1.Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women
Claudia Ha-ting TAM ; Ying WANG ; Chi Chiu WANG ; Lai Yuk YUEN ; Cadmon King-poo LIM ; Junhong LENG ; Ling WU ; Alex Chi-wai NG ; Yong HOU ; Kit Ying TSOI ; Hui WANG ; Risa OZAKI ; Albert Martin LI ; Qingqing WANG ; Juliana Chung-ngor CHAN ; Yan Chou YE ; Wing Hung TAM ; Xilin YANG ; Ronald Ching-wan MA
Diabetes & Metabolism Journal 2025;49(1):128-143
Background:
The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.
Methods:
We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.
Results:
Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.
Conclusion
Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.
2.Residual Inflammatory Risk and Intracranial Atherosclerosis Plaque Vulnerability: Insights From High-Resolution Magnetic Resonance Imaging
Ying YU ; Rongrong CUI ; Xin HE ; Xinxin SHI ; Zhikai HOU ; Yuesong PAN ; Mingyao LI ; Jiabao YANG ; Zhongrong MIAO ; Yongjun WANG ; Rong WANG ; Xin LOU ; Long YAN ; Ning MA
Journal of Stroke 2025;27(2):207-216
Background:
and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS).
Methods:
This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement.
Results:
Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage.
Conclusion
In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.
3.Mebendazole effectively overcomes imatinib resistance by dualtargeting BCR/ABL oncoprotein and ββ-tubulin in chronic myeloid leukemia cells
Li YANG ; Zhuanyun DU ; Yuhang PENG ; Wenyao ZHANG ; Wenli FENG ; Ying YUAN
The Korean Journal of Physiology and Pharmacology 2025;29(1):67-81
To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.
4.Effect of Modified Chaihu Shugansan on CaMKⅡ/CREB Signaling Pathway in Rats with Myocardial Ischemia and Depression
Fen WAN ; Xiaohong LI ; Ying CHEN ; Yangyu PAN ; Yanna LUO ; Fangge LU ; Chuncheng ZHENG ; Pengyun KONG ; Chengxiang WANG ; Liqiang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):1-11
ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)/cAMP-response element binding protein (CREB) signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet, intraperitoneal injection of isoproterenol (ISO), and chronic unpredictable mild stress (CUMS). A total of 108 SD male rats were randomly divided into normal group, model group, high (23.4 g·kg-1), medium (11.7 g·kg-1), and low (5.85 g·kg-1) dose groups of modified Chaihu Shugansan, CaMKⅡ inhibitor (KN93) group, and KN93 + high, medium, and low dose groups of modified Chaihu Shugansan, with 12 rats in each group. From the first day of modeling to the end of modeling, drugs were administered once a day. In the seventh and eighth weeks, the KN93 group and the KN93 + high, medium, and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week, behavioral tests including sucrose preference, open field, and elevated plus maze were conducted. Electrocardiogram (ECG) lead Ⅱ changes were observed in each group of rats, and hematoxylin-eosin (HE) staining was performed to observe changes in heart tissue. Serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and lactate dehydrogenase (LDH) were measured by using an enzyme-labeled instrument. Creatine kinase (CK) and creatine kinase-MB (CK-MB) were detected by ultraviolet spectrophotometry, while serum monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue, and Western blot was performed to assess protein expression of CaMKⅡ, phosphorylated (p)-CaMKⅡ, CREB, and p-CREB. ResultsCompared to the normal group, the model group showed significant reductions in sucrose preference rate, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01). The ECG showed ST-segment elevation, and HE staining showed serious degeneration of myocardial fibers, disordered arrangement, and infiltration of a large number of inflammatory cells. In addition, serum TC and LDL levels increased (P<0.01), and HDL level decreased (P<0.01). CK, CK-MB, LDH, and MCP-1 levels significantly increased (P<0.05, P<0.01). The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue (P<0.05, P<0.01), but those increased in the heart tissue (P<0.01). Compared to the model group, the high, medium, and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01), as well as decreased serum CK, CK-MB, LDH, and MCP-1 levels (P<0.05, P<0.01). KN93 also reduced ST-segment elevation, alleviated the degeneration degree of myocardial fibrosis, and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced (P<0.05, P<0.01). The KN93 + high, medium, and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression, possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway, with the high-dose modified Chaihu Shugansan showing the best effects.
5.Prevalence and influencing factors of work-related musculoskeletal disorders of coal miners in a coal mine group
Xiaolan ZHENG ; Liuquan JIANG ; Ying ZHAO ; Hongxia ZHAO ; Fan YANG ; Qiang LI ; Li LI ; Yingjun CHEN ; Qingsong CHEN ; Gaisheng LIU
Journal of Environmental and Occupational Medicine 2025;42(3):278-285
Background The positive rate of work-related musculoskeletal disorders (WMSDs) among coal mine workers remains high, which seriously affects the quality of life of the workers. Objective To estimate the prevalence of WMSDs among coal miners in Shanxi Province and analyze their influencing factors. Methods From May to December 2023,
6.Structural and Spatial Analysis of The Recognition Relationship Between Influenza A Virus Neuraminidase Antigenic Epitopes and Antibodies
Zheng ZHU ; Zheng-Shan CHEN ; Guan-Ying ZHANG ; Ting FANG ; Pu FAN ; Lei BI ; Yue CUI ; Ze-Ya LI ; Chun-Yi SU ; Xiang-Yang CHI ; Chang-Ming YU
Progress in Biochemistry and Biophysics 2025;52(4):957-969
ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.
7.Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity
Wenjing LI ; Zhongyu WANG ; Yongxin HUANG ; Jingjing XU ; Ying DING ; You WU ; Zhiwei QI ; Ruifeng YANG ; Xiaotong YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):70-79
ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma (ASR-PR) herb pair in the treatment of simple obesity through network pharmacology and molecular docking, and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to simple obesity were identified by retrieving the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction (PPI) network, and topological analysis was conducted to identify core genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR (2.06 g·kg-1), PR (2.06 g·kg-1), or ASR-PR (4.11 g·kg-1) for 10 weeks, while the model group received an equal volume of purified water by gavage. After the administration period, the mice were sacrificed to measure body fat weight and serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Hematoxylin-eosin (HE) staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in liver tissue were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 (Siberian glycoside A_qt), MOL003889 (methyl protodioscin_qt), MOL009766 (resveratrol), MOL006331 (4′,5-dihydroxyflavone), and MOL004941 (baicalin), thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group, the model group had significantly increased body weight, body fat weight, and serum levels of TG, TC, TNF-α, IL-6, and leptin (P<0.01). EGFR mRNA expression was significantly elevated (P<0.05), while STAT3 mRNA expression was significantly decreased (P<0.01). Histological analysis revealed disordered hepatic architecture in the model group, with pronounced lipid vacuoles, cytoplasmic loosening, lipid accumulation, and steatosis. Adipocytes in white adipose tissue (WAT) and brown adipose tissue (BAT) of the model group exhibited markedly increased diameters, reduced cell counts per unit area, and irregular morphology. Compared with the model group, the ASR-PR group significantly reduced body weight, body fat weight, serum TC, IL-6, TNF-α, leptin levels, and EGFR mRNA expression (P<0.01). TG levels were also significantly decreased (P<0.05), while STAT3 mRNA expression was significantly increased (P<0.01). Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased, and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components, modulate the PI3K/Akt and JAK/STAT signaling pathways, repair damaged liver and adipose tissues, and thereby alleviate the progression of obesity in mice.
8.Construction and Validation of a Large Language Model-Based Intelligent Pre-Consultation System for Traditional Chinese Medicine
Yiqing LIU ; Ying LI ; Hongjun YANG ; Linjing PENG ; Nanxing XIAN ; Kunning LI ; Qiwei SHI ; Hengyi TIAN ; Lifeng DONG ; Lin WANG ; Yuping ZHAO
Journal of Traditional Chinese Medicine 2025;66(9):895-900
ObjectiveTo construct a large language model (LLM)-based intelligent pre-consultation system for traditional Chinese medicine (TCM) to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function, BLEU-4, and ROUGE-L metrics, through which training convergence, text generation quality, and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content, TCM pharmacist licensure content, TCM symptom terminology recognition, and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy, consultation rounds, and consultation duration. ResultsAfter 100 000 iterations, the training loss value was gradually stabilized at about 0.7±0.08, indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L, suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms, 505 relationships between diseases and syndromes, 1011 relationships between diseases and main symptoms, and 1 303 600 relationships among different symptoms, and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners, licensed pharmacists of Chinese materia medica, recognition of TCM symptom terminology, and meridian recognition were 94.09%, 78.00%, 87.50%, and 68.80%, respectively. In clinical tests, the syndrome differentiation accuracy of the system reached 88.33%, with fewer consultation rounds and shorter consultation time compared to the attending physicians (P<0.01), suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language, it collects all the patient's symptom through guided questioning, thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.
9.A Randomized Controlled Trial of Stone Needle Thermocompression and Massage for Treating Chronic Musculoskeletal Pain in the Shoulder and Back:A Secondary Analysis of Muscle Elasticity as a Mediator
Jingjing QIAN ; Yuanjing LI ; Li LI ; Yawei XI ; Ying WANG ; Cuihua GUO ; Jiayan ZHOU ; Yaxuan SUN ; Shu LIU ; Guangjing YANG ; Na YUAN ; Xiaofang YANG
Journal of Traditional Chinese Medicine 2025;66(9):935-940
ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back, and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group, with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes, three times per week; the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement, as the primary outcome, was assessed using the Global Pain Scale (GPS) at baseline, after 2 weeks of treatment, and again 2 weeks post-treatment. To explore potential mechanisms, a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration, the between-group mean difference was -8.8 [95% CI (-18.2, -0.7), P<0.05]. Part of the therapeutic effect was mediated by changes in deep muscle elasticity, with a mediation effect size of -1.5 [95% CI (-2.0, -0.9), P = 0.024], accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back, partly through a mediating effect of improved deep muscle elasticity.
10.Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity
Wenjing LI ; Zhongyu WANG ; Yongxin HUANG ; Jingjing XU ; Ying DING ; You WU ; Zhiwei QI ; Ruifeng YANG ; Xiaotong YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):70-79
ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma (ASR-PR) herb pair in the treatment of simple obesity through network pharmacology and molecular docking, and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to simple obesity were identified by retrieving the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction (PPI) network, and topological analysis was conducted to identify core genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR (2.06 g·kg-1), PR (2.06 g·kg-1), or ASR-PR (4.11 g·kg-1) for 10 weeks, while the model group received an equal volume of purified water by gavage. After the administration period, the mice were sacrificed to measure body fat weight and serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Hematoxylin-eosin (HE) staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in liver tissue were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 (Siberian glycoside A_qt), MOL003889 (methyl protodioscin_qt), MOL009766 (resveratrol), MOL006331 (4′,5-dihydroxyflavone), and MOL004941 (baicalin), thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group, the model group had significantly increased body weight, body fat weight, and serum levels of TG, TC, TNF-α, IL-6, and leptin (P<0.01). EGFR mRNA expression was significantly elevated (P<0.05), while STAT3 mRNA expression was significantly decreased (P<0.01). Histological analysis revealed disordered hepatic architecture in the model group, with pronounced lipid vacuoles, cytoplasmic loosening, lipid accumulation, and steatosis. Adipocytes in white adipose tissue (WAT) and brown adipose tissue (BAT) of the model group exhibited markedly increased diameters, reduced cell counts per unit area, and irregular morphology. Compared with the model group, the ASR-PR group significantly reduced body weight, body fat weight, serum TC, IL-6, TNF-α, leptin levels, and EGFR mRNA expression (P<0.01). TG levels were also significantly decreased (P<0.05), while STAT3 mRNA expression was significantly increased (P<0.01). Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased, and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components, modulate the PI3K/Akt and JAK/STAT signaling pathways, repair damaged liver and adipose tissues, and thereby alleviate the progression of obesity in mice.

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