Background: A systematic evaluation of potential living liver donors is essential to ensure donor safety and optimize recipient outcomes in living donor liver transplantation (LDLT). This study aimed to assess donor acceptance rates and reasons for disqualification among individuals evaluated for LDLT at a high-volume transplant center over a one-year period. Methods: We retrospectively reviewed 1,087 potential living liver donors who presented for LDLT evaluation in 2023. Of these, 991 candidates advanced beyond the initial screening (Stage 1) and underwent comprehensive clinical, imaging, and pathological assessments (Stages 2 and 3). Candidates who discontinued after Stage 1 were excluded due to the absence of documented reasons for non-progression. Results: Among the 991 candidates who proceeded beyond initial screening, 473 (47.7%) completed the full donor evaluation, of whom 466 were judged to be suitable donors. Among suitable donors, 384 (82.4%) proceeded to donor hepatectomy, whereas 82 did not, primarily due to recipient-related factors such as clinical deterioration or withdrawal of consent. Donor ineligibility was determined in 422 candidates (42.6%), most commonly due to inadequate remnant liver volume (52.8%), hepatic steatosis (20.6%), and insufficient graft size (10.2%). Among candidates undergoing Stage 2 evaluation, 162 (16.3%) failed to meet steatosis criteria; 126 were excluded solely for steatosis and advised weight reduction, and 39 subsequently became eligible and successfully donated. Conclusion In this high-volume LDLT center, donor disqualification was primarily driven by remnant liver volume and hepatic steatosis. Targeted interventions such as weight reduction enabled successful donation in a subset of initially ineligible candidates, underscoring the importance of individualized donor evaluation and pre-donation optimization.

Background: We developed a simplified variant of the ADV score, the AFP-PIVKAII (AP) score for post-transplant hepatocellular carcinoma (HCC) prognosis, which considers only AFP and PIVKA-II levels excluding morphometric tumor size information from the ADV score. This study investigated the prognostic performance of the AP score in predicting HCC recurrence and overall survival (OS) after living donor liver transplantation (LDLT). Methods: We analyzed 843 patients with HCC who underwent LDLT between 2006 and 2015, assessing HCC recurrence and OS in relation to AP score. Results: The median pretransplant AFP and PIVKA-II levels were 12.8 ng/mL and 27 mAU/mL, respectively. The median and mean AP scores were 2.6 log (range: 0.6–9.2 log) and 2.9±1.1 log, respectively. The 5-year time-dependent area under the receiver operating characteristic curve for the AP score in predicting post-transplant HCC recurrence was 0.672 (p<0.001). HCC recurrence and OS curves along AP score intervals of 1.0 log showed statistical differences in accordance with the AP scores (both p<0.001). Using a Youden index J-derived AP score cutoff of 4.0 log, two-tiered groups (ADV <4.0 log vs. ADV ≥4.0 log) showed statistically significant differences in HCC recurrence and OS (both p<0.001). Harrell’s c-indices for AP score with cutoff of 4.0 log and ADV scores with cutoff of 5.0 log regarding HCC recurrence and OS were similar. Conclusion The AP score functions as an integrated surrogate marker for predicting post-transplant outcomes in patients with HCC undergoing LDLT. It may serve as a simplified alternative to the ADV score, particularly in patients with small HCCs.

Periodontitis is a chronic inflammatory disease triggered by periodontal pathogens and mediated by immune responses. Traditionally, gingival fibroblasts (GFs) were considered to be primarily responsible for maintaining periodontal matrix homeostasis. However, recent studies reveal that GFs play a significant immunoregulatory role in periodontitis. Through signaling pathways, such as the Toll-like receptor 4 (TLR4) pathway, GFs recognize virulence factors from pathogens, such as Porphyromonas gingivalis, and secrete various inflammatory mediators, thus driving extracellular matrix degradation and osteoclast differentiation. Simultaneously, GFs modulate immune cells, including neutrophils and macrophages, amplifying inflammatory responses and fostering a chronic inflammatory microenvironment. Risk factors, such as hyperglycemia and smoking, exacerbate GFs dysfunction via oxidative stress-mediated activation of the nuclear factor kappa B (NF-κB) pathway and other mechanisms, while inflammation and cellular senescence form a vicious cycle. Senescent GFs further aggravate alveolar bone destruction by activating the mechanistic target of the rapamycin (mTOR) pathway. Therapeutic strategies targeting GFs, such as suppressing NF-κB signaling or modulating mTOR-mediated senescence, may disrupt the link between inflammation and tissue destruction, showing promising therapeutic potential. Future studies should employ advanced technologies such as spatial multi-omics and single-cell proteomics to elucidate the spatial distribution, functional interactomes, and heterogeneity of GFs subsets, in order to deepen our understanding of their roles in periodontitis progression. This review summarizes the multifaceted mechanisms of GFs in periodontitis and explores potential therapeutic strategies targeting GFs, offering novel insights for periodontitis prevention and treatment.

Objective: To explain process of developing basic veterinary clinical performance guidelines, based on frequently observable clinical manifestations, thereby supporting competencybased veterinary education in Korea. Methods: A structured review of learning outcomes established by Korean Association of Veterinary Medical Colleges (KAVMC) was conducted by a planning committee including veterinary educators, practitioners, and advisory members. Owner-oriented descriptions were used to frame each performance task, and each was mapped to corresponding learning outcomes. These tasks were aligned with learning outcomes recommended by the KAVMC to support the development of communication, clinical reasoning, and performance-related competencies among veterinary students, thereby enhancing day-one clinical readiness. Results: In total, 63 clinical manifestations for a guidebook format that can be used for clinical education were identified and categorized by organ systems that are described in language understandable to animal owners. Conclusions and Relevance: The basic veterinary clinical performance guidelines based on common clinical manifestations would serve as a vital component in veterinary education to reinforce core graduation competencies.

Background: Studies on whether donor-to-recipient sex match status affects long-term survival after liver transplantation (LT) have yielded contradictory results. This study evaluated whether donor-to-recipient sex match status influenced long-term survival after living donor liver transplantation (LDLT) or deceased donor liver transplantation (DDLT) at a high-volume center. Methods: The study included 6,664 patients who underwent primary LT between January 2000 and December 2022 at our institution. Patients were divided into four groups according to donor-to-recipient sex match status: male-to-male (n=3,427 [51.4%]), male-to-female (n=1,152 [17.3%]), female-to-male (n=1,385 [20.8%]), and female-to-female (n=700 [10.5%]). Results: Regarding clinical characteristics, the four groups differed significantly regarding background liver disease (P<0.001), model for end-stage liver disease score (P<0.001), serum protein induced by vitamin K absence or antagonist II level (P=0.003), presence of concurrent hepatocellular carcinoma (HCC; P<0.001), and type of LT (P=0.003). Overall survival (OS) of all LT recipients did not differ significantly among the groups (P=0.377). Donor-to-recipient sex match status did not affect long-term OS in either LDLT (P=0.176) or DDLT (P=0.220) groups. In addition, sex match status did not significantly influence posttransplant OS among patients who underwent LDLT without HCC (P=0.464), LDLT with HCC (P=0.236), DDLT without HCC (P=0.338), or DDLT with HCC (P=0.818). Conclusions Donor-to-recipient sex match status does not significantly affect posttransplant patient survival or HCC prognosis after LDLT or DDLT.

Background and Objectives: We evaluated 20-year trends in heart failure (HF) epidemiology in Korea to quantify changes in its burden from 2002 to 2023. Methods: A nationwide analysis was conducted using a random 50% sample from the Korean National Health Information Database linked to mortality records (2002–2023). HF was defined using diagnostic codes recorded as a primary or secondary condition. We calculated crude and age-standardized rates of prevalence, incidence, hospitalization, and mortality. Survival was assessed using the Kaplan–Meier method, stratified by inpatient versus outpatient diagnosis.Trends in heart transplantation and left ventricular assist device implantations were also examined. Results: By 2023, approximately 1,750,228 individuals had HF (3.41% prevalence). The age-standardized prevalence has more than doubled from 2002 to 2023. The crude incidence increased over time; the age-standardized incidence remained stable in men and declined in women.Hospitalization rates for any cause or secondary HF diagnoses have increased substantially, whereas primary HF hospitalization rates have remained relatively stable. The annual mortality rate in patients with HF was approximately 6.0% in 2023, being markedly higher in older adults.Although short-term survival has improved, particularly in hospitalized patients, long-term survival remains limited. Use of advanced therapies significantly increased. Conclusions The burden of HF in Korea has increased substantially over the past two decades, driven primarily by population aging and improved survival rather than increasing age-adjusted incidence. Despite therapeutic advances, hospitalization and long-term mortality rates remain high, highlighting the need for comprehensive HF strategies in aging societies.

ObjectiveCerebral ischemic injury triggers a complex pathological cascade characterized by excessive reactive oxygen species (ROS) accumulation, persistent oxidative stress, and sustained neuroinflammation in the injured brain microenvironment. These events collectively drive mitochondrial dysfunction, microglial overactivation, pro-inflammatory cytokine release, and progressive neuronal apoptosis, ultimately leading to severe and irreversible neurological deficits. However, conventional therapeutic strategies face critical limitations, including poor blood-brain barrier penetration, insufficient local drug concentration, uncontrolled drug release, and off-target systemic side effects. To address this pathological process, we rationally designed and fabricated an injectable ROS-responsive hydrogel loaded with polydopamine nanoparticles (PDA NPs) for spatiotemporally controlled antioxidation, anti-inflammation, and neuroprotection in the ischemic injury microenvironment. The present study aimed to systematically characterize the physicochemical properties, ROS-responsive drug release behavior, biocompatibility, and neuroprotective efficacy of this composite hydrogel system in vitro. MethodsPDA NPs were fabricated via oxidative self-polymerization. The ROS-responsive hydrogel was cross-linked using N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1, 3-diaminium (TSPBA) and polyvinyl alcohol (PVA). Morphology, particle size, Zeta potential, and structure of PDA NPs were characterized by dynamic light scattering (DLS), Zeta potential analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Microstructure, rheological properties, shear-thinning behavior, and ROS-triggered release profiles of the hydrogel were examined by SEM and rheometry. Biocompatibility was evaluated using HT22 mouse hippocampal neurons with CCK-8 and live/dead staining. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was established to simulate ischemic injury in vitro. ROS levels and neuronal apoptosis were detected by DHE staining and TUNEL assay. Microglial polarization and pro-inflammatory cytokine expression were analyzed using immunofluorescence and RT-qPCR in BV-2 microglia. Transwell co-culture was used to verify the indirect neuroprotection mediated by modulated microglia. ResultsCharacterization results confirmed that the as-prepared PDA NPs were monodispersed spherical nanoparticles with uniform diameter and negative surface potential, demonstrating favorable dispersibility and robust ROS-scavenging activity. The TSPBA-PVA hydrogel exhibited a highly porous interconnected network, suitable mechanical strength, and obvious shear-thinning behavior, supporting its application as an injectable implant. More importantly, the hydrogel displayed typical ROS-responsive degradation and on-demand PDA NP release in a ROS-concentration-dependent manner. In vitro cellular experiments demonstrated that the PDA NP-loaded hydrogel possessed excellent biocompatibility with HT22 cells. In the OGD/R model, the hydrogel significantly reduced intracellular ROS accumulation and markedly suppressed neuronal apoptosis. Furthermore, the composite hydrogel effectively redirected BV-2 microglia from the pro-inflammatory M1 toward the anti-inflammatory M2 phenotypes, downregulated the expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6, and reduced inflammatory damage. Transwell co-culture assays further validated that M2-polarized microglia mediated by the hydrogel significantly enhanced the survival of OGD/R-injured HT22 neurons and attenuated apoptosis. ConclusionIn this study, we successfully developed a novel injectable ROS-responsive hydrogel loaded with PDA NPs for synergistic antioxidative and anti-inflammatory neuroprotection. This intelligent hydrogel system enables ROS-triggered on-demand release of PDA NPs, efficiently scavenges excessive ROS, inhibits oxidative stress injury, modulates microglial polarization, and suppresses neuroinflammation, thereby exerting robust neuroprotective effects in vitro. This biomaterial platform provides a promising strategy for the targeted and controlled delivery of bioactive nanomaterials in the central nervous system diseases and establishes a solid experimental foundation for the development of in situ injectable therapies for ischemic brain injury.

Liver cancer is one of the world's serious diseases today because of its high frequency and fatality rate, genetic differences, and limited effectiveness of late-stage therapy. Although chemotherapy, targeted therapy, immunotherapy, ablation and transarterial chemoembolisation (TACE) have improved the disease control of some patients, recurrence and acquired resistance are still common, especially for tumors that are hypoxic, nutrient-deprived, acidic-stressed, vascularly insufficient and exposed to repeated drug pressure. A bad environment will cause a change in the quality-control system and metabolism of cancer cells, and as a result, lysosomes have started to alter. In addition to the above catabolic functions of lysosomes, they also take part in autophagic flux, substrate recycling, iron and lipid metabolism, nutrient sensing, drug distribution, membrane repair and cell death signalling. Under the stress of therapy in liver cancer cells, increased lysosomal acidification and enhanced terminal degradation lead to prolonged autophagy; TFEB/TFE3 promotes the formation of new lysosomes and lysophagosomes to sequester weakly basic drugs, thereby reducing the concentration of active drugs and mitigating proteotoxicity and oxidative stress to promote cell survival. The above processes produce a lysosome-dependent resistant phenotype that is particularly relevant to sorafenib and doxorubicin and other drugs whose effectiveness can be reduced by protective autophagy or changes in intracellular location. Conversely, the same dependency on lysosomal homeostasis is also a vulnerability. Natural products and monomeric compounds derived from Chinese herbal medicines have various structures, multiple target regulation capabilities, and the potential to act on several lysosome-related nodes simultaneously. Based on the evidence in this review, it is believed that such compounds may sensitise liver cancer cells by inhibiting V-ATPase-mediated acid hydrolysis, obstructing late-stage autophagy-mediated degradation, disrupting lysosomal calcium or membrane homeostasis, causing lysosomal membrane permeabilisation, reducing compensatory lysosomal biogenesis, promoting ferritin degradation and ferroptosis, or enhancing acid-responsive intracellular delivery. Agents that impair lysosomal function and protective autophagy, compounds that convert enlarged or drug-sequestering lysosomes into lethal targets, and nanodelivery systems that exploit the acidic environment of endolysosomes to co-deliver natural products with chemotherapeutic drugs are examples. Lysosome-targeted intervention will have different effects under different circumstances; for example, inhibiting autophagy may result in an increase in cytotoxic stress in some areas, whereas overstimulation of autophagy or iron release from lysosomes may induce autophagic cell death or ferroptosis in other areas. Therefore, the design of therapy should take into account the status of the tumour microenvironment, autophagic flux, lysosomal pH, TFEB/TFE3 activity, drug sequestration capacity, ferroptosis sensitivity, dosing sequence and delivery route. This review systematically examines the lysosomal homeostasis in the microenvironment of liver cancer, the mechanisms through which lysosomal adaptation contributes to chemoresistance, and the rationale for combining natural products with standard agents such as sorafenib and doxorubicin. Based on basic lysosome biology, pharmacodynamic and delivery data have also been collected; as a result, some applications for future studies have been proposed, such as dynamic monitoring of autophagy flux, in vivo spatial measurements of lysosomal functions, rational optimisation of combination therapy timings, and safety assessments in immunocompetent liver cancer models prior to clinical translation. Translation difficulties are also evident, such as insufficient tumour selectivity, pharmacokinetic limitations, compensatory lysosomal regeneration, toxicity to normal liver and immune cells, and a lack of validated predictive biomarkers. A new way will be found to use biomarkers to divide the patient group, optimize nanoparticles for better delivery, design specific schedules for combined treatments based on the problem they cause within the cell, etc., thereby overcoming drug resistance and reducing the harm patients suffer from toxic treatments. This system can help select biomarkers and rational drug pairs for the next round of lysosome-centred precision trials.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

ObjectiveTo study the mechanism by which Shexiang Tongxin dropping pills （STDP） ameliorate the dysfunction of coronary microvascular endothelial cells in the rat model of heart failure. MethodsThe heart failure model was established by ligation of the left anterior descending coronary artery in rats， which were then allocated into sham， model， STDP， and telmisartan （TLM） groups and treated for 21 days. The heart function was detected by echocardiography， and the levels of myocardial injury markers， nitric oxide （NO）， endothelin-1 （ET1）， and angiotensinⅡ （AngⅡ） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were determined by Western blot. The model of cardiac microvascular endothelial cell injury was established by AngⅡ induction and then treated with the STDP-containing serum （5%， 10%， and 20%） for 24 h. The levels of NO and ET1 were measured by ELISA. Western blot was employed to determine the protein levels of eNOS， iNOS， angiotensin-converting enzyme 2 （ACE2）， and angiotensinⅡ receptor 2 （AT2）. MLN-4760， an ACE2 inhibitor， was used to explore the mechanism underpinning the regulatory effect of STDP on the ACE2-AT2/MAS pathway. ResultsCompared with the sham group， the model group showed decreases in left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.05）， a decline in serum NO level， elevations in serum AngⅡ and ET1 levels， a reduction in p-eNOS/eNOS ratio， and up-regulation in iNOS expression （P<0.05）. Compared with the model group， STDP increased LVEF， LVFS， and cardiac output （P<0.05）， raised the level of NO and lowered the levels of AngⅡ and ET1 in the serum （P<0.05）， increased the p-eNOS/eNOS value， and inhibited iNOS expression （P<0.05）. Compared with the AngⅡ group， STDP increased the NO content and decreased the ET1 content in endothelial cells （P<0.05）， increased the p-eNOS/eNOS ratio， and inhibited the iNOS expression （P<0.05）. The ACE2 inhibitor MLN-4760 reversed the regulatory effects of STDP on p-eNOS， eNOS， and iNOS. ConclusionSTDP improves the cardiac function in the rat model of heart failure， enhances the synthesis and release of NO in cardiac microvascular endothelial cells， reduces AngⅡ and ET1 levels， and regulates the expression of p-eNOS and eNOS， thereby ameliorating the dysfunction of microvascular endothelial cells in heart failure. This mechanism is related to the upregulation of the expression of proteins in the ACE2-AT2/MAS pathway.