ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

Objective: This study compared the effects of personalized exercise versus acupuncture on multidimensional cognitive function in individuals at high risk for stroke with mild cognitive impairment (MCI). Methods: A randomized controlled trial enrolled 200 stroke-risk adults aged 50−80 years. Ninety participants diagnosed with MCI (MMSE, HIS, CDR criteria) were randomly assigned to exercise (n = 30), acupuncture (n = 30), or control (n = 30) groups. Interventions lasted 6 months. Cognitive outcomes (MMSE, Raven’s Progressive Matrices, Digit Symbol Substitution Test, Animal Fluency, Rey-Osterrieth test, Stroop test) were assessed before and after intervention. Multivariate regression identified risk factors for MCI. ANOVA was used for group comparisons. Results: Hypertension (aOR = 1.5) and diabetes (aOR = 1.3) were significant risk factors for MCI. After intervention, the exercise group showed the largest MMSE improvement (Δ = 5.0), compared with acupuncture (Δ = 3.0) and control (Δ = 1.0) (p < 0.001). Exercise produced greater gains in non-verbal reasoning (31.8% vs. 26.1% in acupuncture, p < 0.01). Acupuncture more effectively enhanced processing speed and attention (DSST: Δ = 26 vs. Δ = 20 in exercise, p = 0.03) and executive function (Stroop interference time: Δ = 16 vs. Δ = 15 seconds in exercise, p = 0.04). Both interventions significantly improved verbal fluency (p < 0.001), with larger benefits in those with baseline MMSE ≤ 20. Conclusion Hypertension and diabetes are key risk factors for MCI in stroke-prone individuals. Exercise yields greater improvement in global cognition and memory, whereas acupuncture is more effective for enhancing attention and executive function. Both modalities benefit verbal fluency, particularly in lower-functioning participants.

OBJECTIVES: Obtaining informed consent from research participants is an ethical and legal obligation for medical researchers in clinical studies. Electronic informed consent (eIC) is increasingly being adopted in clinical research worldwide. However, there is limited data on Chinese medical researchers' knowledge and attitudes toward eIC. This study aims to investigate their knowledge, attitudes, and influencing factors regarding eIC use in clinical research. METHODS: This cross-sectional study was conducted using stratified random sampling. From June to August 2022, medical researchers from 8 tertiary hospitals were surveyed via an online platform (Wenjuanxing). A self-developed eIC knowledge questionnaire and attitude scale were used to assess participants' understanding and perceptions of eIC. Univariate analysis was employed to explore factors influencing attitude scores and the correlation between knowledge and attitudes. A generalized linear model was used to analyze associations between demographic characteristics and attitude scores, including the frequency of difficulties in using smartphones or computers, preferred device for using eIC, and their interaction effects. Stratified analysis was further performed for significant interactions. RESULTS: A total of 399 valid questionnaires were collected. The mean accuracy rate on the eIC knowledge questionnaire was (94.88±15.50)%. Of the respondents, 74.9% had heard of eIC, and 84.5% preferred using mobile devices over computers to access eIC. The median attitude score was 3.41 (3.18, 3.76), indicating generally positive attitudes. Specifically, 81.7% found eIC more convenient than paper-based consent, 79.7% considered it more efficient, and 51.1% believed it could fully replace paper forms. However, 60.7% expressed concerns about data security and privacy, and 89.7% believed that relevant laws and regulations need improvement. Spearman correlation analysis showed a weak positive correlation between knowledge and attitude scores (r=0.171, P=0.001). Univariate analysis indicated that the frequency of difficulty using devices and preferred device for eIC were significantly associated with attitude scores (P<0.05). After adjusting for confounding factors, the generalized linear model demonstrated that participants who occasionally experienced had difficulty using devices had significantly lower attitude scores compared to those who never had difficulty (β=-0.040, 95% CI -0.071 to -0.009, P=0.012). Those who preferred using PCs had significantly lower attitude scores than those who preferred mobile devices (β=-0.066, 95% CI -0.108 to -0.023, P=0.002). Interaction analysis showed a significant interaction analysis showed a significant interaction between age and preferred device (P=0.011), particularly among participants aged ≥45-year (P<0.001). No other interactions were found to be significant (all P>0.05). CONCLUSIONS Medical researchers in China generally have a high level of knowledge and positive attitudes toward eIC, though concerns remain regarding data security and privacy. Future promotion of eIC in Chinese clinical research should be grounded in ethical considerations and address the specific needs of older users and mobile device users, while also enhancing researchers' competencies in using digital tools and eIC systems.
Humans ; Cross-Sectional Studies ; Informed Consent ; Surveys and Questionnaires ; Female ; Male ; Health Knowledge, Attitudes, Practice ; Adult ; Biomedical Research ; Research Personnel/psychology* ; Middle Aged ; China

Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration. Syntaphilin (Snph), known for its potent mitochondrial anchoring action, has emerged as a significant inhibitor of both mitochondrial transport and axonal regeneration. Therefore, investigating the molecular mechanisms that influence the expression levels of the snph gene can provide a viable strategy to regulate mitochondrial trafficking and enhance axonal regeneration. Here, we reveal the inhibitory effect of microRNA-146b (miR-146b) on the expression of the homologous zebrafish gene syntaphilin b (snphb). Through CRISPR/Cas9 and single-cell electroporation, we elucidated the positive regulatory effect of the miR-146b-snphb axis on Mauthner cell (M-cell) axon regeneration at the global and single-cell levels. Through escape response tests, we show that miR-146b-snphb signaling positively regulates functional recovery after M-cell axon injury. In addition, continuous dynamic imaging in vivo showed that reprogramming miR-146b significantly promotes axonal mitochondrial trafficking in the pre-injury and early stages of regeneration. Our study reveals an intrinsic axonal regeneration regulatory axis that promotes axonal regeneration by reprogramming mitochondrial transport and anchoring. This regulation involves noncoding RNA, and mitochondria-associated genes may provide a potential opportunity for the repair of central nervous system injury.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Nerve Regeneration/physiology* ; Mitochondria/metabolism* ; Zebrafish Proteins/genetics* ; Axons/metabolism* ; Signal Transduction/physiology* ; Axonal Transport/physiology* ; Nerve Tissue Proteins/genetics*

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Piper nigrum L. is an evergreen climbing vine, which belongs to the genus Piperia in the Piperaceae family. Piper nigrum L., which known as the “king of spices”, is used as both food and medicine. The main active substances in Piper nigrum L. are alkaloids mainly composed of amides, and essential oil, as well as phenolic compounds. In this paper, the chemical compositions, especially amide alkaloids, and their biological activities of Piper nigrum L. were summarized. These studies showed that Piper nigrum L., as a medicinal and food plant, had a wide range of biological activities and was deserved further research and in-depth utilization.

Glutathione peroxidase （GSH-Px） is a key selenoenzyme that protects the body from oxidative damage. A series of small molecular organic selenium compounds have been designed and synthesized as functional mimics of GPx, among which isoselenazolones are the most widely studied. Taking ebselen as a representative, the catalytic mechanism of isoselenazolones in mimicing GSH-Px activity in vivo, the therapeutic effects of isoselenazolones in stroke, sensorineurium deafness and tinnitus, treatmentresistant depression （TRD） and coronavirus disease 2019 （COVID-19）, and research on their chemical synthesis methods were summarized and discussed in this paper.

The neurophysiological mechanisms by which exercise improves cognitive function have not been fully elucidated. A comprehensive and systematic review of current domestic and international neurophysiological evidence on exercise improving cognitive function was conducted from multiple perspectives. At the molecular level, exercise promotes nerve cell regeneration and synaptogenesis and maintains cellular development and homeostasis through the modulation of a variety of neurotrophic factors, receptor activity, neuropeptides, and monoamine neurotransmitters, and by decreasing the levels of inflammatory factors and other modulators of neuroplasticity. At the cellular level, exercise enhances neural activation and control and improves brain structure through nerve regeneration, synaptogenesis, improved glial cell function and angiogenesis. At the structural level of the brain, exercise promotes cognitive function by affecting white and gray matter volumes, neural activation and brain region connectivity, as well as increasing cerebral blood flow. This review elucidates how exercise improves the internal environment at the molecular level, promotes cell regeneration and functional differentiation, and enhances the brain structure and neural efficiency. It provides a comprehensive, multi-dimensional explanation of the neurophysiological mechanisms through which exercise promotes cognitive function.
Animals ; Humans ; Brain/physiology* ; Cognition/physiology* ; Exercise/physiology* ; Nerve Regeneration/physiology* ; Neuronal Plasticity/physiology*