BACKGROUND:Chondrocyte apoptosis is an important factor in the development of osteoarthritis,and Complanatoside A has a flavonoid effect,which can inhibit apoptosis of various cells,but its effect on chondrocyte apoptosis and the mechanism of action are not clear. OBJECTIVE:To investigate the intrinsic association and mechanism of Complanatoside A in chondrocyte apoptosis based on the Wnt/β-catenin signaling pathway. METHODS:(1)The cartilage tissues of the femur and tibia transected during knee arthroplasty were collected,and chondrocytes were isolated,cultured in vitro,and identified.(2)Cell counting kit-8 was used to detect the optimal intervention concentration of Complanatoside A in the concentration range of 0-160 μmol/L.(3)Chondrocytes were divided into blank group,sodium nitroprusside(1.5 mmol/L)-induced group,and sodium nitroprusside(1.5 mmol/L)+Complanatoside A(5 μmol/L)group.The viability and apoptosis rate of the cells in each group were detected by cell counting kit-8 and flow cytometry.The expression of type Ⅱ collagen and SOX9 was detected by immunofluorescence staining.The expression of apoptosis-related proteins and Wnt/β-catenin pathway proteins was detected by western blot assay. RESULTS AND CONCLUSION:The cells extracted in vitro were cultured and stained,and were clearly identified as chondrocytes.Complanatoside A had no obvious cytotoxicity to chondrocytes in the concentration range of 0-80 μmol/L,and significantly improved the chondrocyte viability in the concentration range of 2.5-10 μmol/L,especially when the concentration was 5 μmol/L.The apoptotic rate of chondrocytes was higher in the sodium nitroprusside-induced group than the blank control group,while the apoptotic rate was lower in the sodium nitroprusside+Complanatoside A group than the sodium nitroprusside-induced group.The fluorescence intensity of type Ⅱ collagen and SOX9 in chondrocytes was weaker in the sodium nitroprusside-induced group than the blank control group,while the fluorescence intensity of type Ⅱ collagen and SOX9 in the sodium nitroprusside+Complanatoside A group was higher than that of the sodium nitroprusside-induced group.In the sodium nitroprusside-induced group,the protein expression of Bax,Caspase-3,matrix metalloproteinase 13,Wnt3a,Wnt5a and β-catenin was higher than that of the blank control group,while the protein expression of Bcl-2 was lower than that of the blank control group.In the sodium nitroprusside+Complanatoside A group,except for the protein expression of Bcl-2 which was higher than that of the sodium nitroprusside-induced group,the expression of the other aforementioned proteins was lower than that of the sodium nitroprusside-induced group.To conclude,Complanatoside A has a certain inhibitory effect on chondrocyte apoptosis,which could regulate apoptosis-related proteins and promote the expression of chondrocyte regulatory factors,and presumably might play a role through inhibiting the Wnt/β-catenin signaling pathway.

Objective To screen ferroptosis genes related to the prognosis of cervical cancer and to construct a prognosis model. Methods Ferroptosis genes were obtained from FerrDb database, and cervical cancer related data were obtained from The Genome-Wide Association Study Catalog database and The Cancer Genome Atlas database. Transcriptome-Wide Association Study, colocalization analysis and differential expression analysis were conducted to screen out candidate ferroptosis genes; Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted on candidate genes. Univariate Cox regression analysis was used to further screen out genes related to the prognosis of cervical cancer. Kaplan-Meier method was used to analyze the relationship between genes and the overall survival of patients. The expression levels of genes in pan-cancer were analyzed through the TIMER database. Two prognostic models were conducted, Model 1 included age and tumor stage, while Model 2 incorporated age, tumor stage, and prognostic genes. The predictive capabilities of the two models were compared. Results A total of 91 candidate genes related to ferroptosis were obtained. Univariate Cox regression analysis showed that 15 genes were associated with the prognosis of cervical cancer. CA9, SCD, TFRC, QSOX1 and CDO1 were risk factors affecting the prognosis of cervical cancer patients (P＜0.05), while PTPN6, ALOXE3, HELLS, IFNG, MIOX, ALOX12B, DUOX1, ALOX15, AQP3 and IDO1 were protective factors (P＜0.05). The mRNA expression levels of the 15 genes showed significant upregulation or downregulation in at least 7 types of cancers, among which TFRC was associated with the largest number of cancer types. Kaplan-Meier analysis showed that HELLS, DUOX1 and ALOXE3 were associated with poor prognosis in cervical cancer. The AUC of the model 1 for predicting 1-year and 3-year overall survival rates of cervical cancer patients was 0.455 and 0.478, and the AUC of Model 2 was 0.854 and 0.595. Model 2 (C-index = 0.727) had better predictive ability than Model 1 (C-index = 0.502). Conclusion The prognostic model composed of 15 prognostic-related genes selected based on bioinformatics has better predictive performance for the survival outcomes of cervical cancer patients, providing important reference value for the prognostic assessment of cervical cancer patients.

[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

Hypercoagulable state (HCS) after kidney transplantation is one of the common and serious complications in kidney transplant recipients, which has attracted increasing attention in recent years. HCS refers to the abnormal and excessive activation of blood coagulation function, leading to the increased risk of thrombosis. After kidney transplantation, the combined effects of hemodynamic changes, surgical trauma and severe rejection increase the incidence of HCS, not only raising the risk of thrombosis but also potentially causing graft failure and affecting the postoperative survival rate of patients. This article reviews the influencing factors, clinical manifestations, diagnostic methods and preventive strategies of HCS after kidney transplantation, aiming to provide a theoretical basis for optimizing perioperative management and improving the prognosis of patients.

Clathrin-mediated endocytosis (CME) is a critical process by which cells internalize macromolecular substances and initiate vesicle trafficking, serving as the foundation for many cellular activities. Central to this process are clathrin-coated structures (CCSs), which consist of clathrin-coated pits (CCPs) and clathrin plaques. While clathrin-coated pits are well-established in the study of endocytosis, clathrin plaques represent a more recently discovered but equally important component of this system. These plaques are large, flat, and extended clathrin-coated assemblies found on the cytoplasmic membrane. They are distinct from the more typical clathrin-coated pits in terms of their morphology, larger surface area, and longer lifespan. Recent research has revealed that clathrin plaques play roles that go far beyond endocytosis, contributing to diverse cellular processes such as cellular adhesion, mechanosensing, migration, and pathogen invasion. Unlike traditional clathrin-coated pits, which are transient and dynamic structures involved primarily in the internalization of molecules, clathrin plaques are more stable and extensive, often persisting for extended periods. Their extended lifespan suggests that they serve functions beyond the typical endocytic role, making them integral to various cellular processes. For instance, clathrin plaques are involved in the regulation of intercellular adhesion, allowing cells to better adhere to one another or to the extracellular matrix, which is crucial for tissue formation and maintenance. Furthermore, clathrin plaques act as mechanosensitive hubs, enabling the cell to sense and respond to mechanical stress, a feature that is essential for processes like migration, tissue remodeling, and even cancer progression. Recent discoveries have also highlighted the role of clathrin plaques in cellular signaling. These plaques can serve as scaffolds for signaling molecules, orchestrating the activation of various pathways that govern cellular behavior. For example, the recruitment of actin-binding proteins such as F-actin and vinculin to clathrin plaques can influence cytoskeletal dynamics, helping cells adapt to mechanical changes in their environment. This recruitment also plays a pivotal role in regulating cellular migration, which is crucial for developmental processes. Additionally, clathrin plaques influence receptor-mediated signal transduction by acting as platforms for the assembly of signaling complexes, thereby affecting processes such as growth factor signaling and cellular responses to extracellular stimuli. Despite the growing body of evidence that supports the involvement of clathrin plaques in a wide array of cellular functions, much remains unknown about the precise molecular mechanisms that govern their formation, maintenance, and turnover. For example, the factors that regulate the recruitment of clathrin and other coat proteins to form plaques, as well as the signaling molecules that coordinate plaque dynamics, remain areas of active research. Furthermore, the complex interplay between clathrin plaques and other cellular systems, such as the actin cytoskeleton and integrin-based adhesion complexes, needs further exploration. Studies have shown that clathrin plaques can respond to mechanical forces, with recent findings indicating that they act as mechanosensitive structures that help the cell adapt to changing mechanical environments. This ability underscores the multifunctional nature of clathrin plaques, which, in addition to their role in endocytosis, are involved in cellular processes such as mechanotransduction and adhesion signaling. In summary, clathrin plaques represent a dynamic and versatile component of clathrin-mediated endocytosis. They play an integral role not only in the internalization of macromolecular cargo but also in regulating cellular adhesion, migration, and signal transduction. While much has been learned about their structural and functional properties, significant questions remain regarding the molecular mechanisms that regulate their formation and their broader role in cellular physiology. This review highlights the evolving understanding of clathrin plaques, emphasizing their importance in both endocytosis and a wide range of other cellular functions. Future research is needed to fully elucidate the mechanisms by which clathrin plaques contribute to cellular processes and to better understand their implications for diseases, including cancer and tissue remodeling. Ultimately, clathrin plaques are emerging as crucial hubs that integrate mechanical, biochemical, and signaling inputs, providing new insights into cellular function and the regulation of complex cellular behaviors.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.

Aim To investigate the protective effects of curcumin(CUR)on crystal-induced renal injury and its underlying mechanism in the mouse model of neph-rolithiasis.Methods The mouse model of stone for-mation was established via successive intraperitoneal injection of glyoxylate.Proximal tubular epithelial cell line HK-2 treated with calcium oxalate monohydrate(COM)was used as an in vitro model.The protective role of CUR on nephrolithiasis was tested by determina-tion of tubular injury,crystal deposition and adhesion,levels of inflammatory cytokines.In vitro,the effects of CUR on the cell viability and inflammatory factors of HK-2 cells were measured.The proteins in the Toll-like receptor 4(TLR4)/nuclear factor κB(NF-κB)and nuclear factor erythroid 2-related factor 2(NRF2)/hemeoxygenase-1(HO-1)signaling path-ways were measured by Western blot for confirming the relationship between CUR and these pathways.Final-ly,NRF2 inhibitor ML385 and TLR4 activator CCL-34 were respectively used on COM-induced HK-2 cells ex-posed to CUR for the conduction of gain-of-function and loss-of-function assays.Results CUR improves the damage in the mouse model of kidney stone forma-tion,inhibits inflammation and antioxidative effects;promotes the viability of HK-2 cells induced by COM,and inhibits the expression of inflammatory factors.CUR suppresses the expression of proteins in the TLR4/NF-κB pathway,promotes the transfer of NRF2 from the cytoplasm to the nucleus,and enhances the ex-pression of HO-1.ML385 and CCL-34 respectively counteract the anti-inflammatory effects of CUR on COM-induced HK-2 cells.Conclusions Taken togeth-er,our study demonstrates the protective effect of CUR on the deposition of kidney stone and consequent tubu-lar injury.CUR through regulation of the TLR4/NF-κB and NRF2/HO-1 pathways improves renal injury.

Aim To investigate the mechanism of Banxia Baizhu Tianma Decoction(BBTD)in interfer-ing methamphetamine(MA)addiction using network pharmacology.Methods The mechanism of BBTD intervention in MA addiction was analyzed using net-work pharmacology,and MA-dependent SH-SY5Y cell model was further constructed to observe the effects of BBTD on cell model and PI3K-Akt pathway.Results A total of 88 active ingredients and 583 potential tar-gets of BBTD were screened.KEGG analysis showed that BBTD might intervene in MA addiction through PI3K-Akt,cAMP and other pathways.The molecular docking results showed that key active ingredients ex-hibited strong binding ability with core targets of PI3K-Akt pathway.In vitro experiments showed that MA-de-pendent model cells had shorter synapses,tended to be elliptical in morphology,had blurred cell boundaries,showed typical cell damage morphology,and had high intracellular expression of cAMP(P＜0.01)and low expression of 5-HT(P＜0.05).BBTD intervention could counteract the above morphology,cAMP,and 5-HT changes,suggesting that it had therapeutic effects on MA-dependent model cells.Western blot showed that MA modeling elevated the p-PI3K/PI3K(P＜0.05)and p-Akt/Akt(P＜0.01);BBTD inter-vention decreased their relative expression.Conclu-sions Gastrodin and other active ingredients in BBTD have therapeutic effects on MA addiction,and the mechanism may be related to regulation of PI3K-Akt pathway relevant targets.

Aim To explore the effects of sirolimus on the growth and development of motor,vascular,nerv-ous,and immune systems through zebrafish models.Methods After 3 hours of fertilization of zebrafish embryos,different concentrations of sirolimus were add-ed to the growth environment,and the growth and de-velopment of the embryos was recorded.Transgenic ze-brafish models labeled with blood vessels,nerves or im-mune cells were used to compare the drug effects on the growth and development of those systems.Results At the concentration of 0.5 μmol·L-1,the hatching rate and the body length(P＜0.01)were significantly smaller than those of the control group,and movement was also significantly slowed down.Meanwhile,the length of axons of the nervous system,the development of intersegmental vessels,and the growth of immune cells were significantly delayed by drug treatment.But when the concentration was below 0.1 μmol·L-1,there was no statistically difference between the control group and the sirolimus group.Conclusions When the concentration of sirolimus exceeds a certain level,it can significantly slow down the growth and development of movement,blood vessels,nervous system and im-mune system of zebrafish.Therefore,in clinical prac-tice,it is important to monitor the blood concentration of sirolimus in children on time.

Objective To analyze the relationship between bone cement leakage after balloon kyphoplasty(BKP)and balloon expansion pressure(BEP)in patients with osteoporotic vertebral compression fracture(OVCF).Methods The clinical data of 116 elderly patients with OVCF who received BKP in our hospital were retrospectively analyzed.All patients underwent X-ray examination and CT enhanced scan before surgery and 72 hours after surgery to evaluate the efficacy and the occurrence of bone cement leakage.According to whether the bone cement leaked or not,he patients were divided into the bone cement leakage group and the non-bone cement leakage group.The pain was assessed by visual analogue scale(VAS)score,and the disturbance of daily living was assessed by Barthel index score.The area under the curve(AUC)and optimal cut-off value of BEP and bone cement volume to predict bone cement leakage were analyzed using receiver operating characteristic(ROC)curve.The risk factors of bone cement leakage was analyzed by multivariate Logistic regression analysis.Results There were 82 cases of mono-segment operation,27 cases of double-segment operation,and 7 cases of three-segment operation,involving 157 vertebrae.The anterior vertebral height and posterior vertebral height,the local kyphosis Cobb angle at the sagittal plane,and thoracolumbar kyphosis angle after surgery were significantly corrected,and the VAS score and Barthel index score were better than those before surgery(P<0.05).The bone cement leakage after surgery occurred in 24 patients,including 1 case with pulmonary cement embolism.The intraoperative BEP and volume of bone cement in the bone cement leakage group were significantly higher than those in the non-bone cement leakage group(P<0.05).ROC curve analysis showed that both the intraoperative BEP(AUC=0.756)and bone cement volume(AUC=0.661)could predict cement leakage,with the optimal cut-off value of 135 psi and 6.08 mL,respectively.Multivariate Logistic regression analysis showed that BEP≥135 psi was a risk factor for bone cement leakage(OR=1.038,95%CI:1.018 to 1.058,P<0.001).Conclusion BKP is a safe and effective treatment for OVCF in elderly patients,higher BEP is a risk factor for cement leakage,and patients with BEP≥135 psi are at higher risk of bone cement leakage.