Metabolic diseases have seen a steady increase in incidence in recent years, becoming one of the main causes of sub-health status globally. Neutrophil extracellular traps(NETs) are reticular complexes containing DNA, which trap foreign microorganisms or induce an immune response. Current research indicates that NETs are widely active in various metabolic diseases and can cause severe damage to the body through multiple mechanisms, including promoting blood glucose elevation, damaging vascular endothelial cells, forming vascular embolisms, triggering intense inflammation, and promoting lipid accumulation. Therefore, intervening in NETs is an important approach to treating metabolic diseases. Research has shown a close relationship between the theory of spleen heat-turbid toxin theory and metabolic diseases-NETs mechanism. The basic pathogenesis include the internal accumulation of phlegm-dampness, qi stagnation and blood stasis, internal accumulation of dampness-heat, phlegm and blood stasis, and flourishing toxic heat. Various Chinese herbal medicines with the functions of dispelling dampness, resolving phlegm, promoting blood circulation to remove blood stasis, and clearing heat and toxins, along with their extracts and compound prescriptions, can treat metabolic diseases by regulating NETs and delaying disease progression. This paper systematically outlined the formation mechanisms of NETs, their connection to metabolic diseases, the theoretical basis in TCM, their roles in numerous metabolic diseases, and the current research status of TCM in regulating NETs to prevent and control metabolic diseases, aiming to provide effective reference ideas for developing therapeutic strategies for metabolic diseases.
Humans ; Extracellular Traps/metabolism* ; Metabolic Diseases/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Neutrophils/metabolism* ; Medicine, Chinese Traditional

OBJECTIVES: To investigate the therapeutic effects and mechanisms of 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) in a mouse model of asthma. METHODS: SPF-grade BALB/c mice were randomly divided into 7 groups (n=8 each group): normal control group, ovalbumin (OVA) group, dimethyl sulfoxide+corn oil group, budesonide (BUD) group, and low, medium, and high dose 2,6-DMBQ groups. An asthma mouse model was established by OVA induction, followed by corresponding drug interventions. Non-invasive lung function tests were performed to measure airway hyperresponsiveness, and enzyme-linked immunosorbent assay was used to determine levels of interleukin (IL)-17, IL-10, and serum immunoglobulin E in bronchoalveolar lavage fluid. A cell counter was employed to detect eosinophil counts in bronchoalveolar lavage fluid, while hematoxylin-eosin staining and periodic acid-Schiff staining were used to assess lung tissue pathological changes. Western blot was conducted to examine the expression of proteins related to the mammalian target of rapamycin pathway (p-AKT/AKT and p-p70S6K/p70S6K), and a fully automated biochemical analyzer was used to evaluate liver and kidney functions. RESULTS: Compared with the normal control group, the OVA group showed increased enhanced pause values, inflammation scores from hematoxylin-eosin staining, positive area from periodic acid-Schiff staining, percentage of eosinophils, IL-17/IL-10 ratio, serum immunoglobulin E levels, and relative expression levels of p-AKT/AKT and p-p70S6K/p70S6K (P<0.05). The BUD group and the medium and high dose 2,6-DMBQ groups exhibited decreased values for these indicators compared to the OVA group (P<0.05). CONCLUSIONS 2,6-DMBQ can inhibit the mTOR pathway to alleviate airway inflammation in asthmatic mice, possibly by mitigating the imbalance between Th17 and regulatory T cells.
Animals ; Asthma/pathology* ; Mice, Inbred BALB C ; Signal Transduction/drug effects* ; Mice ; TOR Serine-Threonine Kinases/physiology* ; Female ; Benzoquinones/pharmacology* ; Immunoglobulin E/blood* ; Interleukin-10/analysis* ; Interleukin-17/analysis* ; Bronchoalveolar Lavage Fluid ; Lung/pathology*

OBJECTIVE: To investigate the therapeutic potential of pseudolaric acid B (PAB) on non-alcoholic fatty liver disease (NAFLD) and its underlying molecular mechanism in vitro and in vivo. METHODS: Eight-week-old male C57BL/6J mice (n=32) were fed either a normal chow diet (NCD) or a high-fat diet (HFD) for 8 weeks. The HFD mice were divided into 3 groups according to a simple random method, including HFD, PAB low-dose [10 mg/(kg·d), PAB-L], and PAB high-dose [20 mg/(kg·d), PAB-H] groups. After 8 weeks of treatment, glucose metabolism and insulin resistance were assessed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Biochemical assays were used to measure the serum and cellular levels of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). White adipose tissue (WAT), brown adipose tissue (BAT) and liver tissue were subjected to hematoxylin and eosin (H&E) staining or Oil Red O staining to observe the alterations in adipose tissue and liver injury. PharmMapper and DisGeNet were used to predict the NAFLD-related PAB targets. Peroxisome proliferator-activated receptor alpha (PPARα) pathway involvement was suggested by Kyoto Encyclopedia of Genes and Genomes (KEGG) and search tool Retrieval of Interacting Genes (STRING) analyses. Luciferase reporter assay, cellular thermal shift assay (CETSA), and drug affinity responsive target stability assay (DARTS) were conducted to confirm direct binding of PAB with PPARα. Molecular dynamics simulations were applied to further validate target engagement. RT-qPCR and Western blot were performed to assess the downstream genes and proteins expression, and validated by PPARα inhibitor MK886. RESULTS: PAB significantly reduced serum TC, TG, LDL-C, AST, and ALT levels, and increased HDL-C level in HFD mice (P<0.01). Target prediction analysis indicated a significant correlation between PAB and PPARα pathway. PAB direct target binding with PPARα was confirmed through luciferase reporter assay, CETSA, and DARTS (P<0.05 or P<0.01). The target engagement between PAB and PPARα protein was further confirmed by molecular dynamics simulations and the top 3 amino acid residues, LEU321, MET355, and PHE273 showed the most significant changes in mutational energy. Subsequently, PAB upregulated the genes expressions involved in lipid metabolism and mitochondrial biogenesis downstream of PPARα (P<0.05 or P<0.01). Significantly, the PPARα inhibitor MK886 effectively reversed the lipid-lowering and PPARα activation properties of PAB (P<0.05 or P<0.01). CONCLUSION PAB mitigates lipid accumulation, ameliorates liver damage, and improves mitochondrial biogenesis by binding with PPARα, thus presenting a potential candidate for pharmaceutical development in the treatment of NAFLD.
Animals ; PPAR alpha/metabolism* ; Non-alcoholic Fatty Liver Disease/pathology* ; Male ; Mice, Inbred C57BL ; Lipid Metabolism/drug effects* ; Diterpenes/therapeutic use* ; Organelle Biogenesis ; Diet, High-Fat ; Humans ; Mice ; Liver/metabolism* ; Insulin Resistance ; Mitochondria/metabolism* ; Molecular Docking Simulation

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Airway management in complex tracheobronchial surgery(TBS)remains a challenge in thoracic sur-gery.The use of extracorporeal membrane pulmonary oxygenation(ECMO)in thoracic surgery is rather rare,except for lung transplantation.To report the safety and efficacy of ECMO in complex TBS,a total of 5 patients with tracheobronchial and bronchial reconstructive surgery supported by ECMO in the Department of Thoracic Surgery of Tangdu Hospital,Air Force Medical University from May 2019 to June 2024 were collected.Among them,4 cases of tracheal tumor(including long-segment trachea resection and reconstruction,or carinal resection and reconstruction)and 1 case of acute airway obstruction caused by tracheal rupture were included,all of which were performed in veno-venous ECMO(V-V ECMO)mode.Systemic heparinization was used in 2 patients,and anticoagulation was not performed in 3 patients,which were maintained only by ECMO heparin-coated lines.4 patients recovered well after surgery,and 1 patient died 1 month after surgery due to immune-related pneumonia.For complex TBS,or in emergency situations(tracheal stenosis with risk of asphyxiation),ECMO can pro-vide adequate support and safeguard.

Objective:To investigate the clinical outcomes of using autologous mandibular outer cortex "sandwich" grafting to augment mandible for correcting lower facial asymmetry with normal occlusal relationships.Methods:A retrospective analysis was conducted on the clinical data of patients with lower facial asymmetry treated at the Department of Plastic Surgery, the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, from January 2016 to December 2019. Preoperative cone-beam CT (CBCT) scans of the maxillofacial region were obtained to acquire three-dimensional data of the maxillofacial skeleton. Computer-aided design was used to determine the osteotomy range of the mandibular outer cortex and design osteotomy guide template. The outer cortex of the larger mandibular side (donor site) was harvested according to the osteotomy guide template and sectioned. The segmented mandibular outer cortex was then contoured to match the arc of the recipient side’s mandibular outer cortex and fixed to the inner side of the recipient mandibular outer cortex, thus increasing the width and thickness of the expanded mandible. Follow-up was conducted at 7th day and 6 months postoperatively, CBCT scan was performed to measure the changes in ramus height (Co-Go), mandibular body length (Go-Me), and mandibular outer cortex thickness, and volume, and the patient satisfaction with facial appearance (1 to 5 points, with higher scores indicating higher satisfaction), were assessed to evaluate surgical outcomes. Statistical analysis was performed using SPSS 12.0 software. Paired t-tests were used to compare patient satisfaction scores preoperatively and six months postoperatively. Repeated measurement ANOVA was used to compare Co-Go and Go-Me measurements preoperatively, 7th day, and 6 months postoperatively. If a statistically significant difference is found, further analysis using post-hoc testing(Tukey’s HSD test) will be conducted to examine the data. Results:Sixteen patients with lower facial asymmetry were included, comprising of 5 males and 11 females, aged 18 to 40 years, with an average age of 25.2 years. Surgical method included contralateral mandibular outer cortex "sandwich" grafting to the expanded mandible in 9 cases and simultaneous genioplasty in 7 cases. Follow-up ranged from 6 months to 5 years, with an average follow-up of 18.6 months. All patients experienced numbness of the lower lip postoperatively, which resolved within six months, and no severe complications occurred. The symmetry of lower facial contour improved significantly and remained stable. Patient satisfaction score for facial appearance increased from (1.63±0.62) points preoperatively to (4.19±0.75) points six months postoperatively( P<0.01). The differences in Co-Go on the donor side and Go-Me on the recipient side across the three time points(preoperatively, 7th day and 6 months postoperatively) were not statistically significant(all P>0.05). However, the differences in Go-Me on the donor side and Co-Go on the recipient side across the three time points were statistically significant(all P<0.05). On the donor side, the mandibular outer cortex thickness decreased by a maximum of 6 mm on 7th day postoperatively and increased by a maximum of 2 mm at 6 months postoperatively compared to 7th day. On the recipient side, mandibular outer cortex thickness increased by a maximum of 6 mm on 7th day postoperatively and decreased by a maximum of 2 mm at six months postoperatively compared to 7th day. The volume of the mandibular outer cortex on the recipient side increased by (4 415.94±1 017.21)mm 3 at 7th day postoperatively compared to preoperatively, and decreased by (202.63±300.85)mm 3 at 6 months postoperatively. Conclusion:For lower facial asymmetrical with normal occlusal relationships and no occlusal plane deviation, contralateral mandibular outer cortex "sandwich" bone grafting can effectively increase the width and volume of the mandible on the grafted side, achieving favorable clinical outcomes.

Objective:To investigate the clinical outcomes of using autologous mandibular outer cortex "sandwich" grafting to augment mandible for correcting lower facial asymmetry with normal occlusal relationships.Methods:A retrospective analysis was conducted on the clinical data of patients with lower facial asymmetry treated at the Department of Plastic Surgery, the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, from January 2016 to December 2019. Preoperative cone-beam CT (CBCT) scans of the maxillofacial region were obtained to acquire three-dimensional data of the maxillofacial skeleton. Computer-aided design was used to determine the osteotomy range of the mandibular outer cortex and design osteotomy guide template. The outer cortex of the larger mandibular side (donor site) was harvested according to the osteotomy guide template and sectioned. The segmented mandibular outer cortex was then contoured to match the arc of the recipient side’s mandibular outer cortex and fixed to the inner side of the recipient mandibular outer cortex, thus increasing the width and thickness of the expanded mandible. Follow-up was conducted at 7th day and 6 months postoperatively, CBCT scan was performed to measure the changes in ramus height (Co-Go), mandibular body length (Go-Me), and mandibular outer cortex thickness, and volume, and the patient satisfaction with facial appearance (1 to 5 points, with higher scores indicating higher satisfaction), were assessed to evaluate surgical outcomes. Statistical analysis was performed using SPSS 12.0 software. Paired t-tests were used to compare patient satisfaction scores preoperatively and six months postoperatively. Repeated measurement ANOVA was used to compare Co-Go and Go-Me measurements preoperatively, 7th day, and 6 months postoperatively. If a statistically significant difference is found, further analysis using post-hoc testing(Tukey’s HSD test) will be conducted to examine the data. Results:Sixteen patients with lower facial asymmetry were included, comprising of 5 males and 11 females, aged 18 to 40 years, with an average age of 25.2 years. Surgical method included contralateral mandibular outer cortex "sandwich" grafting to the expanded mandible in 9 cases and simultaneous genioplasty in 7 cases. Follow-up ranged from 6 months to 5 years, with an average follow-up of 18.6 months. All patients experienced numbness of the lower lip postoperatively, which resolved within six months, and no severe complications occurred. The symmetry of lower facial contour improved significantly and remained stable. Patient satisfaction score for facial appearance increased from (1.63±0.62) points preoperatively to (4.19±0.75) points six months postoperatively( P<0.01). The differences in Co-Go on the donor side and Go-Me on the recipient side across the three time points(preoperatively, 7th day and 6 months postoperatively) were not statistically significant(all P>0.05). However, the differences in Go-Me on the donor side and Co-Go on the recipient side across the three time points were statistically significant(all P<0.05). On the donor side, the mandibular outer cortex thickness decreased by a maximum of 6 mm on 7th day postoperatively and increased by a maximum of 2 mm at 6 months postoperatively compared to 7th day. On the recipient side, mandibular outer cortex thickness increased by a maximum of 6 mm on 7th day postoperatively and decreased by a maximum of 2 mm at six months postoperatively compared to 7th day. The volume of the mandibular outer cortex on the recipient side increased by (4 415.94±1 017.21)mm 3 at 7th day postoperatively compared to preoperatively, and decreased by (202.63±300.85)mm 3 at 6 months postoperatively. Conclusion:For lower facial asymmetrical with normal occlusal relationships and no occlusal plane deviation, contralateral mandibular outer cortex "sandwich" bone grafting can effectively increase the width and volume of the mandible on the grafted side, achieving favorable clinical outcomes.