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.

Objectives:To investigate the clinical value of cardiac magnetic resonance imaging(CMR)feature-tracking strain analysis in risk stratification of diabetic heart failure with preserved ejection fraction(HFpEF).Methods:In this retrospective study,a total of 215 patients with diabetic HFpEF who underwent CMR at Chinese Academy of Medical Sciences Fuwai Hospital from January 2012 to December 2018 were included.Myocardial strain parameters were calculated using CMR feature-tracking technology.Patients were followed up by medical records or telephone calls.Composite endpoint event,all-cause death or heart failure hospitalization during follow-up were recorded.Patients were divided into event group and event-free group.Univariable and multivariable Cox proportional hazard regression analyses were performed to determine the risk factors for the outcomes in diabetic HFpEF.The effects of hypertension and obesity on the prognosis of diabetic HFpEF patients and whether they affect the prognostic value of CMR feature-tracking strain analysis were also analyzed.Results:During a follow-up of(7.1±1.8)years,93(43.3%)patients had endpoint events(event group),including 28 all-cause deaths and 65 heart failure hospitalization.Compared with the event-free group(n=122),patients in the event group had significantly lower left ventricular ejection fraction,higher prevalence and extent of late gadolinium enhancement,and significantly reduced global longitudinal strain(GLS),global circumferential strain,global radial strain,and global systolic longitudinal strain rate(all P<0.05).The absolute GLS value was significantly lower in event group than in event-free group,regardless of the presence of hypertension and obesity.Multivariate Cox regression analysis showed that estimated glomerular filtration rate(HR=0.983,95%CI:0.972-0.993,P=0.001),left atrial volume index(HR=1.015,95%CI:1.005-1.026,P=0.004),and GLS(HR=1.142,95%CI:1.060-1.231,P<0.001)were independent risk factors for adverse cardiovascular events in diabetic HFpEF patients.However,adjusted N-terminal pro-brain natriuretic peptide was not an independent prognostic factor.The cut-offvalue of GLS to predict outcome was-14.09%from ROC curve analysis.The Kaplan-Meier curve showed that in patients with and without hypertension and obesity,patients with the GLS>-14.09%had lower event-free survival compared to patients with GLS≤-14.09%(all P<0.05),and the ability of GLS to predict adverse outcomes was not affected by hypertension and obesity.Conclusions:GLS obtained by CMR feature-tracking strain analysis is an independent predictor of adverse outcomes in diabetic HFpEF,and its ability to predict adverse outcomes is independent of hypertension and obesity.

Objective:To explore the characteristics of nutrition self-management of home-based elderly chronic obstructive pulmonary disease (COPD) patients based on user persona, in order to provide reference for accurate home nutrition management.Methods:From July to December 2023, home-based elderly COPD patients in the Department of Respiratory and Critical Care Medicine of General Hospital of Ningxia Medical University were selected by convenience sampling method. The Mini Nutritional Assessment, COPD Assessment Test, Modified Medical Research Council Dyspnea Scale, Physical Activity Rating Scale-3, COPD Patients Self-Management Scale were used to conduct questionnaire survey. The SPSS 26.0 software was used to analyze the influencing factors of patients′ self-management of nutrition. Attributes with statistical significance ( P<0.05) were extracted as labels, and the visualization of patients′ self-management of nutrition portraits was completed in the form of pictures combined with labels. Results:A total of 320 questionnaires were distributed, and 309 valid questionnaires were collected. Among 309 home-based elderly COPD patients, there were 210 males and 99 females with an age of (69.14 ± 6.84) years old. According to the data analysis results, three dimensions of natural attributes, social attributes, and behavioral tracks were artificially extracted to construct three types of nutritional self-management user persona for home-based elderly COPD patients, respectively namely blind management type, independent attempt type, and powerless type.Conclusions:There are great differences in the nutritional status and self-management of home-based elderly patients with COPD. Accurate management measures can be developed based on user persona analysis to improve their nutritional status.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

Objective:To conduct a systematic review of risk prediction models for enteral feeding intolerance in ICU patients.Methods:Relevant literature was searched in China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, VIP, PubMed, Web of Science, Cochrane Library, Embase, CINAHL, and Scopus, with search limits from the establishment of the databases up to July 24, 2024. Two researchers independently screened the literature and extracted data, using Prediction model Risk Of Bias ASsessment Tool to evaluate the quality of the included studies.Results:A total of 12 studies were included, which included 20 prediction models. The area under the receiver operating characteristic curve or C-index for these models ranged from 0.70 to 0.94. The overall bias risk of the 12 studies was high, with three studies having good applicability. The bias risk primarily stemmed from issues such as measurement of prediction factors, variable handling, sample size, outcome definition, and model performance evaluation.Conclusions:Existing risk prediction models for enteral feeding intolerance in ICU patients exhibit a high risk of bias. Further validation, optimization, or development of new models is required in the future.

Objective:To explore the current status of quality of life of rheumatoid arthritis (RA) patients and its influencing factors based on the health ecology model (HEM) , and to provide a scientific basis for the development of health education programs for RA patients.Methods:From November 2023 to April 2024, 230 RA patients in the Department of Rheumatology and Immunology, General Hospital of Ningxia Medical University, were selected for the study using convenience sampling method. Patients were surveyed using the General Information Questionnaire, Quality of Life Instruments for Chronic Diseases in RA (QLICD-RA) , Health Literacy Management Scale, Social Support Rate Scale, Brief Illness Perception Questionnaire, 8-item Morisky Medication Adherence Scale, Pain Catastrophizing Scale, Chronic Disease Self-Management Study Measures, Fear of Progression Questionnaire-Short Form, Tampa Scale for Kinesiophobia and Visual Analogue Scale. Pearson and Spearman correlation was used to analyze the correlation between quality of life and health literacy, social support, disease perception, self-management behaviors, fear of disease progression, fear of exercise, medication adherence, pain catastrophizing, and pain in RA patients. Multiple linear regression was used to analyze the factors influencing the quality of life of RA patients.Results:A total of 230 questionnaires were distributed and 228 valid questionnaires were recovered, with a valid recovery rate of 99.13% (228/230) . The total QLICD-RA score of 228 RA patients was (137.53±27.57) . Duration of disease, disease perception, pain, pain catastrophizing, self-management behavior, joint deformity, morning stiffness duration, gastrointestinal response, sleep, social support, and main economic sources were the factors influencing the quality of life of RA patients ( P<0.05) , explaining 83.6% of the total variance. Conclusions:The quality of life of RA patients is moderate, and its influencing factors are distributed at all levels of HEM. Healthcare professionals can optimize the health education program for the main influencing factors of each layer, focusing on guiding patients to correctly understand the disease, stimulating the subjective initiative of patients, enhancing the ability of patients to actively manage the disease, and improving the quality of life of patients.

Objective To develop an animal model that replicates the clinical phenotype of severe asthma.Methods Ovalbumin(OVA)combined with IL-33 or varying doses of lipopolysaccharides(LPS)was used to explore the construction of a severe asthma mouse model.Established model animals were assessed for lung function,number of inflammatory cells,and lung tissue pathology were assessed.Expression of key genes associated with severe asthma identified from the GEO database were validated in the new model.Results Compared with OVA alone,OVA combined with IL-33 or 5 μg LPS significantly increased airway resistance and the number of inflammatory cells in bronchoalveolar lavage fluid,and aggravated the pathological damage to lung tissues.The expression patterns of key genes in the newly constructed severe asthma models were consistent with those observed in clinical patients with severe asthma.Conclusions The modeling method of combining OVA with IL-33 or LPS(5 μg)can be used to construct experimentalanimal models of severe asthma.

Objective To develop an animal model that replicates the clinical phenotype of severe asthma.Methods Ovalbumin(OVA)combined with IL-33 or varying doses of lipopolysaccharides(LPS)was used to explore the construction of a severe asthma mouse model.Established model animals were assessed for lung function,number of inflammatory cells,and lung tissue pathology were assessed.Expression of key genes associated with severe asthma identified from the GEO database were validated in the new model.Results Compared with OVA alone,OVA combined with IL-33 or 5 μg LPS significantly increased airway resistance and the number of inflammatory cells in bronchoalveolar lavage fluid,and aggravated the pathological damage to lung tissues.The expression patterns of key genes in the newly constructed severe asthma models were consistent with those observed in clinical patients with severe asthma.Conclusions The modeling method of combining OVA with IL-33 or LPS(5 μg)can be used to construct experimentalanimal models of severe asthma.

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*