1.Early clinical efficacy of Yiqi Tongluo Decoction on ischemic cerebrovascular disease after interventional therapy
Qinghua WANG ; Gesheng WANG ; Ruiping LI ; Can ZHENG ; Wenjing LI ; Jiaqi CHEN ; Kaihang GUO ; Xiaobo DONG ; Wenxin WANG ; Rongjuan GUO ; Le WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):108-121
Objective:
To observe the clinical efficacy and safety of Yiqi Tongluo Decoction in the intervention of early traditional Chinese medicine (TCM) syndromes after ischemic cerebrovascular disease (ICVD) intervention.
Methods:
From October 2020 to July 2023, a randomized, double-blind, placebo-controlled study was conducted to include 60 patients with qi deficiency, blood stasis, and phlegm obstruction syndrome after ICVD interventional therapy. They were assigned to the Yiqi Tongluo Decoction treatment group (30 cases) and the TCM placebo routine treatment control group (30 cases) according to the randomized block design. Both groups received routine standardized treatment of Western medicine, including dual antiplatelet, lipid regulation, and control of risk factors for cerebrovascular disease. The treatment group was treated with Yiqi Tongluo Decoction based on the control group. The course of treatment was 60 days and follow-up was carried out 2 and 6 months after the operation. The improvement of qi deficiency syndrome, blood stasis syndrome, phlegm syndrome score and TCM syndrome score, modified Rankin score (mRS), Barthel index (BI) score, Fatty acid-binding protein 4 (FABP4) level, incidence of transient ischemic attack (TIA) and ischemic stroke (IS) and incidence of adverse reactions, Head and neck CT angiography (CTA) or digital subtraction angiography (DSA) examination were collected. The clinical efficacy of the patients 2 months after the operation was taken as the main outcome index to preliminarily evaluate the early and long-term efficacy of Yiqi Tongluo Decoction after the ICVD intervention. The early and long-term clinical efficacy and safety of Western medicine standardized treatment combined with TCM Yiqi Tongluo Decoction on patients with qi deficiency, blood stasis and phlegm obstruction syndrome after ICVD intervention were evaluated. The safety of Yiqi Tongluo Decoction in the treatment of patients after ICVD intervention with white blood cell (WBC), C-reactive protein (CRP), fibrinogen (FIB), plasminogen time (PT), recurrence of cerebral ischaemia and restenosis in patients at 2 and 6 months after treatment were evaluated.
Results:
Compared to the control group, the TCM syndrome scores for qi deficiency, blood stasis and phlegm syndrome in the treatment group reduced significantly, the clinical efficacy improved significantly, the mRS score and FABP4 were reduced, and the BI score was increased. Adverse events such as cerebral ischaemia were fewer in the treatment group than in the control group, but the difference was not statistically significant; levels of CRP, WBC and PT were reduced, and levels of FIB were reduced at 6 months post-treatment, all P<0.01, and images were intuitively compared. The treatment group was superior to the control group.
Conclusion
Yiqi Tongluo Decoction combined with Western medicine standard treatment can improve the early clinical efficacy of ICVD patients with qi deficiency, blood stasis and phlegm obstruction syndrome after interventional surgery, improve neurological impairment and daily living ability, reduce the state of qi deficiency syndrome, blood stasis syndrome and phlegm syndrome after interventional surgery, and improve the clinical efficacy of TCM. At the same time, it can reduce the level of FABP4, the target of atherosclerosis and restenosis after interventional surgery, reduce the level of inflammation after interventional surgery in patients with ICVD, regulate coagulation function, and reduce the incidence of long-term recurrence of cerebral ischemia after interventional surgery, with good safety.
2.Artificial mesenchymal stem cell extracellular vesicles enhanced ischemic stroke treatment through targeted remodeling brain microvascular endothelial cells.
Shengnan LI ; Wei LV ; Jiangna XU ; Jiaqing YIN ; Yuqin CHEN ; Linfeng LIU ; Xiang CAO ; Wenjing LI ; Zhen LI ; Hua CHEN ; Hongliang XIN
Acta Pharmaceutica Sinica B 2025;15(8):4248-4264
Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the HII phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).
3.The Icarian flight of antibody-drug conjugates: target selection amidst complexity and tackling adverse impacts.
Han LIU ; Hongye ZENG ; Xiaojing QIN ; Wenjing NING ; Lin XU ; Shiting YANG ; Xue LIU ; Wenxin LUO ; Ningshao XIA
Protein & Cell 2025;16(7):532-556
Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans
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Immunoconjugates/adverse effects*
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Neoplasms/immunology*
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Animals
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Antibodies, Monoclonal/therapeutic use*
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Antineoplastic Agents/therapeutic use*
4.Evaluation index system of oral health literacy for children's parents based on Delphi method
CEN Qiong ; JIANG Yang ; JIANG Jingyue ; LI Xiaofei ; XIANG Wenjing ; LÜ ; Yunyun
Journal of Preventive Medicine 2024;36(3):193-197
Objective:
To construct an evaluation index system of oral health literacy for children's parents, so as to provide an index system for the evaluation of oral health literacy for children's parents in China.
Methods:
The evaluation index system of oral health literacy for children's parents was designed based on literature review and semi-structured interview. Experts from oral prevention and pediatric oral medicine were invited to participate in two-round Delphi consultations. The indicators were scored and screened according to the importance, and the weight determined using analytic hierarchy process. The effectiveness of the consultation was evaluated by positive coefficient, authority coefficient and coordination coefficient.
Results:
Twenty-four experts participated in the consultation, including 6 males and 18 females. There were 21 experts with a master degree, 3 experts with a doctor degree, and 20 experts with vice senior professional titles and above. The recovery rates of the two rounds of consultations were 96.00% and 100.00%, the authority coefficients were 0.866 and 0.917, the Kendall's coefficient of concordance were 0.120 and 0.156 (both P<0.05), and the coefficient of variation was 0.15-0.38 and 0.03-0.17, respectively. The final evaluation index system included 3 primary indicators, 11 secondary indicators and 40 tertiary indicators. The primary indicators were basic knowledge and concepts related to oral health, promoting lifestyle and behaviors related to oral health, and maintaining basic skills related to oral health.
Conclusion
The evaluation index system of oral health literacy for children's parents has been established in this study and needs to be further applied and evaluated.
5.Modified Shuyuwan Ameliorates Depressive Behaviors and Promotes Myelin Regeneration in Mouse Model of Vascular Dementia Complicated with Depression by Regulating Energy Metabolism of Myelin Axons via MCT1
Wenjing YAN ; Zihu TAN ; Qiong YANG ; Qingwei XIANG ; Jianjie ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):21-29
ObjectiveTo explore the mechanism of modified Shuyuwan in treating vascular dementia (VaD) complicated with depression in mice. MethodThe VaD model was established by bilateral carotid artery stenosis (BCAS) in seven 3-month-old male C57/BL6 mice. The regional cerebral blood flow (rCBF) of mice was measured by laser speckle imaging before and after BCAS surgery. Then, the BCAS method was combined with chronic unpredictable mild stress (CUMS) to establish a mouse model of VaD complicated with depression. BCAS/CUMS mice were assigned into BCAS/CUMS, fluoxetine (0.01 g·kg-1), and high-, medium-, and low-dose (20, 10, 5 g·kg-1, respectively) modified Shuyuwan groups. The shame group underwent sham operation without CUMS (n=10). The tail suspension test and sucrose preference test were carried out to examine the depressive behaviors of mice. The distribution and expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), neurofilament heavy polypeptide (NF200), and anti-non-phosphorylated neurofilament epitope antibody (SMI32) in the corpus callosum (CC) were detected by the immunofluorescence assay. Western blot was employed to determine the protein levels of monocarboxylate transporter 1 (MCT1), MBP, MAG, oligodendrocyte glycoprotein (MOG), amyloid precursor protein (APP), NF200, contactin-associated protein (Caspr), and voltage-gated sodium channel (Nav1.6) in the corpus callosum. The level of lactic acid in the serum was measured by the lactic acid assay kit, and the ultrastructure of myelin was observed by ultraprojective electron microscope. ResultLaser speckle imaging showed that rCBF decreased immediately 10 min after BCAS surgery (P<0.01), and the rCBF was still cerebral hypoperfusion and did not return to the preoperative level 2 weeks after surgery. Behavioral test results showed that compared with the sham group, the BCAS/CUMS group presented decreased percentage of sucrose preference (P<0.01) and prolonged immobile time in the tail suspension test (P<0.01). Compared with the BCAS/CUMS group, fluoxetine and modified Shuyuwan increased the percentage of sucrose preference (P<0.01) and shortened the immobile time in the tail suspension test (P<0.01). The level of lactic acid was the highest in the BCAS/CUMS mice (P<0.01), and modified Shuyuwan lowered the lactic acid level (P<0.01). Immunofluorescence results showed that compared with the sham group, the BCAS/CUMS group presented decreased fluorescence intensity of MAG, MBP and NF200 and increased fluorescence intensity of SMI32 in the corpus callosum, and such changes were reversed by modified Shuyuwan at different doses and fluoxetine. Western blot results showed that compared with the sham group, the BCAS/CUMS modeling down-regulated the protein levels of MCT1, MBP, MOG, MAG, NF20, and Caspr (P<0.05, P<0.01) and up-regulated the protein levels of APP and Nav1.6 in the corpus callosum, and the above trends were reversed by modified Shuyuwan (P<0.05, P<0.01). Compared with the sham group, BCAS/CUMS modeling led to myelin ultrastructure damage and axon atrophy, which were alleviated by modified Shuyuwan. ConclusionModified Shuyuwan can ameliorate the transport disorder of lactic acid between myelin sheath and axon by upregulating the expressin of MCT1, promote the regeneration of myelin sheath in the corpus callosum, and improve the integrity of myelin sheath structure, thereby alleviating depression in VaD mice.
6.Effects of full-process pharmaceutical services on drug cost control in patients of cardiovascular FM35 disease group
Wenjing CAO ; Peng ZHANG ; Can XIAO ; Xiang LIU
China Pharmacy 2024;35(17):2136-2141
OBJECTIVE To optimize drug treatment plans for patients in cardiovascular FM35 disease group using full-process pharmaceutical services, and achieve the goals of ensuring patient medication safety and controlling drug costs. METHODS Overall 213 patients in the cardiovascular FM35 disease group who were discharged from July to August 2023 were selected as control group; all medical orders were screened and complex network analysis and drug evaluation standards of our hospital were used to establish an optimized treatment drug library; 83 FM35 patients who newly admitted to the cardiovascular department in September 2023 were selected as intervention group; a model of policy promotion-treatment plan intervention was established and applied to provide full process pharmaceutical services to patients. The treatment cost, length of stay and outcome were analyzed and compared between 2 groups. RESULTS Through the full process pharmaceutical services provided by clinical pharmacists, compared with the control group, the total hospitalization cost, drug cost, drug proportion, and case proportion of medical insurance settlement amount in the intervention group significantly decreased (P<0.05). The median length of hospital stay in the intervention group was shortened by 1 d, and the discharge improvement outcome rates of both groups of patients were ≥99%. CONCLUSIONS Clinical pharmacists can effectively improve the efficiency of medical services and save the medical costs through full-process pharmaceutical services, meanwhile ensuring medical quality and safety. This can effectively assist in the smooth implementation of DRGs.
7.Analysis of Material Basis of Famous Classical Formula Baoyuantang Based on UPLC-Q-TOF-MS/MS
Wenjing GAO ; Shanshan LI ; Xiaomei XIANG ; Yi SUN ; Yang QU ; Chunling ZHOU ; Shufan ZHOU ; Lun YU ; Bing LI ; Ping WANG ; Haiyu XU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):243-248
ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) and self-established database information, the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column(2.1 mm×100 mm, 1.8 μm) with mobile phase of 0.1% formic acid aqueous solution(A)-0.1% formic acid acetonitrile solution(B) for gradient elution(0-3 min, 2%-19%B; 3-8 min, 19%B; 8-8.1 min, 19%-22%B; 8.1-14 min, 22%-29%B; 14-16 min, 29%B; 16-32 min, 29%-45%B; 32-32.1 min, 45%-90%B; 32.1-35 min, 90%-95%B; 35-36 min, 95%-98%B; 36-37 min, 98%-2%B; 37-40 min, 2%B). Based on electrospray ionization(ESI), continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching, control comparison, The Encyclopedia of Traditional Chinese Medicine(ETCM) database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode, with a total of 322 components after removing duplicates, including 116 triterpene saponins, 66 flavonoids, 19 organic acids, 6 gingerphenols, 6 gingerols, 5 gingerones, 10 amino acids, 7 saccharides, 5 coumarins and 82 other components. Among them, 83, 141, 39, 35 and 38 components were attributed to Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Astragali Radix, Cinnamomi Cortex and Zingiberis Rhizoma Recens, respectively. ConclusionIn this study, the rapid characterization and identification of multi-class components in Baoyuantang was realized, and it was confirmed that the material basis of this formula was mainly triterpenoid saponins, flavonoids, gingerols and organic acids, and the chemical composition was attributed and analyzed, which provided a reference for the subsequent quality control research.
8.Investigation on the Utilization and Dissemination Behavior of Online Dietary Health Information of Residents in Yangtze River Delta
Wenjing JIANG ; Mingjun ZHOU ; Renwei WANG ; Jingyi XIANG ; Tian LI ; Jing YAN
Journal of Medical Informatics 2024;45(9):69-74
Purpose/Significance To understand the current status and influencing factors of residents'utilization and dissemination of online dietary health information in the Yangtze River Delta region,so as to provide theoretical references for strengthening education on online dietary health information,and eliminating misinformation related to online dietary health.Method/Process The purposive sam-pling method is used to investigate residents in the Yangtze River Delta region,and the data is analyzed by descriptive analysis,inde-pendent sample t-tests,and multiple linear regression analysis.Result/Conclusion The dissemination of online dietary health informa-tion presents interactive characteristics of interpersonal communication and online communication.WeChat and Sina Weibo are the main sources of dietary health information.In addition to information screening,information search,systematic information processing,demand degree,information sharing intention and information concern motivation have significant and positive effects on the public's willingness to receive information.
9.Study on the mechanism of Yishen daluo decoction in alleviating nervous system inflammation in EAE model mice
Xiang WANG ; Shiyang WANG ; Yuan WU ; Wenjing DING ; Mingzong XIE ; Jingwen HE ; Tianye XING ; Xiaoling SHANG
China Pharmacy 2023;34(11):1326-1331
OBJECTIVE To study the effects of Yishen daluo decoction on inflammatory factors and cyclic adenosine monophosphate(cAMP)/protein kinase A (PKA)/cAMP response element binding protein (CREB) signal pathway in experimental autoimmune encephalomyelitis (EAE) model mice by inhibiting the expressions of β-arrestin1, and to explore the mechanism of Yishen daluo decoction in the treatment of EAE. METHODS Sixty mice were randomly divided into normal group, model group, TCM group (Yishen daluo decoction 20 g/kg), positive control group (prednisone acetate 3.9 mg/kg), β-arrestin1 siRNA adeno- associated virus (AAV-β) group, AAV-β+TCM group, with 10 mice in each group. Except for normal group, EAE model was made in other groups. AAV-β group and AAV-β+TCM group were injected with AAV-β via tail vein to interfere with the expression of β -arrestin1 protein. Starting from the 8th day of modeling, they were given corresponding drug solution/normal saline intragastrically, once a day, for consecutive 14 days. The neurological function score of mice was detected; the pathological and morphological changes were observed in the brain and spinal cord tissues of mice; the serum levels of inflammatory factors [interleukin-2 (IL-2), IL-23, interferon-γ (IFN-γ)] in mice were determined; the expressions of β-arrestin1, cAMP, PKA and CREB in brain and spinal cord were detected. RESULTS Compared with normal group, neurological function scores, serum levels of inflammatory factors, and protein expressions of β-arrestin1 in brain and spinal cord were significantly increased (P<0.05 or P< 0.01); protein expressions of PKA, CREB and cAMP in brain and spinal cord were decreased significantly(P<0.05 or P<0.01). The deep staining of cellular shrinkage and aggregation of inflammatory cells were observed in most neurons of the brain and spinal cord, with varying degrees of demyelinating. Compared with model group, the neurological function scores, pathological changes in brain and spinal cord tissues, and most indicators (except for CREB and cAMP proteins in the brain tissue of AAV-β group) were significantly reversed (P<0.05 or P<0.01).Compared with AAV- β group, the neurological function scores, the levels of IFN-γ in serum and β-arrestin1 in spinal cord were significantly decreased (P<0.05 or P<0.01), PKA and cAMP in brain and spinal cord tissues were significantly increased in AAV- β +TCM group (P<0.05 or P<0.01). CONCLUSIONS Yishen daluo decoction can inhibit the expression of β-arrestin1 in the central nervous system thus activating the cAMP/PKA/CREB signaling pathway, relieving nervous system inflammation, and ultimately alleviates the symptoms of EAE.
10.Effect of Yishen Daluo Prescription on Rho/ROCK Signaling Pathway in EAE Mice Based on Silencing of β-arrestin1
Wenjing DING ; Zhongmin WANG ; Jiayan REN ; Xiang WANG ; Xiaoling SHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(10):110-116
ObjectiveTo investigate the effects of Yishen Daluo prescription (YSDL) on Ras homolog(Rho)/Rho-associated coiled-coil containing protein kinase(ROCK)signaling pathway in mice with experimental autoimmune encephalomyelitis (EAE) based on the silencing of β-arrestin1 gene. MethodSixty C57BL/6 female mice were randomly divided into a blank group, a model group, a virus group, a YSDL group, a virus + YSDL group, and a prednisone acetate group (hormone group). The EAE model was induced in mice except for those in the normal group. Adeno-associated virus(AAV)solution (150 μL, 1×1011 vg·mL-1) was injected into the tail vein of each mouse in the virus group and the virus + YSDL group on the 4th day of immunization. Drugs were administered on the 8th day of modeling. Specifically, normal saline was given to the mice in the normal group,the model group,and the virus group at 10 mL∙kg-1, prednisone acetate suspension to those in the hormone group at 3.9 g∙kg-1,and YSDL to those in other groups at 20 g∙kg-1 for 14 consecutive days. The mice were weighed and scored every day. The neurological function scores of mice in each group were recorded every day after immunization. Hematoxylin-eosin (HE) staining was used to determine the inflammatory response and lesion location in the brain tissues and spinal cord tissues of mice. The protein expression of β-arrestin1,Ras homolog gene family member A(RhoA), and Rho-associated coiled-coil forming protein kinase Ⅰ(ROCK Ⅰ) in spinal cord and brain tissues of EAE mice was determined by Western blot. ResultCompared with the model group, the virus group and the virus + YSDL group showed decreased neurological function scores (P<0.01),and the YSDL group also showed decreased neurological function scores(P<0.05). HE results showed that there was obvious inflammatory reaction in the central nervous system (CNS) of the model group, which was alleviated to varying degrees in other groups compared with the model group. Western blot results showed that compared with the blank group, the model group showed increased protein expression levels of β-arrestin1, RhoA, and ROCK Ⅰ in the spinal cord tissues (P<0.01). Compared with the model group, the virus group, the YSDL group, the virus + YSDL group, and the hormone group showed decreased protein expression levels of β-arrestin1, RhoA, and ROCKⅠ in the spinal cord tissues (P<0.01). Compared with the blank group, the model group showed increased protein expression levels of β-arrestin1, RhoA, and ROCK Ⅰ in the brain tissues (P<0.01). Compared with the model group, the virus group, the YSDL group, the virus + YSDL group, and the hormone group showed decreased protein expression level of β-arrestin1 in the brain tissues (P<0.01), and the virus group and the YSDL group showed decreased protein expression levels of RhoA, and ROCKⅠ in the brain tissues (P<0.05). Additionally, the virus + YSDL group and the hormone group showed decreased protein expression levels of RhoA and ROCKⅠ in the brain tissues (P<0.01). ConclusionYSDL can improve the clinical symptoms of EAE mice and improve the inflammatory response of CNS. The mechanism is presumably attributed to the fact that YSDL inhibits the expression of β-arrestin1 in CNS,thereby reducing the expression of Rho/ROCK signaling pathway. Furthermore, YSDL may have a synergistic effect with the inhibition of β-arrestin1 gene expression.


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