OBJECTIVE: To investigate the characteristics of central nervous system regulation in patients with refractory overactive bladder (rOAB) using resting-state functional magnetic resonance imaging (rs-fMRI), and to analyze the differences in brain function and connection between the patients and healthy population. METHODS: From May 1 to November 30, 2024, we performed rs-fMRI for 47 rOAB patients and another 47 matched healthy controls, documented relevant clinical data from all the participants and obtained their Overactive Bladder Symptom Scores (OABSS) and Overactive Bladder Questionnaire (OAB-Q) scores. Based on rs-fMRI, we compared the results of Independent Component Analysis (ICA), amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo) and degree centrality (DC) between the rOAB patients and healthy controls. RESULTS: The rOAB patients, in comparison with the healthy controls, showed dramatically higher daytime urination frequency (11.64 ± 3.85) vs (5.76 ± 0.91), nighttime urination frequency (3.72 ± 1.64) vs (0.31 ± 0.47), OABSS (8.22 ± 2.21) vs (0.64±0.78), OAB-Q1 score (20.85 ± 5.28) vs (6.78 ± 1.04), and OAB-Q2 score (45.04 ± 12.11) vs (14.51 ± 1.66) (all P<0.01). No statistically significant differences were observed in the results of ICA and ALFF between the right superior frontal and right middle frontal regions in the rOAB patients (P>0.05), but fALFF, ReHo and DC were significantly decreased in the patients compared with those in the healthy controls (P<0.01). CONCLUSION Compared with healthy population, the functions and connection of the frontal superior right and frontal middle right brain regions in rOAB patients are significantly down-regulated, which may serve as new therapeutic targets.
Humans ; Urinary Bladder, Overactive/physiopathology* ; Magnetic Resonance Imaging ; Brain/physiopathology* ; Female ; Male ; Adult ; Surveys and Questionnaires ; Case-Control Studies ; Middle Aged ; Rest ; Brain Mapping

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Objective To investigate the effects of a 100 mT static magnetic field(SMF)on emotional behavior and brain damage-related molecules in mice.Methods Fifty-eight C57BL/6N mice were randomly divided into control group(n=25)and observation group(n=33).Mice in observation group were exposed to a 100 mT SMF for 0.5 h/d over 14 consecutive days,while mice in control group underwent pseudo-exposure.On the 7 and 14 days of exposure,anxiety-like behavior was assessed using open field and elevated plus maze tests.Cerebral blood flow was monitored using laser speckle imaging,and the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-4,central nervous system specific protein β(S100β),neuron-specific enolase(NSE),and brain-derived neurotrophic factor(BDNF)were measured by radioimmunoassay.BDNF expression in the brain was detected by immunofluorescence.Results On the 7 and 14 days of SMF exposure,the open field and elevated plus maze tests showed no statistically significant differences between observation and control groups in the frequencies,durations,and distance entering the central area of the open field and the open arm of the elevated plus maze(P>0.05).Laser speckle imaging revealed no significant difference in cerebral cortical perfusion compared with pre-exposure period(P>0.05).The results of radioimmunoassay showed that compared with control group,on the 7 d of SMF exposure,the serum IL-1β,NSE and S100β levels were significantly increased(P<0.05),the serum BDNF level was significantly decreased(P<0.05),and the IL-1β and TNF-α contents in brain tissues were significantly increased in observation group(P<0.01).On the 14 d of SMF exposure,serum IL-1β,TNF-α,NSE,and S100β levels were significantly increased(P<0.05,P<0.0001),and the brain IL-1β and TNF-α levels were significantly increased(P<0.01)in observation group.No statistically significant differences were found in anti-inflammatory cytokine IL-4 level of serum and brain tissue or BDNF content of brain tissue between the two groups(P>0.05).Conclusion Continuous exposure to a 100 mT SMF for 14 d at 0.5 h/d induces neuroinflammation and brain damage in mice,without inducing anxiety-like behavior.