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.

ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

Objective To analyze the infection status and epidemic trends of soil-borne nematode infections in Yubei, Chongqing City, in 2010,2021, and 2022. Methods The local populations from four survey sites of four towns in 2010 and five sites of five towns in 2021 and 2022 were surveyed regarding their basic information using a unified form. Fecal samples of the participants were collected and tested for soil-borne nematode infections using the modified Kato-Katz thick smear method. Results In 2010, 2 049 participants were surveyed, followed by 1 000 participants in 2021 and 2022. The overall prevalence of parasitic infections declined significantly from 3.86% to 0.20%. In 2010, soil-transmitted nematode included hookworms(3.81%) and roundworms(0.29%). In 2021, the infection rates of roundworms and hookworms were 1.70% and 0.10% respectively. Notably, only Ascaris was identified in 2022(0.20%). The≥60 age group consistently exhibited the highest infection rates across all surveys, followed by the 40-59 age group. The infection rates of males in the three surveys were 3.31%,1.92%, and 0.20% respectively, and those of females were 4.37%, 1.46%, and 0.20% respectively. There was no statistically significant difference in the infection rates between males and females. Educational attainment was inversely associated with infection; in 2010, the highest prevalence was observed among those with primary education or below, whereas in 2021, illiterate or semi-literate individuals showed the highest susceptibility. The occupational distribution of infections in 2010 indicated that retirees (8.33%), farmers(4.86%), and homemakers or unemployed individuals(3.45%)were the most affected. However, in 2021 and 2022, farmers emerged as the predominant occupational group with soil-transmitted nematode infections. Conclusions The infection rate of soil-borne nematodes showed a decreasing trend in Yubei, and the infection species changed from hookworms in 2010 to Ascaris in 2022. Farmers, the elderly, and people with low education levels should continue to be the focus of preventive and control efforts.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To explore the efficacy of"internet+"family doctor contract service model on controlling risk factors related to atherosclerotic cardiovascular disease(ASCVD)such as hypertension,dyslipidemia,and diabetes in young and middle-aged patients in the community.Methods A total of 231 young and middle-aged patients with ASCVD who were contracted and treated regularly in Shanghai Yangpu District Xinjiangwancheng Community Health Service Center from Jan to Dec 2020.According to the different intervention models,they were divided into the traditional group receiving the conventional family doctor contract service and the Internet group taking"internet+"family doctor contract service mode for intervention.The systolic blood pressure,diastolic blood pressure,fasting plasma glucose(FPG),low density lipoprotein(LDL-C),triglyceride(TG)and total cholesterol(TC)were compared within and between the two groups before intervention,three months after intervention,and one year after intervention,to evaluate the control effects of the two intervention modes.Results The 231 patients,of which 113 cases in traditional group and 118 cases in Internet group,were recruited in the study.there were no significant differences in gender,age and proportions of hypertension,diabetes and dyslipidemia between the two groups.Before intervention,there were no significant differences in systolic blood pressure,diastolic blood pressure,FPG,LDL-C,TG and TC between the two groups.Three months after intervention,the systolic blood pressure,diastolic blood pressure,FPG,LDL-C,TG and TC of the two groups were significantly lower than those before the intervention(all P<0.05),and the systolic blood pressure and diastolic blood pressure of the Internet group were significantly lower than those of the traditional group(all P<0.05),but there was no significant difference between the two groups in FPG,LDL-C,TG and TC.One year after the intervention,the systolic blood pressure,diastolic blood pressure,FPG,LDL-C,TG and TC of the patients in the two groups decreased significantly compared with those before intervention(all P<0.05),while the Internet group decreased more significantly(all P<0.05).Conclusion Compared with the traditional contract model,"internet+"family doctor contract service had better management effect on ASCVD-related risk factors in young and middle-aged patients in the community,and benefits the patients to a higher degree.

Liquid-liquid phase separation(LLPS)is the process where intracellular biomolecules rapidly form reversible high concentrations of liquid-phase condensates,resulting in the compartmentalization and the formation of intracellular membraneless organelles.LLPS is involved in various biological processes and pathologic processes,such as neurodegenerative diseases and cancers.Long noncoding RNAs(lncR-NAs)have been revealed to be closely related to phase separation.It has become a research hotspot in life science recently,because it provides new insight into the mechanism of lncRNAs.In this review,we focuses on the effect of lncRNA SLERT on the phase separation of nucleolar fibrillar center/dense fibrillar component(FC/DFC)by interacting with DDX21 protein as a molecular chaperone;LINC00657(NO-RAD)forms NP bodies with PUM proteins,which drives PUM protein liquid droplets and inhibits its ac-tivity,and promotes genomic stability;DilncRNA regulates DNA damage response small RNAs(DDR-NAs)and LLPS of p53 binding protein 1(53BP1)in response to DNA damage,and lncRNA LINP1 phase separation droplets bind to Ku protein to promote DNA damage repair;LncRNA SNHG9,MELTF-AS1 and MALR drive LATS1,YBX1 and ILF3 protein LLPS respectively to promote cancer,while GIR-GL and lncFASA act as tumor suppressor genes in cancer development through regulating the phase sepa-ration of CAPRIN1 and PRDX1 respectively;LncRNA XIST drives X chromosome inactivation by LLPS.In a word,we summarize the latest research progress about the functional roles of lncRNAs in FC/DFC nucleolus,genomic stability and DNA damage and repair,cancer and X-chromosome inactivation through regulating LLPS.This paper shows that lncRNAs can participate in multiple pathophysiological processes by regulating LLPS,which is expected to provide a new direction for the treatment of LLPS-mediated diseases.

AIM To investigate the clinical effects of Yifei Tongluo Decoction combined with azithromycin on patients with childern severe Mycoplasma pneumoniae pneumonia due to Toxic Heat Blocking Lung.METHODS One hundred and fifty-six patients were randomly assigned into control group(78 cases)for 7-day administration of azithromycin,and observation group(78 cases)for 7-day administration of both Yifei Tongluo Decoction and azithromycin.The changes in clinical effects,disappearance time of local symptoms,mycoplasmas,pulmonary imaging score,Toxic Heat Blocking Lung score,pulmonary function indices(PEF,VPTEF,MMF,TPTEF),inflammatory factors(sB7-H3,Cgp-39,sICAM-1,CCL5),immune function indices(RBC-C3bR,RBC-ICR,CD3+,CD4+)and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05),along with shorter disappearance time of local symptoms(P＜0.05).After the treatment,the two groups displayed decreased mycoplasmas,pulmonary imaging score,Toxic Heat Blocking Lung score,inflammatory factors,RBC-ICR(P＜0.05),and increased pulmonary function indices,RBC-C3bR,CD3+,CD4+(P＜0.05),especially for the observation group(P＜0.05).No obvious difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with childern severe Mycoplasma pneumoniae pneumonia due to Toxic Heat Blocking Lung,Yifei Tongluo Decoction combined with azithromycin can safely and effectively alleviate clinical symptoms,improve pulmonary functions,and reduce body inflammatory responses.

Liquid-liquid phase separation(LLPS)is the process where intracellular biomolecules rapidly form reversible high concentrations of liquid-phase condensates,resulting in the compartmentalization and the formation of intracellular membraneless organelles.LLPS is involved in various biological processes and pathologic processes,such as neurodegenerative diseases and cancers.Long noncoding RNAs(lncR-NAs)have been revealed to be closely related to phase separation.It has become a research hotspot in life science recently,because it provides new insight into the mechanism of lncRNAs.In this review,we focuses on the effect of lncRNA SLERT on the phase separation of nucleolar fibrillar center/dense fibrillar component(FC/DFC)by interacting with DDX21 protein as a molecular chaperone;LINC00657(NO-RAD)forms NP bodies with PUM proteins,which drives PUM protein liquid droplets and inhibits its ac-tivity,and promotes genomic stability;DilncRNA regulates DNA damage response small RNAs(DDR-NAs)and LLPS of p53 binding protein 1(53BP1)in response to DNA damage,and lncRNA LINP1 phase separation droplets bind to Ku protein to promote DNA damage repair;LncRNA SNHG9,MELTF-AS1 and MALR drive LATS1,YBX1 and ILF3 protein LLPS respectively to promote cancer,while GIR-GL and lncFASA act as tumor suppressor genes in cancer development through regulating the phase sepa-ration of CAPRIN1 and PRDX1 respectively;LncRNA XIST drives X chromosome inactivation by LLPS.In a word,we summarize the latest research progress about the functional roles of lncRNAs in FC/DFC nucleolus,genomic stability and DNA damage and repair,cancer and X-chromosome inactivation through regulating LLPS.This paper shows that lncRNAs can participate in multiple pathophysiological processes by regulating LLPS,which is expected to provide a new direction for the treatment of LLPS-mediated diseases.

Excessive fat accumulation,viral infections and sustained inflammatory responses caused by non-alcoholic and alcoholic factors can contribute to liver inflammation,fibrosis and carcinogenesis,promoting the development of chronic liver disease.Gaining an in-depth understanding of the etiologic factors and underlying mechanisms that lead to chronic liver disease can help identify potential therapeutic targets for targeted therapy.Lactate,as an important substance in hepatic metabolism,has been found to be involved in the process of chronic liver disease through various pathways,and this review will provide a useful reference for the prevention and treatment of chronic liver disease.

With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.