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.

Background Polycyclic aromatic hydrocarbons (PAHs) readily adsorb onto the surface of fine particulate matter (PM_2.5) and are representative components of organic pollutants in the atmosphere. PAHs are known for their significant carcinogenic, teratogenic, and mutagenic toxicity, and long-term exposure to PAHs has adverse effects on human health. Objective To investigate the concentration, composition, and pollution sources of 16 priority PAHs in PM_{2. 5} of Yanta District, Xi'an, and to evaluate the associated health risks. Methods PM_2.5 samples were collected from March 2023 to February 2024. The concentrations of 16 PAHs (ΣPAHs) were determined by high performance liquid chromatography (HPLC). Diagnostic ratios (DR) and positive matrix factorization (PMF) were used to identify the sources of PAHs. Pearson correlation analysis was applied to examine the relationship between PAHs concentrations and meteorological factors. Furthermore, the toxicity of individual PAHs was converted into benzo[a]-pyrene (BaP) toxicity equivalents to calculate the toxicity of total PAHs. An incremental lifetime carcinogenic risk (ILCR) model was established to evaluate the health risks of PAHs inhalation across different demographic groups. Results The average concentration of ΣPAHs in PM_2.5 of Yanta District, Xi'an followed a seasonal descending order: winter (15.71 ng·m⁻³) > spring (5.55 ng·m⁻³) > autumn (4.34 ng·m⁻³) > summer (1.47 ng·m⁻³). The relative abundances of PAHs in PM_2.5 varied significantly by ring number, 4-ring PAHs accounted for the largest proportion, followed by 5-ring, 3-ring and 6-ring PAHs, while 2-ring PAHs were the least abundant. This ring distribution pattern remained consistent across seasons. The contribution rates of different emission sources to ΣPAHs concentration exhibited seasonal variations. Source apportionment revealed that industrial and traffic emissions were major contributors in spring; traffic emissions dominated in summer and autumn; and coal, natural gas, and biomass combustion were the predominant sources in winter. Correlation analysis showed that ΣPAHs concentration was highly positively correlated with atmospheric pressure and negatively correlated with temperature, but not significantly correlated with precipitation, wind speed, solar radiation, and relative humidity. The ILCR model indicated significant seasonal differences (winter > spring > autumn > summer) in inhalation health risks between adults and children, primarily due to variations in inhalation rates and body weight. Adults faced higher health risks than children across all seasons. Conclusion PAHs pollution in PM_2.5 of Yanta District, Xi 'an is primarily driven by traffic emissions and the combustion of coal, natural gas, and biomass. PAHs concentrations are significantly influenced by meteorological factors, particularly air pressure, and temperature. Inhalation exposure poses distinct health risks to adults in winter. To effectively reduce ΣPAHs concentrations and mitigate air pollution, emission controls on winter coal combustion should be prioritized.

OBJECTIVE To provide a reference for clinical pharmacists to participate in the treatment of rare and complex cases of CTLA-4 haploid deficiency combined with severe malnutrition. METHODS The clinical pharmacist participated in the diagnosis and treatment of a complex case of CTLA-4 haploid deficiency with severe malnutrition， type 1 diabetes， blood coagulation abnormalities with gastrointestinal bleeding and virus infection， assisted the doctor to develop an individualized parenteral nutrition program， and dynamically adjusted the ratio of glucose and insulin （from 3.9∶1 to 15.6∶1）. When patient had severe coagulation abnormalities and gastrointestinal bleeding， the clinical pharmacist recommended discontinuing fat emulsion and switching to glucose amino acid dual energy supply； when the patient had a high fever accompanied by a sudden drop in platelets， the clinical pharmacist recommended to improve the second-generation sequencing of plasma metagenomics. Based on positive results for both EB virus and cytomegalovirus， the clinical pharmacist recommended to discontinue meropenem and switch to ganciclovir for antiviral treatment； when the patient experienced systemic itching and mental excitement， the clinical pharmacist quickly diagnosed as an adverse reaction of ganciclovir and recommended to switch to acyclovir for antiviral treatment. The clinical pharmacist simultaneously carried out parenteral nutrition medication education， and standardized infusion speed， and continuously monitored bleeding-related indicators. RESULTS The physician adopted the advice of the clinical pharmacist. After comprehensive intervention， the patient’s body temperature returned to normal， gastrointestinal bleeding stopped， coagulation indicators significantly improved， blood sugar control reached the standard， and the condition improved and the patient was discharged. CONCLUSIONS Clinical pharmacists rely on comprehensive pharmaceutical services to balance the benefits and risks of treatment for rare and complex cases. They play a key role in individualized nutrition planning， refined blood glucose control， infection identification and anti-infection optimization， and identification and treatment of adverse drug reactions to ensure patient medication safety and efficacy.

Objective To evaluate the short-term efficacy of the VISULYZE software generated nomogram in assis-ting small incision lenticule extraction(SMILE)for the correction of myopia and astigmatism.Methods Non-randomized controlled trial.Patients who underwent SMILE surgery with the original nomogram,assisted by the same surgeon at the Laser Myopia Treatment Center of Xi'an NO.1 Hospital between February 2023 and January 2024,were included.A total of 52 patients(102 eyes)of myopic astigmatism with 3-month postoperative follow-up were collected.VISULYZE software was then used to generate a new nomogram.Subsequently,a total of 40 patients(70 eyes)with myopic with-the-rule astigmatism and a preoperative cylinder of ≤2.00 D,who underwent SMILE assisted by the new nomogram at the same center between August and November 2024,were enrolled.Among them,50 eyes had a target refraction of plano and were assigned to the experimental group.In addition,from the database of patients who underwent SMILE assisted by the origi-nal nomogram,42 patients(70 eyes)with myopic with-the-rule astigmatism and a cylinder of ≤2.00 D were screened,of which 51 eyes had a target refraction of plano,and these were assigned to the control group.The postoperative visual and refractive outcomes of both groups were compared at 3 months.Astigmatism results were analyzed using Alpins vector analysis.Results At 3 months postoperatively,among eyes with a target refraction of plano,50 eyes(98.0％)in the control group and all 50 eyes(100.0％)in the experimental group achieved an uncorrected distance visual acuity(UDVA)of ≥ 20/20.No eye in either group experienced a loss of more than one line in corrected distance visual acuity(CDVA)compared with the preoperative level.At 3 months postoperatively,63 eyes(90.0％)in the control group and 66 eyes(94.3％)in the experimental group had a spherical equivalent(SE)within-0.50 to 0.50 D.The postoperative cylinder was significantly lower in the experimental group than in the control group(P＜0.05).Vector analysis revealed that the ex-perimental group had smaller values for the difference vector,index of success,and absolute angle of error than the control group,with all differences being statistically significant(all P＜0.05).At 3 months postoperatively,43 eyes(61.4％)in the control group and 57 eyes(81.4％)in the experimental group had an angle of error within-5° to 5°.Conclusion The use of the VISULYZE software generated nomogram can optimize SMILE surgery design,offering good efficacy,safety,and predictability,and improving the precision of SMILE surgery for correcting myopia and astigmatism.

Objective:To explore the occurrence and clinical characteristics of nephrogenic systemic fibrosis (NSF) induced by gadolinium-based contrast agents (GBCA).Methods:CNKI, Wanfang, VIP and PubMed databases were searched (as of October 28, 2024) and case reports on GBCA-related NSF were collected; the following information was extracted, including the publication year of the literature, country, patient gender, age, basic kidney diseases and renal replacement therapy, variety of GBCA used, exposure frequency, time of occurrence or diagnosis of NSF, clinical manifestations, pathological examination, main intervention measures and outcomes. The data were analyzed by descriptive statistics.Results:A total of 45 case reports were collected, involving 97 patients. The literature were reported mainly from the United States and published mainly in 2006 and 2007. Number of the relevant literature decreased significantly after 2008, but there were still new cases reports in China in the following years (for example, in 2023). Among the 97 patients, 53 (54.6%) were male and 44 (45.4%) were female; the age ranged from 9 to 83 years with a median age of 53 years. One patient was with severe malnutrition, while the other 96 had severe basic kidney diseases, including chronic kidney disease in 85 (88.5%) patients and acute kidney injury in 11 (11.5%) patients. Variety of GBCA exposed was described in 76 patients, including gadodiamide in 67 (88.2%) patients. Exposure frequency of GBCA before NSF occurrence was described in 88 patients, 48 (54.5%) of which were exposed only once and 23 (26.1%) were exposed twice. Time from the first GBCA exposure to the occurrence of NSF was described in 92 patients, with the shortest time of 2 days and the longest time of more than 10 years; 70.7% (65/92) occurred within 3 months after GBCA exposure. All patients had typical skin symptoms of NSF, which were confirmed by pathological examination. Among them, 43 (44.3%) had joint disorders, 9 patients had eye involvement, a few patients had cardiac fibrosis, respiratory failure, metabolic acidosis, rhabdomyolysis, muscle necrosis, etc. Follow-up information was described in 82 patients with a range of 4 months to 11 years. Among them, 21 patients (25.6%) died, mainly due to the basic kidney diseases and complications; 11 (13.4%) were severely disabled; 7 (8.5%) were mildly disabled or slowly deteriorated; 43 (52.4%) had stable disease or slightly improved condition.Conclusion:NSF caused by GBCA mainly occurs in patients with severe basic renal diseases, mostly caused by gadodiamide. Severe skin damage is often accompanied by joint involvement or even disability, and the overall prognosis is poor.

Objective To establish a forensic age inference method based on age-related changes in maxillofacial CBCT imaging of Han population in North China.Methods CBCT imaging data of Han people aged 7～50 years were collected from September 2021 to September 2023.Mimics 17.0 software was used to perform 3D reconstruction on 480 cases that met the inclusion criteria(420 cases in the experimental group,60 cases in the blind test group,with a 50%male-to-female ratio)and obtain measured values for 16 indicators.The data were then statistically analyzed using SPSS 27.0 to identify age-related significant indicators and establish regression equations.Results Regression equations based on age-related significant indicators were established for different genders and age intervals.The accuracy of the equations decreased as the age interval increased.The blind test accuracy rates of regression equations for males across different age groups ranged between 62.6%and 80.6%,while for females,they ranged between 55.3%and 76.6%.Conclusion This study enriches maxillofacial skeletal data for Chinese population and establishes multivariate age inference regression equations based on significant indicators of age-related changes in maxillofacial CBCT,providing a new reference basis and inference method for forensic age assessment.

Objective:To evaluate the role of fibrinogen in perioperative neurocognitive disorder (PND) in aged mice.Methods:Sixty SPF healthy male C57BL/6J mice, aged 16-18 months, weighing 25-30 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), PND group (group P), urokinase group (group U) and PND+ urokinase group (group PU). Abdominal surgery was performed under 3% sevoflurane anesthesia to establish the mouse model of PND. In PU group, urokinase 20 000 U/kg was intraperitoneally administered at 1 h after surgery, once a day, for 5 consecutive days. In group U, urokinase was intraperitoneally injected once a day for 5 consecutive days without anesthesia and surgery. The cognitive function was assessed after operation using the novel object recognition test (discrimination index) and the Morris water maze test (frequency of crossing the original platform and percentage of the time spent in the target quadrant). The expression of occludin, claudin-5, fibrinogen and ionized calcium-binding adapter molecule 1 (Iba-1) and CD11b in hippocampal tissues was detected using Western blot, the area of fibrinogen extravascular deposits was measured and the morphology of microglia was observed using the immunofluorescence staining, and the mRNA expression of pro-inflammatory factors (interleukin-1beta, tumor necrosis factor-alpha, and inducible nitric oxide synthase), anti-inflammatory factors (interleukin-4 and arginase-1), and chemokines (chemokine 2 and chemokine ligand 10) in hippocampal tissues was detected by quantitative real-time polymerase chain reaction after surgery. Results:Compared with group C, the parameters of cognitive function were significantly decreased, the expression of occludin and claudin-5 was down-regulated, the expression of fibrinogen was up-regulated, the area of fibrinogen extravascular deposits was increased, the number of branches was decreased and the average process length was shortened in the microglia around fibrinogen deposits, the expression of Iba-1 and CD11b was up-regulated, the mRNA expression of proinflammatory cytokines and chemokines was up-regulated, and the mRNA expression of the anti-inflammatory factors was down-regulated in group PND ( P<0.05). Compared with group PND, the parameters of cognitive function were significantly increased, the expression of occludin and claudin-5 was up-regulated, the expression of fibrinogen was down-regulated, the area of fibrinogen extravascular deposits was decreased, the number of branches was increased and the average process length was prolonged in the microglia around fibrinogen deposits, the expression of Iba-1 and CD11b was down-regulated, the mRNA expression of proinflammatory cytokines and chemokines was down-regulated, and the mRNA expression of the anti-inflammatory factors was up-regulated in group PU ( P<0.05). Conclusions:Fibrinogen deposits in the brain parenchyma through the damaged blood-brain barrier after anesthesia and surgery and participates in the development of PND, and the underlying mechanism may be related to the promotion of microglial activation and the induction of neuroinflammation in aged mice.

Objective:To evaluate the relationship between the mechanism of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) preventing sevoflurane-induced neurotoxicity and phosphorylated Tau glymphatic system clearance pathway in neonatal mice.Methods:Eighteen C57BL/6 pregnant mice were used in this study and subjected to 2 feeding regiments using the random number table method. Twelve mice were selected to receive a standard diet, and 6 mice were selected to receive a diet supplemented with fish oil (ω-3 polyunsaturated fatty acids [300 mg was added to every 20 g of standard diet from the 2nd day of gestation to 14 days after parturition). The healthy neonatal mice of both sexes, aged 6 days, weighing 3-5 g, were selected after parturition. Forty-eight neonatal pups from 6 pregnant mice that were fed a standard diet were assigned to control group (C group), 48 neonatal pups from 6 pregnant mice that were fed a standard diet were assigned to sevoflurane group (S group), and 48 neonatal pups from pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus sevoflurane group (PS group) using the random number table method. All the offspring mice in all groups were breastfed until 21 days of birth and then were housed in separate cages from their mothers after 21 days of birth and provided with ad libitum access to standard food. S group and PS group inhaled 3% sevoflurane and 40% oxygen for 2 h daily on postnatal days 6, 7 and 8. C group inhaled only 40% oxygen at the same flow rate. Y maze test was performed at postnatal day 33 to assess the spatial memory and cognitive function. The rotarod test was performed at postnatal day 35 to assess the fine motor coordination. The influx and efflux functions of the glymphatic system were assessed through intracisternal tracer infusion with the fluorescent tracer at postnatal days 14 and 35. The influx function was evaluated by the percentage of the area of tracer penetration 30 min after injection, while the efflux function was determined by the percentage of the residual area of the tracer 90 min after injection. The mice were sacrificed and the hippocampal tissue was obtained at postnatal day 14 for determination of the expression of phosphorylated Tau protein at serine 202 site and threonine 205 site (Tau-PS202/PT205) and total Tau protein by Western blot. The cerebrospinal fluid (CSF) was collected at postnatal day 14 for determination of the concentration of phosphorylated Tau protein by enzyme-linked immunosorbent assay. The mice were sacrificed and the hippocampal tissue was obtained at postnatal day 35 for determination of the expression of caspase-3, caspase-9 and cytochrome C (Cyt c) (by Western blot) and the apoptosis rate of neurons (by TUNEL).Results:Compared with C group, the time of staying at the new arm and in the rotarod test was significantly shortened, the percentage of new arm movement distance was decreased, the percentage of tracer penetration area was decreased at postnatal day 14, the percentage of residual tracer area was increased at postnatal day 14, the expression of Tau-PS202/PT205 in the hippocampus was up-regulated at postnatal day 14, the concentration of phosphorylated Tau protein in CSF was reduced at postnatal day 14, the apoptosis rate of hippocampal neurons was increased at postnatal day 35 ( P<0.05), and the expression of caspase-3, caspase-9 and Cyt c in the hippocampus was up-regulated at postnatal day 35 in S group ( P<0.05). Compared with S group, the time of staying at the new arm and in the rotarod test was significantly prolonged, the percentage of new arm movement distance was increased, the percentage of tracer penetration area was increased at postnatal day 14, the percentage of residual tracer area was decreased at postnatal day 14, the expression of Tau-PS202/PT205 in the hippocampus was down-regulated at postnatal day 14, the concentration of phosphorylated Tau protein in CSF was increased at postnatal day 14, the apoptosis rate of hippocampal neurons was decreased at postnatal day 35, and the expression of caspase-3, caspase-9 and Cyt c in the hippocampus was down-regulated at postnatal day 35 in PS group ( P<0.05). Conclusions:The mechanism by which ω-3 PUFAs prevents cerebral neurotoxicity induced by repeated neonatal sevofurane exposure may be related to the enhancement of phosphorylated Tau protein clearance via the glymphatic system.

Objective:To evaluate the relationship between the mechanism of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) in preventing brain neurotoxicity caused by multiple sevoflurane anesthesia and peroxisome proliferator-activated receptor gamma (PPARγ)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) signaling pathway in neonatal mice.Methods:This study was performed in 2 parts. Part Ⅰ Using a random number table method, 6 C57BL/6 pregnant mice were assigned to receive a standard diet, 3 pregnant mice were assigned to receive a diet supplemented with fish oil from day 2 of gestation to day 14 after parturition (ω-3 PUFAs 300 mg were added to every 20 g of conventional diet). Healthy C57BL/6 mice of both sexes, aged 6 days, weighing 3-5 g, were selected after parturition. Seventeen neonatal pups from 3 pregnant mice that were fed a conventional diet were assigned to control group (C group), 17 neonatal pups from 3 pregnant mice that were fed a conventional diet were assigned to sevoflurane group (S group), and 17 neonatal pups from pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus sevoflurane group (PS1 group) using the random number table method. Part Ⅱ Four C57BL/6 pregnant mice were assigned to receive a diet supplemented with fish oil from day 2 of gestation to day 14 after parturition. After parturition, 12 neonatal pups from 2 pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus sevoflurane group (PS2 group), and 12 neonatal pups from 2 pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus PPARγ inhibitor GW9662 plus sevoflurane group (PGS group) using a random number table method. GW9662 (2 mg/kg) was intraperitoneally injected at 30 min before exposure to sevoflurane in PGS group. All offspring mice were breastfed until 21 days of age, after which they were housed separately from the mother and allowed ad libitum access to a conventional diet. S, PS1, PS2 and PGS groups inhaled 3% sevoflurane in 40% oxygen for 2 h daily on postnatal days 6, 7 and 8. C group inhaled only 40% oxygen instead. Y maze test was performed on days 33 after birth. The rotarod test was performed on day 35 after birth. After the behavioral testing, the expression of PPARγ, PGC1α, mitofusin-1 (MFN1), MFN2, dynamin-related protein 1 (DRP1), interleukin-6 (IL-6), interleukin-1 β (IL-1 β), and tumor necrosis factor-α (TNF-α) was detected by Western blot, the ultrastructure of mitochondria in hippocampal neurons was observed with a transmission electron microscope, and the mitochondrial membrane potential (MMP), level of reactive oxygen species (ROS) and content of ATP were determined.Results:Part Ⅰ Compared with C group, the time of stay at the new-arm and time spent on the rotarod were significantly shortened, the percentage of movement distance in the new-arm was decreased, the expression of PPARγ, PGC1α, MFN1 and MFN2 in the hippocampus was down-regulated, the expression of DRP1, IL-6, IL-1β and TNF-α in the hippocampus was up-regulated, the MMP and content of ATP were decreased, and the level of ROS was increased in S group ( P<0.05). Compared with S group, the time of stay at the new-arm and time spent on the rotarod were significantly prolonged, the percentage of movement distance in the new-arm was increased, the expression of PPARγ, PGC1α, MFN1 and MFN2 in the hippocampus was up-regulated, the expression of DRP1, IL-6, IL-1β and TNF-α in the hippocampus was down-regulated, the MMP and content of ATP were increased, and the level of ROS was decreased in PS1 group ( P<0.05). Part Ⅱ Compared with PS2 group, the time of stay at the new-arm and time spent on the rotarod were significantly shortened, the percentage of movement distance in the new-arm was decreased, the MMP and content of ATP were decreased, the level of ROS was increased, and the expression of IL-6, IL-1β and TNF-α was up-regulated ( P<0.05). Conclusions:The mechanism by which ω-3 PUFAs prevent brain neurotoxicity caused by multiple sevoflurane anesthesia is related to the activation of the PPARγ/PGC1α signaling pathway and alleviation of mitochondrial dysfunction and neuroinflammation in neonatal mice.

Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.