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.

ObjectivePhotoacoustic tomography (PAT) holds significant potential for high-resolution deep-tissue imaging. In preclinical research, custom-designed concave arc-shaped ultrasound transducer arrays are often used to maximize the detection aperture. However, manufacturing limitations and assembly tolerances frequently cause the actual physical positions of array elements to deviate from their theoretical design. Additionally, concave arrays are typically covered with an acoustic lens, which introduces a mismatch in the speed of sound between the coupling medium and the lens material. The combination of these geometric and acoustic-phase errors leads to severe image artifacts, reduced contrast, and degraded resolution. This study proposes a systematic two-step calibration strategy to address these issues and substantially improve image quality. MethodsFirst, a high-intensity isotropic photoacoustic point source was constructed using a multi-mode optical fiber coated with carbon nanotubes (CNTs) to acquire high signal-to-noise ratio calibration data. The Akaike information criterion (AIC) was employed to accurately determine the time of arrival (ToA) of photoacoustic signals. Subsequently, a geometric calibration algorithm based on nonlinear least-squares (NLS) estimation was developed. This algorithm iteratively solves for the true spatial coordinates of each array element by minimizing the residual between theoretical and measured acoustic path lengths. To further address sound-speed inhomogeneity caused by the acoustic lens, a phase compensation algorithm based on bilinear interpolation was proposed. This algorithm computes a pixel-specific phase delay map across the imaging region and performs point-by-point signal correction during delay-and-sum (DAS) reconstruction. The proposed methods were validated using a custom 96-channel concave arc-shaped array (center frequency: 12  MHz) through both phantom imaging and in vivo mouse tumor models. ResultsPhantom experiments showed that at an imaging depth of14 mm, the reconstruction position deviation of the point source in the uncalibrated system reached up to 1  mm. After applying the combined calibration, the lateral resolution (full width at half maximum, FWHM) at the focal point of the arc array reached 95  μm—representing a 85% reduction compared to the uncalibrated state and a 79% reduction compared to geometric calibration alone without phase compensation. In vivo experiments demonstrated that the calibrated system clearly resolved the microvascular network of subcutaneous tumors in mice. Photoacoustic signals were strictly confined within tumor boundaries delineated by ultrasound imaging (USI), eliminating the vascular spillover artifacts commonly observed in uncalibrated images. Furthermore, after intravenous injection of indocyanine green (ICG), the system successfully detected weak photoacoustic signals at a depth of 5 mm, performing significantly better than the uncalibrated system. ConclusionThe proposed calibration method, which integrates nonlinear least-squares estimation with phase compensation, significantly improves image fidelity and spatial resolution consistency across a wide field of view by correcting systemic geometric errors and acoustic phase aberrations. This approach demonstrates high robustness and provides a reliable technical foundation for the clinical translation of photoacoustic probes with non-standard geometries.

ObjectiveTo evaluate the feasibility of various strength levels of deep learning image reconstruction （DLIR） algorithms for improving non-contrast abdominal CT image quality at ultra-low radiation doses， by comparing ultra-low-dose DLIR images with low-dose filtered back projection （FBP） images. MethodsA prospective collection of 85 patients undergoing non-contrast abdominal CT scans was performed， and a self-controlled study method was employed to conduct low-dose （LD） group and ultra-low-dose （ULD） group scans. The LD group used a noise index of 10 and employed FBP for image reconstruction （LD-FBP group）. The ULD group used a noise index of 30 and employed DLIR at different levels （low， medium， high）， resulting in three subgroups of reconstructed images： ULD-DLIR-L， ULD-DLIR-M， and ULD-DLIR-H. For each group， CT values， standard devia-tion （SD）， signal-to-noise ratio （SNR）， and contrast-to-noise ratio （CNR） were measured and calculated for the liver， spleen， kidneys， aorta， psoas major， and subcutaneous fat. Effective dose （ED） was also recorded. Two radiologists independently performed subjective evaluations of image quality using a 5-point scale. ResultsCompared with the LD-FBP group， the ULD-DLIR-L group showed significantly lower SNR and CNR values in the liver， spleen， kidneys， aorta， and psoas major （P<0.001）， while the ULD-DLIR-H group exhibited significantly higher values （P<0.001）. The difference of SNR and CNR values for the ULD-DLIR-M group showed no statistically significant difference. For subjective evaluation， the scores of the ULD-DLIR-L and ULD-DLIR-M groups were lower than those of the LD-FBP group， while there was no statistically significant difference in scores between the ULD-DLIR-H group and the LD-FBP group. The ED value of the ULD group was approximately 88% lower than that of the LD group. ConclusionCompared with the LD-FBP group， the ULD-DLIR-H group significantly reduces SD values while increasing SNR and CNR values， effectively improving the image quality of non-contrast abdominal CT scans.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Membrane proteins are integral components of cellular membranes, accounting for approximately 30% of the mammalian proteome and serving as targets for 60% of FDA-approved drugs. They are critical to both physiological functions and disease mechanisms. Their functional protein-protein interactions form the basis for many physiological processes, such as signal transduction, material transport, and cell communication. Membrane protein interactions are characterized by membrane environment dependence, spatial asymmetry, weak interaction strength, high dynamics, and a variety of interaction sites. Therefore, in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.

Objective: This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH). Methods: A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups. Results: The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05). Conclusion This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.

Achieving periodontal regeneration in class III furcation defects is challenging. Many studies have applied growth factors to periodontal defects, including fibroblast growth factors (FGFs), which demonstrate angiogenic activity and mitogenic ability. This study aimed to evaluate periodontal regeneration following the application of FGF-2 to deproteinized bovine bone mineral (DBBM) in surgically created supra-alveolar class III furcation defects of the mandibular premolars of beagles. The defects were divided into the control, DBBM, and FGF/DBBM groups. For the control group, only root planing was performed. For the DBBM group, only DBBM particles were implanted into the furcation. For the FGF/DBBM group, DBBM was soaked with 0.3% FGF-2 solution, and FGF-2/ DBBM was then positioned into the furcation. After 8 weeks, the dogs were euthanized. The micro-computed tomography analysis revealed that the changes in the bone volume of the furcation area were significantly greater in the FGF/DBBM group than in the DBBM group. In the histomorphometric analysis, the area of the newly formed bone was significantly greater in the FGF/DBBM group than in the DBBM or control group. The cementum extension was significantly longer in the FGF/DBBM or DBBM group than in the control group. The epithelial area was significantly less in the FGF/DBBM group than in the DBBM or control group. The application of FGF combined with DBBM to a class III defect enhanced the regeneration of periodontal tissues and increased the healing rate. This finding indicates that FGF-2 combined with DBBM can be applied to class III defects clinically.

Objective: This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH). Methods: A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups. Results: The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05). Conclusion This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.

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

OBJECTIVES: Older adults in rural areas with multiple chronic conditions (MCC) generally exhibit poorer medication adherence than the general elderly population. Considering individual heterogeneity helps to design precise subgroup-based interventions. This study aims to identify latent profile types of medication adherence mechanisms among rural older adults with MCC based on the capability-opportunity-motivation-behavior (COM-B) model, and to explore factors influencing medication adherence. METHODS: A multistage sampling method was used to recruit 349 rural older adults with MCC from 10 administrative villages in Jianghua County, Yongzhou City, Hunan Province, between July and September, 2024. Participants were surveyed using a general information questionnaire, the Health Literacy Scale for Chronic Patients, the Beliefs about Medicines Questionnaire-Specific, the Multidimensional Scale of Perceived Social Support, and the Morisky Medication Adherence Scale. Latent profile analysis based on the COM-B model was conducted to identify subgroups of medication adherence mechanisms. Univariate and Logistic regression analyses were used to identify influencing factors associated with different latent profiles and adherence levels. RESULTS: Among the participants, 33.5% demonstrated good medication adherence. The 5 most prevalent chronic diseases were hypertension (86.5%), diabetes (36.7%), arthritis or rheumatism (34.4%), stroke (21.8%), and heart disease (17.5%). Overall, rural older adults with MCC exhibited relatively good medication capability, opportunity, and motivation. Their medication adherence mechanisms were classified into 3 latent profiles: "family-support restrained type" (5.2%), "family-support driven type" (52.1%), and "comprehensive advantage type" (42.7%). Significant differences were observed among the three profiles in terms of education level, marital status, living arrangement, and per capita monthly household income (all P<0.05). Multivariate Logistic regression revealed that higher education level was a protective factor for belonging to the "comprehensive advantage type" rather than the "family-support driven type" [OR=0.277, 95% CI (PL) 0.126 to 0.614, P=0.002]. Furthermore, significant differences in education level, self-rated health status, and latent profile type were found between participants with good and poor adherence (P<0.05). Binary Logistic regression indicated that with each one-level increase in self-rated health status, the risk of poor adherence increased by 293.9% [OR=3.939, 95% CI (PL) 1.610 to 9.636, P=0.003]. Compared with the "family-support restrained type", individuals classified as the "comprehensive advantage type" had a 96.8% [OR=0.032, 95% CI (PL) 0.008 to 0.123, P<0.001] lower risk of poor medication adherence. CONCLUSIONS The mechanisms underlying medication adherence among rural older adults with MCC show clear heterogeneity. Primary healthcare providers should focus on the "family-support restrained type" subgroup, strengthen social support networks, and implement targeted interventions to improve medication adherence.
Humans ; Aged ; Rural Population ; Male ; Female ; China ; Medication Adherence/psychology* ; Surveys and Questionnaires ; Chronic Disease/drug therapy* ; Multiple Chronic Conditions/drug therapy* ; Social Support ; Motivation ; Middle Aged ; Health Literacy ; Aged, 80 and over