Natural product-based drug combinations (NPDCs) present distinctive advantages in treating complex diseases. While high-throughput screening (HTS) and conventional computational methods have partially accelerated synergistic drug combination discovery, their applications remain constrained by experimental data fragmentation, high costs, and extensive combinatorial space. Recent developments in artificial intelligence (AI), encompassing traditional machine learning and deep learning algorithms, have been extensively applied in NPDC identification. Through the integration of multi-source heterogeneous data and autonomous feature extraction, prediction accuracy has markedly improved, offering a robust technical approach for novel NPDC discovery. This review comprehensively examines recent advances in AI-driven NPDC prediction, presents relevant data resources and algorithmic frameworks, and evaluates current limitations and future prospects. AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.
Artificial Intelligence ; Biological Products/chemistry* ; Humans ; Drug Combinations ; Drug Discovery/methods* ; Machine Learning ; Algorithms

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective To investigate the acute toxicology and intervention effect of Panacis Majoris Rhizoma on rats with chronic pharyngitis.Methods A single,maximum dose of Panacis Majoris Rhizoma(74.4 g·kg-1)was administered to Kunming mice to evaluate its toxicity,involving the assessment of the survival status of the mice,organ indices,morphological changes in major organs,blood routine,and biochemical indicators.SD rats were randomly divided into the control group,model group,prednisone group(6.25 mg·kg-1),and low-,medium-,and high-dose Panacis Majoris Rhizoma groups(0.58,1.16,and 2.32 g·kg-1).All rats received the corresponding drugs(or normal saline)via intragastric administration once daily for a duration of 30 days.Except the control group,chronic pharyngitis was induced in rats of the other groups by using β-hemolytic streptococcus.Following euthanasia,serum inflammatory levels of interleukin-6(IL-6),cyclooxygenase-2(COX-2),interleukin-1β(IL-1β),intercellular adhesion molecule-1(ICAM-1),C-reactive protein(CRP),tumor necrosis factor(TNF-α),monocyte chemoattractant protein-1(MCP-1),and prostaglandin E2(PGE2)were measured.Additionally,pharyngeal tissues were stained with HE and pathological characteristics were observed.Results Toxicological studies have demonstrated that the administration of Panacis Majoris Rhizoma resulted in significant increase in plasma alanine transaminase levels and spleen index of mice,along with corresponding tissue pathological alterations.Nevertheless,no noteworthy pathological changes were observed in other organs,and there were no notable changes in blood routine and plasma biochemical indicators.Pharmacodynamic investigations have revealed that Panacis Maioris Rhizoma effectively reduces the serum levels of inflammatory factors and improves pathological changes in pharyngeal tissues.Conclusion Panacis Maioris Rhizoma alleviated β-hemolytic streptococcus-induced CP by inhibiting inflammatory responses,and may show potential toxicity to the spleen.

Purpose::Autologous osteoperiosteal transplantation (AOPT) is one of the most feasible and effective techniques for cystic osteochondral lesions of the talus (OLT). However, few reports have been reported about the process of graft-host bone healing and bone articular surface reconstruction, which help us to further understand the actual situation of bone healing and modify surgical methods.Methods::The case series study retrospectively evaluated 33 osteochondral lesions in 30 patients undertaking AOPT for OLT with subchondral cysts from December 2016 to October 2021. According to CT observation, we used 4 variables to describe the bony articular repair, including the integration of the articular surface, the height of the bone filling, the status of bone union, and the appearance of bone resorption or cystic change. We also analyzed the demographic data and clinical function. Descriptive statistics were used for demographic and clinical variables. Normally distributed data were presented as mean ± SD, and non-normally distributed data were presented as median (Q 1, Q 3). Associations between these variables and the primary clinical outcomes were examined using t-test or one-way ANOVA test for continuous variables. Results::The patients’ mean age was (41.7 ± 14.0) years old and the mean follow-up time was (29.6 ± 17.8) months. The chondral lesion size was (14.3 ± 4.1) mm. The cyst depth was (10.9 ± 3.7) mm. Significant improvements were observed in functional outcomes (according to the numeric rating scale for pain when walking and the American orthopedic foot and ankle society score) between the preoperative and latest follow-up evaluations, from 4.2 ± 2.1 to 2.2 ± 2.0 ( p < 0.001), and from 66.8 ± 12.9 to 83.2 ± 10.4, respectively ( p < 0.001). The overall satisfaction reached 8.3 of 10 points. All patients returned to sports and their median daily steps reached 8000 steps with 27 (81.8%) patients walking over 6000 steps daily. According to CT observation, "discontinuous bony articular surface and gap > 1 mm" was found in 27 grafts (81.8%), and "below the level of the adjacent articular surface, ≤1 mm" in a third of the grafts. Abnormal height of bone filling affected numeric rating scale score ( p=0.049) and American Orthopedic Foot and Ankle Society score ( p =0.027). Of note, bone resorption or cystic changes appeared in up to 13 autografts (39.4%). Conclusions::AOPT is an effective and acceptable technique for cystic OLT. Bone reconstruction is essential for large cystic OLT. How to get better bony articular reconstruction and avoid cyst recurrence should still be paid more attention.

ObjectiveThis study explores the efficacy and pharmacological mechanism of Wujiwan in rats with inflammatory bowel disease （IBD） from the perspectives of the peroxisome proliferator-activated receptor γ （PPARγ） signaling pathway and T-cell immunity， providing reference for the treatment of IBD with traditional Chinese medicine. MethodThe study involved administering 2，4，6-trinitrobenzenesulfonic acid （TNBS） enemas to 35 rats to induce acute IBD. After 24 hours， the animals were divided into the following groups： normal group， model group， Wujiwan treatment group， and positive drug control group. Each group received gastric gavage for 8 consecutive days before the rats were dissected to compare the disease activity index （DAI） of the rat colon tissue， the colon mucosal damage index （CMDI）， and the spleen index. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α） in the serum. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of T-bet （T-box expressed in T cells） and Gata3 （Gata-binding protein-3） in the colon tissue. Western blot analysis was conducted to detect the protein expression levels of PPARγ， T-bet， and nuclear factor-κB p65 （NF-κB p65） in the rat colon. ResultThe rat model of IBD was successfully established. Compared with the model group， the Wujiwan treatment group showed reduced DAI， CMDI， and spleen index， decreased content of TNF-α in the serum（P<0.01）， significantly increased content of IL-10（P<0.01）， and elevated mRNA content of T-bet and Gata3（P<0.05） in the colon tissue. The expression of PPARγ protein was augmented（P<0.05）， and the expression of T-bet and NF-κB p65 protein was decreased（P<0.05，P<0.01）. ConclusionWujiwan activates or upregulates PPARγ expression in IBD rats to inhibit the generation of pro-inflammatory factors， participates in the inflammatory immune process， and alleviates inflammatory reactions. Its mechanism may involve regulating the NF-κB pathway through PPARγ， enhancing Th2 cell transcription expression， and reducing Th1 cell transcription.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

Objective It conducted a grounded theory on the factors influencing the sense of job significance of hospital administrators to provide suggestions and references for the promotion of high-quality development of hospital management work.Methods From April to September 2023,it interviewed 23 administrators from various departments across Provinces/Cities,including Zhejiang,Heilongjiang,Guangdong,Shanghai,Henan,Jilin,Sichuan and others,using a theoretical sampling method.Employing Grounded Theory,it encoded over transcriptional information at three levels.Results Three-level coding process yielded 66 free nodes,19 initial concepts,7 main categories,and 3 dimensions,leading to the development of a theoretical model encompassing existence,relatedness,and growth.Conclusion The job meaning for hospital administrators is shaped by existence,relatedness,and growth.It recommend revising performance assessments,fostering an empowering culture,enhancing informal communication,providing professional growth pathways,and offering diverse career development options to deepen administrators'job meaning.

Objective To explore the influencing factors of the career plateau among hospital administrators,to provide scientific reference for enhancing the quality of hospital management and operation.Methods The interview data were analyzed by grounded theoretical research methods.It conducted semi-structured interviews with 22 tar-get objects and conducted qualitative research on the influencing factors of hospital administrators'career plateau with the help of NVivo 11.0 software.Results After a three-level coding,114 initial concepts,30 subcategories,10 main categories,and 3 core categories were summarized.A theoretical model was developed,encompassing three dimensions:aggravating factors,dissipating factors,and convertible factors.Conclusion The career plateau of hospi-tal administrators is affected by a complex interplay of aggravating,dissipating and convertible factors.Hospitals need to provide regular vocational training to cultivate organizational loyalty for their employees.Hospital administra-tors should engage in proactive career planning and skill diversification.and the government should coordinate the es-tablishment of links between hospitals and the external system to promote the openness and connection of the healthcare system to the outside world.

Objective:To analyze the eye lens dose and annual effective dose to interventional radiation workers in some hospitals of Xinxiang city from 2020 to 2022, and to ascertain the dose to interventional radiation workers.Methods:By using TLDs, the eye lens dose Hp(3) and annual effective dose Hp(10) were monitored for three consecutive years in six hospitals in Xinxiang city. The lens doses and annual effective doses to intervention radiation workers in different years in different-level hospitals and departments were analyzed. Results:From 2020 to 2022, a total of 117 people were monitored. The left eye lens dose range was 0.12-164.24 mSv, and the right eye lens dose range was 0.07-51.64 mSv. The average annual dose was 8.56 mSv for left eye lens and 4.49 mSv for right eye lens The average annual dose distribution in the MDL-5 mSv range for the left and right eye lens was 60.68% and 73.50%, respectively. 9.41% (11 people) of the left eye lens doses exceeded 20 mSv. The annual effective doses range was 0.11-31.27 mSv, with average annual dose of 2.56 mSv. The proportion of average annual effective doses mainly distributed in the range of MDL to 1.25 mSv was 52.14%, with 2.56% annual effective dose exceeding 20 mSv. There was no significant difference in left and right eye lens dose and annual effective dose between the tertiary hospitals and the secondary hospitals in three years ( P>0.05). Compared with different departments, the cumulative per capita dose in three years was statistically significant (left eye H=11.42, right eye H=13.72, annual effective dose H=25.94, P<0.05). The lens dose and annual effective dose in neurology department were lower than those in cardiology department and comprehensive intervention department ( Zcardiology department=-3.33, -3.78, -4.83, P<0.05; Zcomprehensive intervention department=-2.71, -2.63, -4.39, P<0.05). Conclusions:Most of the annual equivalent dose and annual effective dose to eye lens of the interventional radiation workers in Xinxiang city meet the national limits, but some of them have higher doses and exceed the national limits. It is suggested that the routine and continuous monitoring of eye lens doses to interventional radiologists should be strengthened while routine monitoring of annual effective dose, and attention should be paid to the eye lens and annual effective dose to interventional radiologists in secondary hospitals to improve the awareness of protection.