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.

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.

Sinisan is a classical prescription developed and applied by ancient medical experts and it is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Eastern Han Dynasty. Later physicians have modified this prescription based on this original one. The bibliometrics methods were used to analyze the key information and research trend of Sinisan. According to the inclusion and exclusion criteria， 69 pieces of effective data were extracted， involving 67 ancient traditional Chinese medicine （TCM） books. The results showed that the name， composition， and decocting methods of Sinisan in later generations were inherited from the original record in the Treatise on Cold Damage. The original plants of medicinal materials used in Sinisan are basically clear. We recommend Bupleuri Radix as the dried root of Bupleurem scorzonerifolium， Paeoniae Radix Alba as the dried root of Paeonia lactiflora， Aurantii Fructus as the dried fruit of Citrus aurantium， Glycyrrhizae Radix et Rhizoma as the dry root and rhizome of Glycyrrhiza uralensis. Raw materials of Bupleuri Radix and Paeoniae Radix Alba， Aurantii Fructus stir-fried with bran， and stir-fried Glycyrrhizae Radix et Rhizoma should be used for preparation of Sinisan. According to measurement system in the Han Dynasty， a bag of Sinisan is composed of 1.25 g Bupleuri Radix， 1.25 g Paeoniae Radix Alba， 1.25 g Aurantii Fructus， and 1.25 g Glycyrrhizae Radix et Rhizoma. The materials should be grounded into coarse powder and taken with a proper amount of rice soup， 3 times a day. Sinisan has the effects of regulating qi movement and harmonizing the liver and spleen. It can be used for treating reversal cold in limbs and cold damage. In modern clinical practice， Sinisan can be used to treat chronic gastritis， irritable bowel syndrome， and dyspepsia. The above research results provide scientific reference for the future research and development of Sinisan.

OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

Objective: To explore the mechanism of Buzhong Yiqi Decoction in modulating macrophage polarization and intervening in autoimmune thyroiditis (AIT) mice. Methods: Using the random number table method, 48 SPF-grade NOD.H-2h4 mice were assigned to the normal, model, low-dose (4.10 g/kg), medium-dose (8.19 g/kg), high-dose group (16.38 g/kg) of Buzhong Yiqi Decoction, and selenium yeast tablet (0.026 mg/kg) groups, with eight mice in each group. All groups, except the normal group, were free to drink high iodine water (0.05% sodium iodide) to prepare AIT mouse models for 8 consecutive weeks. After the modeling was complete, each treatment group was orally administered with the corresponding medication, while the normal and model groups were orally administered with an equal volume of distilled water once a day for 8 consecutive weeks. High-performance liquid chromatography with an oscillometric refractive detector was used to analyze the content of Astragaloside Ⅳ in Buzhong Yiqi Decoction. Hematoxylin and eosin staining was used to observe the pathological morphology of mouse thyroid tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α). An immunofluorescence assay was used to detect the positive area percentage of M1 and M2 macrophages in mouse thyroid tissue. Flow cytometry assay was used to detect macrophage polarization in mouse spleen tissue. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), nuclear factor kappa B inhibitory protein α (IκBα), and nuclear factor-κB (NF-κB) p65 in mouse spleen tissue. Western blotting was used to detect the expression of the phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), and NLRP3 protein in mouse spleen tissue. Results: The content of Astragaloside Ⅳ in Buzhong Yiqi Decoction was (7.09±0.06) g/L. Compared to the normal group, significant lymphocyte infiltration was observed in the thyroid tissue of mice in the model group. The levels of serum TPO-Ab, TgAb, IL-6, and TNF-α increased (P<0.05). The positive area percentage of M1 macrophages in thyroid tissue increased (P<0.05). The proportion of M1 macrophages and M1/M2 in spleen tissue increased (P<0.05). The relative expression levels of NF-κB p65 and NLRP3 mRNA in spleen tissue increased (P<0.05). The relative expression of p-IκBα, p-NF-κB p65, and NLRP3 proteins increased (P<0.05). Compared to the model group, the inflammation infiltration degree in the thyroid tissue of mice in each dose group of Buzhong Yiqi Decoction and selenium yeast tablet group was reduced, the serum TPO-Ab, TgAb, IL-6, TNF-α content was decreased, the spleen tissue M1/M2 was reduced, the expression of NF-κB p65 mRNA was reduced, and the relative expression levels of p-IκBα, p-NF-κB p65 protein were reduced (P<0.05). The Buzhong Yiqi Decoction high-dose and selenium yeast tablets groups showed an increase in IL-10 content, an increase in positive area percentage of M2 macrophages in thyroid tissue, an increase in M2 macrophages proportion in spleen tissue, and a decrease in NLRP3 mRNA and protein relative expression levels (P<0.05). Conclusion Buzhong Yiqi Decoction may regulate macrophage polarization by inhibiting the NF-κB/NLRP3 signaling pathway, thus improving the inflammatory damage in mice with AIT.

Humans ; Acute Disease ; Pancreatitis/diagnosis* ; Follow-Up Studies ; Patient Discharge ; Disease Progression

The BTB (broad-complex, tramtrack, and bric-à-brac) domain is a highly conserved protein interaction motif in eukaryotes. They are widely involved in transcriptional regulation, protein degradation and other processes. Recently, an increasing number of studies have shown that these genes play important roles in plant growth and development, biotic and abiotic stress processes. Here, we summarize the advances of these proteins ubiquitination-mediated development and abiotic stress responses in plants based on the protein structure, which may facilitate the study of this type of gene in plants.
Eukaryota ; Plant Development/genetics* ; Proteolysis ; Ubiquitination