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.

ObjectiveTo investigate the mutation status of the MET gene in tumor patients， with a focus on its expression in lung cancer tissues and its impact on patient prognosis， providing theoretical basis and potential targets for precise diagnosis and treatment of the tumors. MethodsA total of 1，627 tumor patient samples were collected from January 2021 to September 2025. High-throughput sequencing technology was used to conduct DNA-level gene detection on 137 tumor patients with MET mutations. The distribution of mutation sites in exons and introns， as well as the occurrence frequencies of MET gene amplification and gene fusion were analyzed， with particular attention paid to the mutation frequencies of each exon and the high-frequency variant types. Immunohistochemical staining was performed to analyze the expression levels of c-MET protein in tumor tissues of the 137 patients. Immunohistochemical analysis was conducted on tumor tissues of 9 patients with MET gene exon 14 skipping mutations to study the association between c-MET protein expression and this specific mutation type. RNA sequencing results， immunohistochemical staining data， and follow-up prognosis of lung cancer from the GEPIA2 database and TCGA database were comprehensively analyzed to explore the potential relationship between MET gene expression in tumor tissues and patient prognosis. ResultsAmong 1，627 tumor patients， 137 MET mutation patients were detected， including 93 males with an average age of （66.85±9.61） years and 44 females with an average age of （59.43±11.08） years. Lung cancer was the most common tumor type （117 cases）. MET gene expression was lower in breast cancer and glioblastoma multiforme， but higher in lung cancer and colorectal cancer as compared with the expression in normal tissues. Survival analysis showed that patients with high MET gene expression in lung adenocarcinoma had a shorter overall survival time than those with low expression. A total of 961 mutations were detected by next-generation sequencing， including 547 exon mutations and 374 intron mutations. MET gene amplification was found in 13 cases and gene fusion in 27 cases. The highest mutation frequency was in exon 2， followed by exon 5， exon 4， and exon 19. High-frequency variant types included c.2890C>A （p.L964M） on exon 4 and c.3028G>T （p.D1010Y） on exon 5. The c-MET protein expression was closely related to the type of gene mutation. Missense mutations often led to positive or strongly positive c-MET protein expression， while nonsense mutations often resulted in weak or absent c-MET protein expression. Among the 9 patients with MET gene exon 14 skipping mutations， the c-MET protein expression score was mostly 0 - 1， with only 1 case scoring 2. Among the 117 lung cancer patients， the incidence rate was higher in males than in females， and more common among stage Ⅲ-Ⅳ patients than among stage I-Ⅱ patients. Out of the 41 patients treated with surgery + targeted drugs （gutemitinib， savolitinib）， 8 cases of recurrence or metastasis were found during follow-up. ConclusionMET gene mutations exhibit specific mutation characteristics in different tumor types， and its expression levels show significant differences between various tumor tissues and normal tissues. It is closely related to the poor prognosis of lung adenocarcinoma patients. We found that c-MET protein expression is closely related to the type of MET gene mutation， especially in patients with MET gene exon 14 skipping mutations， which presents a characteristic expression pattern. This provides an important basis for the preliminary screening using immunohistochemistry in clinical practice.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective To analyze the expression levels of miR-27a-3p mRNA and Yes-associated protein 1(YAP1)mRNA in breast cancer,and to explore their relationships with clinicopathological features and the survival prognosis of patients.Methods A total of 130 breast cancer patients who underwent mastectomy in our hospital between January 2019 and January 2021 were enrolled.The expression levels of miR-27a-3p and YAP1 mRNA in breast tumor tissues and adjacent normal breast tissues were assessed by qRT-PCR.Furthermore,the relationships between their expression and clinicopathological features,as well as the survival prognosis of patients,were investigated.Results Compared with adjacent normal breast tissues,the expression of miR-27a-3p mRNA in breast tumor tissues was lower(P＜0.05),while that of YAP1 mRNA was higher(P＜0.05).A negative correlation was observed between the expression of miR-27a-3p mRNA and YAP1 mRNA in breast tumor tissues(r=-0.456,P＜0.05).The expression of miR-27a-3p mRNA was correlated with tumor diameter,histological grade,tumor staging by the TNM system,lymph node metastasis,and vascular invasion in patients with breast cancer(P＜0.05).The YAP1 mRNA expression was correlated with histological grade,tumor staging by the TNM system,lymph node metastasis,and vascular invasion(P＜0.05).Kaplan-Meier survival analysis revealed that the 3-year overall survival rate of the miR-27a-3p low-expression group was 71.60％(48/67),which was lower than the 91.50％(54/59)of the miR-27a-3p high-expression group(log-rank x2=8.211,P=0.004).The 3-year overall survival rate of the YAP1 high-expression group was 73.80％(45/61),lower than that of the YAP1 low-expression group(87.70％,57/65)(log-rank x2=4.429,P=0.035).Multivariate regression analysis indicated that lymph node metastasis(hazard ratio[HR]=1.409;95％CI,1.057-1.644;P=0.046),vascular invasion(HR=1.541;95％CI,1.076-1.869;P=0.045),low miR-27a-3p mRNA expression(HR=0.593;95％CI,0.388-0.925;P=0.018),and high YAP1 mRNA expression(HR=0.628;95％CI,0.405-0.912;P=0.022)were relevant factors affecting the 3-year overall survival of patients with breast cancer.Conclusion A significant downregulation of miR-27a-3p mRNA and upregulation of YAP1 mRNA are observed in breast tumor tissues.The low expression of miR-27a-3p mRNA and the high expression of YAP1 mRNA are associated with adverse clinicopathological features and poor survival prognosis,and are risk factors affecting the 3-year overall survival of patients with breast cancer.They show promise as new potential therapeutic targets for breast cancer.

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

BACKGROUND:Ilizarov bone transport is very effective in the treatment of open large tibial bone defects,but there are still complications,among which the difficulty of junction healing is one of the difficult points in treatment. OBJECTIVE:To investigate the effect of Ilizarov bone transport combined with antibiotic bone cement on junction healing after operation of open large tibial bone defect. METHODS:Totally 51 patients with open large tibial bone defect(bone defect>4 cm)admitted to Binzhou Medical University Hospital from August 2010 to January 2022 were selected,of which 28 received Ilizarov bone transport alone(control group)and 23 received Ilizarov bone transport combined with antibiotic bone cement treatment(trial group).External fixation time,bone healing time,bone healing index,visual analog scale score during bone removal,bone defect limb function,junction healing and complications at the final follow-up were statistically compared between the two groups. RESULTS AND CONCLUSION:(1)All the 51 patients were followed up for a mean of(22.53±5.77)months.External fixation time,bone healing time,bone healing index,postoperative infection rate,and non-healing rate of junction were less in the trial group than those in the control group(P<0.05).There was no significant difference between the two groups in visual analog scale scores at 6 months after the second surgery and in the functional excellence and good rate of limb with bone defect at the final follow-up(P>0.05).(2)These findings indicate that compared with the Ilizarov bone transport alone,Ilizarov bone transport combined with antibiotic bone cement treatment can promote the healing of open tibial fracture junction and increase the rate of bone healing.

Objective:To investigate the clinical outcomes of arthroscopic suture anchor fixation for acute bony Bankart lesions.Methods:Data of 49 patients with acute bone Bankart injury treated with suture anchor fixation under arthroscopy at the Affiliate Nanjing Drum Tower Hospital of Nanjing University School of Medicine from February 2019 to July 2024 were retrospectively analyzed, including 34 males and 15 females, aged 46.4±17.7 years (range, 18-81 years). Body mass index was 26.3±4.2 kg/m 2 (range, 19.8-37.9 kg/m 2). There were 17 patients with left shoulder and 32 patients with right shoulder. The time from injury to operation was 12.6±10.5 d (range, 1-50 d). CT three-dimensional reconstruction showed that the area of bone defect accounted for 20.1%±11.4% (range, 8%-49%) of the glenoid area. According to the degree of bone defect, there were 38 cases in the bone defect area ≤25% group and 11 cases in the bone defect area >25% group. All 49 patients received shoulder arthroscopic fixation with wire anchor. All 49 the patients were treated under shoulder arthroscopy using suture anchor technique. Using American Shoulder & Elbow Surgeon (ASES) score, University of California, Los Angeles (UCLA) score, Rowe score as well as shoulder range of motion to evaluate shoulder function. The position and healing of the fracture mass were evaluated with shoulder joint CT and three-dimensional reconstruction at immediate and final follow-up. Results:The incision healed in one stage and no infection occurred in all patients. All 49 patients were followed up for a period of 3 to 81 months, with an average follow-up of 23.8±20.2 months. At the final follow-up, the mean forward elevation, external rotation, and internal rotation improved from 126.1°±20.3°, 36.9°±14.0°, and 10±2 preoperatively to 167.1°±15.5°, 66.8°±8.3°, and 6±1 at the last follow-up, respectively ( P<0.05). At the final follow-up, the mean ASES score, UCLA score, and Rowe score were all significantly improved from 41.3±11.9, 14.2±6.1 and 46.9±14.7 preoperatively to 89.7±7.8, 31.5±3.6 and 92.4±7.4, respectively ( P<0.05). The differences between the final follow-up and preoperative values for forward elevation in the bone defect area >25% group and the bone defect area ≤25% group were 43°±20° and 41°±21°, respectively. The differences in lateral external rotation were 34°±8° and 29°±18°, while the differences in internal rotation (measured by hand-behind-back reach) were 5±2 and 4±2, respectively. None of these differences were statistically significant. The differences between the final follow-up and preoperative scores in the bone defect area >25% fracture fragment group and the bone defect area ≤25% group were as follows: ASES score, 50.9±14.4 vs. 47.7±12.8; UCLA score, 18.4±3.2 vs. 17.0±6.9; and Rowe score, 40.5±13.5 vs. 46.9±15.0. None of these differences were statistically significant. CT examination at the last follow-up showed that all fractures were healed, all patients in the bone defect area ≤25% group achieved good reduction, and 3 patients in the bone defect area >25% group had step-offs on the glenoid surface. Postoperative shoulder adhesion occurred in 5 patients, which was improved after intensive abduction and external rotation exercise. Conclusions:Arthroscopic suture anchor fixation is effective for the bone defect area ≤25% bony Bankart lesions, offering advantages of minimal invasiveness and rapid recovery. For lesions involving more than the bone defect area 25% of the glenoid surface, enhanced fixation strength is recommended to prevent fracture fragment displacement.

Objective:To analyze the prevalence trends and epidemiological characteristics of cardiometabolic multimorbidity(CMM) in Beijing from 2005 to 2022.Methods:A series of representative cross-sectional surveys were conducted in Beijing between 2005 and 2022 using a stratified multistage cluster random sampling method. A total of 110 496 permanent residents aged 18-79 years participated in face-to-face interviews, physical examinations, and laboratory testing. Complex sampling logistic regression models were employed to identify factors associated with CMM, and Joinpoint regression was used to assess temporal trends in prevalence. Results:The prevalence of CMM was 22.3% in 2005 and 24.3% in 2022, with an average annual percent change of 0.1%(95% CI -1.3%-1.3%, P>0.05). In rural areas, the prevalence increased by 1.3% per year(95% CI 0.2%-2.6%, P<0.05), while among obese individuals, it decreased by 1.0% annually( P<0.05). The most common CMM patterns were hypertension combined with dyslipidemia(13.2%), hypertension combined with diabetes(7.0%), and diabetes combined with dyslipidemia(5.8%). The prevalence of hypertension and dyslipidemia comorbidity showed a long-term decline among females, those aged 60-79 and obese individuals( P<0.05). In contrast, the prevalence of hypertension and diabetes comorbidity increased over time in rural residents and individuals with normal body weight( P<0.05). Furthermore, diabetes and dyslipidemia comorbidity rates increased significantly among males, adults aged 18-59 years, those with a college education or above, rural residents and individuals with normal body weight( P<0.05). Multivariable logistic regression indicated that male, older age, overweight, obese, and lower education level were independently associated with a higher risk of CMM( P<0.05). Conclusion:From 2005 to 2022, the prevalence of CMM remained high among adults in Beijing. While prevalence decreased among obese individuals, it increased significantly in rural areas. Hypertension combined with dyslipidemia was the most common multimorbidity pattern throughout the study period.

Objective:To investigate the risk factors for kidney injury during anti-retroviral therapy (ART) with zidovudine (AZT) or tenofovir disoproxil fumarate (TDF) in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients, and to construct and validate a prediction model for the risk of kidney injury in HIV/AIDS patients based on a nomogram.Methods:A total of 923 HIV/AIDS patients admitted to Liuzhou People′s Hospital between January 1st, 2004 and December 31st, 2020 were included in this study. The modeling set (647 cases) and the validation set (276 cases) were divided in a 7∶3 ratio. Risk factors were screened using the least absolute shrinkage and selection operator (LASSO) regression analysis, and a nomogram prediction model for renal impairment risk in HIV/AIDS patients was constructed based on the selected variables. The model′s predictive performance was assessed by calculating the area under the curve (AUC) using the receiver operating characteristics curve (ROC curve). The performance of this model was evaluated using calibration curves. The clinical utility of the model was assessed using decision curve analysis (DCA).Results:Among 923 HIV/AIDS patients, there were 91 cases with kidney injury, including 67 in the modeling set and 24 in the validation set. AZT was used in 29 cases, and TDF was used in 62 cases. LASSO regression analysis was employed to screen seven non-zero variables, including age, ART regimen, baseline estimated glomerular filtration rate (eGFR), baseline CD4 + T lymphocyte count, baseline human immunodeficiency virus (HIV) RNA, baseline hemoglobin, and baseline aspartate aminotransferase (AST), their LASSO regression coefficient were 1.296, 0.250, 1.443, 0.240, 0.120, 0.395, and 0.002, respectively. Based on these variables, a visual nomogram model was constructed and subsequently validated. Through ROC curve analysis, the AUC for the modeling set was 0.826 (95% confidence interval ( CI) 0.767 to 0.884), with a sensitivity of 0.731 and a specificity of 0.809. For the validation set, the AUC was 0.872 (95% CI 0.807 to 0.956), with a sensitivity of 0.875 and a specificity of 0.778. The calibration curve results for the modeling set showed a mean absolute error (MAE) of 0.012 and a consistency index of 0.826, while the validation set had an MAE of 0.021 and a consistency index of 0.872. These results indicated that the model had a high goodness-of-fit, excellent calibration performance, and was reliable and stable. When the risk threshold for the modeling set ranged from 2% to 73%, the model demonstrated favorable net benefits, indicating its excellent clinical utility. Conclusion:The nomogram-based risk prediction model for kidney injury in HIV/AIDS patients is constructed using seven variables including age, ART regimen, baseline eGFR, baseline CD4 + T lymphocyte count, baseline HIV RNA, baseline hemoglobin, and baseline AST, which provides a valuable tool for early identification of individuals at risk of kidney injury and supports timely clinical interventions.

AIM To investigate the impact of varying dosages of Supplemented Wendan Decoction on the PI3K/Akt/FOXO1 glycolipid metabolic pathway in 3T3-L1 adipocytes.METHODS The CCK-8 assay was used to determine the concentration of Supplemented Wendan Decoction-medicated serum.The mature adipocytes differentiated from 3T3-L1 preadipocytes after induction were further divided into the blank control group,the model group,the rosiglitazone group(10 mg/L),and the Supplemented Wendan Decoction groups(5％,10％,and 20％),followed by the sample collections after 48 hours of treatment.Oil red O staining quantified lipid accumulation in 3T3-L1 adipocytes;extracellular glucose levels were measured using glucose oxidase(GOD)assay;RT-qPCR analyzed mRNA expressions of IRS-1,PI3K,Akt,GLUT4,IL-6,TNF-α and IL-1β;Western blot assessed protein expressions of INSR,IRS-1,PI3K-p85,Akt,FOXO1 and GLUT4.RESULTS No significant changes in cell viability(P＞0.05)were observed in 3T3-L1 preadipocytes exposed to serum containing supplemented Wendan Decoction at different concentrations for 24,48,or 72 hours.The 3T3-L1 preadipocytes held the capacity to differentiate into mature adipocytes within a 14-day induction period.Compared to the model group,all supplemented Wendan Decoction groups exhibited reduced lipid accumulation in adipocytes and downregulated mRNA expression of IRS-1,IL-6,TNF-α and IL-1β(P＜0.01);the low-dose group demonstrated increased mRNA expressions of PI3K and GLUT4(P＜0.05,P＜0.01),alongside elevated protein expressions of INSR,IRS-1,PI3K-p85,Akt and GLUT4(P＜0.05,P＜0.01);the medium-dose group showed enhanced GLUT4 mRNA expression,and upregulated protein expressions of INSR and FOXO1(P＜0.01).After 24 hours intervention,the high-dose Supplemented Wendan Decoction group exhibited increased glucose consumption in adipocytes(P＜0.01),and elevated protein expression of INSR,Akt and FOXO1(P＜0.05,P＜0.01).CONCLUSION Supplemented Wendan Decoction reduces lipid accumulation in adipocytes,regulates glucose and lipid metabolism,and promotes metabolic homeostasis through PI3K/Akt/FOXO1 signaling pathway.