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

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

OBJECTIVE: To compare the efficacy and safety of intravenous colistin sulfate combined with nebulized inhalation versus intravenous monotherapy for pulmonary infections caused by carbapenem-resistant organism (CRO). METHODS: A multicenter retrospective cohort study was conducted. Clinical data were collected from patients admitted to the intensive care unit (ICU) of 10 tertiary class-A hospitals in Henan Province between July 2021 and May 2023, who received colistin sulfate for CRO pulmonary infections. Data included baseline characteristics, inflammatory markers [white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), C-reactive protein (CRP)], renal function indicators [serum creatinine (SCr), blood urea nitrogen (BUN)], life support measures, anti-infection regimens, clinical efficacy, microbiological clearance rate, and prognostic outcomes. Patients were divided into two groups: intravenous group (colistin sulfate monotherapy via intravenous infusion) and combination group ((intravenous infusion combined with nebulized inhalation of colistin sulfate). Changes in parameters before and after treatment were analyzed. RESULTS: A total of 137 patients with CRO pulmonary infections were enrolled, including 89 in the intravenous group and 48 in the combination group. Baseline characteristics, life support measures, daily colistin dose, and combination regimens (most commonly colistin sulfate plus carbapenems in both groups) showed no significant differences between two groups. The combination group exhibited higher clinical efficacy [77.1% (37/48) vs. 59.6% (52/89)] and microbiological clearance rate [60.4% (29/48) vs. 39.3% (35/89)], both P < 0.05. Pre-treatment inflammatory and renal parameters showed no significant differences between two groups. Post-treatment, the combination group showed significantly lower WBC and CRP [WBC (×10⁹/L): 8.2±0.5 vs. 10.9±0.6, CRP (mg/L): 14.0 (5.7, 26.6) vs. 52.1 (24.4, 109.6), both P < 0.05], whereas NEU, PCT, SCr, and BUN levels showed no significant between two groups. ICU length of stay was shorter in the combination group [days: 16 (10, 25) vs. 21 (14, 29), P < 0.05], although mechanical ventilation duration and total hospitalization showed no significant differences between two groups. CONCLUSIONS Intravenous colistin sulfate combined with nebulized inhalation improved clinical efficacy and microbiological clearance in CRO pulmonary infections with an acceptable safety profile.
Humans ; Colistin/therapeutic use* ; Retrospective Studies ; Administration, Inhalation ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/pharmacology* ; Male ; Female ; Middle Aged ; Gram-Negative Bacteria/drug effects* ; Aged ; Treatment Outcome ; Respiratory Tract Infections/drug therapy*

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

Objective:To investigate the level of serum lipoprotein a [Lp (a)] in patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:A retrospective cohort study was performed. The clinical data of 87 patients with DLBCL who were treated at Changshu No.2 People's Hospital from January 2017 to June 2022 (the newly treated DLBCL group) were retrospectively analyzed, and 78 healthy physical examination subjects were selected as the control group. The level of Lp(a) in the two groups and the level of Lp(a) in DLBCL patients achieving different therapeutic effects after treatment were compared. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum Lp(a) in predicting the therapeutic effect of DLBCL patients, and the area under the curve (AUC) was calculated to determine the optimal critical value. Based on the optimal critical value, patients with DLBCL were divided into low Lp(a) group and high Lp(a) group, and the clinicopathological characteristics of DLBCL patients with different Lp(a) levels were compared. Cox proportional hazards model was used to analyze the factors affecting the prognosis of DLBCL patients. Kaplan-Meier method was used to compare the relapse-free survival (RFS) and overall survival (OS) of DLBCL patients with different Lp(a) levels.Results:The level of Lp (a) in the newly treated DLBCL group was higher than that in the control group[ (0.24±0.09) g/L vs. (0.09±0.06) g/L], and the difference was statistically significant ( t = 3.61, P = 0.019). Among 87 patients, 54 achieved complete remission (CR), 23 achieved partial remission (PR), and 10 achieved progression of the disease (PD). The Lp (a) levels of patients achieving CR, PR, and PD were (0.09±0.09) g/L, (0.12±0.08) g/L, and (0.25±0.15) g/L, respectively. The Lp (a) levels in patients achieving CR and PR were lower than those in the newly treated DLBCL patients [(0.24±0.09) g/L], and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in the Lp (a) levels between patients achieving PD and the newly treated DLBCL patients ( P > 0.05). The ROC curve results showed that the optimal critical value of serum Lp (a) in predicting the efficacy of DLBCL patients was 0.25 g/L, AUC was 0.776 (95% CI: 0.676-0.876, P < 0.05), and its sensitivity and specificity was 66.67%, 82.76%, respectively. According to the optimal critical value of Lp (a) (0.25 g/L), patients were divided into the low Lp (a) group (≤ 0.25 g/L) (57 cases) and the high Lp (a) group (>0.25 g/L) (30 cases). The proportion of patients with lactate dehydrogenase level >227 U/L, Ann Arbor stage Ⅲ-Ⅳ, and extranodal organ involvement >1 in the high Lp (a) group was higher than that in the low Lp (a) group, and the differences were statistically significant (all P < 0.05). Cox multivariate analysis results showed that Ann Arbor stage Ⅲ-Ⅳ, international prognostic index (IPI) score 3-5, and Lp (a)>0.25 g/L were independent risk factors for OS in DLBCL patients (all P < 0.05); Ann Arbor stage Ⅲ-Ⅳ and IPI score 3-5 were independent risk factors for RFS in DLBCL patients (all P < 0.05). The median OS in the low Lp (a) group was not reached; the median OS of the high Lp (a) group was 21 months, and there was a statistically significant difference in OS between the two groups ( P = 0.001). The median RFS time was not reached in the low Lp (a) group and the high Lp (a) group; and there was no statistically significant difference in RFS between the two groups ( P = 0.102) . Conclusions:Lp(a) level of DLBCL patients is increased, and Lp(a) could be a factor influencing the prognosis of DLBCL.

[摘 要] 目的：探讨溶瘤新城疫病毒（NDV）对IL-6诱导的人胶质母细胞瘤U87MG细胞增殖、迁移和侵袭的作用及其可能的机制。方法：将U87MG细胞分为对照组、IL-6组、NDV组、NDV+IL-6组，其中IL-6组与NDV+IL-6组用75 ng/mL IL-6预处理1 h，其余组用DMEM预处理1 h，后分别用DMEM、75 ng/mL IL-6、1 HU NDV、1 HU NDV+75 ng/mL IL-6处理24 h。MTT法、细胞划痕实验和Transwell侵袭实验分别检测IL-6、NDV对U87MG细胞增殖、迁移和侵袭的影响，WB法检测各组细胞JAK2、p-JAK2、STAT3、p-STAT3和MMP2蛋白的表达水平。结果：与对照组相比，IL-6组细胞迁移率显著升高（P<0.05），侵袭细胞数目显著增多（P<0.01）；与IL-6组相比，NDV+IL-6组U87MG细胞增殖率显著降低（P<0.05），细胞迁移率和侵袭细胞数目均显著降低（均P<0.01）。WB实验结果显示，与对照组相比，IL-6组p-STAT3/STAT3比值显著升高（P<0.01），NDV组p-JAK2/JAK2、p-STAT3/STAT3比值显著降低（P<0.05，P<0.01），MMP-2蛋白表达量显著降低（P<0.01）；与IL-6组相比，NDV+IL-6组p-STAT3/STAT3比值、MMP-2蛋白表达量均显著降低（均P<0.05）。结论：NDV能抑制IL-6对人脑胶质瘤U87MG细胞迁移和侵袭的诱导作用，其机制可能与JAK2/STAT3信号通路的参与调控有关。

Objective     To construct a radiomics model for identifying clinical high-risk carotid plaques. Methods     A retrospective analysis was conducted on patients with carotid artery stenosis in China-Japan Friendship Hospital from December 2016 to June 2022. The patients were classified as a clinical high-risk carotid plaque group and a clinical low-risk carotid plaque group according to the occurrence of stroke, transient ischemic attack and other cerebrovascular clinical symptoms within six months. Six machine learning models including eXtreme Gradient Boosting, support vector machine, Gaussian Naive Bayesian, logical regression, K-nearest neighbors and artificial neural network were established. We also constructed a joint predictive model combined with logistic regression analysis of clinical risk factors. Results    Finally 652 patients were collected, including 427 males and 225 females, with an average age of 68.2 years. The results showed that the prediction ability of eXtreme Gradient Boosting was the best among the six machine learning models, and the area under the curve (AUC) in validation dataset was 0.751. At the same time, the AUC of eXtreme Gradient Boosting joint prediction model established by clinical data and carotid artery imaging data validation dataset was 0.823. Conclusion     Radiomics features combined with clinical feature model can effectively identify clinical high-risk carotid plaques.

OBJECTIVE To evaluate the medication adherence of patients with hypertension in medication consultation clinics， and to analyze its influencing factors. METHODS The data of 389 patients who visited the medication consultation clinics of our hospital from June 2021 to June 2023 were collected. Univariate and multivariate Logistic regression analysis were used to analyze the related factors affecting medication adherence of hypertensive patients or those receiving different types of drugs. RESULTS Among 389 patients with hypertension， 302 cases （77.63%） had good adherence. Multivariate Logistic analysis showed that higher education level [corrected OR＝2.25， 95%CI （1.29， 3.93）， P＝0.004] was positively correlated with medication adherence， average blood pressure level [corrected OR＝0.19， 95%CI （0.10， 0.37）， P＜0.001]， without complication [corrected OR＝0.47， 95%CI（0.26，0.84），P＝0.010] and antihypertensive drug regimen being free dose combination [corrected OR＝0.27，95%CI（0.15， 0.47）， P＜0.001] were negatively correlated with adherence. Results of univariate Logistic regression analysis showed that patients who used β-receptor blocking agents [OR＝1.65，95%CI（1.06，2.57），P＝0.027]， calcium channel blockers [OR＝2.13，95%CI（1.33， 3.42），P＝0.002] and agents acting on the renin-angiotensin system [OR＝2.04，95%CI（1.29，3.22），P＝0.002] had good medication adherence. CONCLUSIONS The medication adherence of hypertension patients needs to be improved. Hypertension patients with higher education level， lower average blood pressure level， complications and fixed-dose combination regimen and those who use agents acting on the renin-angiotensin system， calcium channel blockers and β-receptor blocking agents may have better medication adherence.