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.

Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

Aim To investigate the effect of Senecio scandens Buch.-Ham on inflammatory pain mediated by mast cell P2X7 receptor.Methods Using the ATP-induced foot inflammatory pain,immunofluores-cence and toluidine blue staining techniques were used to investigate whether Senecio scandens has inhibitory effect on P2X7 receptor on mast cells.Using the calci-um ion imaging experimental technology,to explore whether Senecio scandens inhibit the intracellular cal-cium ion enrichment caused by activation of P2X7 re-ceptor on mouse peritoneal mast cell.The whole-cell patch clamp technique was used to investigate whether senecio scandens could inhibit the inward current in-duced by activation of P2X7 receptor on mouse perito-neal mast cell.Results In vivo,Senecio scandens alle-viate ATP induced inflammatory pain(3.9 g·kg-1:P＜0.05),and significantly inhibited the infiltration of P2X7 receptor-positive mast cells(3.9 g·kg-1:P＜0.05).Knockout of mast cell can reduce the analgesic effect of Senecio scandens(3.9 g·kg-1:P=0.645).In vitro.The experiment results show that senecio scandens can significantly inhibit the calcium influx(300 mg·L-1:P＜0.05;1 g·L-1:P＜0.01;3 g·L-1:P＜0.01)and the inward current mediated by P2X7 receptor in mast cell(1 g·L-1:P＜0.01).Conclusion Senecio scandens alleviate inflammatory pain by inhibiting mast cell P2X7 receptor.

Objective:Exploring the therapeutic effect of triple antibiotic paste combined with pulp revascularization on pediatric permanent tooth pulp necrosis.Methods:A retrospective study was conducted on 90 young children with permanent tooth pulp necrosis treated from October 2019 to October 2022.Based on different treatment methods,the children were divided into two groups,namely the traditional group and the experimental group,with 45 cases in each group.All patients were treated with pulp revascularization.The traditional group used conventional calcium hydroxide paste for root canal disinfection during the operation,while the experimental group used triple antibiotic paste.Two groups of patients were followed up for 2 years.After 6 months of treatment,the clinical efficacy,changes in gingival crevicular fluid growth factors and inflammatory factors before and after treatment were compared between the two groups.The growth and development of tooth roots were also compared between the two groups after 2 years of treatment,as well as the pulp activity at 6 months,1 year,and 2 years after treatment.The incidence of complications during the follow-up period was also compared between the two groups.Results:The total effective rate of the combined group was 82.22％,which was higher than the traditional group's 66.67％(P＜0.05);There was no significant difference in the levels of growth factor and inflammatory factor in the gingival crevicular fluid between the two groups before treatment(P＞0.05).After a 6-month follow-up,the levels of VEGF and bFGF in the gingival crevicular fluid of both groups increased,with the combined group being higher than the traditional group(P＜0.05).The inflammatory factors interleukin-8 and IL-6 in the gingival crevicular fluid of both groups decreased,while the combined group was lower than the traditional group(P＜0.05);Before treatment,there was no significant difference in the thickness of the root canal wall,crown to root ratio,and apical foramen diameter between the two groups(P＞0.05).After a 2-year follow-up,the levels of root canal wall thickness and crown to root ratio increased in both groups,with the combined group being higher than the traditional group(P＜0.05).The apical foramen diameter decreased in both groups,with the combined group being lower than the traditional group(P＜0.05).After treatment,the deposition rate of dental pulp bone like tissue in the combined group was lower than that in the traditional group(P＜0.05);Follow up for 6 months,1 year,and 2 years revealed that the positive rate of pulp vitality in the combined group was higher than that in the traditional group(P＜0.05);There was no significant difference in the incidence of complications between the two groups(P＞0.05).Conclusion:The application of triple antibiotic paste in pulp revascularization surgery can improve the clinical efficacy of pediatric permanent tooth pulp necrosis,promote root growth and development,enhance pulp activity,and may be related to improving periodontal tissue related growth factors and stronger antibacterial and anti-inflammatory effects in children.Moreover,this therapy has high safety.

Objective:Exploring the therapeutic effect of triple antibiotic paste combined with pulp revascularization on pediatric permanent tooth pulp necrosis.Methods:A retrospective study was conducted on 90 young children with permanent tooth pulp necrosis treated from October 2019 to October 2022.Based on different treatment methods,the children were divided into two groups,namely the traditional group and the experimental group,with 45 cases in each group.All patients were treated with pulp revascularization.The traditional group used conventional calcium hydroxide paste for root canal disinfection during the operation,while the experimental group used triple antibiotic paste.Two groups of patients were followed up for 2 years.After 6 months of treatment,the clinical efficacy,changes in gingival crevicular fluid growth factors and inflammatory factors before and after treatment were compared between the two groups.The growth and development of tooth roots were also compared between the two groups after 2 years of treatment,as well as the pulp activity at 6 months,1 year,and 2 years after treatment.The incidence of complications during the follow-up period was also compared between the two groups.Results:The total effective rate of the combined group was 82.22％,which was higher than the traditional group's 66.67％(P＜0.05);There was no significant difference in the levels of growth factor and inflammatory factor in the gingival crevicular fluid between the two groups before treatment(P＞0.05).After a 6-month follow-up,the levels of VEGF and bFGF in the gingival crevicular fluid of both groups increased,with the combined group being higher than the traditional group(P＜0.05).The inflammatory factors interleukin-8 and IL-6 in the gingival crevicular fluid of both groups decreased,while the combined group was lower than the traditional group(P＜0.05);Before treatment,there was no significant difference in the thickness of the root canal wall,crown to root ratio,and apical foramen diameter between the two groups(P＞0.05).After a 2-year follow-up,the levels of root canal wall thickness and crown to root ratio increased in both groups,with the combined group being higher than the traditional group(P＜0.05).The apical foramen diameter decreased in both groups,with the combined group being lower than the traditional group(P＜0.05).After treatment,the deposition rate of dental pulp bone like tissue in the combined group was lower than that in the traditional group(P＜0.05);Follow up for 6 months,1 year,and 2 years revealed that the positive rate of pulp vitality in the combined group was higher than that in the traditional group(P＜0.05);There was no significant difference in the incidence of complications between the two groups(P＞0.05).Conclusion:The application of triple antibiotic paste in pulp revascularization surgery can improve the clinical efficacy of pediatric permanent tooth pulp necrosis,promote root growth and development,enhance pulp activity,and may be related to improving periodontal tissue related growth factors and stronger antibacterial and anti-inflammatory effects in children.Moreover,this therapy has high safety.

Objective:Through the meta-analysis of activation likelihood estimation (ALE), the functional magnetic resonance imaging research evidence of acupuncture in the treatment of depression was systematically integrated to analyze the effect of acupuncture on brain activity in patients with depression and systematically reveal its potential neural mechanism.Methods:The literatures which used functional magnetic resonance imaging to explore brain image changes of patients with depression after receiving acupuncture intervention were retrieved from CNKI, VIP database, Wanfang database, PubMed, Embase, EBSCO host MEDLINE and Web of Science database. The retrieval time is from the establishment of the database to March 2025. Data processing was performed using the ALE method by the Ginger ALE 2.3 software. The coordinates of the subjects included in the study were extracted, and the brain regions with abnormal spontaneous brain activity in patients with depression were integrated and analyzed.Results:A total of 28 articles involving 770 subjects were included. Depressed patients receiving acupuncture exhibited increased brain activity in the bilateral medial frontal gyrus and bilateral anterior cingulate cortex. Exploratory analysis revealed that depressed patients receiving acupuncture exhibited reduced activation in the left posterior cerebellar lobe (MNI: x, y, z = -6, -68, -21; x, y, z = -9, -81, -9) compared to healthy controls (voxel sum=5 824 mm 3,P<0.05). Conclusion:Patients with depression who received acupuncture intervention exhibited relatively consistent activation in brain regions compared to depressed patients who did not receive acupuncture and healthy individuals. Compared to healthy individuals, patients with depression who received acupuncture showed reduced activation in the left posterior cerebellum. It is suggested that acupuncture intervention may play a therapeutic role by regulating the functional state of emotion-related brain regions and brain networks.

Objective:Through the meta-analysis of activation likelihood estimation (ALE), the functional magnetic resonance imaging research evidence of acupuncture in the treatment of depression was systematically integrated to analyze the effect of acupuncture on brain activity in patients with depression and systematically reveal its potential neural mechanism.Methods:The literatures which used functional magnetic resonance imaging to explore brain image changes of patients with depression after receiving acupuncture intervention were retrieved from CNKI, VIP database, Wanfang database, PubMed, Embase, EBSCO host MEDLINE and Web of Science database. The retrieval time is from the establishment of the database to March 2025. Data processing was performed using the ALE method by the Ginger ALE 2.3 software. The coordinates of the subjects included in the study were extracted, and the brain regions with abnormal spontaneous brain activity in patients with depression were integrated and analyzed.Results:A total of 28 articles involving 770 subjects were included. Depressed patients receiving acupuncture exhibited increased brain activity in the bilateral medial frontal gyrus and bilateral anterior cingulate cortex. Exploratory analysis revealed that depressed patients receiving acupuncture exhibited reduced activation in the left posterior cerebellar lobe (MNI: x, y, z = -6, -68, -21; x, y, z = -9, -81, -9) compared to healthy controls (voxel sum=5 824 mm 3,P<0.05). Conclusion:Patients with depression who received acupuncture intervention exhibited relatively consistent activation in brain regions compared to depressed patients who did not receive acupuncture and healthy individuals. Compared to healthy individuals, patients with depression who received acupuncture showed reduced activation in the left posterior cerebellum. It is suggested that acupuncture intervention may play a therapeutic role by regulating the functional state of emotion-related brain regions and brain networks.

Objective:To investigate disease characteristics of patients with psoriatic arthritis (PsA) based on the PsA cohort in West China Hospital, so as to provide a reference for clinicians in its diagnosis, treatment, and evaluation strategy formulation.Methods:A cross-sectional study was carried out, and a descriptive analysis was conducted on clinical data from PsA patients who were treated at the Department of Dermatology, West China Hospital, Sichuan University between April 2, 2020, and January 21, 2025. Demographic characteristics, clinical manifestations, laboratory and imaging findings, and treatment modalities were analyzed.Results:A total of 530 PsA patients were included, of whom 332 (62.6%) were males and 198 (37.4%) were females, with ages of 44.1 ± 12.4 years. Skin lesions preceded joint symptoms in 452 patients (85.3%), with time intervals ( M [ Q1, Q3]) of 8.0 (3.0, 15.0) years. Overweight or obesity was observed in 319 patients (60.2%), and 188 (35.5%) had comorbid fatty liver. Peripheral joint involvement was common (485 cases, 91.5%), with the proximal interphalangeal joints being most frequently affected by tenderness (172 cases, 35.5%) and swelling (119 cases, 24.5%) ; the number of enthesitis cases identified by ultrasonography (116 cases, 23.9%) was significantly higher than that by clinical examination (82 cases, 15.5%) ; axial joint involvement was observed in 258 patients (48.7%), with the sacroiliac joints most commonly affected (201 cases, 77.9%). Regarding treatment, conventional systemic drugs were predominant in the treatment of psoriasis prior to the diagnosis of PsA; after the diagnosis of PsA, the number of patients receiving targeted therapies increased to 334 (63.0%), with interleukin-17 inhibitors being the most common (140 cases, 26.4%), followed by tumor necrosis factor-α inhibitors (106 cases, 20.0%) and Janus kinase inhibitors (39 cases, 7.4%) . Conclusions:PsA predominantly affects males over 40 years old and is characterized by preceding skin lesions, delayed diagnosis, and multiple comorbidities. High-frequency ultrasound has advantages in the early detection of peripheral enthesitis. Further attention is needed for managing comorbidities such as fatty liver and obesity-related metabolic conditions.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.