Lonicerae Japonicae Flos refers to the dried flower buds or flowers about to open of Lonicera japonica （Caprifoliaceae）. Its dried flower buds or early blooming flowers are listed in the Pharmacopoeia of the People's Republic of China （2020 edition） as official medicinal materials. As a Chinese medicine with "heat-clearing and detoxifying" properties and a classic medicinal-edible resource， it is mainly produced in northern authentic producing regions such as Shandong， Henan， and Hebei in China. Lonicerae Japonicae Flos contains abundant bioactive substances that are considered safe and effective， with functions including relieving sore throat， antibacterial and anti-inflammatory effects， and immune regulation. In recent years， with the modernization of traditional Chinese medicine （TCM） and the rapid development of the "big health" industry， Lonicerae Japonicae Flos has become a research hotspot in the fields of natural medicines and functional foods due to its multi-target pharmacological activities and broad application potential. To date， chemical constituents identified from Lonicerae Japonicae Flos include organic acids， flavonoids， iridoids， triterpenes， triterpenoid saponins， and volatile oils. Modern pharmacological studies have shown that Lonicerae Japonicae Flos possesses anti-inflammatory， antibacterial， antioxidant， antiviral， antidiabetic， cardiovascular and neuroprotective， and immunomodulatory activities. In terms of modern applications， Lonicerae Japonicae Flos has developed into a full industrial chain covering pharmaceuticals， health products， daily chemical products， and food additives， demonstrating high medicinal and health value. Strengthening the development of Lonicerae Japonicae Flos-based health products is of great significance. Based on relevant domestic and international literature， this paper systematically reviews the innovative applications of Lonicerae Japonicae Flos in traditional medicine， modern clinical formulations， health foods， and daily chemical products from the perspectives of chemical composition， pharmacological effects， and modern applications， aiming to further deepen basic research on Lonicerae Japonicae Flos. Meanwhile， this paper analyzes and proposes suggestions for promoting applied research on Lonicerae Japonicae Flos， in order to provide a scientific basis for its sound development and to offer references for the rational development and comprehensive utilization of medicinal and edible resources.

Edema， as a common pathological phenomenon， is essentially the abnormal accumulation of body fluids in the interstitial spaces of human tissues and is often a direct manifestation of various underlying diseases， such as heart failure， impaired renal filtration function， or liver metabolic disorders. In the Western medical system， strategies for treating edema primarily focus on the use of diuretics to promote the excretion of excess fluid in the body， while simultaneously addressing the underlying causes through targeted treatment. However， long-term reliance on the use of diuretics may lead to a decrease in drug sensitivity and induce side effects， including electrolyte disorders such as hypokalemia and hypercalcemia， posing a potential threat to patients' overall health. Compared with Western medicine， traditional Chinese medicine （TCM） has demonstrated well-recognized and sustained efficacy in treating edema with its unique theoretical system. Zhulingtang， as a classic and commonly used TCM formula， is widely applied as it can effectively relieve edema and related symptoms. In recent years， ongoing in-depth studies on the treatment of edema with Zhulingtang have revealed multiple mechanisms of action of Zhulingtang， including the regulation of water metabolism and the reduction of inflammatory responses， thereby providing a solid theoretical basis for clinical practice. This review summarized the research progress on the treatment of edema with Zhulingtang in recent years and analyzed the active ingredients and action pathways of Zhulingtang. Additionally， the primary mechanisms of action and efficacy were systematically analyzed， so as to provide references for the clinical application of Zhulingtang in treating various types of edema， such as cardiogenic edema， renal edema， and hepatogenic edema. This review aims to offer theoretical support and practical guidance for clinicians in deciding treatment approaches， as well as references for subsequent in-depth studies， thereby promoting further development of TCM in the treatment of edema.

Edema， as a common pathological phenomenon， is essentially the abnormal accumulation of body fluids in the interstitial spaces of human tissues and is often a direct manifestation of various underlying diseases， such as heart failure， impaired renal filtration function， or liver metabolic disorders. In the Western medical system， strategies for treating edema primarily focus on the use of diuretics to promote the excretion of excess fluid in the body， while simultaneously addressing the underlying causes through targeted treatment. However， long-term reliance on the use of diuretics may lead to a decrease in drug sensitivity and induce side effects， including electrolyte disorders such as hypokalemia and hypercalcemia， posing a potential threat to patients' overall health. Compared with Western medicine， traditional Chinese medicine （TCM） has demonstrated well-recognized and sustained efficacy in treating edema with its unique theoretical system. Zhulingtang， as a classic and commonly used TCM formula， is widely applied as it can effectively relieve edema and related symptoms. In recent years， ongoing in-depth studies on the treatment of edema with Zhulingtang have revealed multiple mechanisms of action of Zhulingtang， including the regulation of water metabolism and the reduction of inflammatory responses， thereby providing a solid theoretical basis for clinical practice. This review summarized the research progress on the treatment of edema with Zhulingtang in recent years and analyzed the active ingredients and action pathways of Zhulingtang. Additionally， the primary mechanisms of action and efficacy were systematically analyzed， so as to provide references for the clinical application of Zhulingtang in treating various types of edema， such as cardiogenic edema， renal edema， and hepatogenic edema. This review aims to offer theoretical support and practical guidance for clinicians in deciding treatment approaches， as well as references for subsequent in-depth studies， thereby promoting further development of TCM in the treatment of edema.

OBJECTIVE To construct three-class （insufficient， normal， excessive） and two-class （insufficient， normal） models for predicting plasma concentration of valproic acid （VPA）， and compare the performance of these two models， with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 （a total of 695 sets of data）. In this study， predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation， and the performance of the models was evaluated using three indexes: accuracy， F1 score， and the area under the working characteristic curve of the subject （AUC）. RESULTS XGBoost feature importance scores revealed that in the three-class model， the importance ranking of kidney disease and electrolyte disorders was higher. However， in the two-class model， the importance ranking of these features significantly decreased， suggesting a close association with the excessive blood concentration of VPA. In the three-class model， Random Forest method performed best， with F1 score of 0.704 0 and AUC of 0.519 3 on the test set； while in the two-class model， CatBoost method performed optimally， with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration， but its prediction and model generalization abilities are poor； the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases， but its model performance is stronger.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

As a novel form of cell death, ferroptosis is mainly regulated by the accumulation of soluble iron ions in the cytoplasm and the production of lipid peroxides and is closely associated with several diseases, including acute kidney injury, ischemic reperfusion injury, neurodegenerative diseases, and cancer. The term "immunosuppression" refers to various factors that can directly harm immune cells' structure and function and affect the synthesis, release, and biological activity of immune molecules, leading to the insufficient response of the immune system to antigen production, failure to successfully resist the invasion of foreign pathogens, and even organ damage and metabolic disorders. An immunosuppressive phase commonly occurs in the progression of many ferroptosis-related diseases, and ferroptosis can directly inhibit immune cell function. However, the relationship between ferroptosis and immunosuppression has not yet been published due to their complicated interactions in various diseases. Therefore, this review deeply discusses the contribution of ferroptosis to immunosuppression in specific cases. In addition to offering new therapeutic targets for ferroptosis-related diseases, the findings will help clarify the issues on how ferroptosis contributes to immunosuppression.
Ferroptosis/immunology* ; Humans ; Immune Tolerance/immunology* ; Animals ; Immunosuppression Therapy ; Iron/metabolism* ; Neoplasms/immunology*

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

This study aims to investigate the optimal ratio of Astragali Radix-Curcumae Rhizoma(AC) for inhibiting the proliferation of 143B osteosarcoma cells, and to investigate the mechanism by which AC inhibits osteosarcoma growth and metastasis through angiogenesis and cell adhesion mediated by the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor-1α(HIF-1α) pathway. A subcutaneous 143B tumor-bearing nude mouse model was successfully established and randomly divided into the model group, and the AC 1∶1, 2∶1, and 4∶1 groups. Body weight, tumor volume, and tumor weight were recorded. Real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of PI3K, Akt, phosphorylated Akt(p-Akt), HIF-1α, vascular endothelial growth factor A(VEGFA), transforming growth factor-β1(TGF-β1), epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, matrix metalloproteinase 2(MMP2), matrix metalloproteinase 9(MMP9), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3 in the hypoxic core region of the tumor tissue. A cell hypoxia model was established, and the effects of AC-medicated serum(model group, AC 1∶1, 2∶1, and 4∶1 groups) on angiogenesis, proliferation, adhesion, invasion, and migration of 143B osteosarcoma cells were examined through CCK-8, flow cytometry, Transwell assay, cell adhesion assay, and HUVEC tube formation assay. The results showed that compared with the model group, the tumor weight and volume were smallest in the 2∶1 group. The expression levels of PI3K, Akt, p-Akt, HIF-1α, VEGFA, and TGF-β1 were significantly decreased, and the protein expression of E-cadherin was significantly increased, while the protein expression of N-cadherin, vimentin, MMP2, and MMP9 was significantly decreased. Additionally, the protein expression of Bax and caspase-3 was significantly increased, and Bcl-2 protein expression was significantly decreased. In vitro experiments showed that after intervention with AC-medicated serum at a 2∶1 ratio, the cell activity, adhesion, invasion, and migration of 143B cells were significantly reduced, apoptosis was significantly increased, and HUVEC tube formation was significantly decreased. In conclusion, the 2∶1 ratio of AC showed the most effective inhibition of 143B cell growth. AC can inhibit the growth and metastasis of osteosarcoma 143B cells by regulating the PI3K/Akt/HIF-1α signaling pathway, inhibiting angiogenesis and reducing cell adhesion, invasion, and migration.
Osteosarcoma/pathology* ; Animals ; Proto-Oncogene Proteins c-akt/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Humans ; Mice ; Cell Adhesion/drug effects* ; Cell Proliferation/drug effects* ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Cell Line, Tumor ; Mice, Nude ; Signal Transduction/drug effects* ; Astragalus Plant/chemistry* ; Bone Neoplasms/physiopathology* ; Male ; Rhizome/chemistry* ; Mice, Inbred BALB C ; Angiogenesis