Objective: This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction (XFBD) in a mouse model of dampness-heat toxin pneumonia. By exploring how XFBD exerts its effects, we seek to deepen our understanding of its role in treating pulmonary diseases and to address the current knowledge gap regarding its mechanisms of action, thereby supporting its clinical application. Methods: Ultra-high-performance liquid chromatography and high-resolution mass spectrometry (HRMS) were employed to analyze the chemical constituents of XFBD. The protective effects of XFBD were evaluated using a dampness-heat toxin-induced mouse model, established through dampness-heat exposure and HCoV-229E infection. XFBD was administered orally, followed by assessments including lung index measurement, micro-CT imaging, viral load quantification, cytokine analysis, and histological evaluation via hematoxylin-eosin staining. Proteomics and single-cell transcriptomic analyses were conducted to explore the potential mechanisms underlying XFBD’s pharmacological effects. A cellular model of HCoV-229E infection was developed to investigate changes in the cAMP/PKA signaling pathway. Molecular docking and surface plasmon resonance (SPR) experiments confirmed the strong binding affinity between key XFBD components and PKA. Finally, PKA activators and inhibitors were applied in vitro to validate these mechanistic findings. Results: In vivo studies demonstrated that XFBD significantly reduced the lung index, improved the structural integrity of lung and tongue tissues, and decreased levels of proinflammatory mediators, including IL-6, IL-8, and TNF-α. Proteomic and single-cell transcriptomic analyses showed that the differentially expressed proteins after XFBD treatment were primarily associated with inflammatory responses and immune regulation. The cAMP/PKA signaling pathway was identified as a key mechanism underlying these therapeutic effects. Notably, Western blot, ELISA, molecular docking, and SPR analyses confirmed that XFBD elevated cAMP levels and p-PKA expression, thereby activating the cAMP/PKA signaling pathway in vitro. Conclusion: This study demonstrated that XFBD significantly alleviates symptoms in mice with dampness-heat toxin pneumonia. Its therapeutic effects are mediated, at least in part, through activation of the cAMP/PKA signaling pathway. These findings provide compelling evidence that XFBD is an effective herbal remedy against HCoV-229E infection.

Liquiritigenin(LG)is a flavone of pharmacological importance,however,its application potential is severely limited due to its poor water solubility.LG could be disassociated slightly in water to form phenolate anion,therefore,better solubilization effect is expected by inclusion with cationic cyclodextrins(CCDs).In this work,four kinds of CCDs modified with amino groups at the primary face were synthesized,and their solid inclusion complexes with LG were successfully prepared by preparing their saturated solutions.The formation of the solid inclusion complexes was confirmed by scanning electron microscopy(SEM)and powder X-ray diffraction(PXRD),and their supramolecular binding behavior in solution was studied using multiple techniques.A 1∶1 inclusion stoichiometry of inclusion complexation was defined using Job plot by ultraviolet-visible(UV-vis)spectroscopy,and their binding stability constants(Ks)were determined as 2862.77,3494.70,6521.85 and 9599.48 L/mol using UV-vis spectroscopic titration,far more superior to that of nativeβ-CD(Ks=236.79 L/mol).This indicated that the amino side chains on CCDs could actively participate in the inclusion complexation through anion-cation interactions,significantly strengthening the host-guest binding between CCDs and LG.The inclusion modes were further elucidated based on proton and two-dimensional rotating-frame overhauser enhancement spectroscopy(2D-ROESY)nuclear magnetic resonance(NMR)experiments and molecular docking.Water solubility of LG was dramatically promoted up to 4.9 mg/mL,which was 70-fold higher than that of native LG.This study could draw inspiration for the binding and solubilization of phenols such as flavones by design of cationic macrocyclic molecules.

A dielectric barrier discharge ionization source with rapid evaporation and self-aspiration sampling(RE-SADBDI)was developed,integrating a rapid evaporation(RE)module and a dielectric barrier discharge ionization(DBDI)module.The sample was introduced into the RE module via a sampling swab and rapidly vaporized within it.The sealed design of the ionization source could enable the sample to be self-aspirated into the ionization region without the need of additional inert gas.All vaporized sample was efficiently directed into the ionization region due to the relatively enclosed environment for sample transfer and ionization,resulting in improved transfer and ionization efficiencies.Experimental results showed that the limit of detection(LOD)under ion isolation mode reached 0.05 ng/mL(caffeine),with a relative standard deviation(RSD)of 6.9%.Furthermore,when coupled with a miniaturized linear ion trap mass spectrometer,the source enabled real-time analysis of various sample types.The developed RE-SADBDI source was suitable for on-site analysis with miniaturized mass spectrometers.

To explore the clinical characteristics of primary intracranial germ cell tumors (iGCT) and analyze the risk factors for the occurrence of neuroendocrine dysfunction.Methods:A case series study was conducted. The data of 130 children diagnosed with iGCT who were admitted to the Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, from February 2021 to December 2023 was collected. The clinical characteristics of iGCT were summarized, including general information, clinical manifestations, imaging findings, laboratory tests and outcomes. Children were divided into groups aged 0-9 and 10-18 years, and divided into group non-neuroendocrine dysfunction, group partial neuroendocrine dysfunction and group combined hypothalamic and pituitary-target gland axis dysfunction. Multivariate Logistic regression was employed for statistical analysis to identify risk factors for neuroendocrine dysfunction in iGCT children.Results:A total of 130 iGCT children were included, with an age of (10±3) years, 87 males and 43 females. Among them, 82 children (63.1%) had germinoma and 48 children (36.9%) had non-germinomatous germ cell tumors (NGGCT). One hundred and ten children (84.6%) had single lesions, including 47 cases in the sellar region, 29 cases in the pineal region and 34 cases in the basal ganglia region. Multi-leisions presented in the 20 children (15.4%), with 10 cases in the sellar+pineal region, 6 cases in the sellar+basal ganglia region, 3 cases in the pineal+ganglia region and 1 case in the sellar+pineal+basal ganglia region. Dissemination was presented to 26 children (20.0%). Initial clinical manifestations presented with symptoms of cranial hypertension like headache and vomiting in 75 cases, vision changes in 28 cases, limb movement disorders in 42 cases, diabetes insipidus in 67 cases, precocious puberty in 23 cases, growth retardation in 22 cases and delayed puberty in 2 cases. Among the 72 children aged 0-9 years, 37 cases (51.4%) had germinoma and 35 cases (48.6%) had NGGCT, while among the 58 children aged 10-18 years, 45 cases (77.6%) had germinoma and 13 cases (22.4%) had NGGCT. Non neuroendocrine dysfunction group included 39 children, partial neuroendocrine dysfunction group 54 children, and combined hypothalamic and pituitary-target gland axis dysfunction group 37 children. Univariate analysis showed statistical difference in gender, disease duration, tumor location, and serum human chorionic gonadotropin level among the 3 groups (all P<0.05). Multivariate Logistic regression analysis revealed that girl ( OR=5.29, 95% CI 1.54-18.16) and long disease duration ( OR=1.07, 95% CI 1.01-1.14) were risk factors for neuroendocrine dysfunction in iGCT patients (both P<0.05). Conclusions:iGCT occurs in children of all ages, with a higher incidence in males. The proportions of germinoma and NGGCT are similar in children aged 0-9 years, while germinoma is more common in patients aged 10-18 years. The clinical symptoms are atypical and diverse. Female gender and longer disease duration demonstrate the presence of neuroendocrine dysfunction in iGCT.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

ObjectiveTo evaluate the clinical efficacy and safety of Huaban Jiedu Formulation （化斑解毒方， HJF） in treating psoriasis vulgaris with blood-heat syndrome. MethodsA randomized， double-blind， placebo-controlled study was conducted with 60 patients diagnosed with psoriasis vulgaris of blood-heat syndrome. Patients were randomly assigned to either a treatment group or a control group， with 30 cases in each. The treatment group received HJF granules orally， one dose a day， combined with topical Qingshi Zhiyang Ointment （青石止痒软膏）， while the control group received placebo granules， one dose a day， combined with the same topical ointment. Both groups were topically treated twice daily of 28 days treatment cours. Psoriasis area and severity index （PASI）， visual analogue scale for pruritus （VAS）， traditional Chinese medicine （TCM） syndrome scores， dermatology life quality index （DLQI）， and psoriasis life stress inventory （PLSI） were assessed before treatment and on day 14 and day 28. Response rates for PASI 50 （≥50% reduction） and PASI 75 （≥75% reduction）， as well as overall clinical efficacy， were compared between groups. Serum levels of interleukin-6 （IL-6） and interleukin-17 （IL-17） were measured before and after 28 days of treatment. Adverse reactions during treatment were recorded. ResultsAfter 28 days of treatment， both groups showed significant reductions in PASI total score， lesion area score， erythema， scaling， and infiltration scores， pruritus VAS score， TCM syndrome score， DLQI， PLSI， and serum IL-6 and IL-17 levels （P＜0.05）. Compared to the control group， the treatment group had significantly greater improvements in PASI total score and erythema score， TCM syndrome score， serum IL-6 and IL-17 levels， and PASI 50 response rate after 28 days （P＜0.05）. Between-group comparisons of score differences before and after 28-day treatment revealed that the treatment group showed significantly better improvements in PASI total， lesion area score， erythema score， TCM syndrome score， DLQI， PLSI， and inflammatory markers （P＜0.05 or P＜0.01）. The total effective rate on day 14 and day 28 was 40.00% （12/30） and 83.33% （25/30） in the treatment group， versus 6.90% （2/29） and 41.38% （12/29） in the control group， respectively. The clinical efficacy in the treatment group was significantly superior to that in the control group （P＜0.05）. Mild gastric discomfort occurred in 3 patients in the treatment group and 1 in the control group. ConclusionHJF can effectively improve skin lesions and TCM symptoms relieve pruritus， enhance quality of life， and reduce inflammatory markers IL-6 and IL-17， in patients with blood-heat syndrome of psoriasis vulgaris， with a good safety profile.

ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

The evaluation of blood compatibility of biomaterials is crucial for ensuring the clinical safety of implantable medical devices. To address the limitations of traditional testing methods in real-time monitoring and electrical property analysis, this study developed a portable electrical impedance tomography (EIT) system. The system uses a 16-electrode design, operates within a frequency range of 1 to 500 kHz, achieves a signal to noise ratio (SNR) of 69.54 dB at 50 kHz, and has a data collection speed of 20 frames per second. Experimental results show that the EIT system developed in this study is highly consistent with a microplate reader ( R ²=0.97) in detecting the hemolytic behavior of industrial-grade titanium (TA3) and titanium alloy-titanium 6 aluminum 4 vanadium (TC4) in anticoagulated bovine blood. Additionally, with the support of a multimodal image fusion Gauss-Newton one-step iterative algorithm, the system can accurately locate and monitor in real-time the dynamic changes in blood permeation and coagulation caused by TC4 in vivo. In conclusion, the EIT system developed in this study provides a new and effective method for evaluating the blood compatibility of biomaterials.
Electric Impedance ; Animals ; Tomography/instrumentation* ; Biocompatible Materials ; Materials Testing/instrumentation* ; Cattle ; Titanium ; Alloys ; Prostheses and Implants

OBJECTIVE: To investigate the load distribution on the more painful and less painful limbs in patients with mild-to-moderate and severe bilateral knee osteoarthritis (KOA) and explore the compensatory mechanisms in both limbs among bilateral KOA patients with different severity levels. METHODS: A total of 113 participants were enrolled between July 2022 and September 2023. This cohort comprised 43 patients with mild-to-moderate bilateral KOA (Kellgren-Lawrence grade 2-3), 43 patients with severe bilateral KOA (Kellgren-Lawrence grade 4), and 27 healthy volunteers (healthy control group). The visual analogue scale (VAS) score for pain, the Hospital for Special Surgery (HSS) score, passive knee range of motion (ROM), and hip-knee-ankle angle (HKA) were used to assess walking pain intensity, joint function, and lower limb alignment in KOA patients, respectively. Motion trajectories of reflective markers and ground reaction force data during walking were captured using a gait analysis system. Musculoskeletal modeling was then employed to calculate biomechanical parameters, including the peak knee adduction moment (KAM), KAM impulse, peak joint contact force (JCF), and peak medial/lateral contact forces (MCF/LCF). Statistical analyses were performed to compare differences in clinical and gait parameters between bilateral limbs. Additionally, one-dimensional statistical parametric mapping was utilized to analyze temporal gait data. RESULTS: Mild-to-moderate KOA patients showed the significantly higher HSS score (67.7±7.9) than severe KOA patients (51.9±8.9; t=8.747, P<0.001). The more painful limb in all KOA patients exhibited significantly greater HKA and higher VAS scores compared to the less painful limb ( P<0.05). While bilateral knee ROM did not differ significantly in mild-to-moderate KOA patients ( P>0.05), the severe KOA patients had significantly reduced ROM in the more painful limb versus the less painful limb ( P<0.05). Healthy controls showed no significant bilateral difference in any biomechanical parameters ( P>0.05). All KOA patients demonstrated longer stance time on the less painful limb ( P<0.05). Critically, severe KOA patients exhibited significantly higher peak KAM, KAM impulse, and peak MCF in the more painful limb ( P<0.05), while mild-to-moderate KOA patients showed the opposite pattern with lower peak KAM and KAM impulse in the more painful limb ( P<0.05) and a similar trend for peak MCF. CONCLUSION Patients with mild-to-moderate KOA effectively reduce load on the more painful limb through compensatory mechanisms in the less painful limb. Conversely, severe bilateral varus deformities in advanced KOA patients nullify compensatory capacity in the less painful limb, paradoxically increasing load on the more painful limb. This dichotomy necessitates personalized management strategies tailored to disease severity.
Humans ; Osteoarthritis, Knee/physiopathology* ; Range of Motion, Articular ; Male ; Female ; Middle Aged ; Biomechanical Phenomena ; Knee Joint/physiopathology* ; Pain Measurement ; Severity of Illness Index ; Aged ; Gait/physiology* ; Walking/physiology* ; Case-Control Studies ; Adult ; Weight-Bearing