ObjectiveTo explore the effectiveness and safety of Shenlong Dingji Formula （参龙定悸方） on the quality of life in patients with paroxysmal atrial fibrillation （PAF） of qi-yin deficiency and phlegm-stasis obstructing collaterals syndrome. MethodsA total of 60 patients with PAF of qi-yin deficiency and phlegm-stasis obstructing collaterals syndrome were recruited and randomly divided into a treatment group and a control group， with 30 patients in each group. The control group received standard western medicine treatment， while the treatment group was additionally given Shenlong Dingji Formula orally， one dose per day. Both groups were treated for 4 weeks. The primary outcome measure is the Atrial Fibrillation Effect on Quality of Life （AFEQT） score including scores of four dimensions，i.e. atrial fibrillation-related symptoms， treatment concerns， daily activities， and treatment satisfaction. The secondary outcome measures included the frequency and duration of symptomatic atrial fibrillation episodes and traditional Chinese medicine （TCM） syndrome scores covering symptoms such as palpitations， chest tightness， fatigue， shortness of breath， reluctance to speak， spontaneous sweating， stabbing pain， and insomnia. These indicators were assessed at baseline （before treatment）， after 2-week of treatment， after 4-week of treatment， and 4 weeks after the end of treatment （follow-up）. Additionally， safety indicators before and after treatment and adverse events occurring during the trial were recorded to evaluate safety. ResultsA total of 56 patients completed the study， with 28 in each group. Primary outcome indicators： 1） the treatment group showed significant improvement in the total score of the AFEQT scale， with significantly higher total scores after 2-week treatment， 4-week treatment， and follow-up compared to the previous time point （P＜0.05）. In the control group， the AFEQT score significantly increased only after 4-week treatment compared to baseline （P＜0.05）. In the treatment group， the AFEQT scores after 2-week， 4-week treatment， and during follow-up were all higher than those of the control group at the corresponding time points （P＜0.01）. 2） In the treatment group， there was no statistically significant difference in the AFEQT treatment satisfaction dimension score during follow-up compared to that after 4-week treatment （P＞0.05）. However， the scores for all other dimensions at each time point were higher than those at the previous time point （P＜0.05）. In the control group， the scores for the atrial fibrillation-related symptom dimension were higher after 2-week and 4-week treatment than those of the previous time points （P＜0.05）. For the treatment satisfaction dimension， significant increases were observed only after 2-week and 4-week treatment compared to baseline （P＜0.05）. Secondary outcome indicators： 1） In the treatment group， the frequency and duration of symptomatic atrial fibrillation episodes decreased significantly at each time point compared to the previous time point （P＜0.05）， except for the duration of trial fibrillation at follow-up. In the control group， the frequency of episodes decreased significantly at all time points compared to baseline （P＜0.05）， while the duration of trial fibrillation showed a significant reduction at follow-up compared to those after 2-week treatment （P＜0.05）. 2） In the treatment group， TCM syndrome scores significantly reduced after 2-week treatment， 4-week treatment， and during follow-up compared to the previous time point and baseline （P＜0.05）. In the control group， significant reductions were observed only after 4-week after treatment and during follow-up （P＜0.05）. The TCM syndrome scores in the treatment group were lower than those in the control group at the same time points （P＜0.01）. No adverse events occurred during the trial in either group， and safety indicators showed no significant changes after treatment. ConclusionShenlong Dingji Formula effectively improves the quality of life， alleviates TCM syndromes， and reduces the frequency and duration of symptomatic atrial fibrillation in patients with PAF of qi-yin deficiency and phlegm-stasis obstructing collaterals syndrome， and demonstrates good safety.

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Stroke ranks as the third leading cause of death and the fourth leading cause of disability worldwide. Its high disability rate and prolonged recovery period not only severely impact patients' quality of life but also impose a significant burden on families and society. Primary prevention is the cornerstone of stroke control, as early intervention on risk factors can effectively reduce its incidence. Therefore, the development of predictive models for first-ever stroke risk holds substantial clinical value. In recent years, advancements in big data and artificial intelligence technologies have opened new avenues for stroke risk prediction. This article reviews the current research status of traditional methods and machine learning models in predicting first-ever stroke risk and outlines future development trends from three perspectives: First, emphasis should be placed on technological innovation by incorporating advanced algorithms such as deep learning and large models to further enhance the accuracy of predictive models. Second, there is a need to diversify data types and optimize model architectures to construct more comprehensive and precise predictive models. Lastly, particular attention should be given to the clinical validation of models in real-world settings. This not only enhances the robustness and generalizability of the models but also promotes physicians' understanding of predictive models, which is crucial for their application and dissemination.

[Objective] : To predict the potential targets of Qingfu Juanbi Decoction (青附蠲痹汤, QFJBD) in treating rheumatoid arthritis (RA) using an improved Transformer model and investigate the network pharmacological mechanisms underlying QFJBD’s therapeutic effects on RA. Methods: First, a traditional Chinese medicine herb-target interaction (TCMHTI) model was constructed to predict herb-target interactions based on Transformer improvement. The performance of the TCMHTI model was evaluated against baseline models using three metrics: area under the receiver operating characteristic curve (AUC), precision-recall curve (PRC), and accuracy. Subsequently, a protein-protein interaction (PPI) network was built based on the predicted targets, with core targets identified as the top nine nodes ranked by degree values. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the targets predicted by TCMHTI and the targets identified through network pharmacology method for comparison. Then, the results were compared. Finally, the core targets predicted by TCMHTI were validated through molecular docking and literature review. Results: The TCMHTI model achieved an AUC of 0.883, PRC of 0.849, and accuracy of 0.818, predicting 49 potential targets for QFJBD in RA treatment. Nine core targets were identified: tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-10, IL-17A, cluster of differentiation 40 (CD40), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), IL-4, and signal transducer and activator of transcription 3 (STAT3). The enrichment analysis demonstrated that the TCMHTI model predicted 49 targets and enriched more pathways directly associated with RA, whereas classical network pharmacology identified 64 targets but enriched pathways showing weaker relevance to RA. Molecular docking demonstrated that the active molecules in QFJBD exhibit favorable binding energy with RA targets, while literature research further revealed that QFJBD can treat RA through 9 core targets. Conclusion The TCMHTI model demonstrated greater accuracy than traditional network pharmacology methods, suggesting QFJBD exerts therapeutic effects on RA by regulating targets like TNF-α, IL-1β, and IL-6, as well as multiple signaling pathways. This study provides a novel framework for bridging traditional herbal knowledge with precision medicine, offering actionable insights for developing targeted TCM therapies against diseases.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

This study aimed to investigate the effects of acupuncture on dynamic changes in Ca²⁺, Na⁺, and H₂O₂ flux following eccentric exercise-induced muscle injury. The total of 324 healthy male Wistar rats were randomly divided into 6 groups: control group (C), eccentric exercise group (E), eccentric exercise with acupuncture group (EA), EA with TRP channel blocker group (EAT), EA with NOX2 blocker group (EAN) and EA with placebo group (EAP). Gastrocnemius muscles were subject to lengthening contractions with percutaneous electrical stimulation, followed by immediate pretreatment with blocking agents. After 30 min, acupuncture needling was administered to the gastrocnemius muscle, and real-time dynamic changes of Ca²⁺, Na⁺ and H₂O₂ flux were measured with non-invasive micro-test technique during the needle retention period, immediately, 3 h, 6 h, and 24 h post-extraction respectively. Results showed that compared with the E group, acupuncture significantly increased net Ca²⁺ efflux (P < 0.05), extended the period of net Na⁺ influx, and significantly decreased net H₂O₂ efflux (P < 0.05). However, these effects were significantly attenuated in the EAT and EAN groups, where excessive net H₂O₂ efflux was observed (P < 0.001). These findings indicate that acupuncture regulates the dynamic changes of Ca²⁺, Na⁺ and H₂O₂ flux by activating the TRP channels and interacting with NOX2 activity following eccentric exercise-induced skeletal muscle injury.
Animals ; Muscle, Skeletal/metabolism* ; Rats, Wistar ; Rats ; Male ; Calcium/metabolism* ; Hydrogen Peroxide/metabolism* ; Physical Conditioning, Animal ; Sodium/metabolism* ; Acupuncture Therapy ; NADPH Oxidase 2

Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

The ocular fundus vasculature, serving as a critical window for monitoring disease progression, represents one of the primary targets of hypoxic injury. A growing body of evidence suggests associations between specific ocular vascular pathologies and sleep-disordered breathing. Obstructive sleep apnea(OSA)has been implicated in fundus lesions through its detrimental effects on the central retinal artery, retinal veins, retinal microvasculature, and choroidal vessels. Mechanistically, these effects are linked to OSA-induced intermittent hypoxia, which drives hemodynamic disturbances, oxidative stress, inflammatory responses, altered blood composition, endothelial dysfunction, and neuroendocrine/metabolic dysregulation. This review synthesizes current evidence on OSA-related retinal vascular injury and elucidates its mechanistic pathways. The goal is to identify sensitive and specific retinal vascular biomarkers to facilitate the early detection of OSA and its associated complications.