ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Endoscopic transforaminal lumbar interbody fusion (TLIF) offers substantial advantages in the management of degenerative spinal diseases, including accelerated postoperative recovery. However, its technical complexity and steep learning curve pose risks for nerve root injury. Optimizing nerve root protection in full-endoscopic facet-sparing TLIF (FE fs-TLIF) and full-endoscopic facet-resecting TLIF (FE fr-TLIF) is essential for enhancing surgical safety. This study aimed to improve the nerve root protection in FE fs-TLIF and FE fr-TLIF by optimizing cage glider selection and insertion techniques based on the specific cage shape—banana-shaped or bullet-shaped. The goal was to ensure safe cage positioning and mitigate nerve root injury during discectomy, endplate preparation, and cage insertion. These strategies were validated through cadaveric simulations and clinical implementation. In FE fr-TLIF utilizing bullet-shaped (straight) cages, one-tip and two-tip cage gliders effectively protected the traversing nerve root by facilitating medial cage entry, thereby minimizing irritation of the exiting nerve root. Conversely, in FE fr-TLIF with banana-shaped cages, the lateral tilt of the cage holder during implantation required the use of a two-tip cage glider to protect the traversing and exiting nerve roots, thereby mitigating the potential risk of nerve irritation. In FE fs-TLIF, a one-tip cage glider is preferred for safeguarding the exiting nerve root, while the traversing root is inherently protected by the medial wall of the facet joint. The use of a two-tip cage glider in FE fs-TLIF can cause injury to the nerve root during glider insertion. In addition to the selection of cage gliders, improper cage insertion steps can also contribute to postoperative neurapraxia. The appropriate selection of cage gliders with corresponding insertion techniques is critical for nerve root protection in endoscopic TLIF. Tailoring these choices to the specific approach (FE fs-TLIF or FE fr-TLIF) and cage type (banana or bullet) enhances surgical safety and clinical outcomes.

ObjectiveTo systematically review the effect of dual-task training (DTT) on mobility and balance in stroke patients. MethodsCNKI, Wanfang Data, VIP, PubMed, Web of Science, Embase and Cochrane Library were searched for randomized controlled trials (RCT) on DTT in stroke rehabilitation from inception to June, 2025. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool and the PEDro scale. Meta-analysis was performed using RevMan 5.4. ResultsA total of eleven RCT involving 517 stroke patients were included, and the scores of PEDro scale were four to eight. DTT was more effective on the score of Fugl-Meyer Assessment-Lower Extremity (MD = 3.70, 95%CI 1.88 to 5.53, P < 0.001) and Berg Balance Scale (BBS) (MD = 3.04, 95%CI 1.58 to 4.49, P < 0.001), fall incidence (OR = 0.32, 95%CI 0.11 to 0.87, P = 0.025), gait speed under a single-task condition (MD = 0.08, 95%CI 0.03 to 0.12, P = 0.002), gait speed under a dual-task condition (MD = 0.13, 95%CI 0.10 to 0.16, P < 0.001), Timed Up and Go Test time (MD = -2.78, 95%CI -3.85 to -1.72, P < 0.001), and score of modified Barthel Index (MD = 4.77, 95%CI 1.88 to 7.66, P = 0.001). Subgroup analysis indicated that motor-motor DTT was more effective than cognitive-motor DTT on BBS scores and single-task gait speed. ConclusionsDTT can improve mobility and balance in stroke patients, especially with motor-motor tasks.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Objective Performing physical tasks in the low-pressure environment of space poses a significant physiological challenge for astronauts.This study investigates the localized thermophysiological effects of typical physical tasks on different body segments and analyzes the mechanisms by which low-pressure environments influence human task performance.The findings aim to provide a theoretical basis for the thermal control design of spacesuits,focusing on both localized thermoregulation and overall task performance.Methods Two typical physical tasks—15 kg weighted walking and 25 kg load-carrying—were conducted in a simulated low-pressure composite environment chamber.The chamber was set to an altitude-equivalent pressure of 57 kPa(4500 m),with a temperature of 26℃and humidity of 40％.Six non-acclimatized adult male participants were recruited.After environmental stabilization,12-point skin temperatures were recorded throughout the tasks,and localized temperature data were statistically analyzed.Results Under low-pressure conditions,different body regions exhibited distinct thermal responses over time depending on the task type,while the same body region showed varied responses under different task conditions.During walking,temperatures in the primary active regions(thighs and calves)decreased,with most other body regions(except the pelvis and feet)gradually cooling as the task progressed.In contrast,during load-carrying,temperatures in the primary active regions(back and upper arm muscles)increased significantly.Conclusion Astronauts performing different tasks in low-pressure environments experience distinct localized thermophysiological effects.Therefore,spacesuit thermal control systems should not only account for task intensity and metabolic differences but also adapt localized heating/cooling based on task-specific thermal profiles.This approach enables targeted intelligent thermal regulation,enhancing operational support in specific mission scenarios.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

OBJECTIVE: To investigate the effect of relaxing needling at the contracted sites of meridian-muscle regions in the patients with post-stroke shoulder-hand syndrome (SHS) at acute stage. METHODS: Eighty patients with post-stroke SHS at acute stage were randomized into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 1 case was eliminated). In the control group, the routine medication, basic rehabilitation training, and hyperbaric oxygen therapy were administered. In the observation group, besides the treatment as the control group, relaxing needling was delivered at the contracted sites of meridian-muscle regions. These contracted sites were distributed along three yin meridians of hand and three yang meridians of hand on the affected upper limbs. The intervention was given once daily, 5 times a week and for 4 weeks. Before and after treatment, the scores of visual analogue scale (VAS) for pain, edema degree, modified Barthel index (MBI), and Fugl-Meyer assessment (FMA) for motor function, and the integrated electromyography (iEMG) of surface electromyogram (sEMG) were observed in the two groups. The curative effect was evaluated after treatment and in follow-up of 2 months after treatment in the two groups. RESULTS: After treatment, VAS scores and the scores of edema degree were reduced when compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than those in the control group (P<0.05). MBI and FMA scores increased after treatment compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05) after treatment. The iEMG values of the biceps brachii, triceps brachii, and wrist extensors were elevated after treatment in comparison with those before treatment (P<0.05) in the two groups, and the values in the observation group were larger than those in the control group after treatment (P<0.05). The total clinical effective rate in the observation group was 92.3% (36/39), which was better than that of the control group (74.4%, 29/39, P<0.05) after treatment; and that of the observation group was 97.4% (38/39), which was better than 82.1% (32/39) in the control group (P<0.05) in follow-up. CONCLUSION Relaxing needling at the contracted sites of meridian-muscle regions in treatment of post-stroke SHS at acute stage can attenuate the symptoms such as upper limb pain, swelling and spasm, improve motor function and the activity of daily living of patients.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Therapy ; Aged ; Meridians ; Stroke/complications* ; Reflex Sympathetic Dystrophy/etiology* ; Adult ; Acupuncture Points

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*