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.

ObjectiveTo evaluate the effect of neuromuscular electrical stimulation (NMES) on pain, quadriceps strength and motor function of patients after total knee arthroplasty (TKA). MethodsThe databases of CNKI, Wanfang data, VIP, PubMed, Embase, Cochrane, Web of Science and Scopus were retrieved from inception to April, 2025. Randomized controlled trials (RCT) related to the intervention of NMES after TKA were collected. The quality of the included literature was evaluated using the Cochrane Risk of Bias Assessment Tool and the Physical Therapy Evidence Database (PEDro) scale. Meta-analysis was performed with RevMan 5.4. ResultsA total of twelve RCT were included, involving 772 subjects. The PEDro scale score ranged from four to seven. NMES improved postoperative quadriceps muscle strength (SMD = 0.61, 95%CI 0.34 to 0.88, P < 0.001) and knee flexion range of motion (SMD = 1.35, 95%CI 0.30 to 2.41, P = 0.010), and reduced the Timed Up and Go Test (TUGT) time (SMD = -0.86, 95%CI -1.45 to -0.26, P = 0.005). Compared with the control group, the intervention group achieved better outcomes in the 2-Minute Walk Test (2MWT) (SMD = 19.44, 95%CI 10.44 to 30.43, P < 0.001), 3-Minute Walk Test (SMD = 23.57, 95%CI 14.77 to 32.36, P < 0.001), 6-Minute Walk Test (SMD = 42.29, 95%CI 9.71 to 74.86, P = 0.010), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (SMD = -0.52, 95%CI -1.00 to -0.04, P = 0.040), as well as the Physical Component Summary (PCS) (SMD = 2.90, 95%CI 0.73 to 5.06, P = 0.009) and Mental Component Summary (MCS) (SMD = 2.84, 95%CI 1.40 to 4.28, P = 0.040) of the 36-Item Short Form Health Survey (SF-36). Subgroup analysis demonstrated that two to four weeks after surgery, NMES enhanced patients' quadriceps muscle strength (SMD = 0.90, 95%CI 0.58 to 1.21, P < 0.001), shortened TUGT time (SMD = -1.28, 95%CI -2.57 to -0.02, P < 0.05) and increased walking distance in 2MWT (SMD = 20.43, 95%CI 10.44 to 30.43, P < 0.001). For patients followed up for two to three months, NMES yielded improvements in WOMAC scores (SMD = -0.44, 95%CI -0.79 to -0.09, P = 0.010) and SF-36 MCS scores (SMD = 4.17, 95%CI 2.43 to 5.91, P < 0.001). ConclusionNMES can significantly improve the quadriceps strength and walking ability of the TKA patients two to four weeks after surgery, and enhance the quality of life of patients two to three months after surgery.

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.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective To detect the content of rheumatoid factor(RF)after RF-CIC dissociation using serum circulating immune complexes(CIC)dissociation technology and evaluate its diagnostic and clinical value in rheumatic arthritis(RA).Methods 55 RA patients diagnosed and treated in the 903rd Hospital of the People's Liberation Army from January 2024 to December 2024 were selected as the RA disease group,and 20 healthy individuals were selected as the control group.In addition,57 non RA pa-tients with symptoms resembling RA[patients with systemic lupus erythematosus(SLE),gout,ankylosing spondylitis(AS),osteo-arthritis,etc)]as the non RA disease group.Using CIC dissociation technology,RF content after RF-CIC dissociation was detect-ed in the serum of all three groups of study subjects,and C-reactive protein(CRP)and RF levels in all subjects were detected using a biochemical analyzer.Analyzed and compared the differences in the positive rate and levels of RF-CIC among three groups object of study.In addition,analyze and compare the correlation between RF-CIC and inflammatory index CRP.Results The positive rates of RF-CIC in the serum of RA disease group,non RA disease group,and control group were 87.27%(48/55),10.53%(6/57)and 0.0%(0/20),respectively,and the differences between the three groups was statistically significant(χ2=84.520,P<0.05).Further subgroup analysis showed that the RF-CIC positivity rate in the RF negative subgroup of RA disease patients[61.11%(11/18)]higher than that in the non RA disease group[1.92%(1/52)]and the control group[0%(0/20)],and the differ-ences were statistically significant(χ2=44.493,21.671,all P<0.05).The RF-CIC positivity rate was higher in RF positive pa-tients than in RF negative patients in the RA disease group(100%vs 61.11%),and the difference was statistically significant(χ2=16.487,P<0.05).The RF-CIC content in the serum of RF positive patients in the RA disease group was higher than that of RF negative patients[16.35(10.53,26.49)vs 3.57(2.53,3.89)],and the difference was statistically significant(Z=-4.243,P<0.05).Correlation analysis showed that the levels of CRP and RF in the serum of RA patients were positively correlated with the levels of RF-CIC(r=0.490,0.970,all P<0.05).Conclusion RF-CIC demonstrates high positivity even in RF-negative RA patients,and their levels correlate with CRP.RF-CIC shows potential as a serological indicator for early diagnosis and disease activity assess-ment in RA.

Objective:To investigate the risk factors of medical insurance fund management for the neurological disease group under the background of Diagnosis Related Groups(DRG)reform,and to construct a warning model to provide references for optimizing the management of medical institutions.Methods:A total of 5 615 medical records from Beijing Tiantan Hospital Affiliated to Capital Medical University in 2024 were selected to simulate and compare the differences in medical insurance fund compensation under the Version 1.1 of China Health-care Security Diagnosis-Related Groups(CHS-DRG),hereinafter referred to as DRG 1.1,and the Version 2.0 of Diagnosis-Related Groups(DRG),hereinafter referred to as DRG 2.0.LASSO regression was used to screen variables,and logistic regression analysis was employed to identify the risk factors of fund management and construct Nomogram prediction model.Results:With the implementation of DRG 2.0,the proportion of cases with fund management risks increased from 23.47％to 25.16％,and the overall surplus rate decreased from 14.97％to 12.57％.Logistic regression showed that age,type of medical insurance,mode of admission,and the CCI comorbidity index were significant influencing factors in fund risk management(P＜0.05),while the use of centrally procured medical consumables had a protective effect.The constructed model had an AUC of 0.827,indicating a certain level of predictive performance.Analysis of high-risk management combinations showed that cases with employee medical insurance,emergency admission,no use of centrally procured medical consumables,and non-surgical treatment were the focus of fund payment management.Conclusions:The adjustment of DRG 2.0 has reduced the deviation of overruns and surpluses among cases.Medical institutions need to strengthen their own management,optimize practical processes,and focus on the refinement of medical insurance fund management.

Excessive stress has a significant impact on an indi-vidual's physical and mental health and quality of life.Al-though psychotherapy is commonly used for post-traumatic stress disorder(PTSD),pharmacotherapy plays an important role in the treatment of severe PTSD.At present,there are limited types of approved medications for PTSD,and their efficacy and safety have certain limitations,such as low remission rates,high relapse rates,and increased behavioral risks.Studies have shown that hallucinogens such as psilocybin and ketamine can enhance neuroplasticity,modulate brain network connections,and regulate the immune system by interacting with different re-ceptors,so as to effectively alleviate PTSD symptoms such as anxiety,depression and fear,showing great potential in PTSD treatment.However,these hallucinogens are not yet widely used in clinical practice.This review summarizes the effects and neu-robiological mechanisms of hallucinogens in the treatment of stress-related symptoms,aiming to provide references for the clinical treatment of PTSD.

Objective To investigate the cIinicopathological features and immunohistochemical expression of gastric hyperplastic polyps(GHPs)with dysplasia/adenocarcinoma.Methods A retrospective analysis of 24 cases(44 polyps)that were diagnosed as GHPs with dysplasia/adenocarcinoma in our hospital from January 2020 to December 2024 was reviewed,and clinical,histomorphological,immunophenotypic and follow-up data were analyzed.Results There were 20 female and 4 male cases,with a mean age of(65.5±7.9)(range 56～76)years.Among 44 polyps,3 occurred in the antrum of the stomach,1 in the gastric horn,and 40 in the fundus/body.Among the polyps,32 cases were diagnosed as high-grade dysplasia,4 cases as low-grade dysplasia,4 cases as coexistence of low-grade+high-grade dysplasia,2 cases as mucinous adenocarcinoma,1 cases as poorly differentiated adenocarcinoma,and 1 cases as signet-ring cell carcinoma.The histological manifestations of 23 cases of background mucosa were autoimmune metaplastic atrophic gastritis(AMAG).the P53 of 8 polyps showed a mutant expression pattern.Through MUC5/MUC6/MUC2/CD10 joint examination,33 cases showed gastric type(25 cases of which were foveal epithelium type),4 cases were intestinal type,5 cases were mixed gastrointestinal type,and 2 cases were non-gastrointestinal type.Conclusion The neoplastic transformation of GHPs is closely related to AMAG.It is necessary for clinicians and pathologists to strengthen their evaluation of background mucosa,to achieve early detection,early diagnosis and early treatment.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.