Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

BACKGROUND: Post-stroke disability diminishes the physical activity (PA) level of survivors, potentially affecting their long-term prognosis. This study endeavors to explore the correlation between daily PA level and the all-cause mortality in patients with a history of stoke in the United States. METHODS: Data of stroke survivors were sourced from the National Health and Nutritional Examination Survey (NHANES) 2007-2018. The population was stratified into three groups based on their PA level. Kaplan-Meier method with log-rank tests for significance was used for survival analysis. Weighted Cox proportional hazards regression models were employed to estimate the hazard ratios (HRs) for all-cause mortality. Subgroup analysis was conducted to strengthen the results. RESULTS: A total of 1395 participants were recruited, comprising 679 males and 716 females, with a median age of 68 years. Based on their PA levels, 779 individuals were classified as inactive, 156 as insufficiently active, and 460 as sufficiently active. Following a median observation period of 59 months, there were 476 recorded deaths, with 349, 47, and 80 cases in the three respective groups. Compared to the inactive group, the HRs and 95% confidence intervals (CIs) for all-cause mortality in participants who were insufficiently active and sufficiently active were 0.58 (0.40, 0.84) and 0.47 (0.33, 0.67), respectively. The Kaplan-Meier curve revealed a significant difference in overall survival between the three groups, as confirmed by the log-rank test (P < 0.0001). Subgroup analysis further validated our results and demonstrated that the protective impact of PA on stroke prognosis varies according to distinct characteristics. CONCLUSIONS The results indicate that increased levels of PA are associated with a protective effect on long-term mortality among stroke survivors. Further prospective longitudinal studies are necessary to elucidate the optional PA level and special exercise guideline targeting this population.
Humans ; Male ; Female ; Aged ; Exercise ; Middle Aged ; Nutrition Surveys ; Stroke/mortality* ; United States/epidemiology* ; Survivors/statistics & numerical data* ; Aged, 80 and over ; Mortality

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

As a crucial barrier to ensuring blood transfusion safety, blood virus inactivation technology plays an irreplaceable role in addressing the "window period" of detection, the threat of emerging pathogens, and the limitations of detection technologies. This article systematically reviews the current status and technical characteristics of mainstream blood virus inactivation technologies, and conducts an in-depth discussion on the application prospects and challenges of emerging technologies in this field. Among conventional technologies, the photochemical methods (including methylene blue, psoralen S-59/INTERCEPT system, and riboflavin/Mirasol system) have been widely used in clinical practice due to their broad-spectrum inactivation capacity. However, these methods are associated with functional impairment of blood components. The organic solvent/detergent (S/D) method performs excellently in inactivating viruses in plasma products yet is ineffective against non-lipid-enveloped viruses. Short-wave ultraviolet (UVC) direct irradiation technology eliminates the need for chemical additives, though its inactivation efficiency and compatibility with blood components requires optimization. The chemical modification method, while specifically designed for red blood cells, faces safety challenges such as potential immunogenicity. For emerging technologies, cold plasma technology shows great potential owing to its multi-target synergistic inactivation mechanism, though challenges regarding its biocompatibility and selectivity remain. Electrolyzed water technology has the advantages of low cost and operational simplicity, yet in-depth research is needed on the non-specific damage caused by active substances to blood components. Novel photodynamic therapy significantly improves inactivation efficiency by developing high-efficiency targeted photosensitizers and has broad prospects for combined applications with antibodies, nanomaterials, and other substances. Future development trends point to the "combination therapy" strategy, which leverages the synergy of multiple technologies to achieve the optimal balance between efficient virus inactivation and functional prservation of blood components. The development of such technologies needs to shift from "single-method" to "integrated approach", from "inactivation" to "viability preservation", and bridge the translation gap from "laboratory" to "global application". The ultimate goal is to establish a standardized, automated, and cost-controllable comprehensive blood safety assurance system.

Objective: To investigate the antidepressant effects of Yuanzhi (Polygalae Radix, PR) aqueous extract on chronic unpredictable mild stress (CUMS)-induced depression rat models and the underlying mechanisms. Methods: A total of 40 male Sprague Dawley (SD) rats were randomly divided into control, model, low dose of PR (PR-L, 0.5 g/kg), high dose of PR (PR-H, 1 g/kg), and fluoxetine (10 mg/kg) groups, with 8 rats in each group. Except for the rats in control group, those in the other four groups underwent CUMS-induced depression modeling. PR and fluoxetine were administered intragastrically once daily, 30 min prior to the CUMS procedure, for 14 consecutive days until the behavioral tests were performed. After CUMS modeling, the sucrose preference test (SPT), open field test (OFT), novelty-suppressed feeding test (NSFT), forced swim test (FST), and tail suspension test (TST) were employed to assess the pharmacological effects of PR on the mitigation of depressive-like behaviors in rat models. Additionally, the enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the rats. Western blot analysis was also conducted to evaluate the protein expression levels of nuclear factor kappa-B (NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing caspase recruitment domain (ASC), and caspase-1 in the hippocampal tissues of the rats. Immunofluorescence staining was performed to observe the morphological changes in ionized calcium-binding adapter molecule 1positive (Iba-1+) cells in the dentate gyrus (DG) of rats with CUMS-induced depression. Result: (i) Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests (P < 0.01 and P < 0.05, respectively). Post-administration of PR-H and fluoxetine also led to statistically significant increase in sucrose preference among rats (P < 0.05). Besides, PR-L, PR-H, and fluoxetine treatment markedly decreased the latency of ingestion (P < 0.05, P < 0.05, and P < 0.01, respectively). As observed from the FST, PR-L, PR-H, and fluoxetine presented antidepressant effects on rats with CUMS-induced depression, leading to the reduction in time of their immobility (P < 0.05, P < 0.01, and P < 0.01, respectively). The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well (P < 0.01). (ii) Rats in model group showed an increase in the levels of Iba-1+ microglia in their left and right brains in comparison with control group (P < 0.01). However, such increase was negated post PR treatment (P < 0.01). Treatment with PR-L, PR-H, and fluoxetine considerably reduced the levels of inflammatory factors (TNF-α, IL-1β, and IL-6, P < 0.01). In addition, treatment of PR-L and PR-H effectively counteracted the elevated levels of NLRP3, ASC, and caspase-1, and markedly down-regulated the expression levels of phosphorylated p65 (p-p65), COX-2, and iNOS in rats’ hippocampus (P < 0.01). Conclusion Collectively, these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.

Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.

[Objective] To summarize the diagnosis and treatment of Antopol Goldman lesion (AGL) in clinical practice. [Methods] Clinical data and diagnosis and treatment process of one AGL case treated in our hospital were retrospectively analyzed, and relevant literature was reviewed. [Results] The patient presented with painless gross hematuria and right-sided lower back pain.Imaging examination suggested swelling of the right kidney, blood accumulation in the right calyx, renal pelvis and lower ureter, blood clot in the bladder, and multiple small stones in the left kidney.After multidisciplinary consultation, close imaging follow-up, interventional and flexible ureterdscope examination, tumors of hematological diseases, renal hematuria, arteriovenous fistula and collection system were excluded.After conservative treatment, the patient gradually recovered.During the follow-up of 1 year, no hematuria or low back pain recurred. [Conclusion] There is no clear diagnostic standard for AGL.Diagnosis relies on imaging, interventional methods and ureteroscopy.It is necessary to exclude other diseases and adopt conservative treatment.

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components, namely quercetin, β-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.