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.

Objective To explore the characteristics and correlation between perivascular spaces (PVS) and diffusion tensor image analysis along perivascular spaces (DTI-ALPS) index in patients with amnestic mild cognitive impairment (aMCI). Methods A retrospective study was conducted on a total of 118 participants, including cognitive normal (CN) healthy controls and aMCI patients, recruited from the Department of Neurology, Zhongshan Hospital, Fudan University from September 2020 to September 2022. All participants underwent structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). An automatic segmentation algorithm was used to quantify PVS metrics in the brain, and DTI-ALPS index was calculated based on DTI. Differences in DTI-ALPS index and PVS metrics between the CN and aMCI groups were compared. Multivariate logistic regression was used to identify independent factors influencing aMCI. Correlation analysis was performed to assess relationships among DTI-ALPS index, PVS metrics, and cognitive scores. Results A total of 80 CN healthy controls and 38 aMCI patients were included. The DTI-ALPS index was significantly lower in the aMCI group compared with the CN group (1.28±0.18 vs 1.37±0.21, P＝0.018), while differences in PVS metrics between groups were not statistically significant. Multivariate logistic regression analysis indicated that DTI-ALPS index was an independent factor affecting aMCI (OR＝0.097, 95%CI 0.011–0.833, P＝0.033). Correlation analysis revealed a positive relationship between DTI-ALPS index and MMSE score (r＝0.210, P＝0.023) as well as PVS length in the centrum semiovale (r＝0.216, P＝0.019). Conclusions The DTI-ALPS index may serve as an imaging biomarker for identifying early cognitive impairment, and patients with aMCI exhibit abnormal DTI-ALPS indices, suggesting that brain glymphatic system dysfunction may occur prior to morphological changes.

OBJECTIVE To evaluate the cost-effectiveness of onradivir versus oseltamivir in the treatment of influenza A in adults from the perspective of the Chinese healthcare system. METHODS Based on data from a phase Ⅲ clinical trial （NCT04683406）， a decision tree model was constructed to simulate the efficacy and cost of using onradivir versus oseltamivir in treating adult patients with influenza A， with a cycle length of 5 days and a simulation period of 29 days. The two drug prices correspond to the median listing prices published by Yaozhi Network and the national negotiated prices. Patient characteristics and influenza utility values were derived from the phase Ⅲ clinical trial of onradivir， and medical costs and complication utility values were sourced from published literature. Quality-adjusted life year（QALY） was used as an effect indicator， and the incremental cost-effectiveness ratio（ICER） of onradivir versus oseltamivir was calculated， using China’s per capita disposable income in 2025 （43 377 yuan） as the willingness-to-pay （WTP） threshold to evaluate the cost-effectiveness of the results. One-way and probabilistic analyses were performed to verify the robustness of the results. RESULTS Compared with the oseltamivir regimen， the onradivir regimen yielded an incremental 0.000 67 QALY with direct medical cost savings of 12.41 yuan， thus being a dominant strategy. One-way sensitivity analysis showed that the utility values on day 15 of oseltamivir treatment， the incidence of influenza pneumonia in the oseltamivir group and the costs of the two drugs significantly affected the results. Probabilistic sensitivity analysis indicated that at the pre-specified WTP threshold， onradivir had a 70.6% probability of being cost-effective. CONCLUSIONS At a WTP threshold set at the 2025 per capita disposable income of China， compared with oseltamivir， onradivir can improve the health outcomes of adult patients with influenza A and reduce costs， demonstrating greater cost-effectiveness.

OBJECTIVE To evaluate the cost-effectiveness of anlotinib combined with penpulimab versus sorafenib as first- line treatment for unresectable hepatocellular carcinoma （uHCC） from the perspective of China’s healthcare system. METHODS Based on data from the APOLLO study， a partitioned survival model was established with a 21-day model cycle to simulate patient survival status over 10 years under anlotinib combined with penpulimab regimen or sorafenib monotherapy. Quality-adjusted life year （QALY） was used as the core evaluation parameter to assess the incremental cost-effectiveness ratio （ICER） of different treatment regimens. Using 3 times China’s per capita gross domestic product （GDP） in 2024 （287 247 yuan/QALY） as the willingness-to-pay （WTP） threshold， cost-utility analysis was performed to evaluate the cost-effectiveness of the treatment regimens. Sensitivity analysis was conducted to validate the robustness of the baseline analysis conclusion. Scenario analysis was performed to consider the impact of anlotinib and penpulimab assistance programs on the results； the price reduction of penpulimab to ensure the cost-effectiveness of the combination regimen was examined under varying WTP thresholds （specifically， 1， 2， and 3 times China’s per capita GDP in 2024）. RESULTS The baseline analysis revealed that the ICER of anlotinib combined with penpulimab regimen relative to the sorafenib regimen was 338 611.20 yuan/QALY， which exceeded the WTP threshold set in this study. Univariate sensitivity analysis indicated that the utility value of progression free survival and penpulimab price significantly influenced the baseline analysis results. Probabilistic sensitivity analysis validated the robustness of the baseline results. The results of scenario analysis indicated that when considering the assistance programs for anlotinib and penpulimab， the obtained ICER values were all below the WTP threshold set at 3 times China’s per capita GDP in 2024. When the price of penpulimab was reduced by 58%， 35%， and 13%， the ICER values were below the WTP threshold， which was 1， 2 and 3 times the per capita GDP of China in 2024， respectively. CONCLUSIONS From the perspective of China’s healthcare system， anlotinib combined with penpulimab regimen for first-line treatment of uHCC lacks cost-effectiveness compared to sorafenib regimen. However， this conclusion would be reversed if the anlotinib and penpulimab assistance programs are taken into account or if the price of penpulimab is reduced by more than 13% and above.

OBJECTIVE To evaluate the cost-effectiveness of amivantamab combined with lazertinib （hereinafter referred to as “AL”） regimen as first-line treatment for EGFR -mutated advanced non-small cell lung cancer （NSCLC） from the perspective of China’s healthcare system. METHODS A partitioned survival model was established based on updated data from the MARIPOSA study， with a 10-year time horizon and 28-day cycles. The primary outcome index was quality adjusted life year （QALY）， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024 （287 247 yuan/QALY）. Cost-utility analysis was used to calculate the incremental cost-effectiveness ratio （ICER） of AL regimen versus osimertinib monotherapy regimen as first-line treatment for EGFR -mutated advanced NSCLC. One-way and probabilistic sensitivity analyses were performed to test model robustness. Scena rio analyses were conducted to explore the impact of utility values for different health states on the outcomes and determine the required price reductions of amivantamab and lazertinib to achieve cost-effectiveness. RESULTS Compared with the osimertinib monotherapy regimen， the ICER for the AL regimen as first-line treatment for advanced EGFR -mutated NSCLC was 2 062 096.15 yuan/QALY， significantly exceeding the WTP threshold established in this study. One-way sensitivity analysis revealed that the utility value of progression-free survival state and the price of amivantamab were the primary factors influencing the ICER. Probabilistic sensitivity analysis revealed that the AL regimen only became cost-effective when the WTP threshold was set at 2 050 000 yuan/QALY. Scenario analysis indicated that altering the utility value still rendered the AL regimen non-cost-effective. When amivantamab （350 mg） prices decreased by 80%， 85%， and 90% respectively， lazertinib （80 mg） prices would need to decrease by 95.97%， 40.63%， 5.29%， respectively. This would enable the AL regimen’s ICER to consistently fall within the WTP threshold established in this study. CONCLUSIONS At the WTP threshold established in this study， the AL regimen does not demonstrate cost-effectiveness for first-line treatment of advanced EGFR -mutated NSCLC compared to the osimertinib monotherapy regimen. Significant price reductions for both drugs would be required to alleviate the financial burden on patients.

OBJECTIVE To evaluate the cost-effectiveness of culmerciclib combined with fulvestrant as second-line treatment for patients with hormone receptor-positive（HR+）/human epidermal growth factor receptor 2-negative （HER2–） locally advanced or metastatic breast cancer， within the context of the Chinese healthcare system. METHODS A partitioned survival model was established based on the CULMATE-1 study， with a simulation time horizon set at 15 years and a cycle length of 28 days. The incremental cost-effectiveness ratio （ICER） of culmerciclib combined with fulvestrant versus fulvestrant monotherapy as second-line treatment for HR+/HER2– breast cancer was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Meanwhile， scenario analysis of culmerciclib price reduction was conducted； the required price reduction and price to reach the willingness-to-pay （WTP） threshold in this study were calculated. RESULTS The results of the base-case analysis indicated that， compared with the fulvestrant monotherapy regimen， culmerciclib combined with fulvestrant yielded an additional 0.823 quality-adjusted life year （QALY）， with a corresponding ICER of 371 696.26 yuan/QALY， which exceeded the WTP threshold （199 330 yuan/QALY）. The results of the univariate sensitivity analysis indicated that the cost of culmerciclib， the discount rate， the utility values for progression disease and progression free survival status were significant factors influencing the ICER； both the univariate sensitivity analysis and the probabilistic sensitivity analysis validated the robustness of the model results. Scenario analysis indicated that when the price of culmerciclib was reduced by 30%， 55% and 85% respectively， the corresponding ICER values fell below 3， 2， and 1 times China’s per capita GDP in 2025， with the probability of cost-effectiveness being 3.00%， 94.90%， 100%. When the cost of culmerciclib （60 mg） was reduced by 52.6% to 50.96 yuan， the ICER value met the WTP threshold established in this study. CONCLUSIONS When the WTP threshold is set at twice China’s per capita GDP in 2025， second-line treatment with culmerciclib combined with fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer does not exhibit cost-effectiveness advantage over fulvestrant monotherapy. Therefore， a reasonable price reduction is required to alleviate the financial burden on patients.

OBJECTIVE To evaluate the cost-utility of benmelstobart combined with anlotinib and chemotherapy as first-line treatment for extensive-stage small cell lung cancer （ES-SCLC） from the perspective of China’s healthcare system. METHODS Based on the data from the ETER 701 study， a partitioned survival model was constructed with a cycle of 3 weeks to simulate the total cost， quality-adjusted life years （QALY）， and incremental cost-effectiveness ratio （ICER） over 10 years for patients with ES- SCLC treated with benmelstobart plus anlotinib and chemotherapy， or chemotherapy alone. One-way sensitivity analysis and probability sensitivity analysis were performed to verify the robustness of the simulation results. The willingness-to-pay （WTP） threshold was set at 3 times the per capita gross domestic product （GDP） of China in 2023， which amounted to 268 074 yuan/QALY. RESULTS Compared with chemotherapy alone， benmelstobart combined with anlotinib and chemotherapy gained 0.438 QALY more at the cost of 403 505.55 yuan more， with an ICER of 922 031.37 yuan/QALY， which was higher than the WTP threshold set in this study. One-way sensitivity analysis showed that benmelstobart’s cost and utility value of the progression-free survival state had a greater impact on the ICER value； probabilistic sensitivity analysis confirmed the robustness of the model； only when the price of benmelstobart was reduced by 75.4%， the combined regimen would be cost-effective. CONCLUSIONS The first-line treatment of ES-SCLC with benmelstobart combined with anlotinib and chemotherapy is not cost-effective from the perspective of China’s healthcare system at present.

Objective To construct the animal model,and to study the expression and clinical signifi-cance of YKL-40 in the progress of chronic renal failure complicating cardiac dysfunction.Methods C57BL/6N mice were chosen as the experimental subjects and divided into the blank control(BC)group,renal failure(RF)group,heart failure(HF)group and renal combined heart failure group.The renal failure model was constructed by adenine perfusion.The heart failure model was constructed by subcutaneous injection of isopro-terenol.The renal failure and heart failure group model was established by adenine perfusion combined with subcutaneous injection of isoproterenol.The validity of constructed models was evaluated by creatinine(SCr),urea nitrogen(BUN)and BNP levels,renal ultrasound and ultrasonic cardiogram examination results.The levels of C-reactive protein(CRP)and YKL-40 were detected by ELISA,and the YKL-40 mRNA expression level in kidney and heart tissues was measure by RT-qPCR.The Image J software was used to calculate the collagen fiber area of the Masson staining results.Results Except the blank control group,the mice weights in the other 3 groups were decreased,and the differences were statistically significant(P＜0.05).SCr,BUN,average renal cross sectional area,average renal volume and renal CVF in the renal failure group and renal combined heart failure group were higher than those in the blank control group and heart failure group(P＜0.05).The levels of LVEF,LVCO,LVSV,LVFS,LVPWd and LVPWs in the heart failure group and renal combined heart failure group were lower than those in the blank control group and renal failure group(P＜0.05).LVEF and LVFS in the renal combined heart failure group were higher than those in the heart failure group(P＜0.05).Compared with the blank control group,the serum CRP and YKL-40 levels in the other three groups were higher(P＜0.05);the CRP and YKL-40 levels in the renal combined heart failure group were higher than those in the renal failure group and heart failure group(P＜0.05).In the myocardial tis-sues,the YKL-40 mRNA expression level in the heart failure group and renal combined heart failure group was higher than those in the blank control group and renal failure group(P＜0.05).YKL-40 had the correla-tion with CRP(r=0.88,P＜0.05).Serum YKL-40 had the correlation with renal tissue YKL-40 gene expres-sion(r=0.77,P＜0.05),and had the correlation with the renal tissue CVF(r=0.89,P＜0.05).Conclusion YKL-40 has the influencing effect on renal failure complicating heart dysfunction,and could serve as the biomarker to mo-nitor the renal insufficiency complicating heart function abnormality.

Objective:To explore the emotion regulation effects in trait-anxious college students under differ-ent working memory loads.Methods:A total of 40 undergraduates with elevated trait anxiety(STAI-T＞40)com-pleted a 2(working memory load:high vs.low)× 3(emotion regulation phase:neutral,engagement,regulation)within-subjects design experiment.Dependent variables included emotional valence ratings and emotion regulation efficacy scores.The protocol consisted of three phases,namely free viewing of neutral images during the neutral phase,viewing negative images without regulation during the engagement phase,and implementing cognitive reap-praisal strategies for negative images during the regulation phase.Working memory tasks(n-back paradigm)were administered concurrently across all phases.Results:Emotional valence ratings during the engagement phase were lower than those during the neutral phase(P＜0.001),emotional valence ratings during the regulation phase were higher than those during the engagement phase(P＜0.01).Emotion regulation effect scores under high working memory load were higher than those under low load(P＜0.05).Conclusion:Higher working memory load may enhance the efficacy of cognitive reappraisal in trait-anxious individuals.

OBJECTIVE To observe the clinical efficacy of Yijinjing in the treatment of elderly sarcopenia and its effect on chro-nic inflammatory response in patients,and to explore the Yijinjing exercise prescription suitable for elderly patients with sarcopenia.METHODS A total of 120 elderly patients with sarcopenia admitted to the Department of Rehabilitation Medicine,Suzhou Hospital of Traditional Chinese Medicine from September 2022 to September 2024 were selected and randomly divided into a control group and a Yijinjing group,with 60 cases in each group.The control group received health education and dietary guidance,and the Yijinjing group received Yijinjing exercises on the basis of the intervention of the control group.The changes in skeletal muscle mass,upper and lower limb muscle strength,muscle thickness,muscle cross-sectional area,physical fitness and chronic inflammation level were observed in the two groups before and after the intervention.RESULTS After intervention,the skeletal muscle mass,grip strength,30 s sit-stand test times,rectus femoris thickness and cross-sectional area,vastus intermedius thickness,and physical fit-ness assessment of the patients in the Yijinjing group were significantly increased compared with those before treatment(P<0.05),and the indicators after intervention were higher than those in the control group(P<0.05);the serum TNF-α and IL-18 levels in the Yi-jinjing group were significantly decreased compared with those before treatment(P<0.05),and the indicators after intervention were lower than those in the control group(P<0.05);there was no statistically significant change in the biceps brachii thickness and serum IL-6 level in the Yijinjing group compared with those before treatment(P>0.05);there was no significant correlation between the bi-ceps brachii thickness and grip strength after Yijinjing intervention,r=0.139 8,P>0.05;there was a significant negative correlation between the TNF-α level and grip strength after Yijinjing intervention,r=-0.313 8,P<0.05.CONCLUSION Yijinjing exercises can improve muscle mass and strength in elderly patients with sarcopenia,and improve the physical fitness of patients,which may be related to improving the chronic inflammatory state of the body.