Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

OBJECTIVE To explore the mechanism of Jiawei xiaochaihu decoction against hippocampal neuronal apoptosis in acute epileptic model mice. METHODS Thirty-six male KM mice were randomly divided into four groups with 9 mice in each group： normal control group （normal saline）， epilepsy model group （normal saline）， Jiawei xiaochaihu decoction group [7 g/（kg·d）] and carbamazepine group [positive control， 30 mg/（kg·d）]. Except for the normal control group， the acute epilepsy model was established in the other groups. After successful modeling， mice in each group were given corresponding drugs or normal saline by intragastric administration once a day for 2 consecutive weeks. After drug intervention， the ultrastructure and pathological morphology of hippocampal CA1 region were observed. The number of TUNEL-positive cells in hippocampus was detected， and the expression levels of protein kinase B （AKT）， Caspase-3， B-cell lymphoma-extra large （Bcl-xL）， Bcl-2-associated X protein （Bax）， as well as the ratio of phosphorylated AKT（p-AKT） to AKT were determined. RESULTS Compared with the normal control group， severe ultrastructural and pathological damages were observed in the hippocampal CA1 region of epilepsy model group； the number of TUNEL-positive cells was significantly increased （ P ＜0.05）. The expression levels of p-AKT and Bcl-xL were significantly down-regulated （ P ＜0.05）， while the Bax and Caspase-3 were significantly up-regulated （ P ＜0.05），accompanied by a remarkable decrease of p-AKT/AKT ratio （ P ＜0.05）. Compared with the epilepsy model group， hippocampal tissue ultrastructure， pathological damage， and the aforementioned indicators were significantly improved in Jiawei xiaochaihu decoction group （ P ＜0.05）. CONCLUSIONS Jiawei xiaochaihu decoction can inhibit hippocampal neuronal apoptosis in acute epileptic mice， and its mechanism may be related to activating AKT phosphorylation， increasing p-AKT/AKT ratio， up-regulating Bcl-xL expression and down-regulating the expression of Bax and Caspase-3.

OBJECTIVE To explore the mechanism of Jiawei xiaochaihu decoction against hippocampal neuronal apoptosis in acute epileptic model mice. METHODS Thirty-six male KM mice were randomly divided into four groups with 9 mice in each group： normal control group （normal saline）， epilepsy model group （normal saline）， Jiawei xiaochaihu decoction group [7 g/（kg·d）] and carbamazepine group [positive control， 30 mg/（kg·d）]. Except for the normal control group， the acute epilepsy model was established in the other groups. After successful modeling， mice in each group were given corresponding drugs or normal saline by intragastric administration once a day for 2 consecutive weeks. After drug intervention， the ultrastructure and pathological morphology of hippocampal CA1 region were observed. The number of TUNEL-positive cells in hippocampus was detected， and the expression levels of protein kinase B （AKT）， Caspase-3， B-cell lymphoma-extra large （Bcl-xL）， Bcl-2-associated X protein （Bax）， as well as the ratio of phosphorylated AKT（p-AKT） to AKT were determined. RESULTS Compared with the normal control group， severe ultrastructural and pathological damages were observed in the hippocampal CA1 region of epilepsy model group； the number of TUNEL-positive cells was significantly increased （ P ＜0.05）. The expression levels of p-AKT and Bcl-xL were significantly down-regulated （ P ＜0.05）， while the Bax and Caspase-3 were significantly up-regulated （ P ＜0.05），accompanied by a remarkable decrease of p-AKT/AKT ratio （ P ＜0.05）. Compared with the epilepsy model group， hippocampal tissue ultrastructure， pathological damage， and the aforementioned indicators were significantly improved in Jiawei xiaochaihu decoction group （ P ＜0.05）. CONCLUSIONS Jiawei xiaochaihu decoction can inhibit hippocampal neuronal apoptosis in acute epileptic mice， and its mechanism may be related to activating AKT phosphorylation， increasing p-AKT/AKT ratio， up-regulating Bcl-xL expression and down-regulating the expression of Bax and Caspase-3.

AIM: To investigate the global research status, hotspots, and trends of exosome studies in ophthalmology, providing a theoretical foundation and constructive references for future research, and promoting in-depth development in this field.METHODS: Relevant literature on exosomes in ophthalmology published up to May 20, 2024, was retrieved from the China National Knowledge Infrastructure(CNKI), Web of Science Core Collection, and PubMed databases. Visual analyses of publication countries, institutions, authors, high-frequency keywords, burst keywords, and timelines were performed using CiteSpace 6.3.R1 and VOSviewer software.RESULTS: A total of 37 Chinese articles and 548 English articles were included. The top five countries in terms of publication volume were the United States(130 articles), China(80 articles), South Korea(24 articles), the United Kingdom(20 articles), and Japan(19 articles). The leading foreign institutions were the University of California System, Duke University, and Harvard University, while the top domestic institutions were Qingdao University, the Department of Ophthalmology at the First Affiliated Hospital of Jinan University, and the School of Physical Education and Sports Science at Beijing Normal University. Analysis of Chinese and English high-frequency and burst keywords indicated that global research hotspots on exosomes in ophthalmology primarily focus on dry eye, extracellular vesicles, mesenchymal stem cells and their derived exosomes, ocular surface diseases, ocular surface inflammation, biomarkers, retinal protection, immune eye diseases, uveitis, degenerative eye diseases, macular degeneration, diabetic retinopathy, neovascularization, thyroid-associated ophthalmopathy, and glaucoma, while English high-frequency words mainly were dry eye, dry eye disease, delivery, regenerative medicine, uveal melanoma, protein, and transplantation. Research has evolved from initial basic biological studies to exploring the pathogenesis of ocular diseases and advancing toward novel diagnostic and therapeutic approaches.CONCLUSION: Over the past 5 a, research on exosomes in ophthalmology has grown rapidly. Exosomes, as novel biomarkers and potential therapeutic targets, have become central to studies on the pathogenesis and clinical applications of ophthalmic diseases. Their roles in the diagnosis, treatment, and prevention of these diseases represent promising directions for future research.

Background Pneumoconiosis is a chronic inflammatory disease that cannot be completely cured. Therefore, how to control lung inflammation and delay of the body aging is one of the keys to treating pneumoconiosis. The studies in past two decades suggested that many small molecule drugs are able to enhance cardiopulmonary function. Objective To explore the effects of homeopathic dosing and combined dosing of β-nicotinamide mononucleotide and taurine on experimental silicosis in rats. Methods Seventy-two SD specific pathogen-free rats were randomized into 4 groups (18 mice in each group): negative control group (ultrapure water, without dust), positive control group, homeopathic treatment group, co-administered treatment group. One mL of quartz dust suspension was injected into the rat trachea by disposable non-exposed tracheal injection method (50 mg·mL⁻¹) to establish a rat silicosis model. Rats were administered by gavage since the 4th day after dust exposure. The homeopathic treatment group rats received taurine solution (0.03 g·mL⁻¹) in the morning and β-nicotinamide mononucleotide (0.03 g·mL⁻¹) in the afternoon; the co-administered treatment group rats received a mixed solution (0.015 g·mL⁻¹ β-nicotinamide mononucleotide + 0.015 g·mL⁻¹ taurine) twice, in the morning and afternoon respectively. The positive and negative control groups received equivalent of ultrapure water in the morning and afternoon. All groups of rats were administered 5 d a week for a total of 6 weeks. The rats were neutralized after 6 weeks of administration. Organ coefficient, lung hydroxyproline content, whole lung dry and wet weights, whole lung free silica content, and cell count and classification in lung lavage fluid were measured and calculated, and lung histopathological changes in lung samples were observed. Results Compared with the positive control group, the whole lung wet weight, whole lung dry weight , total cell count, neutrophil rate, lung organ coefficient, lung hydroxyproline content, and whole lung free silica content were reduce in the homeopathic treatment group, and the co-administered treatment group (P＜0.05). Compared with the negative control group, the total cell count, neutrophil rate, lung organ coefficient, lung hydroxyproline content, and whole lung free silica content were elevated in the homeopathic treatment group and the co-administered treatment group, the whole lung dry weight was elevated in the co-administered treatment group, and those differences were all statistically significant (P＜0.05). The rat lung histopathological results showed that, in the positive control group, round or oval nodules were formed in the lung tissue, which were phagocytic cellular nodules, and the alveolar structures in some areas still existed. The histopathological changes in the homeopathic treatment group and the co-administered treatment group were similar to those of the positive group, but less severe. No pathological change was observed in the lung tissue of the negative control group. Conclusion Some improvement and dust removal in experimental silicosis rats by homeopathic dosing and combined dosing of β-nicotinamide mononucleotide and taurine are observed.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

Objective To evaluate the medical resource consumption due to healthcare-associated infection(HAI)in patients with tumor based on disease diagnosis-related grouping(DRG).Methods Medical records of discharged patients from a tumor center of a hospital in 2022 were analyzed retrospectively,and differences in indicators such as average length of hospital stay and average expenses per hospitalization between the HAI group and the non-HAI group were compared.Results A total of 10 674 cases were included in the analysis,and 217 cases(2.03％)were in the HAI group.The average expense per hospitalization(5.10[2.38,8.43]10 000 Yuan vs 1.16[0.74,2.04]10 000 Yuan)and average length of hospital stay(25[13,40]days vs 6[4,11]days)of patients in the HAI group were both higher than those in the non-HAI group,both with statistically significant differences(both P＜0.05).The most common infection was bloodstream infection and pulmonary infection,accounting for 23.96％and 22.58％,respectively.In the three DRG groups,namely,RC19(radiotherapy for malignant proliferative disea-ses),RU12(supportive treatment for malignant proliferative diseases[length of hospital stay 7-29 days]),and RB19(high-dose chemotherapy and/or other treatments for acute leukemia),patients in the HAI group had higher average expenses per hospitalization and average length of hospital stay than patients in the non-HAI group,diffe-rences were all statistically significant(all P＜0.05).Conclusion DRG assessment can effectively identify key po-pulations for HAI prevention and control,contribute to implement precise infection prevention and control strate-gies,and reduce HAI incidence and related medical resource consumption.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective To explore the effect of curcumin(CUR)on oxidative damage of keratinocytes induced by ultraviolet B(UVB)irradiation through Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/nucleotide-binding oligomerization domain-containing protein 3(NLRP3)signaling pathway.Methods Human keratinocytes of HaCaT were cultured normally in vitro,and the keratinocyte oxidative damage model was established by the irradiation of 57 mJ/cm2 UVB.The cells with normal culture were as the control group,the cells treated after modeling were as the UVB group,the cells treated with 5 μmol/L CUR after modeling were as the CUR group,the cells treated with 100 μg/L TLR4 inhibitor of TAK-242 after modeling were as the TAK-242 group,and the cells treated with 5 μmol/L CUR and 100 nmol/L TLR4 activator of lipopolysaccharide(LPS)were as the CUR+LPS group.qRT-PCR was applied to detect the relative expression levels of TLR4,NF-κB,and NLRP3 mRNAs of cells in each group.CCK-8 was applied to detect the cell proliferation in each group.The relative content of reactive oxygen species(ROS),the viabilities of superoxide dismutase(SOD)and catalase(CAT),and the concentrations of glutathione(MDA)and glutathione(GSH)of cells in each group were detected by fluorescence assay according to the kit instruction.ELISA kit was used to detect the expression of inflammatory factors of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)of cells in each group.Flow cytometry was applied to detect the cell apoptosis in each group.Western blot was applied to detect the expression of proliferation related protein of proliferating cell nuclear antigen(PCNA),apoptosis related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)],and TLR4/NF-κB/NLRP3 signaling pathway related proteins(TLR4,NF-κB and NLRP3)of cells in each group.Results Compared with the Control group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the UVB group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Compared with the UVB group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the TAK-242 group and CUR group increased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 decreased(P<0.05).Compared with the CUR group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the CUR+LPS group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Conclusion CUR can increase the antioxidant stress level of keratinocytes,alleviate inflammatory response,promote cell proliferation,and improve cell damage caused by UVB irradiation,which may be related to the inhibition of TLR4/NF-κB/NLRP3 signaling pathway.