The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

Network pharmacology has gained widespread application in drug discovery, particularly in traditional Chinese medicine (TCM) research, which is characterized by its "multi-component, multi-target, and multi-pathway" nature. Through the integration of network biology, TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms, establishing a novel research paradigm for TCM modernization. The rapid advancement of machine learning, particularly revolutionary deep learning methods, has substantially enhanced artificial intelligence (AI) technology, offering significant potential to advance TCM network pharmacology research. This paper describes the methodology of TCM network pharmacology, encompassing ingredient identification, network construction, network analysis, and experimental validation. Furthermore, it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods. Finally, it addresses challenges and future directions regarding cell-cell communication (CCC)-based network construction, analysis, and validation, providing valuable insights for TCM network pharmacology.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Network Pharmacology/methods* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Drug Discovery

The incomplete degradation of tumour cells by macrophages(Mφ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mφ is mediated through phagosomes and lysosomes.In our preliminary experiments,we found that overactivation of NADPH oxidase 2(NOX2)reduced the ability of Mφ to degrade engulfed tumour cells.Above this,we screened out liquiritin from Glycyrrhiza uralensis Fisch,which can significantly inhibit NOX2 activity and inhibit tumours,to elucidate that suppressing NOX2 can enhance the ability of Mφ to degrade tumour cells.We found that the tumour environment could activate the NOX2 activity in Mφ phagosomes,causing Mφ to produce excessive reactive oxygen species(ROS),thus prohibiting the formation of phagolysosomes before degradation.Conversely,inhibiting NOX2 in Mφ by liquiritin can reduce ROS and promote phagosome-lysosome fusion,therefore improving the enzymatic degradation of tumour cells after phagocytosis,and subse-quently promote T cell activity by presenting antigens.We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox,blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox,thereby inhibiting the activity of NOX2.This study elucidates the specific mechanism by which Mφ cannot degrade tumour cells after phagocytosis,and indicates that liquiritin can promote the ability of Mφ to degrade tumour cells by suppressing NOX2.

Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Ischemic stroke is a cerebrovascular disease characterized by a high incidence rate, significant disability rate, and elevated mortality rate. As a traditional Chinese medicine therapy, acupuncture and moxibustion have shown considerable potential in treating ischemic stroke. This review summarizes the advancements in acupuncture and moxibustion for patients with ischemic stroke, focusing on the mechanisms of action, treatment protocols, and clinical efficacy. The goal is to provide a reference for the further promotion and application of acupuncture and moxibustion in clinical practice.

Ischemic stroke is a cerebrovascular disease characterized by a high incidence rate, significant disability rate, and elevated mortality rate. As a traditional Chinese medicine therapy, acupuncture and moxibustion have shown considerable potential in treating ischemic stroke. This review summarizes the advancements in acupuncture and moxibustion for patients with ischemic stroke, focusing on the mechanisms of action, treatment protocols, and clinical efficacy. The goal is to provide a reference for the further promotion and application of acupuncture and moxibustion in clinical practice.

Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Objective To analyze the situation and study trend of large-scale nurses'health cohort studies based on Web of Science,to help design clinical guidelines and scientific research for nursing staff in China.Methods Articles of large nurses'health cohort studies published from 1993 to 2023 were retrieved from Web of Science(WOS)Core Collection.Citespace and Bibilometrix were used to perform the bibliometric analysis.Results 2882 studies were included in this study.Total volume of papers was enlarging by year.Clustering results showed that the main keywords could be divided into 3 categories:risks of women's health,risks of cardiovascular disease and reproducibility.Results of keywords burst showed that lifestyle,cardiovascular disease,women reproductive health and mental health were the highlights of studies in recent 5 years.Conclusion Research on large-scale nurse health cohorts holds significant scientific significance.It is recommended to establish a nationwide large-scale nurse health cohort as soon as possible.In the study,appropriate exposure factors should be selected,with reproductive health,mental health,and psychiatric disorders being the primary outcome measures,and chronic physical illnesses being the secondary outcome measures.By systematically describing the factors influencing the physical and mental health of nurses in China,we can better safeguard their well-being and promote the development of the nursing discipline.

[Objective] To understand the characteristics of dietary diversity of urban families in Ningbo city and analyze the related factors of dietary diversity level. [Methods] The project was carried out based on the baseline survey project of the primary health comprehensive experimental area of the National Health Commission in 2021. Multi-stage stratified cluster random sampling was adopted and household face-to-face inquiry was conducted. The survey questionnaire was divided into four parts: basic information, dietary knowledge and attitudes, dietary consumption frequency, and 24-hour dietary intake. The generalized estimating equation was used to analyze the influencing factors of dietary diversity score. [Results] A total of 632 people were surveyed. Among the nine groups of food (except cooking oils), foods consumed weekly in frequency from high to low were cereals, vegetables, fruits, fish, meat, eggs, beans, and dairy. The overall dietary diversity score (DDS) was 5.78±1.693. Among the surveyed, 9% had insufficient DDS, 62.2% had moderate DDS, and 28.8% had adequate DDS. Age, dietary knowledge acquisition attitude behavior, and family role were significantly correlated with DDS. DDS was 0.70 higher in the group under 40 years old than in the group over 60 years old (P<0.05), and DDS in the group between 40 and 59 years old was 0.46 higher than that in the group over 60 years old (P<0.05). DDS in the occasionally or never actively collected group was 0.93 lower than that in the frequently actively collected group (P<0.001). Among the family role factors, DDS of ordinary family members was 0.32 higher than that of family opinion leader (P<0.05). [Conclusion] The dietary patterns in this region have the characteristics of plant-based and coastal characteristic dietary ones. The intake level of fruits and fish is relatively good, while the intake of legumes and dairy is relatively low, which needs attention.

Objective:To observe any effects of contralateral repeated transcranial magnetic stimulation (rTMS) of the swallowing motor cortex on the swallowing and brainstem auditory evoked potentials (BAEPs) of stroke survivors with dysphagia.Methods:A total of 83 stroke survivors with dysphagia were randomly divided into an ipsilesional stimulation group ( n=22), a contralesional stimulation group ( n=21), a bilateral stimulation group ( n=20), and a control group ( n=20). In addition to their conventional dysphagia training, those in the three stimulation groups received 3Hz rTMS while the control group was given fake stimulation. The treatment was administered daily for 20 minutes, 6 days a week, for 5 consecutive weeks. Before and after the treatment, swallowing function was assessed videofluoroscopically and using the Dysphagia Outcome and Severity Scale (DOSS). The oral and pharyngeal stages of swallowing were evaluated using the videofluoroscopic dysphagia scale (VDS). Brain stem conduction was assessed using BAEPs. Results:After treatment the average DOSS scores of all 4 groups were significantly better than before the treatment. The average DOSS scores of the contralesional and bilateral sti-mulation groups were then significantly better than those of the other two groups. The sub-item and total VDS scores of all 4 groups had decreased significantly, but the average score of the bilateral stimulation group was significantly lower than the control group′s average. Ipsilesional stimulation significantly improved the VDS sub-item scores for the triggering of pharyngeal swallowing, laryngeal elevation, and pharyngeal transit time compared with the control group. In the contralesional stimulation group the average total score and the VDS sub-item scores for apraxia, premature bolus loss, oral transit times, the triggering of pharyngeal swallowing, vallecular residue, laryngeal elevation, coating on the pharyngeal wall, and pharyngeal transit time were significantly lower than those of the control group, on average. After the treatment the latencies of BAEP waves I, III and V and the I-III, III-V and I-V interpeak intervals had decreased significantly in all four groups, but the average latencies and intervals of the bilateral and contralesional groups were significantly shorter than those of the control group. The latencies and intervals of the bilateral stimulation group were then significantly shorter than those in the ipsilesional stimulation group on average. The average latency of wave V in the bilateral stimulation group (6.53±0.73ms) was significantly shorter than that in the contralesional stimulation group after the treatment.Conclusion:Bilateral rTMS over the swallowing motor cortex combined with conventional dysphagia training can significantly improve the swallowing of dysphagic stroke survivors.