Traditional Chinese medicine (TCM) features complex compatibility mechanisms involving multi-component, multi-target, and multi-pathway interactions. This study presents an interpretable graph artificial intelligence (GraphAI) framework to quantify such mechanisms in Chinese herbal formulas (CHFs). A multidimensional TCM knowledge graph (TCM-MKG; https://zenodo.org/records/13763953) was constructed, integrating seven standardized modules: TCM terminology, Chinese patent medicines (CPMs), Chinese herbal pieces (CHPs), pharmacognostic origins (POs), chemical compounds, biological targets, and diseases. A neighbor-diffusion strategy was used to address the sparsity of compound-target associations, increasing target coverage from 12.0% to 98.7%. Graph neural networks (GNNs) with attention mechanisms were applied to 6,080 CHFs, modeled as graphs with CHPs as nodes. To embed domain-specific semantics, virtual nodes medicinal properties, i.e., therapeutic nature, flavor, and meridian tropism, were introduced, enabling interpretable modeling of inter-CHP relationships. The model quantitatively captured classical compatibility roles such as "monarch-minister-assistant-guide," and uncovered TCM etiological types derived from diagnostic and efficacy patterns. Model validation using 215 CHFs used for coronavirus disease 2019 (COVID-19) management highlighted Radix Astragali-Rhizoma Phragmitis as a high-attention herb pair. Mass spectrometry (MS) and target prediction identified three active compounds, i.e., methylinissolin-3-O-glucoside, corydalin, and pingbeinine, which converge on pathways such as neuroactive ligand-receptor interaction, xenobiotic response, and neuronal function, supporting their neuroimmune and detoxification potential. Given their high safety and dietary compatibility, this herb pair may offer therapeutic value for managing long COVID-19. All data and code are openly available (https://github.com/ZENGJingqi/GraphAI-for-TCM), providing a scalable and interpretable platform for TCM mechanism research and discovery of bioactive herbal constituents.

ChuanWu (CW), the dried mother root of Aconitum carmichaelii Debx., is a well-known traditional Chinese medicine (TCM) recognized for its potent efficacy but inherent toxicity, primarily due to its alkaloid content. Traditional and modern detoxification methods for CW include proper processing, rational compatibility, and specialized decoction techniques, among which honey-boiled CW is particularly distinctive. However, research on the detoxification mechanism of honey-boiled CW remains limited. This study investigated this mechanism by analyzing alkaloid transformation and supramolecular aggregation. Honey-boiled and water-boiled CW preparations were compared. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze CW alkaloids, specifically diester alkaloids (DDAs), monoester alkaloids (MDAs), and non-esterified diterpenoid alkaloids (NDAs). Transmission electron microscopy was employed to observe and identify supramolecular aggregates in the honey-boiled CW decoction. In vivo absorption of water-boiled, honey-boiled, and NADES-boiled CW was compared. Median lethal dose (LD₅₀) tests assessed toxicity, including hepatotoxicity and nephrotoxicity. In vitro experiments evaluated the safety, anti-inflammatory, and analgesic effects of CW-medicated serum on RAW264.7 cells, with in vivo validation in mice. Results showed that honey promoted the conversion of highly toxic DDAs to less toxic MDAs and prevented MDAs from hydrolyzing into NDAs. Honey-boiled CW formed approximately 250 nm supramolecular aggregates that encapsulated MDAs, inhibiting their conversion to NDAs. These encapsulated MDAs acted as a stable delivery system with higher bioavailability than free benzoylmesaconine. Subsequent mouse experiments confirmed that honey-boiled CW significantly increased the LD₅₀ of CW while reducing hepatotoxicity and nephrotoxicity. Additionally, honey-boiled CW significantly improved cell safety and enhanced anti-inflammatory and analgesic effects. Our findings reveal that honey-boiled CW exhibits a potent detoxification mechanism by influencing alkaloid transformation and facilitating the formation of supramolecular aggregates. This study lays the groundwork for developing detoxification or synergistic strategies within honey-boiled TCM.

Objective To explore the clinical efficacy of using 3D patches to repair inguinal hernia in laparoscopic transabdominal preperitoneal inguinal hernia repair(TAPP).Methods A retrospective study was conducted on 102 patients with inguinal hernia.All the patients were treated with laparoscopic TAPP.The patients were divided into two groups based on the different patch methods used after the surgery.The patients who used ordinary patches were in the ordinary patch group(n=50),and the patients who used 3D patches were in the 3D patch group(n=52).The surgery-related conditions,postoperative pain,postoperative complications and recurrence of the two groups of patients were compared.Results The 3D patch group had shorter surgery time,first exhaust time,got out of bed mobility time,less hospital stay and intraoperative bleeding volume than those in the ordinary patch group,the differences were statistically significant(P<0.05).On the 1,3,and 5 d after surgery,the visual analogue scale(VAS)scores of patients in the 3D patch group were lower than those in the ordinary patch group,the differences were statistically significant(P<0.05).The total complications rate in the 3D patch group was 5.77%,which was significantly lower than the 20.00%in the ordinary patch group,the difference was statistically significant(P<0.05).There was no statistically significant difference in the postoperative recurrence rate between the two groups of patients(P>0.05).Conclusion For patients with inguinal hernia,administering 3D hernia patches during laparoscopic TAPP can reduce intraoperative bleeding volume,alleviate postoperative pain,and lower the complications rate such as postoperative urinary retention,scrotal edema,and seroma.It is worthy of clinical promotion and application.

Traditional Chinese medicine(TCM)features complex compatibility mechanisms involving multi-component,multi-target,and multi-pathway interactions.This study presents an interpretable graph artificial intelligence(GraphAI)framework to quantify such mechanisms in Chinese herbal formulas(CHFs).A multidimensional TCM knowledge graph(TCM-MKG;https://zenodo.org/records/13763953)was constructed,integrating seven standardized modules:TCM terminology,Chinese patent medicines(CPMs),Chinese herbal pieces(CHPs),pharmacognostic origins(POs),chemical compounds,biological targets,and diseases.A neighbor-diffusion strategy was used to address the sparsity of compound-target associations,increasing target coverage from 12.0％to 98.7％.Graph neural networks(GNNs)with attention mechanisms were applied to 6,080 CHFs,modeled as graphs with CHPs as nodes.To embed domain-specific semantics,virtual nodes medicinal properties,i.e.,therapeutic nature,flavor,and me-ridian tropism,were introduced,enabling interpretable modeling of inter-CHP relationships.The model quantitatively captured classical compatibility roles such as"monarch-minister-assistant-guide",and uncovered TCM etiological types derived from diagnostic and efficacy patterns.Model validation using 215 CHFs used for coronavirus disease 2019(COVID-19)management highlighted Radix Astragali-Rhi-zoma Phragmitis as a high-attention herb pair.Mass spectrometry(MS)and target prediction identified three active compounds,i.e.,methylinissolin-3-O-glucoside,corydalin,and pingbeinine,which converge on pathways such as neuroactive ligand-receptor interaction,xenobiotic response,and neuronal func-tion,supporting their neuroimmune and detoxification potential.Given their high safety and dietary compatibility,this herb pair may offer therapeutic value for managing long COVID-19.All data and code are openly available(https://github.com/ZENGJingqi/GraphAI-for-TCM),providing a scalable and inter-pretable platform for TCM mechanism research and discovery of bioactive herbal constituents.

Objective To explore the clinical efficacy of using 3D patches to repair inguinal hernia in laparoscopic transabdominal preperitoneal inguinal hernia repair(TAPP).Methods A retrospective study was conducted on 102 patients with inguinal hernia.All the patients were treated with laparoscopic TAPP.The patients were divided into two groups based on the different patch methods used after the surgery.The patients who used ordinary patches were in the ordinary patch group(n=50),and the patients who used 3D patches were in the 3D patch group(n=52).The surgery-related conditions,postoperative pain,postoperative complications and recurrence of the two groups of patients were compared.Results The 3D patch group had shorter surgery time,first exhaust time,got out of bed mobility time,less hospital stay and intraoperative bleeding volume than those in the ordinary patch group,the differences were statistically significant(P<0.05).On the 1,3,and 5 d after surgery,the visual analogue scale(VAS)scores of patients in the 3D patch group were lower than those in the ordinary patch group,the differences were statistically significant(P<0.05).The total complications rate in the 3D patch group was 5.77%,which was significantly lower than the 20.00%in the ordinary patch group,the difference was statistically significant(P<0.05).There was no statistically significant difference in the postoperative recurrence rate between the two groups of patients(P>0.05).Conclusion For patients with inguinal hernia,administering 3D hernia patches during laparoscopic TAPP can reduce intraoperative bleeding volume,alleviate postoperative pain,and lower the complications rate such as postoperative urinary retention,scrotal edema,and seroma.It is worthy of clinical promotion and application.

Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium(EF)and possess excellent therapeutic effects on various diseases.Encouragingly,in 2022,icaritin soft capsules were approved to reach the market for the treatment of hepatocellular carcinoma(HCC)by National Medical Products Administration(NMPA)of China.Moreover,recent studies demonstrate that icaritin can serve as immune-modulating agent to exert anti-tumor effects.Nonetheless,both production effi-ciency and clinical applications of epimedium flavonoids have been restrained because of their low content,poor bioavailability,and unfavorable in vivo delivery efficiency.Recently,various strategies,including enzyme engineering and nanotechnology,have been developed to increase productivity and activity,improve delivery efficiency,and enhance therapeutic effects of epimedium flavonoids.In this review,the structure-activity relationship of epimedium flavonoids is described.Then,enzymatic en-gineering strategies for increasing the productivity of highly active baohuoside I and icaritin are dis-cussed.The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases are summarized.Finally,the challenges and an outlook on clinical translation of epi-medium flavonoids are proposed.

Objective:To study the differences in the cumulative dose between deformable image registration (DIR) and simple dose-volume histogram (DVH) summation in the fractionated brachytherapy of cervical cancer, and to analyze the feasibility of the application of DIR in the dosimetry assessment of targets and organs-at-risk (OARs) in the brachytherapy.Methods:A retrospective analysis was conducted for 13 cases with primary cervical cancer treated with four fractions of interstitial brachytherapy guided by CT images. The four CT images of each cases were registered using an intensity-based DIR. Then, the cumulative doses (the D2 cm 3, D1 cm 3, and D0.1 cm 3 of the bladder, rectum, intestine, and colon and the D90for targets) after DIR were calculated and compared to those obtained using simple DVH summation. Afterward, the correlation between the dose difference and dice similarity coefficient (DSC) was analyzed. With the dose difference (the remaining dose of OARs caused by the DIR) as limits, a new plan was made for the latest CT to calculate the dose increase to targets. Results:Compared to simple DVH summation, DIR allowed the cumulative doses of the D2 cm 3 and D1 cm 3 of bladder to be decreased by (2.47±1.92) and (2.82±2.73) Gy, respectively on average ( t=-3.65, -2.93, P < 0.05), those of the D2 cm 3, D1 cm 3, and D0.1 cm 3 of rectum to be decreased by (2.05 ± 1.61) Gy, (1.51 ± 1.58), and (3.21 ± 2.50) Gy, respectively on average ( t=-4.02, -3.02, -4.06, P < 0.05), and those of the D2 cm 3, D1 cm 3, and D0.1 cm 3 to be decreased by (1.42 ± 0.99), (1.55 ± 1.28) Gy, and (2.43 ± 1.95) Gy, respectively on average ( t=-3.52, -2.96, -3.06, P < 0.05). There was no significant statistical difference in the D90 of targets, the D0.1 cm 3 of the bladder, and the D2 cm 3, D1 cm 3, D0.1 cm 3 of the colon ( P > 0.05) between both methods, and there was no distinct correlation between DSC and dose difference ( P > 0.05). The DIR increased the dose to targets, with a median value of 150 cGy. However, the accuracy of the DIR should be improved. Conclusions:In clinical practice of multiple fractions of brachytherapy for cervical cancer, it′s still recommended to adopt the simple dose summation method to assess the doses to targets and OARs.

Objective:To establish a dosimetric method based on the well-chamber to verify the accuracy of the source positioning and dwelling time for the afterloading machine, aiming to provide a new method for the quality control of afterloading machine.Methods:The principle of this method was explained according to the hardware structure of the well-chamber. Then, the precision of this method was analyzed by the simulation test and data fitting. The feasibility test was also performed. And the advantages and disadvantages of this method were compared with those of the traditional method.Results:The precision of this method for detecting the source positioning was 0.07 mm and the dwelling time was 0.09 s, respectively. In the feasibility test, the standard deviation of the measure value was below 3%.Conclusions:The well-chamber method has high precision and convenient operation. It can be applied in the rapid verification of the relative accuracy of the source positioning and dwelling time of well-chamber.

Objective: To study the feasibility of using the PTW729 2D array ion-chamber to verify the relative dose distribution calculated with the Acuros BV algorithm. Both advantages and disadvantages of the method were analyzed to provide reference for practical clinical practices. Methods: Based on self-built measurement phantoms, the dose distribution on the same slice of the phantom was measured with PTW729 and film, respectively, under the same measurement condition and plan. The dose distributions obtained by the two method were compared with the result calculated with Acuros BV, separately, by using γ analytical tool. And the stability of the PTW729 was tested. Results: The γ comparison value was 95.9% between the film and Acuros BV, 98.9% between the PTW729 and Acuros BV and 88.0% between the film and PTW729, with 95.0%, 100.0%, and 100.0%, in their stability test respectively. Conclusions PTW729 2D array ion-chamber can be applied to the rapid verification of Acuros BV algorithm-calculated relative dose distribution.

Sensory processing is strongly modulated by different brain and behavioral states, and this is based on the top-down modulation. In the olfactory system, local neural circuits in the olfactory bulb (OB) are innervated by centrifugal afferents in order to regulate the processing of olfactory information in the OB under different behavioral states. The purpose of the present study was to explore the organization of neural networks in olfactory-related cortices and modulatory nuclei that give rise to direct and indirect innervations to the glomerular layer (GL) of the OB at the whole-brain scale. Injection of different recombinant attenuated neurotropic viruses into the GL showed that it received direct inputs from each layer in the OB, centrifugal inputs from the ipsilateralanterior olfactory nucleus (AON), anterior piriform cortex (Pir), and horizontal limb of diagonal band of Broca (HDB), and various indirect inputs from bilateral cortical neurons in the AON, Pir, amygdala, entorhinal cortex, hippocampus, HDB, dorsal raphe, median raphe and locus coeruleus. These results provide a circuitry basis that will help further understand the mechanism by which olfactory information-processing in the OB is regulated.