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.

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.

In recent years,the Ross procedure has been increasingly applied in the treatment of aortic valve disease in children and young patients.However,right ventricular outflow tract(RVOT)reconstruction in this procedure often relies on allogeneic or artificial materials,which may lead to complications such as calcification and valve dysfunction.This article reports a case of protective Ross procedure using completely autologous tissue to construct a right ventricular-pulmonary artery(RV-PA)conduit.The patient was an 11-year-old male who presented with severe aortic stenosis combined with regurgitation.During the operation,his dilated ascending aortic wall and fresh pericardium were used to construct an autologous valved conduit for RV-PA reconstruction.This innovative technique achieves RV-PA reconstruction without allogeneic tissue,provides a new technical approach for the Ross procedure.Short-term results are satisfactory and the medium-and long-term outcomes require further follow-up verification.

Objective:To compare the efficacy of O-arm navigation-assisted and conventional posterior cervical expansive open-door laminoplasty (CEOL) via the intermuscular approach in the treatment of cervical spinal cord injury without fracture-dislocation (CSCIWFD).Methods:A prospective cohort study was conducted to analyze the clinical data of 60 CSCIWFD patients who were admitted to Zhengzhou Orthopedic Hospital from May 2021 to May 2023, with compression at C3-C6. Patients were randomly divided into two groups: 30 patients underwent O-arm navigation-assisted intermuscular approach CEOL (navigation-assisted group) and 30 patients underwent conventional intermuscular approach CEOL (conventional surgery group). Surgical duration, intraoperative blood loss, postoperative drainage volume, and total surgical blood loss were compared between the two groups. At 2 weeks postoperatively, CT scan was performed to evaluate the accuracy of hinge or open-door position preparation of the surgical segments. Visual analogue scale (VAS) for neck and shoulder pain and Japanese Orthopedic Association (JOA) scores were compared between the two groups preoperatively, at 2 weeks, 6 months postoperatively, and at the last follow-up. Complication rates were also evaluated.Results:A total of 60 patients with CSCIWFD were included, comprising 35 males and 25 females, aged 35-77 years [(50.9±8.6)years]. All the patients were followed up for 12-24 months [(16.9±3.1)months]. The surgical duration and intraoperative blood loss were (121.6±17.9)minutes and (144.7±44.2)ml in the navigation-assisted group, shorter or less than (132.3±14.6)minutes and (178.7±48.7)ml in the conventional surgery group ( P<0.05). There were no statistically significant differences in postoperative drainage volume and total surgical blood loss between the two groups ( P>0.05). CT scan reviewed at 2 weeks postoperatively revealed that the accuracy rate of hinge and open-door position preparation of the surgical segments in the navigation-assisted group was 99.2% (119/120), significantly higher than 86.7% (104/120) in the conventional surgery group ( P<0.01). Before operation and at 2 weeks, 6 months postoperatively, and at the last follow-up, the VAS scores for neck and shoulder pain and JOA scores in the navigation-assisted group were 5.0(4.0, 7.0)points and (8.7±2.8)points, 3.0(2.0, 4.0)points and (10.2±2.5)points, 2.0(1.0, 2.0)points and (1 3.0±1.8)points, and 1.0(1.0, 2.0)points and (13.9±1.5)points respectively, while in the conventional surgery group, the VAS scores and JOA scores were 5.5(5.0, 6.3)points and (8.8±2.6)points, 4.0(3.0, 4.0)points and (10.4±2.5)points, 2.0(1.0, 3.0)points and (12.9±2.2)points, and 2.0(1.0, 2.0)points and (13.8±2.0)points ( P>0.05). Both groups showed improvement in neck and shoulder VAS scores and JOA scores at 2 weeks, 6 months postoperatively, and at the last follow-up, compared to preoperative scores ( P<0.05); further improvement was observed at 6 months postoperatively and at the last follow-up compared to that at 2 weeks postoperatively ( P<0.05). There were no significant differences between neck and shoulder VAS scores or JOA scores at 6 months postoperatively and at the last follow-up ( P>0.05). In the navigation-assisted group, 2 patients had axial neck-shoulder pain postoperatively, with a complication rate of 7% (2/30); while in the conventional surgery group, 7 patients had axial neck-shoulder pain and one patient developed cerebrospinal fluid leakage and low-pressure headache, with a complication rate of 27% (8/30) ( P<0.05). Conclusion:Compared to the conventional intermuscular approach, O-arm navigation-assisted intermuscular approach CEOL for CSCIWFD reduces surgical duration and intraoperative blood loss, improves the accuracy of hinge and open-door position preparation, and lowers complication rates.

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.

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.

Persistent atrial fibrillation and other factors can cause mitral and tricuspid annular dilation and leaflet regurgitation,leading to severe functional mitral and tricuspid regurgitation.Patients often experience significant heart failure symptoms and poor prognosis.For patients with severe mitral or tricuspid regurgitation who are at high risk or contraindicated for surgical procedures,transbronchial repair(TEER)is an important alternative therapy that can effectively reduce valve regurgitation and improve cardiac function;Although there is a lack of large-scale data on atrial functional reflux,existing experience still shows that TEER can significantly reduce reflux and improve patients'quality of life.However,double valve intervention therapy poses challenges,especially when combined with TEER repair,which is technically more complex,time-consuming,and carries higher risks.Foreign data shows that simultaneous or staged double valve intervention can safely improve cardiac function and increase survival rates,but the optimal intervention strategy still needs further research.Due to the fact that tricuspid TEER devices have not yet been launched in China,only staged treatment can be adopted at present.This case report shows a patient with severe atrial functional mitral and tricuspid regurgitation who underwent staged transcatheter edge to edge repair surgery successfully.During a 1-year follow-up,bilateral valve regurgitation continued to improve,indicating that staged repair of bilateral atrioventricular valve regurgitation through the catheter margin is a feasible and effective treatment option.

Persistent atrial fibrillation and other factors can cause mitral and tricuspid annular dilation and leaflet regurgitation,leading to severe functional mitral and tricuspid regurgitation.Patients often experience significant heart failure symptoms and poor prognosis.For patients with severe mitral or tricuspid regurgitation who are at high risk or contraindicated for surgical procedures,transbronchial repair(TEER)is an important alternative therapy that can effectively reduce valve regurgitation and improve cardiac function;Although there is a lack of large-scale data on atrial functional reflux,existing experience still shows that TEER can significantly reduce reflux and improve patients'quality of life.However,double valve intervention therapy poses challenges,especially when combined with TEER repair,which is technically more complex,time-consuming,and carries higher risks.Foreign data shows that simultaneous or staged double valve intervention can safely improve cardiac function and increase survival rates,but the optimal intervention strategy still needs further research.Due to the fact that tricuspid TEER devices have not yet been launched in China,only staged treatment can be adopted at present.This case report shows a patient with severe atrial functional mitral and tricuspid regurgitation who underwent staged transcatheter edge to edge repair surgery successfully.During a 1-year follow-up,bilateral valve regurgitation continued to improve,indicating that staged repair of bilateral atrioventricular valve regurgitation through the catheter margin is a feasible and effective treatment option.

AIM:To study the mechanism of ac-tion of radix angelica sinensis and astragalus mong-holicus extract(RAS-AM)in inhibiting fibroblast transdifferentiation(CMT)and preventing radiation-induced myocardial fibrosis(RIMF)via the Jagged1/Notch1 pathway.METHODS:Sixty male Wistar rats were randomly divided into blank group,model group,benazepril hydrochloride group,low dose RAS-AM group,medium dose RAS-AM group,and high dose RAS-AM group,with 10 rats in each group.Except for the blank group,all other groups were induced with high-energy radiation at a dose of 38 Gy to establish RIMF models.The blank group and the model group received sterile distilled water by gavage,and the other groups received medica-tion for 4 weeks of intervention:benazepril hydro-chloride group(1.0 mg·kg-1·d-1),low dose RAS-AM group(150 mg·kg-1·d-1),medium dose RAS-AM group(300 mg·kg-1·d-1),and high dose RAS-AM group(600 mg·kg-1·d-1).The general condition of rats,the ultrastructure of myocardial tissue were observed using electron microscopy,changes in myocardial tissue fibers using Masson staining,and CMT related protein Vimentin and α-SMA expres-sion using immunohistochemical staining tech-niques.ELISA was used to detect serum inflammato-ry factors IL-6 and TNF-α in rats.The levels of cTnI and ST2,and the expression of Jagged1 and Notch1 were detected by Western blot.RESULTS:Com-pared with the blank group,the model group rats exhibited symptoms such as mental fatiguem an-orexiam and loose stools;The arrangement of some myofibrils in the myocardium is disordered,with dis-solution and breakage of myofibrilsm abnormal Z-line structure in some partsm disordered mitochon-drial arrangement,rupture of mitochondrial mem-branem,and rupture or disappearance of mitochon-drial ridge structure in some parts.A large amount of collagen fibers proliferate and deposit in the myo-cardium,and the fibrotic area significantly increases(P<0.01);The expression of myocardial tissue Vi-mentin α-SMA protein increased(P<0.05),while the expression of Jagged1 and Notch1 proteins de-creased(P<0.05);serum IL-6 and TNF-α,the expres-sion of inflammatory factors such as cTnI and ST2 in-creased(P<0.05).compared with the model group,the RAS-AM and benazepril hydrochloride groups showed varying degrees of improvement in general conditions;the pathological changes of myocardial ultrastructure have been improved,and myocardial fibrosis has been alleviated;The area of collagen fi-bers significantly decreased(P<0.01);Myocardial tis-sue Vimentin α-SMA protein expression decreased(P<0.05),while Jagged1 and Notch1 expression in-creased(P<0.05);Serum IL-6 and TNF-α,The expres-sion of inflammatory factors such as cTnI and ST2 decreased(P<0.05).CONCLUSION:RAS-AM may al-leviate RIMF by intervening in the Jagged1/Notch1 pathway to inhibit CMT.The specific mechanism still needs further investigation

Objective:To understand the usage situation of e-cigarettes among residents aged 18-65 in Beijing, explore the relationship between e-cigarette use and cigarette smoking as well as smoking cessation behaviors, and provide scientific support for the developing and improving policies and measures related to e-cigarettes.Methods:Using 19 684 residents data from the Beijing Non-communication Chronic Disease and Risk Factors Surveillance in 2022, complex sampling weighted methods were used to estimate proportions, and complex sampling logistic regression analysis was applied to explore the relationship between e-cigarette use, cigarette smoking, and smoking cessation.Results:Among all study participants, the proportion of those who had ever used e-cigarettes was 3.36%, with the current e-cigarette use at 1.26%. The proportion of current e-cigarette users (1.87%) and the former e-cigarette users (3.47%) were higher ( χ2=64.70, P<0.001) among males compared to females (0.60% and 0.64% respectively). The top three reasons for using e-cigarettes were wanting to quit smoking, perceiving e-cigarettes as less harmful, and enjoying the flavors of e-cigarettes. 83.54% of e-cigarette users started with cigarettes. The results of the complex sampling multivariable logistic regression analysis showed that current smoking ( OR=61.35, 95% CI: 36.98-101.76) and former smoking ( OR=31.20, 95% CI: 15.52-62.71) were positively associated with e-cigarette, while current e-cigarette use ( OR=0.13, 95% CI: 0.04-0.39) was negatively associated with quitting cigarette smoking. Conclusions:The proportion of e-cigarette use in Beijing was relatively low. E-cigarette use was associated with cigarette use and was not conducive to smoking cessation. Therefore, stronger regulatory measures and health education campaigns regarding the risks of e-cigarettes should be implemented.