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.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Objective To analyze the acupoint selection law of acupuncture and moxibustion for postherpetic neuralgia(PHN)with R language data mining technology.Methods The clinical research literature on acupuncture and moxibustion treatment of PHN included in CNKI,Wanfang Data,VIP and CBM from January 1,2010 to July 1,2023 was retrieved,and the database was established by Excel 2016.R language was used to statistically analyze the frequency of acupoint usage,meridians,locations,specific acupoints,etc.Through association rule analysis and clustering analysis,the characteristics and law of acupoint selection for acupuncture and moxibustion treatment of PHN were obtained.Results A total of 198 articles were included,including 83 acupoints,with a total frequency of 714 times.The high-frequency acupoints include Ashi acupoint,Jiaji acupoint and Yanglingquan.The commonly used meridians were gallbladder meridian,spleen meridian and large intestine meridiam.The acupoints were mostly in the upper and lower limbs,with the Wushu acupoints,Yuan acupoints and Xiahe acupoints being the most common.The core acupoint was Ashi acupoint,Jiaji acupoint,Hegu,Quchi,and 9 sets of association rules and 5 effective clusters were obtained.Conclusion The most commonly used acupoints for acupuncture and moxibustion treatment of PHN are Ashi acupoint,Jiaji acupoint,Hegu and Quchi,which mainly follow the principle of combining local acupoint selection with distal acupoint selection.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age. METHODS: In total, 1,505 non-pregnant or non-lactating women (18-45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds. RESULTS: The median serum 25(OH)D was 16.63 (11.96-22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49-15.39) ng/mL], and P1NP [13.87 (12.37-15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68-13.91) ng/mL], β-CTX [12.23 (10.22-14.23) ng/mL], and P1NP [11.85 (10.40-13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81-13.68) ng/mL], β-CTX [13.05 (11.78-14.32) ng/mL], and P1NP [12.81 (11.57-14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued. CONCLUSION In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Humans ; Female ; Vitamin D/blood* ; Adult ; Middle Aged ; Polymorphism, Single Nucleotide ; Adolescent ; Young Adult ; China ; Biomarkers/blood* ; Bone Remodeling/genetics* ; Vitamin D-Binding Protein/genetics* ; Procollagen/blood* ; Osteocalcin/blood* ; Peptide Fragments/blood* ; East Asian People

Objective:To explore the related risk factors contributing to re-fracture after hip surgery in elderly patients.Methods:This retrospective analysis was conducted on the clinical data of 2 415 elderly individuals who underwent surgical treatment for hip fractures and were discharged from Shanghai Sixth People's Hospital between January 2016 and December 2021.Patients were grouped into re-fracture and non-re-fracture cohorts based on whether a second fracture occurred within three years after surgery.Demographics, clinical data, and postoperative functional rehabilitation outcomes of the two groups were collected, and univariate and multivariate logistic regression analyses were applied to identify the independent risk factors for re-fractures after surgery.Results:A total of 2, 000 patients who completed follow-up were included in the final analysis, aged 60~91 years, with a mean age of (75.4±8.2) years.Among them, 855 were male(42.75%), and the postoperative re-fracture incidence was 28.25% (565/2 000). Univariate analysis indicated that advanced age, fracture type at first onset, lower Harris scores, insufficient rehabilitation training, osteoporosis, diabetes, cerebrovascular disorders, visual impairment, and syncope were all significantly associated with re-fracture (all P<0.05), while gender differences were not statistically significant ( P>0.05). Multivariate regression confirmed the following as independent risk factors: age ≥75 years, postoperative Harris score <80, non-standard rehabilitation training, combined osteoporosis, diabetes, cerebrovascular disease, visual impairment, and syncope ( OR、 RR>1). Conclusions:Elderly patients are prone to re-fracture after hip surgery, and its occurrence is closely related to advanced age, inadequate functional rehabilitation, osteoporosis, and multiple internal medical comorbidities.In clinical practice, attention should be paid to standardized postoperative rehabilitation, systematic anti-osteoporotic therapy, and active intervention of comorbidities to reduce the incidence of re-fracture and improve the long-term prognosis of patients.

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.