ObjectiveTo establish steroid-induced osteonecrosis of the femoral head （SANFH） cell model by using dexamethasone （DEX）-induced bone marrow mesenchymal stem cells （BMSCs） and demonstrate that Gushing Granules （GSNs） exert an improving effect by activating the phosphatidylinositol-3-kinase/protein kinase B/B-lymphoma-2 gene related promoter （PI3K/Akt/Bad） signalling pathway. MethodsFirstly， SD rats were orally administered with drugs at a dose of 0.9 g·kg^-1 to prepare GSN-containing serum， and CCK-8 screening was used to determine the optimal dosage and duration of action. Then， BMSCs were cultured and treated with 1×10^-6 mol·L^-1 DEX， 10% GSN-containing serum， and inhibitor LY294002 of PI3K/Akt signalling pathway for 24 hours to model and group SANFH cells. Cell viability and proliferation were detected by using CCK-8 assay kit and EdU staining kit. Flow cytometry was used to detect cell apoptosis. An alkaline phosphatase （ALP） assay kit was employed to detect ALP expression. In order to detect the PI3K/Akt/Bad signalling pathway and protein and mRNA expression of apoptosis-related proteins such as apoptosis regulatory factors B-cell lymphoma-2 gene （Bcl-2）， and Bcl-2-associated X protein （Bax）， osteocalcin （OCN）， and Collagen Ⅰ， we used Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsThe CCK-8 assay kit determined that the optimal dosage for GSN-containing serum is 10%， and the duration of action is 48 hours. After modelling and grouping the cells in each group， the detection results showed that the SANFH model group had significantly lower cell viability， cell proliferation， and ALP expression， as well as protein and mRNA expressions of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen I compared to the blank group. The nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly increased （P<0.05，P<0.01）. After treatment with GSN-containing serum， cell viability， cell proliferation， and ALP expression， as well as expressions of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen Ⅰ nucleic acids and proteins were significantly increased， while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly decreased（P<0.05，P<0.01）. Compared with the GSN drug-containing serum group， the simultaneous treatment with the inhibitor LY294002 and GSN drug-containing serum reversed the improvement effect of GSN. Specifically， the cell viability， cell proliferation， ALP expression， and the nucleic acid and protein levels of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen Ⅰ were all significantly decreased， while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry were significantly increased （P<0.05， P<0.01）. ConclusionGSNs antagonize DEX-induced apoptosis of BMSCs by activating the PI3K/Akt/Bad signalling pathway， providing a scientific theoretical basis for the clinical treatment of SANFH with GSNs.

Pancreatic cancers (PCs) is a common malignant tumor with poor prognosis in the digestive system. Its main treatment methods include surgery, radiotherapy, chemotherapy, and targeted therapy. The early diagnosis rate of hidden onset of PCs is low, and most patients have already lost the opportunity to undergo surgery when diagnosed with PCs. Chemotherapy is still the main treatment for advanced PCs, but the use of chemotherapy drugs in PCs can easily lead to drug resistance. The most significant feature that distinguishes PCs from other tumors is its rich and dense matrix, which not only hinders drug penetration but also impedes the infiltration of immune cells. The above reasons have led to a very low survival rate of PCs patients. Therefore, drug delivery systems are very important in the diagnosis and treatment of PCs. They can improve drug delivery, enhance biological barrier penetration, reduce side effects, and combine multiple treatment methods. Therefore, the treatment prospects of PCs are very broad. Currently, drug delivery systems widely applied in PCs primarily include nanodrug delivery systems, tumor microenvironment-targeted drug delivery system, immunotherapy drug delivery system, gene therapy drug delivery system, and combination therapy drug delivery system that synergize multiple therapeutic modalities. Emerging drug delivery systems (DDSs) have revolutionized PCs treatment by addressing these challenges through multiple mechanisms. Nanoformulations improve drug solubility, prolong circulation time, and reduce systemic toxicity via passive/active targeting. Smart DDSs responsive to PCs-specific stimuli enable extracellular matrix degradation, tumor-associated fibroblasts reprogramming, and vascular normalization to enhance drug accessibility. Last but not least, carrier systems loaded with myeloid-derived suppressor cell inhibitors or T cell activators can reverse immunosuppression and potentiate immunotherapy efficacy. Advanced platforms co-deliver chemotherapeutics with immunomodulators, gene-editing tools, or sonodynamic agents to achieve synergistic antitumor effects. These platforms aim to address critical challenges in PCs treatment, such as enhancing drug bioavailability, overcoming stromal barriers, reprogramming immunosuppressive niches, and achieving multi-mechanistic antitumor effects. This article provides a systematic summary and prospective analysis of the current development status, latest cutting-edge advances, opportunities, and challenges of the above-mentioned drug delivery systems in the field of PCs therapy.

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

Prostate cancer(PCa) is a common malignant tumor among elderly men, with high incidence and mortality rates worldwide, posing a serious threat to human health. Traditional treatments face limitations, highlighting the urgent need for novel therapeutic strategies. Recent studies on the regulatory mechanisms of micro ribonucleic acid(microRNA, miRNA) in tumor development has identified miRNA as new targets for PCa diagnosis and treatment. Traditional Chinese medicine(TCM), with its multi-mechanism, multi-target, and multi-pathway regulatory properties, shows promising potential in miRNA-based PCa therapy. This review summarized recent findings on miRNA' roles in PCa and research progress of TCM intervention and found that a variety of miRNA played important regulatory roles in cell differentiation, proliferation, apoptosis, invasion, metastasis, immune microenvironment, and drug resistance, and their potential as biomarkers for PCa diagnosis, prognosis, and therapy, indicating the potential to be a biomarker for the diagnosis, prognosis evaluation, and treatment of PCa. The review concluded that the active components of TCM(terpenoids, flavonoids, alkaloids, and others) and compounds(Yishen Tonglong Decoction, Shenhu Decoction, Zhoushi Qiling Decoction, Fuzheng Yiliu Decoction, and Qilan Formula) could regulate the expression of their downstream target genes by acting on specific miRNA and affect the above biological behaviors of PCa cells, thus playing a role in the treatment of PCa. This review aims to provide a theoretical basis for miRNA as potential biomarkers and therapeutic targets for PCa and suggest new avenues for further development of targeted therapy strategies against miRNA.
Humans ; MicroRNAs/metabolism* ; Prostatic Neoplasms/metabolism* ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Animals ; Gene Expression Regulation, Neoplastic/drug effects*

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

OBJECTIVE: To review the research progress of pathological changes of glenohumeral capsule in patients with recurrent shoulder anterior dislocation (RSAD). METHODS: The literature on shoulder capsules, both domestic and international, was reviewed. The anatomy, histology, and molecular biology characteristics of the glenohumeral capsule in RSAD patients were summarized. RESULTS: Anatomically, the glenohumeral capsule is composed of four distinct parts: the upper, lower, anterior, and posterior sections. The thickness of these sections is uneven, and the stability of the capsule is further enhanced by the presence of the glenohumeral and coracohumeral ligaments. Histologically, the capsule tissue undergoes adaptive changes following RSAD, which improve its ability to withstand stretching and deformation. In the realm of molecular biology, genes associated with the regulation of structure formation, function, and extracellular matrix homeostasis of the shoulder capsule's collagen fibers exhibit varying degrees of expression changes. Specifically, the up-regulation of transforming growth factor β ₁ (TGF-β ₁), TGF-β receptor 1, lysyl oxidase, and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 facilitates the repair of the joint capsule, thereby contributing to the maintenance of shoulder joint stability. Conversely, the up-regulation of collagen type Ⅰ alpha 1 (COL1A1), COL3A1, and COL5A1 is linked to the recurrence of shoulder anterior dislocation, as these changes reflect the joint capsule's response to dislocation. Additionally, the expressions of tenascin C and fibronectin 1 may play a role in the pathological processes occurring during the early stages of RSAD. CONCLUSION Glenohumeral capsular laxity is both a consequence of RSAD and a significant factor contributing to its recurrence. While numerous studies have documented alterations in the shoulder capsule following RSAD, further research is necessary to confirm the specific pathological anatomy, histological, and molecular biological changes involved.
Humans ; Joint Capsule/metabolism* ; Shoulder Dislocation/metabolism* ; Recurrence ; Shoulder Joint/metabolism* ; Tenascin/metabolism* ; Transforming Growth Factor beta1/genetics* ; Collagen Type I/genetics* ; Extracellular Matrix/metabolism*

Objective To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.