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 analyze the school tuberculosis (TB) outbreaks and preventive treatment in Hefei from 2022 to 2024, so as to provide reference for TB prevention and control in schools. Methods: Data were collected on all school based TB outbreaks occurring during 2022-2024 in Hefei, defined as ≥2 epidemiologically linked TB cases within the same school during a single semester. Statistical analyses were performed using the Chi square test. Results: Close contacts exhibited significantly higher TB incidence (2.88%) and latent mycobacterium tuberculosis infection (LTBI) rates (13.80%) in the school TB outbreaks, compared to non close contacts (0.12% and 2.63%, respectively). Among close contacts, secondary school students showed lower TB incidence (0.48%) and LTBI prevalence (3.42%) than both primary school or younger children (0.68%, 6.95%) and college students ( 0.78% , 6.50%), with statistically significant differences ( χ 2=360.91, 6.37; 791.71, 102.03, all P <0.05). The proportion of LTBI individuals recommended for preventive therapy was higher in primary school or younger groups (98.59%) than in secondary (95.25%) or college students (86.34%) ( χ 2=25.86, P <0.01). However, among those recommended, close contacts had higher uptake (85.82%) and completion rates (87.25%) of preventive therapy than non close contacts (69.63% and 70.57%); similarly, secondary school students demonstrated higher uptake (91.21%) and completion rates (86.45%) compared to primary school or younger (88.57%, 83.87%) and college students (57.28%, 64.08%) ( χ 2=30.52, 26.72; 125.17, 38.84, all P <0.01). Subsequent TB incidence among LTBI close contacts (13.30%) and among those who did not complete preventive therapy (22.73%) were significantly higher than among non close contacts (2.80%, 2.41%), respectively ( χ 2=32.19, 13.87, both P <0.05). Conclusions In school TB outbreaks, close contacts face higher LTBI prevalence and subsequent TB risk than non close contacts. College students show notably low adherence to preventive therapy. It is necessary to take targeted measures to improve the compliance of preventive measures among students.

ObjectiveTo investigate the mechanisms by which Renshentang treats atherosclerosis （AS） in mice， focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1 （TRPV1）. MethodsAn AS model was established in apolipoprotein E knockout （ApoE^-/-） mice fed a high-fat diet. The mice were randomly divided into a simvastatin group （0.02 g·kg^-1·d^-1） and low-， medium-， and high-dose Renshentang groups （1.77， 3.54， 7.08 g·kg^-1·d^-1）， with 12 mice in each group. ApoE^-/- mice were fed a high-fat diet and treated simultaneously. C57BL/6J mice fed a normal diet served as the normal group （n=9）. After continuous administration for 12 weeks， mice were anesthetized and the aortas were collected. Oil Red O staining was used to observe lipid plaque formation in the aorta. Hematoxylin-eosin （HE） staining was performed to examine pathological changes in the aortic root. Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， as well as the expression of TRPV1， phosphorylated phosphoinositide 3-kinase （p-PI3K）， and phosphorylated protein kinase B （p-Akt） in the aortic root. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect endothelial nitric oxide synthase （eNOS） mRNA expression in the aorta， and Western blot was used to detect TRPV1 protein expression. ResultsCompared with the normal group， the model group showed a significant increase in aortic plaque formation （P<0.01） and significantly elevated levels of TNF-α and IL-1β in the aortic root （P<0.01）. The expression levels of TRPV1， p-PI3K， and p-Akt were decreased （P<0.05， P<0.01）， and eNOS mRNA expression was reduced （P<0.05， P<0.01）. Compared with the model group， all Renshentang groups significantly reduced aortic plaque formation （P<0.01）， significantly decreased TNF-α and IL-1β levels （P<0.01）， and markedly increased the expression levels of TRPV1， p-PI3K， p-Akt， and eNOS mRNA （P<0.05， P<0.01）. ConclusionRenshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway， which may be one of the molecular mechanisms underlying its therapeutic effect against AS.

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

This paper explored the specific mechanism of ginsenoside Rg_1 in regulating mitochondrial fusion through the neurogenic gene Notch homologous protein 1(Notch1) pathway to alleviate hypoxia/reoxygenation(H/R) injury in HL-1 cells. The relative viability of HL-1 cells after six hours of hypoxia and two hours of reoxygenation was detected by cell counting kit-8(CCK-8). The lactate dehydrogenase(LDH) activity in the cell supernatant was detected by the lactate substrate method. The content of adenosine triphosphate(ATP) was detected by the luciferin method. Fluorescence probes were used to detect intracellular reactive oxygen species(Cyto-ROS) levels and mitochondrial membrane potential(ΔΨ_m). Mito-Tracker and Actin were co-imaged to detect the number of mitochondria in cells. Fluorescence quantitative polymerase chain reaction and Western blot were used to detect the mRNA and protein expression levels of Notch1, mitochondrial fusion protein 2(Mfn2), and mitochondrial fusion protein 1(Mfn1). The results showed that compared with that of the control group, the cell activity of the model group decreased, and the LDH released into the cell culture supernatant increased. The level of Cyto-ROS increased, and the content of ATP decreased. Compared with that of the model group, the cell activity of the ginsenoside Rg_1 group increased, and the LDH released into the cell culture supernatant decreased. The level of Cyto-ROS decreased, and the ATP content increased. Ginsenoside Rg_1 elevated ΔΨ_m and increased mitochondrial quantity in HL-1 cells with H/R injury and had good protection for mitochondria. After H/R injury, the mRNA and protein expression levels of Notch1 and Mfn1 decreased, while the mRNA and protein expression levels of Mfn2 increased. Ginsenoside Rg_1 increased the mRNA and protein levels of Notch1 and Mfn1, and decreased the mRNA and protein levels of Mfn2. Silencing Notch1 inhibited the action of ginsenoside Rg_1, decreased the mRNA and protein levels of Notch1 and Mfn1, and increased the mRNA and protein levels of Mfn2. In summary, ginsenoside Rg_1 regulated mitochondrial fusion through the Notch1 pathway to alleviate H/R injury in HL-1 cells.
Ginsenosides/pharmacology* ; Receptor, Notch1/genetics* ; Signal Transduction/drug effects* ; Mice ; Animals ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Cell Line ; Reactive Oxygen Species/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia/drug effects* ; Cell Survival/drug effects* ; Membrane Potential, Mitochondrial/drug effects* ; Humans

Objective:To explore an evaluation method for the operational status of tertiary public hospitals, identify strengths and weaknesses in hospital operations, and provide decision-making support for hospital managers.Methods:In 2023, an evaluation index system for the operation of tertiary public hospitals was constructed based on literature analysis and the Delphi method. The combined weights of the evaluation indexes were determined using the cooperative game theory method. An evaluation model for hospital operational status based on the extensible cloud model was established, with the determination of evaluation index thresholds and standards based on the operational data of a tertiary public hospital in Liaoning Province from 2020 to 2022. The operational status of the hospital was then comprehensively evaluated using the evaluation model based on the hospital′s operational data from 2023.Results:The constructed evaluation index system for the operation of tertiary public hospitals included five dimensions and 14 indicators: financial health, service efficiency, medical quality, satisfaction, and sustainable development. The indicators with higher weight values were net cash flow (0.135), average appointment rate for outpatient patients (0.088), and budget savings from government procurement (0.087). The overall operational status evaluation score of the sample hospital was 4.48, with an evaluation grade of level V. The scores for the dimensions of financial health, medical quality, and sustainable development were 4.99, 4.74, and 5.00, respectively, all reaching level V. The scores for service efficiency and satisfaction were 4.00 and 3.70, respectively, both at level Ⅳ.Conclusions:The evaluation index system and the determined weights constructed in this study were reasonable to a certain extent. The hospital operational status evaluation model based on the extensible cloud model can objectively reflect the operational status of the hospital, and the evaluation results can provide decision-making support for managers.

Objective:Bibliometric analysis was performed to map scientific knowledge landscape, so that to explore the research status and future trends in the field of carbapenem-resistant Gram-negative bacteria (CRGNB) over the past decade.Methods:Literature on CRGNB published between January 1st, 2015 and December 31st, 2024 was retrieved from the China National Knowledge Internet (CNKI) database and Web of Science Core Collection (WoSCC). VOSviewer and CiteSpace were used for bibliometric analysis.Results:A total of 3 340 Chinese and 10 761 English publications were included in this study. The annual Chinese publications remained stable, while English publications exhibited a linear growth. It was anticipated that the English publications would decline in the forthcoming years, although remaining high. China contributed the highest number of publications, and Zhejiang University was the institution with the largest number of publications. Bonomo RA, Chen L, etc. were high-impact authors in the field of CRGNB and had formed a stable cooperative group. Antimicrobial Agents and Chemotherapy was the journal with the largest number of publications. High-frequency keywords in the domain of CRGNB were comprehensively categorized into four distinct clusters, including carbapenem resistance mechanisms and gene transmission, antimicrobial drugs and combination therapy, management of critically ill patients, and infections and colonization. It was imperative to acknowledge the significance of all of these research areas. Burst word analysis suggested that carbapenem-resistant Enterobacterales virulence genes as well as new isoforms of Klebsiella pneumoniae carbapenemase (KPC) had become a research hotspot. Conclusions:The issue of carbapenem resistance remains a significant concern. Current research focus on the resistance mechanisms and antimicrobial agents, highlighting its significant academic advancement and practical applications. Fostering international collaboration through academic exchanges between research teams worldwide is imperative to establish robust cooperative relationships, facilitate multidisciplinary cooperation, and promote high-quality research.

Objective:To explore the correlation between the lesion imaging characteristics and the parent artery plaques detected by high-resolution magnetic resonance imaging (HR-MRI) in patients with recent small subcortical infarction (RSSI) in the lenticulostriate artery territory with mild stenosis of the parent artery.Methods:Consecutive patients with RSSI in the lenticulostriate artery territory admitted to Department of Neurology, the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were prospectively enrolled. Patients with stenosis of <50% in the ipsilateral middle cerebral artery (MCA) who had completed HR-MRI were included. The RSSI lesion characteristics, such as the lowest slice involved (LS), total number of slices involved (TNS) were evaluated based on serialized axial levels of diffusion weighted imaging. HR-MRI was utilized to assess the presence of dorsal superior plaques in the M1 segment of the responsible MCA. Patients were divided into plaque group and non-plaque group based on the presence or absence of plaque. Logistic regression analysis was carried out to identify the lesion characteristics associated with the presence of dorsal superior plaques in the MCA. A receiver operating characteristic (ROC) curve was employed to estimate the predictive efficacy of these parameters for MCA plaques using the area under the curve (AUC) and the optimal cut-off point.Results:A total of 112 patients were incorporated into the final analysis. The age of these patients was (57.08±11.90) years, and 78 patients (69.64%) were male. Plaques were detected on the dorsal superior wall of the MCA in 57 cases (50.89%) as the plaque group, and the other 55 cases (49.11%) were regarded as the non-plaque group. Multivariate Logistic regression revealed that LS was significantly associated with MCA plaques ( OR=0.674, 95% CI 0.485-0.937, P=0.019). The optimal cut-off point (LS≤1) was determined by ROC curve analysis (AUC=0.640, P=0.007). Conclusion:The findings suggest that in RSSI patients with mild stenosis of the parent artery, an LS≤1 is notably associated with the presence of dorsal superior plaques on MCA as detected by HR-MRI.

Objective:To investigate the effects of area of the posterior malleolus fracture and injury to the distal tibiofibular syndesmosis on functional recovery of the ankle joint in Bartoní?ek type 2 ankle fractures.Methods:A retrospective analysis was conducted of the clinical data of 47 patients with Bartoní?ek type 2 ankle fracture who had been treated at Department of Orthopedics, Huashan Hospital Affiliated to Fudan University from January 2016 to January 2022. There were 22 males and 25 females with an age of (46.0±15.6) years. All patients were treated by open reduction and closed reduction. Pearson correlation analysis and multiple regression analysis were used to investigate the relationships respectively between the American Association of Foot and Ankle Surgeons (AOFAS) ankle-hindfoot scores at the last follow-up and the preoperative proportion of posterior ankle fracture area, and the anterior and posterior tibiofibular distances.Results:All patients were followed up for (17.2±0.6) months after surgery. The Pearson correlation analysis showed that the proportion of posterior ankle fracture area ( P=0.160) and the posterior tibiofibular distance ( P=0.078) were significantly correlated with the AOFAS ankle-hindfoot score at the last follow-up. There was no significant correlation between the anterior tibiofibular distance and the AOFAS ankle-hindfoot score at the last follow-up ( P=0.689). The multiple regression analysis showed that the proportion of posterior ankle fracture area ( P=0.043) and the posterior tibiofibular distance ( P=0.022) had significant negative effects on the AOFAS ankle-hindfoot score at the last follow-up. Conclusions:In Bartoní?ek type 2 ankle fractures, the proportion of posterior ankle fracture area and the posterior tibiofibular distance are important predictors for postoperative functional recovery of the ankle. Therefore, in Bartoní?ek type 2 ankle fractures, surgical indications for the posterior malleolar fracture depend not only on the size of the fracture, but also on whether the fracture involves the lower tibiofibular syndesmosis.

Objective:To analyze the efficacy and safety of different surgical approaches for the treatment of anterior skull base malignancies involving the orbit.Methods:Retrospective analysis was conducted on patients with anterior skull base malignancies involving orbit who attended Xuanwu Hospital of Capital Medical University from April 2013 to July 2021. They were divided into endoscopic endonasal approach(EEA), lateral orbital approach(ELOA), and sublabial transmaxillary approach(ESTMA) groups according to the primary surgical approach. One-way analysis of variance and χ 2 test were used to compare the clinical characteristics, degree of tumour resection, rate of postoperative cranial nerve palsy and improvement of visual acuity; Log-rank test was applied to assess the difference in overall survival (OS). Results:One hundred and ninety-eight patients were enrolled, including 107 males and 91 females, aged (48.5±15.3) years. There were 153, 33, and 12 patients in the EEA, ESTMA, and ELOA groups, respectively. There were no significant differences among the three groups in age, gender, and history of radiotherapy, chemotherapy or surgery ( P>0.05 for all). All patients in ELOA group had preoperative visual impairment (12/12), with a significantly higher percentage than EEA group (56/153) and ESTMA group (14/33) ( χ2=19.72, P<0.001). There was no significant difference between three groups in the degree of tumor resection (gross total resection: 84.97% vs. 81.82% vs. 58.33%, χ2=5.58, P>0.05), postoperative cranial nerve palsy rate (13.07% vs. 30.30% vs. 16.67%, χ2=5.95, P>0.05), visual improvement rate (58.93% vs. 57.14% vs. 58.33%, χ2=0.04, P>0.05) and 5-year OS (60.69% vs. 42.66% vs. 50.00%, χ2=3.22, P>0.05). Conclusion:All three surgical approaches were safe, effective and feasible treatment modalities.