Hepatocellular carcinoma (HCC) is a lethal cancer with high morbidity rates worldwide. It is a major threat to public health in China, due to the combination of known and new risk factors, such as endemic hepatitis B virus (HBV), dietary aflatoxin exposure, and the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although many methods for surveillance and multimodal therapies, such as surgery, local ablation, transarterial therapy, and new systemic agents, have been available, the survival rates of HCC remains poor. They have very limited durable responses, long post-treatment recurrence rates, and high resistance to treatment. This reflects an imperfect picture of the biological cause of the disease and a need for new mechanistic or targeted techniques. A significant characteristic of HCC, in common with other aggressive cancers, is the presence of reprogrammed, hyperactive cell metabolism. Tumor cells hijack metabolic pathways to promote their uncontrolled growth, stress survival, invasion and metastasis. While classical mechanisms such as the Warburg effect, lipid metabolism and glutamine utilization have been understood, the lysosome, which was once viewed as a static “waste disposal unit” to remove old organelles and proteins, is instead a dynamic signaling and metabolic core. The lysosomes incorporate nutrients, energy and stress signals by master regulators such as mTORC1 (activated on its surface) that balance anabolic growth and catabolic recycling to the cellular demands. In HCC, lysosomes are not passive, but are highly active and dysregulated. HCC cells upregulate lysosomes, which scavenge intracellular components via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.

Autophagy, a highly conserved cellular degradation mechanism, maintains intracellular homeostasis by removing damaged organelles and abnormal proteins. Its dysregulation is closely associated with various diseases. Autophagy-related protein 12 (ATG12), a core member of the ubiquitin-like protein family, covalently binds to ATG5 through a ubiquitin-like conjugation system to form the ATG12-ATG5-ATG16L1 complex. This complex directly regulates the formation and maturation of autophagosomes, making ATG12 a key molecule in the initiation of autophagy. Recent studies have revealed that ATG12 functions extend far beyond the classical autophagy context. It promotes apoptosis by binding to anti-apoptotic proteins of the Bcl-2 family (e.g., Bcl-2 and Mcl-1) and enhances host antiviral immunity by regulating the NF-κB and interferon signaling pathways. Moreover, ATG12 deficiency can lead to mitochondrial biogenesis impairment, energy metabolism disorders, and substrate-dependent metabolic shifts, underscoring its pivotal role in cellular metabolic homeostasis. At the disease level, dysregulation of ATG12 expression is closely linked to tumorigenesis and cancer progression. By modulating the dynamic balance between autophagy and apoptosis, ATG12 influences cancer cell proliferation, metastasis, and chemoresistance. Notably, ATG12 is abnormally overexpressed in multiple cancers, including breast, liver, and gastric cancer, highlighting its potential as a therapeutic target. Furthermore, in neurodegenerative diseases such as Parkinson’s disease, ATG12 mitigates protein toxicity by enhancing mitochondrial autophagy. In cardiovascular diseases, it alleviates ischemia-reperfusion injury by regulating cardiomyocyte autophagy and apoptosis, demonstrating its broad regulatory role across various pathological conditions. Genetic studies further underscore the clinical significance of ATG12. Polymorphisms in the ATG12 gene (e.g., rs26537 and rs26538) have been significantly associated with the risk of head and neck squamous cell carcinoma, hepatocellular carcinoma, and atrophic gastritis. Notably, the risk allele of rs26537 enhances ATG12 promoter activity, leading to its overexpression and promoting tumorigenesis. These findings provide a molecular basis for individualized risk assessment and targeted interventions based on ATG12 genotype. Despite significant progress, many aspects of ATG12 biology remain unclear. The precise regulatory mechanisms of its post-translational modifications (e.g., ubiquitination and acetylation) are yet to be fully elucidated. Additionally, the molecular pathways underlying its non-canonical functions, such as metabolic regulation and immune modulation, require further investigation. Moreover, the functional heterogeneity of ATG12 in different tumor microenvironments and its role in drug resistance warrant in-depth exploration. Future research should integrate advanced technologies such as cryo-electron microscopy, single-cell sequencing, and organoid models to decipher the intricate regulatory network of ATG12. Additionally, developing small-molecule inhibitors or gene-editing tools targeting its protein interaction interfaces (e.g., the ATG12-ATG3 binding domain) may help overcome current therapeutic challenges. Through interdisciplinary collaboration and clinical translation, ATG12 holds promise as a next-generation molecular target for precision intervention in autophagy-related diseases. This review summarizes the structure and function of ATG12, its role in autophagy initiation, its physiological functions, and its involvement in disease pathogenesis. Furthermore, it discusses future research directions and potential challenges, emphasizing ATG12’s potential as a biomarker and therapeutic target in autophagy-related diseases.

AIM To evaluate the quality of Tibetan medicine"Sangdi"based on HPLC fingerprints combined with chemometrics.METHODS The analysis was performed on a 30 ℃ thermostatic Welch Ultimate AQ-C18 column(250 mm × 4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 245 nm,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed,the contents of gentiopicroside,sweroside,mangiferin,isoorientin,8-hydroxy-1,3,5-trimethoxyxanthone(R2)and 1,8-dihydroxy-3,7-dimethoxyxanthone(R3)were determined.RESULTS There were 18 common peaks in the fingerprints for 15 batches of samples with the similarities of more than 0.90.Six constituents showed good linear relationships within their own ranges(R 2 ≥ 0.999 2),whose average recoveries were 96.93％-103.58％with the RSDs of 0.82％-2.9％.Various batches of samples were clustered into 2 categories,4 principal components demonstrated the accumulative variance contribution rate of 86.404％,mangiferin,gentiopicroside and isoorientin were taken as quality difference markers.CONCLUSION This stable,reliable and reproducibe method can provide a reference for the comprehensive quality evaluation of"Sangdi".

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

BACKGROUND:Deferoxamine exhibits multiple functions such as stem cell modulation,immune regulation,and promotion of angiogenesis and osteogenesis,but its role in the osteoinhibition induced by dexamethasone in osteoblasts remains unclear.OBJECTIVE:To investigate the effects of deferoxamine on osteoblasts treated with dexamethasone through the hypoxia-inducible factor 1α/vascular endothelial growth factor signaling pathway and to explore its potential mechanisms of action.METHODS:The proliferation of MC3T3-E1 cells treated with various concentrations of deferoxamine for 24,48,and 72 hours was assessed using the cell counting kit-8 assay to determine the optimal intervention concentration.There were control,dexamethasone,dexamethasone plus deferoxamine 10 μmol/L,and dexamethasone plus deferoxamine 20 μmol/L groups in the experiment.Cell counting kit-8 assay and flow cytometry were employed to evaluate the effect of deferoxamine on dexamethasone-induced cell proliferation and apoptosis.Alkaline phosphatase staining and activity assays were conducted to assess alkaline phosphatase levels in MC3T3-E1 cells.Alizarin red staining was used to observe the formation of mineralized nodules.Western blot was employed to detect the expression of osteogenic and signaling proteins.RESULTS AND CONCLUSION:(1)Deferoxamine showed no significant cytotoxicity to MC3T3-E1 cells within the range of 5-20 μmol/L and could ameliorate the inhibitory effects of dexamethasone on MC3T3-E1 cell proliferation and apoptosis.(2)Compared with the dexamethasone group,deferoxamine groups increased alkaline phosphatase activity and cell mineralization,and also significantly increased the protein expression of osteopontin,runt-related transcription factor 2,and alkaline phosphatase in MC3T3-E1 cells.(3)Deferoxamine also activated the hypoxia-inducible factor 1α/vascular endothelial growth factor pathway in dexamethasone-treated MC3T3-E1 cells.To conclude,deferoxamine can alleviate apoptosis in osteoblasts induced by dexamethasone treatment,maintain the vitality of osteoblasts by activating the hypoxia-inducible factor 1α/vascular endothelial growth factor signaling pathway,and promote their proliferation,which may help delay the progression of steroid-induced osteonecrosis of the femoral head.

Objective To evaluate the feasibility and clinical significance of the three-dimensional acetabular oval fossa-guided positioning technique in acetabular prosthesis placement during total hip arthroplasty(THA).Methods Sixty patients with femoral neck fractures who underwent primary THA were randomly divided into two groups(n=30 per group).The observation group received acetabular component placement guided by a three-dimensional positioning technique based on preoperative acetabular angle measurements and pelvic model reconstruction using CT data.During surgery,placement was performed according to the preoperative plan,using anatomical landmarks including the acetabular fossa,transverse acetabular incision,and transverse acetabular ligament.The control group underwent conventional freehand acetabular component placement.The two groups were compared in terms of surgical parameters(operation time,intraoperative fluoroscopy frequency,blood loss),postoperative deviations in acetabular component angles(abduction and anteversion angles),Harris hip score(HHS),visual analog scale(VAS)for pain,and dislocation rate.Results Baseline characteristics were comparable between groups.The observation group exhibited a slightly longer operation time and significantly greater blood loss compared to the control group,with no significant difference in fluoroscopy frequency.Postoperative radiographic measurements showed that deviations in both the abduction and anteversion angles of the acetabular component were significantly smaller in the observation group than in the control group.At one month postoperatively,the HHS was significantly higher and the VAS score was significantly lower in the observation group.However,no significant differences in functional or pain scores were found between the two groups at three and six months postoperatively.No dislocations were observed in the observation group,whereas one dislocation occurred in the control group.Conclusions The three-dimensional acetabulum oval fossa-guided positioning technique,which integrates anatomical landmarks with individualized preoperative planning,enables precise quantitative measurement and significantly enhances the accuracy of acetabular component placement angles in THA.This improvement contributes to faster postoperative functional recovery and leads to favorable clinical outcomes,demonstrating strong practical application value.

Objective To evaluate the feasibility and clinical significance of the three-dimensional acetabular oval fossa-guided positioning technique in acetabular prosthesis placement during total hip arthroplasty(THA).Methods Sixty patients with femoral neck fractures who underwent primary THA were randomly divided into two groups(n=30 per group).The observation group received acetabular component placement guided by a three-dimensional positioning technique based on preoperative acetabular angle measurements and pelvic model reconstruction using CT data.During surgery,placement was performed according to the preoperative plan,using anatomical landmarks including the acetabular fossa,transverse acetabular incision,and transverse acetabular ligament.The control group underwent conventional freehand acetabular component placement.The two groups were compared in terms of surgical parameters(operation time,intraoperative fluoroscopy frequency,blood loss),postoperative deviations in acetabular component angles(abduction and anteversion angles),Harris hip score(HHS),visual analog scale(VAS)for pain,and dislocation rate.Results Baseline characteristics were comparable between groups.The observation group exhibited a slightly longer operation time and significantly greater blood loss compared to the control group,with no significant difference in fluoroscopy frequency.Postoperative radiographic measurements showed that deviations in both the abduction and anteversion angles of the acetabular component were significantly smaller in the observation group than in the control group.At one month postoperatively,the HHS was significantly higher and the VAS score was significantly lower in the observation group.However,no significant differences in functional or pain scores were found between the two groups at three and six months postoperatively.No dislocations were observed in the observation group,whereas one dislocation occurred in the control group.Conclusions The three-dimensional acetabulum oval fossa-guided positioning technique,which integrates anatomical landmarks with individualized preoperative planning,enables precise quantitative measurement and significantly enhances the accuracy of acetabular component placement angles in THA.This improvement contributes to faster postoperative functional recovery and leads to favorable clinical outcomes,demonstrating strong practical application value.

AIM To evaluate the quality of Tibetan medicine"Sangdi"based on HPLC fingerprints combined with chemometrics.METHODS The analysis was performed on a 30 ℃ thermostatic Welch Ultimate AQ-C18 column(250 mm × 4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 245 nm,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed,the contents of gentiopicroside,sweroside,mangiferin,isoorientin,8-hydroxy-1,3,5-trimethoxyxanthone(R2)and 1,8-dihydroxy-3,7-dimethoxyxanthone(R3)were determined.RESULTS There were 18 common peaks in the fingerprints for 15 batches of samples with the similarities of more than 0.90.Six constituents showed good linear relationships within their own ranges(R 2 ≥ 0.999 2),whose average recoveries were 96.93％-103.58％with the RSDs of 0.82％-2.9％.Various batches of samples were clustered into 2 categories,4 principal components demonstrated the accumulative variance contribution rate of 86.404％,mangiferin,gentiopicroside and isoorientin were taken as quality difference markers.CONCLUSION This stable,reliable and reproducibe method can provide a reference for the comprehensive quality evaluation of"Sangdi".

BACKGROUND:Deferoxamine exhibits multiple functions such as stem cell modulation,immune regulation,and promotion of angiogenesis and osteogenesis,but its role in the osteoinhibition induced by dexamethasone in osteoblasts remains unclear.OBJECTIVE:To investigate the effects of deferoxamine on osteoblasts treated with dexamethasone through the hypoxia-inducible factor 1α/vascular endothelial growth factor signaling pathway and to explore its potential mechanisms of action.METHODS:The proliferation of MC3T3-E1 cells treated with various concentrations of deferoxamine for 24,48,and 72 hours was assessed using the cell counting kit-8 assay to determine the optimal intervention concentration.There were control,dexamethasone,dexamethasone plus deferoxamine 10 μmol/L,and dexamethasone plus deferoxamine 20 μmol/L groups in the experiment.Cell counting kit-8 assay and flow cytometry were employed to evaluate the effect of deferoxamine on dexamethasone-induced cell proliferation and apoptosis.Alkaline phosphatase staining and activity assays were conducted to assess alkaline phosphatase levels in MC3T3-E1 cells.Alizarin red staining was used to observe the formation of mineralized nodules.Western blot was employed to detect the expression of osteogenic and signaling proteins.RESULTS AND CONCLUSION:(1)Deferoxamine showed no significant cytotoxicity to MC3T3-E1 cells within the range of 5-20 μmol/L and could ameliorate the inhibitory effects of dexamethasone on MC3T3-E1 cell proliferation and apoptosis.(2)Compared with the dexamethasone group,deferoxamine groups increased alkaline phosphatase activity and cell mineralization,and also significantly increased the protein expression of osteopontin,runt-related transcription factor 2,and alkaline phosphatase in MC3T3-E1 cells.(3)Deferoxamine also activated the hypoxia-inducible factor 1α/vascular endothelial growth factor pathway in dexamethasone-treated MC3T3-E1 cells.To conclude,deferoxamine can alleviate apoptosis in osteoblasts induced by dexamethasone treatment,maintain the vitality of osteoblasts by activating the hypoxia-inducible factor 1α/vascular endothelial growth factor signaling pathway,and promote their proliferation,which may help delay the progression of steroid-induced osteonecrosis of the femoral head.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.