According to the principle and current domestic and international construction processes of core outcome set(COS) and the characteristics of post-stroke aphasia, this study built COS with evidence-based support for traditional Chinese medicine(TCM) treatment of post-stroke aphasia. Firstly, a comprehensive review was conducted on the articles about the TCM treatment of post-stroke aphasia that were published in the four major Chinese databases, three major English databases, and three clinical registration centers over the past five years. The articles were analyzed and summarized, on the basis of which the main part of the COS for clinical research on the TCM treatment of post-stroke aphasia was formed. Secondly, clinical doctors and related nursing personnel were interviewed, and important outcome indicators in the clinical diagnosis and treatment process were supplemented to form a pool of core outcome indicators. Two rounds of Delphi surveys were carried out to score the importance of the core outcome indicators in the pool. Finally, a consensus meeting of experts was held to establish the COS for clinical research on the TCM treatment of post-stroke aphasia. The final COS included a total of 268 studies [236 randomized controlled trials(RCTs), 21 Meta-analysis, and 11 clinical registration protocols] and 20 open questionnaire survey results. After two rounds of Delphi surveys, a total of 14 outcome indicators and their corresponding measurement tools were included in the expert consensus meeting. The final expert consensus meeting determined the COS for post-stroke aphasia, which included 9 indicator domains and 12 outcome indicators.
Humans ; Aphasia/therapy* ; Stroke/complications* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Treatment Outcome

Post-stroke spasticity, a common sequelae of upper motor neuron lesions, results in motor control deficits and pathological hypertonia that not only reduce patients' activities of daily living but may also cause impairment of adaptive neuroplasticity. Repetitive peripheral magnetic stimulation (rPMS), as a novel non-invasive neuromodulation technique, demonstrates unique clinical potential through targeted modulation of electromagnetic coupling effects in the peripheral neuromuscular system. Although current international studies have validated the therapeutic potential of rPMS for spasticity, significant heterogeneity persists in elucidating its mechanisms of action, optimizing parameter protocols, and standardizing outcome assessment systems. This review innovatively synthesized recent randomized controlled trials (RCTs) and mechanistic evidence, systematically summarizing rPMS-mediated multidimensional intervention paradigms for upper- and lower-limb spasticity. It rigorously examined the correlations between stimulation frequency parameters (low-frequency vs. high-frequency), anatomical targeting (nerve trunk vs. motor point), and clinical outcomes including spasticity severity, motor function, and quality of life. Crucially, the analysis reveals that rPMS may ameliorate spasticity after stroke through dual mechanisms involving local neuroelectrophysiological modulation and central sensorimotor network reorganization, thereby providing a theoretical foundation for developing individualized rPMS clinical protocols and establishing precision treatment strategies.
Humans ; Lower Extremity/physiopathology* ; Upper Extremity/physiopathology* ; Muscle Spasticity/physiopathology* ; Stroke/physiopathology* ; Magnetic Field Therapy/methods* ; Spasm/etiology* ; Stroke Rehabilitation ; Randomized Controlled Trials as Topic

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

Stroke is the second leading cause of disability and mortality worldwide, imposing a substantial socioeconomic burden on individuals and healthcare systems. Annually, approximately 14 million people experience stroke, with ischemic stroke comprising nearly 85% of cases, of which 10% to 20% involve large vessel occlusions. Currently, recombinant tissue plasminogen activator (tPA) remains the only approved pharmacological intervention. However, its utility is limited due to a narrow therapeutic window and low recanalization rates, making it applicable to only a minority of patients. Therefore, there is an urgent need for novel therapeutic strategies, including pharmacological advancements and combinatory treatments. Small-molecule natural medicines, particularly those derived from traditional Chinese herbs, have demonstrated significant therapeutic potential in ischemic stroke management. These compounds exert multiple neuroprotective effects, such as antioxidation, anti-inflammatory action, and inhibition of apoptosis, all of which are critical in mitigating stroke-induced cerebral damage. This review comprehensively examines the pathophysiology of acute ischemic stroke (AIS) and highlights the recent progress in the development of small-molecule natural medicines as promising therapeutic agents for cerebral ischemic stroke.
Humans ; Ischemic Stroke/physiopathology* ; Animals ; Neuroprotective Agents/therapeutic use* ; Drugs, Chinese Herbal/chemistry* ; Biological Products/therapeutic use* ; Stroke/drug therapy*

Endovascular treatment has become the primary treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion. Its development and clinical application have expanded significantly in recent years. Imaging assessment plays a pivotal role in guiding both preoperative screening and postoperative management in AIS patients undergoing such interventions. However, updated expert consensus and standardized guidelines remain lacking. To address this gap, the Professional Committee of Interventional Neurology of the Chinese Research Hospital Association convened leading cerebrovascular disease experts to formulate consensus recommendations based on domestic clinical practice, aiming to provide authoritative guidance for imaging evaluation in this patient population.
Humans ; Endovascular Procedures ; Ischemic Stroke/therapy* ; Consensus ; Stroke/therapy* ; Brain Ischemia/therapy*

Objective To investigate the effects and underlying mechanisms of human placental chorionic plate-derived mesenchymal stem cells (hpcMSCs) on cognitive dysfunction, neuroinflammation, neuronal damage and synaptic plasticity in a mouse model of stroke. Methods A mouse model of middle cerebral artery occlusion (MCAO) was adopted. The mice were randomly divided into three groups: sham operation group, MCAO group and hpcMSCs treatment group, with seven mice in each group. The hpcMSCs treatment group received hpcMSCs transplantation on the 1st, 3rd and 10th day after MCAO. One month after MCAO, the cognitive ability of the mice was evaluated by Morris water maze and Y maze behavioral tests; the morphological changes and synaptic functions of hippocampal neurons were analyzed by HE staining, Nissl staining, Golgi staining and immunofluorescence staining techniques; the density and activation status of microglia was analyzed by Fluorescent labeling method; the levels of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and IL-6 in brain tissue were analyzed by ELISA; the expressions of phosphorylated-mitogen-activated protein kinase kinase 1 (p-MEK1), phosphorylated-extracellular regulated protein kinase (p-ERK) and phosphorylated-cAMP-response element binding protein (p-CREB) and other proteins related to neuroprotection in the signal pathways were detected by Western blotting; and electrophysiological detection was performed using hippocampal slices in vitro. Results Compared with the MCAO group, mice in the hpcMSCs treatment group showed significant improvements, including improved cognitive ability, alleviated neuroinflammation (demonstrated by reduced microglial activation and decreased levels of inflammatory factors TNF-α, IL-1β and IL-6), and increased neuronal density with normalized morphology of neurons in the hippocampal CA1 region. The treatment group also demonstrated a significantly increased number of Nissl-positive cells and density of dendritic spines of hippocampal neurons, along with restored frequency of miniature excitatory postsynaptic potential (mEPSP). Moreover, hpcMSCs treatment significantly increased the expression levels of p-MEK1, p-ERK and p-CREB in the hippocampus. Conclusion Transplantation of hpcMSCs ameliorates cognitive dysfunction and hippocampal neuronal injury in stroke mice through the reduction of neuroinflammation, restoration of hippocampal neuronal function, promotion of synaptic plasticity and activation of the MEK/ERK/CREB signaling pathway. These findings suggest a new potential therapeutic approach for post-stroke neural repair.
Animals ; Hippocampus/physiopathology* ; Mice ; Cognitive Dysfunction/etiology* ; Mesenchymal Stem Cell Transplantation ; Male ; Neurons/metabolism* ; Stroke/metabolism* ; Humans ; Neuroinflammatory Diseases/therapy* ; Female ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Disease Models, Animal ; Mesenchymal Stem Cells/cytology* ; Mice, Inbred C57BL

Objective To explore the effects of Shuanglu Tongnao Formula on neuroinflammation in ischemic stroke (IS) rats via the P2X purinoceptor 7 receptor (P2X7R)/NLR family pyrin domain-containing 3 (NLRP3) pathway. Methods The rats were divided into five groups: the IS group, control group, Shuanglu Tongnao Formula group, P2X7R inhibitor brilliant blue G (BBG) group, and Shuanglu Tongnao Formula combined with P2X7R activator adenosine triphosphate (ATP) group, with 18 rats in each group. Except for the control group, rats in all other groups were used to construct an IS model using the suture method. After successful modeling, the drug was given once a day for 2 weeks. Neurological function scores and cerebral infarction volume ratios were measured in rats. Pathological examination of the ischemic penumbra brain tissue was performed. Immunofluorescence staining was used to quantify the proportions of microglia co-expressing both inducible nitric oxide synthase (iNOS) and ionized calcium-binding adapter molecule 1 (Iba1), as well as arginase 1 (Arg1) and Iba1, in the ischemic penumbra brain tissue. ELISA was used to detect tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), interleukin 6 (IL-6) and IL-10 in the ischemic penumbra brain tissue. Western blotting was used to measure P2X7R, NLRP3, and IL-1β proteins in the ischemic penumbra brain tissue. Results Compared with the control group, the IS group showed disordered neuronal arrangement, nuclear condensation, and obvious infiltration of inflammatory cells in the ischemic penumbra; significantly elevated neurological function scores, cerebral infarction volume ratios, proportions of microglia co-expressing iNOS and Iba1, and levels of TNF-α, IL-6, and P2X7R, NLRP3, IL-1β proteins; along with reduced proportions of microglia co-expressing Arg1 and Iba1 and levels of TGF-β and IL-10. Compared with the IS group, the Zhuang medicine Shuanglu Tongnao Formula and BBG groups demonstrated alleviated brain tissue damage; reduced neurological function scores, cerebral infarction volume ratios, proportions of microglia co-expressing iNOS and Iba1, and levels of TNF-α, IL-6, and P2X7R, NLRP3, IL-1β proteins; along with increased proportions of microglia co-expressing Arg1 and Iba1 and levels of TGF-β and IL-10. ATP reversed the effects of Zhuang medicine Shuanglu Tongnao Formula on microglial polarization and neuroinflammation in IS rats. Conclusion Zhuang medicine Shuanglu Tongnao Formula may promote the transformation of microglia from M1 type to M2 type by inhibiting the P2X7R/NLRP3 pathway, thereby improving neuroinflammation in IS rats.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Receptors, Purinergic P2X7/metabolism* ; Male ; Drugs, Chinese Herbal/pharmacology* ; Rats ; Ischemic Stroke/pathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Interleukin-10/metabolism* ; Brain Ischemia/drug therapy* ; Microglia/metabolism*

OBJECTIVE: To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms. METHODS: Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively. RESULTS: The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 β, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01). CONCLUSION XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.
Animals ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Depression/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Hippocampus/metabolism* ; Male ; Mice, Inbred C57BL ; Prefrontal Cortex/pathology* ; Microglia/metabolism* ; Stroke/drug therapy* ; Disease Models, Animal ; Mice ; Behavior, Animal/drug effects*

OBJECTIVE: To observe the effects of antagonistic needling therapy on lower limb spasticity and the muscle morphology of the tibialis anterior and gastrocnemius in patients with stroke. METHODS: A total of 100 patients with post-stroke lower limb spasticity were randomly divided into an antagonistic needling group (50 cases, 1 case dropped out) and a routine acupuncture group (50 cases, 1 case dropped out). Both groups received basic treatment and rehabilitation training. The routine acupuncture group was treated with scalp acupuncture at anterior oblique line of vertex-temporal and vertex lateral line 1, combined with body acupuncture at Jianyu (LI15), Hegu (LI4), Zusanli (ST36), Taichong (LR3), etc. on the affected side, with Quchi (LI11) and Hegu (LI4), Zusanli (ST36) and Fenglong (ST40), Yanglingquan (GB34) and Taichong (LR3) connected to an electroacupuncture device, using disperse wave at 2 Hz of frequency. The antagonistic needling group used the same scalp and upper limb acupoints as the routine acupuncture group, with additional antagonistic needling on the lower limb at Yanglingquan (GB34), Qiuxu (GB40), Jiexi (ST41), and Xuanzhong (GB39) on the affected side, with Quchi (LI11) and Hegu (LI4), Yanglingquan (GB34) and Qiuxu (GB40), Jiexi (ST41), and Xuanzhong (GB39) connected to an electroacupuncture device, using disperse wave at 2 Hz of frequency. Both groups received treatment once daily for 6 consecutive days per course, with a total of 4 courses. The modified Ashworth scale (MAS), Holden functional ambulation classification (FAC), lower limb Fugl-Meyer assessment (FMA), composite spasticity scale (CSS), and musculoskeletal ultrasound parameters (thickness and fiber length of the tibialis anterior and gastrocnemius, and pennation angle of the gastrocnemius on both sides) were evaluated before and after treatment. Clinical efficacy was compared between the two groups. RESULTS: Compared before treatment, the MAS grades and CSS scores were decreased in both groups after treatment (P<0.01), with greater reductions in the antagonistic needling group (P<0.05, P<0.01). FAC grades and FMA scores were increased in both groups after treatment (P<0.01, P<0.05), with greater improvements in the antagonistic needling group (P<0.05). The muscle thickness, fiber length of the tibialis anterior, the muscle thickness, fiber length and pennation angle of the gastrocnemius on the affected side were improved in both groups after treatment (P<0.01), with greater improvements in the antagonistic needling group (P<0.01, P<0.05). On the unaffected side, these parameters were also increased after treatment in both groups (P<0.01, P<0.05), but the antagonistic needling group showed smaller increases than the routine acupuncture group (P<0.01, P<0.05). The total effective rate in the antagonistic needling group was 91.8% (45/49), higher than 81.6% (40/49) in the routine acupuncture group (P<0.05). CONCLUSION Antagonistic needling could effectively reduce spasticity, improve motor function, and enhance muscle structure in patients with post-stroke lower limb spasticity.
Humans ; Male ; Female ; Acupuncture Therapy ; Middle Aged ; Muscle Spasticity/pathology* ; Aged ; Stroke/physiopathology* ; Lower Extremity/physiopathology* ; Acupuncture Points ; Adult ; Muscle, Skeletal/pathology* ; Treatment Outcome