clinical efficacy rate (Z=6.21, P<0.000 01), better improvement in TCM symptoms (Z=5.49, P<0.000 01), and lower clinical recurrence rate (Z=2.88, P=0.004). Three of the included studies mentioned adverse reactions, with the treatment group showing lower adverse reactions than the control group. Conclusion The external treatment of TCM was more effective in treating skin pruritus caused by eczema compared to the control group. Given the biases and heterogeneity in the included literature, this conclusion needs to be further substantiated by more large-scale, multi-center, randomized, controlled, and double-blind studies.
5.Mechanism of Tumor T Cell Exhaustion from Perspective of ''Sanjiao-Yingwei'' Qi Transformation Malfunction
Xinhao TANG ; Bowen CHU ; Yuanyuan QIN ; Yeling LIU ; Xinyan SHU ; Mianhua WU ; Gang YIN ; Jianguo DAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):176-185
In order to promote the innovative application of Sanjiao theory and Yingwei theory, this paper tries to apply the ''Sanjiao-Yingwei'' Qi transformation theory to the treatment of tumor diseases, integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of ''Sanjiao-Yingwei'' Qi transformation and T cell exhaustion. The ''Sanjiao-Yingwei'' Qi transformation function is closely related to the immunometabolic ability of the human body, and the ''Sanjiao-Yingwei'' Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment. Cancer toxicity is generated by the fuzzy Sanjiao Qi, and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion, which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment. Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis, which contributes to T cell exhaustion and is correlated with nutrient deprivation, lipid accumulation, and high lactate levels in the immunosuppressed tumor microenvironment, as well as with the release of transforming growth factor-β and upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment. Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism. Guizhi decoction, Shengming decoction, and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating ''Sanjiao-Yingwei'' Qi transformation, and hypoxia inducible factor-1α (HIF-1α) may be one of the main pathways to correct T cell exhaustion. It was found that HIF-1α may be one of the important prognostic indicators in common tumors by bioinformatics. The use of the ''Sanjiao-Yingwei'' Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.
6.Screening of characteristic genes in early-onset pre-eclampsia and analysis of their association with immune cell infiltration based on bioinformatics analysis and machine-learning algorithms
Zitong WU ; Yuanyuan ZHENG ; Xin DING
Chinese Journal of Perinatal Medicine 2024;27(1):51-61
Objective:To screen the characteristic genes of early-onset pre-eclampsia (EOSP) and to analyze their association with immune cell infiltration based on bioinformatics analysis and machine learning methods.Methods:In the Gene Expression Omnibus (GEO) database, the mRNA sequences of placental tissues from women with EOSP and normal pregnancy were retrieved using the term "early-onset pre-eclampsia". The R language was used for background correction, standardization, summarization, and probe quality control. Annotation packages were downloaded for ID conversion and the expression matrices were extracted. The differentially expressed genes (DEGs) between the EOSP and the normal pregnancy in the metadata were analyzed after correcting for batch effects using the limma package. Characteristic genes were identified through the support vector machine (SVM) -recursive feature elimination (RFE) method and the LASSO regression model. The area under the curve (AUC) was calculated to judge the diagnostic efficiency of the characteristic genes. Placental tissues were retrospectively collected for verification from 15 patients with EOSP and 15 with normal pregnancy who were delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 1, 2022, to February 28, 2023. The expression of characteristic genes was verified using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, which were further validated in the validation dataset. Finally, the CIBERSORT algorithm was used to analyze the relative proportion of infiltrating immune cell in EOSP. A t-test was used for differential analysis. Results:Three gene datasets were downloaded, including GSE44711 (eight cases each for EOSP and normal pregnancy), GSE74341 (seven cases for EOSP and five cases for normal pregnancy), and GSE190639 (13 cases each for EOSP and normal pregnancy). A total of 29 DEGs were screened after combining the GSE44711 and GSE74341 datasets, including 27 upregulated and two downregulated genes. Gene ontology enrichment analysis showed that these genes are mainly involved in the secretion of gonadotropins, female pregnancy, regulation of endocrine processes, secretion of endocrine hormones, and negative regulation of hormone secretion. Eight characteristic genes ( EBI3, HTRA4, TREML2, TREM1, NTRK2, ANKRD37, CST6, and ARMS2) were screened using the LASSO regression algorithm combined with SVM-RFE algorithm and the expression differences of these characteristic genes were verified as statistically significant by qRT-PCR and Western blot (all P<0.05, except for CST6). Logistic regression algorithm showed that the AUC (95% CI) of TREML2, ANKRD37, NTRK2, TREM1, HTRA4, EBI3, and ARMS2 were 0.979 (0.918-1.000), 0.969 (0.897-1.000), 0.969 (0.892-1.000), 0.979 (0.918-1.000), 0.990 (0.954-1.000), 0.990 (0.954-1.000), and 0.903 (0.764-1.000). Immune cell infiltration analysis indicated that the infiltration ratio of M2 macrophages in the placental tissue from EOSP was significantly lower than that in the normal pregnancy (0.167±0.074 vs. 0.462±0.091, P=0.002), but the infiltration ratios of monocytes and eosinophils were significantly higher (0.201±0.004 vs. 0.085±0.006; 0.031±0.001 vs. 0.001±0.000, both P<0.05). The correlation analysis between characteristic genes and infiltrating immune cells found that the seven characteristic genes were closely related to the immune cells (all P<0.05). Conclusion:Seven characteristic genes that are critical for the prediction and early diagnosis of EOSP are screened using bioinformatics analysis and machine-learning algorithms in this study, which provides new research targets and a basis for the prevention and treatment of preeclampsia in the future.
7.Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses.
Liping BAI ; Jin YANG ; Siting YU ; Zhongzheng XIANG ; Yuanyuan ZENG ; Meiling SHEN ; Xiaorong KOU ; Qinjie WU ; Changyang GONG
Acta Pharmaceutica Sinica B 2024;14(2):821-835
Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.
8.Investigation on pathogenic characteristics of hand, foot and mouth disease cases and enterovirus 71 antibody levels in healthy people in Xi'an in 2022
Zerun XUE ; Hailong CHEN ; Quanli DU ; Yuewen HAN ; Shuling LI ; Yuanyuan DUAN ; Rui WU
Journal of Public Health and Preventive Medicine 2024;35(5):134-137
Objective To analyze the pathogenic composition of hand, foot and mouth disease (HFMD) cases and the antibody level of enterovirus 71 (EV-A71) in healthy people in Xi'an in 2022, so as to provide evidence for the prevention and control of HFMD. Methods Anal swabs or stool specimens of HFMD cases were collected. RT-PCR was used to detect enterovirus (EV) and serotype was identified. Enzyme-linked immunosorbent assay (ELISA) was used to detect EV-A71 IgG antibody levels in healthy people. Results A total of 172 positive cases were detected from 274 HFMD clinical specimens with a total detection rate of 62.77%, including 1 case of EV-A71 (0.58%), 95 cases of CV-A16 (55.23%), 64 cases of CV-A6 (37.21%), and 1 case of CV-A10(0.58%). CV-A16 was the dominant pathogen in spring and summer, and CV-A6 was the dominant pathogen in autumn and winter(χ2= 64.376,P<0.001). The age of HFMD cases caused by CV-A16 was older than the cases caused by CV-A6(t = 2.709,P = 0.007). The positive rate of EV-A71 IgG antibodies in healthy people was 36.92% (168/455). The positive rate of EV-A71 IgG antibodies in men (32.35%) was lower than that in women (43.72%), and the difference was statistically significant (χ2= 6.605 , P = 0.014). The positive rate of EV-A71 IgG antibodies in people of all ages ranged from 21.95% to 54.78%, and the difference was statistically significant (χ2= 27.623 , P<0.001). Conclusion The main pathogens of hand, foot and mouth disease in Xi'an in 2022 are CV-A16 and CV-A6 . The positive rate of EV-A71 IgG antibodies in children under 5 years old is low , and EV-A71 vaccination should be strengthened.
9.Investigation of occupational health of nuclear medicine radiation workers in Jiangsu Province, China, 2023
Wei CHEN ; Shihao WU ; Xindi WEI ; Xiangyong FAN ; Yuanyuan ZHOU ; Yuji MIAO ; Yeqing GU ; Jinhan WANG ; Zhili XIA ; Zihao ZHANG ; Jin WANG
Chinese Journal of Radiological Health 2024;33(5):542-548
Objective To investigate the basic situation and occupational health conditions of nuclear medicine radiation workers in Jiangsu Province based on the research protocol developed by the Institute of Radiation Medicine, Chinese Academy of Medical Sciences for the nationwide study on the health effects of nuclear medicine radiation in China, understand the impact of occupational radiation on the physical health of nuclear medicine radiation workers, and provide a basis for improving the occupational protection of nuclear medicine radiation workers and reducing the risk of occupational radiation-related health issues. Methods A census approach was used to collect general data and occupational health information of nuclear medicine radiation workers in Jiangsu Province. The analysis focused on the abnormalities in physical examination indicators among radiation workers of different genders, ages, and working years to evaluate the health effects of occupational radiation exposure. Results The occupational health examination data of 472 nuclear medicine radiation workers were collected from 76 medical institutions in Jiangsu Province. The results showed that the detection rate of abnormal hypothyroidism in female workers (8.90%) was higher than that in male workers (2.54%) (P=0.028). With increasing working years, the detection rates of cataract and continuous decrease in white blood cell count increased (P<0.001). The multivariate logistic regression identified working years as a risk factor for cataract and continuous decrease in white blood cell count (OR=1.59, 95%CI=1.40-3.35, P=
10.Investigation of occupational health of nuclear medicine radiation workers in Jiangsu Province, China, 2023
Wei CHEN ; Shihao WU ; Xindi WEI ; Xiangyong FAN ; Yuanyuan ZHOU ; Yuji MIAO ; Yeqing GU ; Jinhan WANG ; Zhili XIA ; Zihao ZHANG ; Jin WANG
Chinese Journal of Radiological Health 2024;33(5):542-548
Objective To investigate the basic situation and occupational health conditions of nuclear medicine radiation workers in Jiangsu Province based on the research protocol developed by the Institute of Radiation Medicine, Chinese Academy of Medical Sciences for the nationwide study on the health effects of nuclear medicine radiation in China, understand the impact of occupational radiation on the physical health of nuclear medicine radiation workers, and provide a basis for improving the occupational protection of nuclear medicine radiation workers and reducing the risk of occupational radiation-related health issues. Methods A census approach was used to collect general data and occupational health information of nuclear medicine radiation workers in Jiangsu Province. The analysis focused on the abnormalities in physical examination indicators among radiation workers of different genders, ages, and working years to evaluate the health effects of occupational radiation exposure. Results The occupational health examination data of 472 nuclear medicine radiation workers were collected from 76 medical institutions in Jiangsu Province. The results showed that the detection rate of abnormal hypothyroidism in female workers (8.90%) was higher than that in male workers (2.54%) (P=0.028). With increasing working years, the detection rates of cataract and continuous decrease in white blood cell count increased (P<0.001). The multivariate logistic regression identified working years as a risk factor for cataract and continuous decrease in white blood cell count (OR=1.59, 95%CI=1.40-3.35, P=


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