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 investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective To investigate the correlation of corneal α angle and κ angle with lens tilt in normal human eyes using a new swept-source optical biometer.Methods A cross-sectional study was conducted,involving 303 healthy eyes(148 right eyes and 155 left eyes)of patients who visited the First Affiliated Hospital of Kunming Medical University from June to August 2024.ZW-30 swept-source optical biometer was used to collect the lens tilt angle,κ angle(distance from the corneal light reflex to the pupil center),and α angle(distance from corneal light reflex to the corneal geometric center,which is the midpoint of the horizontal white to white(WTW)diameter).The degrees(°)and directions of κ angle and α angle were calculated by the ratio of the above measurements to the anterior chamber depth(ACD)respectively.Spearman correlation analysis and linear regression analysis were employed to evaluate the correlations between the magnitude and direction of corneal α angle,κ angle and lens tilt angle.Results The magnitude and direction of corneal α angle,κ angle,and lens tilt angle in the right eye were as follows respectively:(0.54±0.19)mm(7.81°±3.88°),194.43°±39.75°;(0.27±0.23)mm(4.72°±3.90°),181.07°±79.59°;5.52°±1.67°,188.21°±25.73°.For the left eye,the corresponding values were:(0.47±0.27)mm(8.12°±5.26°),336.04°±46.64°;(0.26±0.27)mm(4.45°±4.80°),322.86°±107.79°;5.50°±1.61°,340.65°±32.84°.Spearman's correlation analysis showed that the correlation coefficients between corneal α angle and lens tilt angle in the right eye were 0.609(distance correlation)and 0.625(angle correlation),while those for κ angle were 0.559(distance correlation)and 0.578(angle correlation).In the left eye,the correlation coefficients between corneal α angle and lens tilt angle were 0.545(distance correlation)and 0.552(angle correlation),and those for κ angle were 0.377(distance correlation)and 0.395(angle correlation).In addition,the correlation coefficient between the direction of corneal α angle and the direction of lens tilt angle in the right eye was 0.343,and that for κ angle direction was 0.284;in the left eye,the correlation coefficients were 0.216(α angle direction)and 0.198(κ angle direction),all with statistical significance(P<0.05).Univariate linear regression analysis showed that lens tilt was positively correlated with both corneal α angle and Kappa angle(P<0.05).Conclusions Corneal α angle and κ angle are highly correlated with lens tilt angle in both eyes,and the correlation of corneal α angle is stronger than that of κ angle in both left and right eyes.The correlation expressed by degree(°)is better than that by distance(mm).It is recommended to refer to the corneal α angle and κ angle expressed in degrees during preoperative evaluation.

Objective To investigate the causal relationship between gut microbiota and viral pneumonia,as well as the underlying mechanisms,using two-sample and two-step Mendelian randomization(MR)approaches,thereby providing novel insights for the prevention and treatment of viral pneumonia.Methods All data were obtained from publicly available genome-wide association studies(GWAS)pooled datasets,including gut microbiota data from the MiBioGen Consortium and the Netherlands Microbiome Project,viral pneumonia data from the FinnGen R10 database,and plasma metabolome data from the publicly available GWAS Catalog.Instrumental variables(IVs)were extracted according to the predefined threshold values.MR analyses were conducted using inverse variance weighting(IVW),MR-Egger,weighted median(WME),weighted mode(WM),and Bayesian-weighted Mendelian randomization(BWMR)methods.Reverse MR analysis was performed to determine whether there was a reverse association.Two-step MR analysis was used to explore the potential mediating role of plasma metabolites,and a series of sensitivity analyses were performed to test the stability of the results.Results Among 196 gut microbiota taxa from the MiBioGen consortium GWAS,11 taxa were associated with viral pneumonia.An increase in the abundance of 4 taxa increased the risk of viral pneumonia,while an increase in the abundance of 7 taxa had a protective effect against viral pneumonia.Among the 207 gut microbiota taxa from the Dutch Microbiome Project GWAS data,10 taxa were associated with viral pneumonia,with 6 risk-increasing and 4 protective taxa identified.Mediation analysis results showed that the causal effect of Defluviitaleaceae on viral pneumonia(OR=0.708,95%CI 0.540-0.929,P=0.013)was mediated to some extent by the N6-acetyllysine levels,with a mediation ratio of 18.4%.Sensitivity analyses did not reveal significant heterogeneity or horizontal pleiotropy.Conclusions Specific gut microbiota are causally associated with viral pneumonia and show potential differences across different populations;the protective effect of Defluviitaleaceae against viral pneumonia may be mediated by the N6-acetyllysine levels.Targeting metabolites may become a potential therapeutic approach for viral pneumonia.

Objective To observe the clinical effect of Zuogui Pill combined with western medi-cine in treatment of gestational diabetes mellitus(GDM)with qi and yin deficiency syndrome.Meth-ods A total of 92 GDM patients with qi and yin deficiency syndrome from the Second Affiliated Hos-pital of Guizhou University of Traditional Chinese Medicine between January 2022 and October 2023 were enrolled and randomly divided into study group and control group,with 46 patients in each group.The control group received western medicine treatment,while the study group received Zuogui Pill combined with western medicine treatment.Both groups were treated for 4 weeks.The treatment effects,as well as the levels of glycolipid indicators[total cholesterol(TC),triglyceride(TG),fast-ing plasma glucose(FPG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and glycated hemoglobin(HbA1c)],insulin resistance indicators[fasting in-sulin(FINS),homeostasis model assessment of β-cell function(HOMA-β),and homeostasis model assessment of insulin resistance(HOMA-IR)],inflammatory and stress factors[serum amyloid A(SAA),interleukin-6(IL-6),malondialdehyde(MDA),and reactive oxygen species(ROS)],serum microRNA(miR)-21 and miR-149 levels,and occurrence of adverse pregnancy outcomes were compared be-tween the two groups before and after treatment.Results After 4 weeks of treatment,the total ef-fective rate was higher in the study group than that in the control group(P＜0.05).After treat-ment,the levels of FPG,HbA1c,TC,LDL-C,and TG were lower,and the levels of HDL-C were higher in both groups than before treatment,and the levels of FPG,HbA1c,TC,LDL-C in the study group were lower than those in the control group,and the level of HDL-C was higher in the study group than that in the control group(P＜0.05).After treatment,the levels of FINS and HOMA-IR were lower in both groups than before treatment,and their levels in the study group were lower than those in the control group;the levels of HOMA-β were higher in both groups than before treatment,and its level in the study group was higher than that in the control group(P＜0.05).After treat-ment,the levels of SAA,IL-6,MDA,and ROS were lower in both groups than before treatment,and their levels in the study group were lower than those in the control group(P＜0.05).Before treatment,there were no statistically significant differences in the levels of serum miR-21 and miR-149 between the two groups(P＞0.05);after treatment,the levels of serum miR-21 and miR-149 were lower in both groups than before treatment,and their levels in the study group were lower than those in the control group(P＜0.05).Before treatment,the traditional Chinese medicine syndrome score was(8.12±1.31)in the study group and(7.86±1.28)in the control group,with no statisti-cally significant difference between the two groups(P＞0.05);after treatment,the traditional Chi-nese medicine syndrome score was(3.31±0.46)in the study group,which was lower than(4.57±0.59)in the control group(t=11.423,P＜0.05).Compared with the control group,the incidence of adverse pregnancy outcomes was lower in the study group(P＜0.05).Conclusion Zuogui Pill combined with western medicine can effectively improve glycolipid metabolism and insulin resistance in GDM patients and reduce the incidence of adverse pregnancy outcomes.

Objective To explore the effects and mechanism of finasteride on epithelial mesenchymal transition in bladder urothelial carcinoma.Methods T24 human bladder cancer cells were treated with different concentrations of finasteride(0.1%,0.5%,and 1%)for 24 hours,with untreated T24 cells as the control group.Some cells were subjected to hypoxic conditions(1%O2)to mimic a low-oxygen microenvironment.Cell proliferation was assessed by immunofluorescence staining for Ki-67.Apoptosis rates were evaluated using Annexin V-FITC/PI double staining followed by flow cytometry,and cell migration was analyzed via scratch wound assays.Western blot was used to detect the expression of EMT-related proteins such as HIF-1α,E-cadherin,N-cadherin,and Vimentin.To further validate the role of the HIF-1α pathway in finasteride's anti-tumor effects,a HIF-1α overexpression lentiviral vector(MOP-1)was constructed and transfected into T24 cells.For animal experiment,T24 tumor-bearing nude mice were randomly divided into four groups:control,MOP-1,1%finasteride,and 1%finasteride+MOP-1(n=4 per group).After 4 weeks of continuous oral administration,tumor growth,metastasis,and perihepatic lymph node changes were recorded,and histological analysis was performed using H&E staining.Results Finasteride affects the proliferation,apoptosis,and epithelial-to-mesenchymal transition of T24 cells in a concentration-dependent manner.Compared to the control group,finasteride-treated T24 cells showed a reduced number of cells in the growth phase,decreased migration,increased expression of epithelial markers,and decreased expression of mesenchymal markers(P<0.05).In T24 cells exposed to hypoxic conditions,the expression of HIF-1α pathway markers was significantly increased(P<0.05),while 1%finasteride treatment inhibited the HIF-1α pathway(P<0.05).The HIF-1α pathway expression level in the 1%finasteride and HIF-1α overexpression plasmid group was lower than that in the control group(P<0.05).Additionally,the tumor mass-to-body weight ratios were lower,with the number of bladder cancer metastases to the liver decreased(P<0.05).Conclusion Finasteride can effectively block the growth of bladder cancer and the transition of epithelial cells into mesenchymal cells by inhibiting HIF-1α/Snail expression.

Objective:To investigate the incidence of shoulder work-related musculoskeletal disorders (WMSDs) among occupational population in China, and to explore their intrinsic association with personal and work-related factors.Methods:In April 2024, 73497 valid questionnaires of the Chinese version of the Musculoskeletal Disorders Electronic Questionnaire were retrospectively analyzed from June 2018 to December 2023 in 22 provinces and 29 key industries in China, and the general information, occurrence of WMSDs and related risk factors of key occupational populations in different regions in China were collected. By using Chi-square test and confirmatory factor analysis, the relationship between shoulder fatigue and pain in key occupational groups and individual factors, work type, work posture and work organization was discussed, and the internal relationship was analyzed based on structural equation model.Results:Higher incidence of shoulder fatigue and pain were associated with female, lack of physical exercise, uncomfortable working posture and neck leaning forward ( P<0.05). Structural equation model analysis showed that work type, work posture and work organization were strongly correlated ( r=0.58, 0.55). Work organization and work type were strongly correlated with shoulder fatigue ( r=0.65) and moderately correlated with shoulder fatigue ( r=0.21). Shoulder fatigue was moderately associated with shoulder pain ( r=0.40). Individual factors, work type, work posture and shoulder fatigue could directly affect shoulder pain ( OR=0.07, -0.09, 0.17 and 0.40), and work type and work posture could also indirectly affect shoulder pain through shoulder fatigue ( OR=0.08, 0.03). Work organization only indirectly affected shoulder pain through shoulder fatigue ( OR=0.26) . Conclusion:The main influencing factor of shoulder pain is shoulder fatigue, followed by work posture and individual factors. Structural equation model can better reflect the complex relationship between work type, work posture and work organization and shoulder WMSDs. Improving work posture and work organization may be an effective way to control the influence of shoulder fatigue on shoulder pain.