1.Residual Inflammatory Risk and Intracranial Atherosclerosis Plaque Vulnerability: Insights From High-Resolution Magnetic Resonance Imaging
Ying YU ; Rongrong CUI ; Xin HE ; Xinxin SHI ; Zhikai HOU ; Yuesong PAN ; Mingyao LI ; Jiabao YANG ; Zhongrong MIAO ; Yongjun WANG ; Rong WANG ; Xin LOU ; Long YAN ; Ning MA
Journal of Stroke 2025;27(2):207-216
Background:
and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS).
Methods:
This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement.
Results:
Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage.
Conclusion
In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.
2.Residual Inflammatory Risk and Intracranial Atherosclerosis Plaque Vulnerability: Insights From High-Resolution Magnetic Resonance Imaging
Ying YU ; Rongrong CUI ; Xin HE ; Xinxin SHI ; Zhikai HOU ; Yuesong PAN ; Mingyao LI ; Jiabao YANG ; Zhongrong MIAO ; Yongjun WANG ; Rong WANG ; Xin LOU ; Long YAN ; Ning MA
Journal of Stroke 2025;27(2):207-216
Background:
and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS).
Methods:
This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement.
Results:
Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage.
Conclusion
In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.
3.Residual Inflammatory Risk and Intracranial Atherosclerosis Plaque Vulnerability: Insights From High-Resolution Magnetic Resonance Imaging
Ying YU ; Rongrong CUI ; Xin HE ; Xinxin SHI ; Zhikai HOU ; Yuesong PAN ; Mingyao LI ; Jiabao YANG ; Zhongrong MIAO ; Yongjun WANG ; Rong WANG ; Xin LOU ; Long YAN ; Ning MA
Journal of Stroke 2025;27(2):207-216
Background:
and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS).
Methods:
This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement.
Results:
Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage.
Conclusion
In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.
4.Historical Evolution and Modern Clinical Application of Huoxiang Zhengqisan
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Cuicui SHEN ; Congcong LI ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG ; Yawei YAN ; Chunyong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):156-167
In this study, bibliometric methods were used to systematically investigate the name and origin, the evolution of prescription composition, dose evolution, origin and processing method, decoction method, ancient application, modified application, modern application and other information of Huoxiang Zhengqisan. After research, Huoxiang Zhengqisan, also known as Huoxiang Zhengqitang, was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium, 41.3 g of Angelicae Dahuricae Radix, 41.3 g of Perilla frutescens(actually Perillae Folium), 41.3 g of Poria, 82.6 g of Pinelliae Rhizoma, 82.6 g of Atractylodis Macrocephalae Rhizoma, 82.6 g of Citri Reticulatae Pericarpium(actually Citri Exocarpium Rubbum), 82.6 g of Magnoliae Officinalis Cortex, 82.6 g of Platycodonis Radix, 123.9 g of Pogostemonis Herba, and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula, Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products, Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products, and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose, take 8.26 g of the powdered formula, add 300 mL of water, along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus, and decoct until reduced to 140 mL. The decoction should be administered hot, with three times daily. To induce sweating, the patient should be kept warm under a quilt, and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness, regulate Qi and harmonize the middle, which is mainly used to treat a series of diseases of digestive and respiratory systems. However, potential adverse reactions, including allergies, purpura and disulfiram-like reactions, should be considered during clinical use. Huoxiang Zhengqisan features a rational composition, extensive clinical application, and strong potential for further research and development.
5.Historical Evolution and Modern Clinical Application of Huoxiang Zhengqisan
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Cuicui SHEN ; Congcong LI ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG ; Yawei YAN ; Chunyong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):156-167
In this study, bibliometric methods were used to systematically investigate the name and origin, the evolution of prescription composition, dose evolution, origin and processing method, decoction method, ancient application, modified application, modern application and other information of Huoxiang Zhengqisan. After research, Huoxiang Zhengqisan, also known as Huoxiang Zhengqitang, was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium, 41.3 g of Angelicae Dahuricae Radix, 41.3 g of Perilla frutescens(actually Perillae Folium), 41.3 g of Poria, 82.6 g of Pinelliae Rhizoma, 82.6 g of Atractylodis Macrocephalae Rhizoma, 82.6 g of Citri Reticulatae Pericarpium(actually Citri Exocarpium Rubbum), 82.6 g of Magnoliae Officinalis Cortex, 82.6 g of Platycodonis Radix, 123.9 g of Pogostemonis Herba, and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula, Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products, Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products, and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose, take 8.26 g of the powdered formula, add 300 mL of water, along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus, and decoct until reduced to 140 mL. The decoction should be administered hot, with three times daily. To induce sweating, the patient should be kept warm under a quilt, and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness, regulate Qi and harmonize the middle, which is mainly used to treat a series of diseases of digestive and respiratory systems. However, potential adverse reactions, including allergies, purpura and disulfiram-like reactions, should be considered during clinical use. Huoxiang Zhengqisan features a rational composition, extensive clinical application, and strong potential for further research and development.
6.Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.
Shuo ZHANG ; Hong-Jin LI ; Chun-Mei YANG ; Liu LIU ; Xiao-Ying SUN ; Jiao WANG ; Si-Ting CHEN ; Yi LU ; Man-Qi HU ; Ge YAN ; Ya-Qiong ZHOU ; Xiao MIAO ; Xin LI ; Bin LI
Chinese journal of integrative medicine 2024;30(3):222-229
OBJECTIVE:
To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.
METHODS:
Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.
RESULTS:
TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).
CONCLUSIONS
TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male
;
Animals
;
Mice
;
Tripterygium
;
Psoriasis/drug therapy*
;
Keratinocytes
;
Skin Diseases/metabolism*
;
Cytokines/metabolism*
;
Imiquimod/metabolism*
;
Dermatitis/pathology*
;
Disease Models, Animal
;
Mice, Inbred BALB C
;
Skin/metabolism*
7.Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer.
Dandan LING ; Xueli JIA ; Ke WANG ; Qiucheng YAN ; Bochuan YUAN ; Lina DU ; Miao LI ; Yiguang JIN
Acta Pharmaceutica Sinica B 2024;14(1):365-377
Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.
8.Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure.
Jiawen ZHOU ; Xinyue SUN ; Xuelian CHEN ; Huimin LIU ; Xiulian MIAO ; Yan GUO ; Zhiwen FAN ; Jie LI ; Yong XU ; Zilong LI
Acta Pharmaceutica Sinica B 2024;14(1):256-272
Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.
9.Role of Flavonoids in Traditional Chinese Medicine to Improve Cerebral Ischaemia-reperfusion Injury and Its Mechanism: A Review
Lu YUE ; Tianbao ZHOU ; Xiangli YAN ; Mingsan MIAO ; Yan LI ; Ming BAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):269-279
Cerebral ischemia-reperfusion injury (CIRI) has a very high incidence, disability, and mortality rates, which seriously affects human life and health. In recent years, modern medicine has made some progress in the diagnosis and treatment of CIRI, but there are still problems such as difficulties in postoperative rehabilitation and adverse drug reactions, and new therapeutic drugs for CIRI are urgently needed. As an important class of active ingredients in traditional Chinese medicine, flavonoids can play antioxidant, apoptosis inhibition, anti-inflammatory, and other pharmacological effects to improve brain tissue damage, which is important for improving the quality of life of CIRI patients and slowing down the aging of the social population. Numerous studies have found that flavonoids in traditional Chinese medicine can regulate cell surface receptors Toll-like receptor 4/nuclear factor-kappaB (TLR4/NF-κB), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), adenylate-activated protein kinase/mammalian target of rapamycin protein (AMPK/mTOR), Ras homologous gene family member A/Rho-associated coiled-coil protein kinase (RhoA/ROCK), nuclear factor E2-associated factor 2/Kelch-like epoxychloropropane-associated protein-1/haemoglobin oxygenase 1 (Nrf2/Keap1/ HO-1), Notch, and other signaling pathways, so as to regulate the transcription and expression of related proteins after CIRI, alleviate brain tissue injury, and improve CIRI. This paper analyzed the relevant literature in China and abroad in recent years, reviewed the mechanism of action and related pathways of flavonoids in traditional Chinese medicine to improve CIRI, and explored the new therapeutic direction of CIRI at the metabolic level, with a view to providing a basis for the further development and application of flavonoids in traditional Chinese medicine.
10.Repeatability of wavefront aberration measured by adaptive optics visual simulator and agreement of OPD-Scan Ⅲ
Yan WANG ; Xuan LIAO ; Changjun LAN ; Biao LI ; Zhuang MIAO ; Qingqing TAN ; Suyun QIN ; Huan HUANG
International Eye Science 2024;24(5):810-815
AIM: To assess the repeatability and agreement of higher-order aberration obtained by adaptive optics visual simulator(VAO)compared with OPD-Scan Ⅲ.METHODS: A cross-sectional study was conducted from August to September 2023, including a total of 204 patients(204 eyes)with myopia whose right eyes were measured. The examinations were performed by the same skilled examiner using both devices separately. The VAO device was used to measure higher order aberrations of orders 3 to 6 at a pupil diameter of 4.5 mm, while both the VAO and OPD-Scan Ⅲ devices were utilized to measure total higher-order aberration(tHOA), spherical aberration(SA), coma aberration(Coma), and trefoil aberration(Trefoil)of the entire eye at pupil diameters ranging from 3 to 6 mm. Furthermore, the repeatability of whole eye aberration measurements obtained with the VAO device was evaluated and the agreement of the two devices was assessed.RESULTS: The whole-eye higher-order aberrations measured by VAO demonstrated excellent repeatability(0.767≤ICC≤0.941, Sw<0.01 μm, TRT<0.1 μm). There was no statistically significant difference in Coma measured by VAO or OPD-Scan Ⅲ for pupil diameters ranging from 4 to 6 mm(P>0.05), while a statistically significant difference was observed in whole-eye tHOA of other pupil diameters(all P<0.05). The agreement of aberration measurements for each order between VAO and OPD-Scan Ⅲ for 3 mm pupil diameters, SA at 4 and 5 mm pupil diameter and Coma at 4 mm pupil diameter showed a 95% limit of agreement(LoA)<0.1, indicating good agreement; however, poor agreement was found for the remaining aberration measurements at different pupil diameters, with a 95%LoA>0.1, and there were significant differences in higher-order aberrations measured by two devices under a pupil diameter of 3 mm(r=0.218-0.317, P<0.01), 4 mm(r=0.406-0.672, P<0.01), 5 mm(r=0.538-0.839, P<0.01 and r=0.030-0.109, P>0.01)and 6 mm(r=0.369-0.766, P<0.01).CONCLUSION: The VAO demonstrates favorable repeatability when assessing whole-eye higher order aberration under pupil diameters of 3-6 mm. However, there is inadequate agreement and interchangeability in whole-eye higher order aberration at 3-6 mm pupil diameter between VAO and OPD-Scan Ⅲ for clinical purposes.

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