Objective: To investigate the bactericidal efficacy and impact on oral mixed biofilm microbial structure of commonly used clinical root canal irrigants under dynamic oxygen conditions, and to provide experimental evidence for clinical root canal irrigant selection. Methods: This study has been reviewed and approved by the Medical Ethics Committee, and written informed consent has been obtained from all of the participants. Two healthy oral volunteers from Beijing Stomatological Hospital, Capital Medical University were selected, and subgingival and supragingival plaque from their mandibular premolars and molars were extracted to construct an oral mixed microbial biofilm model. The plaque was cultivated on hydroxyapatite slices for 1 week (anaerobic conditions for 3 days + aerobic conditions for 4 days) to construct a young oral mixed bacterial biofilm model, and cultivated for 3 weeks (anaerobic conditions for 3 days + aerobic conditions for 18 days) to construct a mature oral mixed bacterial biofilm model. Three root canal irrigating solutions were used: sterile water (control), 2% chlorhexidine (CHX), and 1% sodium hypochlorite (NaOCl). The bacterial biofilms were treated for 1 week and 3 weeks, respectively, and the overall bactericidal rate was assessed using live/dead bacterial staining and laser confocal microscopy. Concurrently, high-throughput 16S rRNA sequencing was performed to analyze the microbial community structure and to evaluate the antibacterial effects of irrigation solution, on common dominant pathogens Results: The proportion of dead bacteria in the biofilm treated with three types of root canal irrigation drugs at 1 week and 3 weeks, from high to low, were as follows: 1% NaOCl >2% CHX >control group (P < 0.001). The bactericidal rate of 1% NaOCl on mature biofilms at 3 weeks was significantly lower than that of light biofilms at 1 year (P < 0.001). High-throughput sequencing revealed minimal effects of 2% CHX and 1% NaOCl on biofilm community structure but demonstrated poor bactericidal activity against dominant root canal pathogens, such as Streptococcus and Fusobacterium. Conclusion Under the initial anaerobic and subsequent aerobic culture conditions, 1% NaOCl exhibits potent bactericidal effects on young bacterial biofilms, but demonstrates limited efficacy against mature biofilms and certain root canal dominant bacteria (Streptococcus and Fusobacterium).

Objective: To compare the effects of 12 week Tai Chi combined with inspiratory muscle resistance training on cardiopulmonary function among male college students in health care classes, so as to provide a reference for improving the cardiopulmonary function of the students. Methods: From March to May 2025, 72 male students from the physical education health care classes at North University of China were selected and randomly divided into the control group ( n =25), the Tai Chi group ( n = 24), and the Tai Chi combined with inspiratory muscle resistance training group (combined group, n =23) by random number table method. The control group maintained normal living habits, the Tai Chi group underwent 12 weeks of Tai Chi exercise (three sessions per week, 90 minutes per session), and the combined group received 12 weeks of Tai Chi training (three sessions per week, 60 minutes per session) combined with 30 minutes of inspiratory muscle resistance training. Cardiovascular function[heart rate(HR), stroke volume(SV), cardiac output(CO), mean systolic pressure(MSP), mean diastolic pressure(MDP), vascular elastic dilatation coefficient (VDC), total peripheral resistance (TPR), viscosity (V)], pulmonary function [vital capacity (VC), forced vital capacity (FVC), maximum minute ventilation volume (MVV), forced expiratory volume in one second (FEV1), FEV1/FVC] and heart rate variability (HRV) [HR, standard deviation of the normal to normal intervals (SDNN), root mean square successive difference (RMSSD), low frequency (LF), high frequency (HF), LF/HF] of the three groups of subjects were tested before and after the experiment, the data were analyzed using analysis of covariance. Results: There were no statistically significant differences in any indicators among the three groups before the intervention ( F =0.00-2.49, all P >0.05). After the intervention, except FEV1/FVC, MDP and V, there were statistically significant differences of pulmonary function, cardiovascular function and HRV indicators among the three groups ( F =4.38-62.93, all P <0.05). Compared with the control group [(VC ( 3.28± 0.30)L, FVC (3.20±0.29)L, MVV (107.01±9.55)L, SV (65.68±2.34)mL, CO (5.36±0.18)L/min, VDC (0.40±0.03), step index (50.64±3.11), MSP (133.17±6.47)mmHg, TPR (1 281.34±100.78)dyn ·s ·cm -5 ], the VC [(3.43±0.24, 3.69±0.21)L], FVC [(3.34±0.16, 3.46±0.20)L], MVV [(112.54±8.95, 117.11±6.37)L], SV [(71.75±4.20, 75.39±3.71)L/time], CO[( 5.53± 0.14, 5.58±0.15)L/min], VDC (0.43±0.03, 0.44±0.02) and step index (53.38±5.77, 56.17±4.91) in the Tai Chi group and the combined group significantly increased, while the MSP [(120.17±6.42, 118.04±12.99)mmHg] and TPR [( 1 227.01 ±107.25, 1 217.69±64.93)dyn ·s ·cm -5 ] significantly decreased (all P <0.05). The HRV showed improvement. Moreover, compared with the Tai Chi group, VC, FVC, MVV, FEV1[(2.99±0.14，3.05±0.15)L], SV, step index, RMSSD[( 45.41± 9.59，52.82±7.67)ms] and HF [(2.74±0.13，2.87±0.16)ms 2] increased, while HR [(77.17±6.01, 73.83± 3.71)beats/min ] decreased in the combined group (all P < 0.05 ). Conclusion Twelve weeks of Tai Chi exercise and Tai Chi combined with inspiratory muscle resistance training can improve the cardiopulmonary function of male college students in health care classes, and the effect of the combined training is superior to that of Tai Chi training alone.

Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the leading cause of dementia in the elderly, is characterized by severe cognitive decline, loss of daily living abilities, and neuropsychiatric symptoms. This condition imposes a substantial burden on patients, families, and society. Despite extensive research efforts, the complex pathogenesis of AD, particularly the early mechanisms underlying cognitive dysfunction, remains incompletely understood, posing significant challenges for timely diagnosis and effective therapeutic intervention. Among the various cellular components implicated in AD, GABAergic interneurons have emerged as critical players in the pathological cascade, playing a pivotal role in maintaining neural network integrity and function in key brain regions affected by the disease. GABAergic interneurons represent a heterogeneous population of inhibitory neurons essential for sustaining neural network homeostasis. They achieve this by precisely modulating rhythmic oscillatory activity (e.g., theta and gamma oscillations), which are crucial for cognitive processes such as learning and memory. These interneurons synthesize and release the inhibitory neurotransmitter GABA, exerting potent control over excitatory pyramidal neurons through intricate local circuits. Their primary mechanism involves synaptic inhibition, thereby modulating the excitability and synchrony of neural populations. Emerging evidence highlights the significant involvement of GABAergic interneuron dysfunction in AD pathogenesis. Contrary to earlier assumptions of their resistance to the disease, specific subtypes exhibit vulnerability or altered function early in the disease process. Critically, this impairment is not merely a consequence but appears to be a key driver of network hyperexcitability, a hallmark feature of AD models and potentially a core mechanism underlying cognitive deficits. For instance, parvalbumin-positive (PV⁺) interneurons display biphasic alterations in activity. Both suppressing early hyperactivity or enhancing late activity can rescue cognitive deficits, underscoring their causal role. Somatostatin-positive (SST⁺) neurons are highly sensitive to amyloid β-protein (Aβ) dysfunction. Their functional impairment drives AD progression via a dual pathway: compensatory hyperexcitability promotes Aβ generation, while released SST-14 forms toxic oligomers with Aβ, collectively accelerating neuronal loss and amyloid deposition, forming a vicious cycle. Vasoactive intestinal peptide-positive (VIP⁺) neurons, although potentially spared in number early in the disease, exhibit altered firing properties (e.g., broader spikes, lower frequency), contributing to network dysfunction (e.g., in CA1). Furthermore, VIP release induced by 40 Hz sensory stimulation (GENUS) enhances glymphatic clearance of Aβ, demonstrating a direct link between VIP neuron function and modulation of amyloid pathology. Given their central role in network stability and their demonstrable dysfunction in AD, GABAergic interneurons represent promising therapeutic targets. Current research primarily explores three approaches: increasing interneuron numbers (e.g., improving cortical PV⁺ interneuron counts and behavior in APP/PS1 mice with the antidepressant citalopram; transplanting stem cells differentiated into functional GABAergic neurons to enhance cognition), enhancing neuronal activity (e.g., using low-dose levetiracetam or targeted activation of specific molecules to boost PV⁺ interneuron excitability, restoring neural network γ‑oscillations and memory; non-invasive neuromodulation techniques like 40 Hz repetitive transcranial magnetic stimulation (rTMS), GENUS, and minimally invasive electroacupuncture to improve inhibitory regulation, promote memory, and reduce Aβ), and direct GABA system intervention (clinical and animal studies reveal reduced GABA levels in AD-affected brain regions; early GABA supplementation improves cognition in APP/PS1 mice, suggesting a therapeutic time window). Collectively, these findings establish GABAergic interneuron intervention as a foundational rationale and distinct pathway for AD therapy. In conclusion, GABAergic interneurons, particularly the PV⁺, SST⁺, and VIP⁺ subtypes, play critical and subtype-specific roles in the initiation and progression of AD pathology. Their dysfunction significantly contributes to network hyperexcitability, oscillatory deficits, and cognitive decline. Understanding the heterogeneity in their vulnerability and response mechanisms provides crucial insights into AD pathogenesis. Targeting these interneurons through pharmacological, neuromodulatory, or cellular approaches offers promising avenues for developing novel, potentially disease-modifying therapies.

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

Bronchiectasis(BE) is the third major chronic airway disease, and its incidence rate shows a continuously increasing trend. Bronchiectasis is a highly heterogeneous chronic airway disease. Due to structural alterations, airflow limitation, and mucus hypersecretion, clinical treatment faces many challenges. Particularly, problems including Pseudomonas aeruginosa-dominant drug-resistant bacterial colonization, recurrent infections, airway mucus hypersecretion, and impaired lung function are the most urgent, requiring long-term and personalized treatment and management integrating traditional Chinese and western medicine to prevent the recurrence and continuous progression of the disease. In recent years, both traditional Chinese medicine and western medicine have made certain progress in pathogenesis theories, clinical studies, and basic research regarding the therapeutic challenges of bronchiectasis. Therefore, this paper summarized relevant research from the past 10 years and explored future directions and potential advantages of integrated traditional Chinese and western medicine treatment, providing references for optimizing the clinical management strategies for bronchiectasis.
Bronchiectasis/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Animals

OBJECTIVE: To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods. METHODS: In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator. RESULTS: The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups. CONCLUSION This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.
Humans ; Female ; Propensity Score ; Embryo Transfer ; Adult ; Acupuncture Therapy ; Retrospective Studies ; Pregnancy ; Live Birth ; Birth Rate ; Cohort Studies

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index