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 This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

The chemical constituents of the petroleum ether extract derived from the 90% ethanol extract of Elephantopus scaber were investigated. By silica gel column chromatography, C_(18), MCI column chromatography and semi-preparative high performance liquid chromatography, ten compounds were isolated. Their structures were identified as 3β-hydroxy-6β,7β-epoxytaraxeran-14-ene(1), 3β-hydroxyolean-12-en-28-oic acid(2), D-friedoolean-14-ene-3β,7α-diol(3), 3β-hydroxy-11α-methoxyolean-12-ene(4), 3β-hydroxyolean-11,13(18)-diene(5), 11α-hydroxy-β-amyrin(6), betulinic acid(7), 3β-hydroxy-30-norlupan-20-one(8), 6-acetonylchelerythrine(9), and 4',5'-dehydrodiodictyonema A(10) by analysis of the 1D NMR, 2D NMR, MS, and IR spectral data. Among them, compound 1 was a new triterpene and other compounds except compounds 2 and 7 were isolated from this plant for the first time.
Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure ; Asteraceae/chemistry* ; Chromatography, High Pressure Liquid ; Magnetic Resonance Spectroscopy

Cistanches Herba(CH) is a famous tonic traditional Chinese medicine, with the effects of tonifying kidney Yang, nourishing kidney Yin, replenishing essence and blood, and moistening the intestines to relieve constipation. Modern pharmacological studies have shown that CH has anti-aging, anti-fatigue, immunomodulatory, neuroprotective, and anti-aging activities, serving as an ideal raw material for the development of pharmaceuticals and health products. In 2023, CH was added in the catalog of medicinal and food substances, which provided policy support for its application in conventional food products and expanding pathways for industrial diversification. To comprehensively understand current development status of CH products, this review systematically investigated professional databases including Yaozhi(https://db.yaozh.com), Chinese Pharmacopoeia, Compendium of National Standards for Chinese Patent Medicines, and Kezhuang and collected market survey data to thoroughly review the applications of CH as a primary ingredient in domestic and international Chinese patent medicines, health foods, cosmetics, and common food products. Furthermore, this review points out challenges in the current industrial development and future potential market prospects, aiming to provide guidance for the development and industrialization of CH-based pharmaceuticals and health products, thereby promoting the vigorous growth of the CH industry.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Cistanche/chemistry* ; Animals ; Medicine, Chinese Traditional

OBJECTIVE: To retrospectively analyze the healing degree of graft in patients who underwent over-the-top reconstruction of the anterior cruciate ligament(ACL) using autologous tendon 1 year postoperatively to find out possible risk factors. METHODS: From January 2017 to March 2023, 207 patients with more than 1 year of follow-up and 1-year postoperative MRI were selected from that receiving ACL autograft tendon over-the-top reconstruction surgery including 137 males and 70 females, with a mean age of (28.01±9.71) years rangeding 12 to 56 years old;time from trauma to surgery was (5.80±3.78) months. All patients had intra-operative pivoshift tested asⅠtoⅡdegree. The 1-year postoperative magnetic resonance imaging (MRI) results were categorized by Howell's method, classifying degreesⅠandⅡas group BHD (better healing degree), while degrees Ⅲ and Ⅳ as group PHD (poorer healing degree). Potential influencing factors such as age, gender, whether it was a sports injury, time from injury to surgery, time to return to sports after surgery, body mass index (BMI), Beighton score, knee hyper-extension, diameter of the graft, whether it was remnant-preserving or not, whether the medial and lateral meniscus were resected, sutured or not, posterior lateral tibial slope, intercondylar notch width ratio (ICNWR), and lateral femoral condyle depth ratio (LFCDR) were analyzed by univariate analysis and Logistic regression to find the influencing factors. RESULTS: All patients were follow-up time for (18.59±4.63) months, and all the patients had good wound healing without any infection after surgery. There were 3 cases of re-ruptrure and 2 cases with secondary medial meniscus barrel handle-like tear 1 year after surgery, which received arthroscopic surgical treatment. Univariate analysis showed statistically significant difference in time from injury to surgery, time from surgery to return to sports, ICNWR, posterior lateral tibial slope, and BMI between the two groups(P<0.05). Multi-factorial regression analysis showed that smaller ICNWR, OR=0.684, 95%CI(0.528, 0.886), P=0.004; larger posterior lateral tibial slope, OR=1.557, 95%CI(1.222, 1.984), P<0.001;larger BMI, OR=1.724, 95%CI(1.369, 2.172), P<0.001;and shorter return-to-sport time<6 months vs. 6 to 12 months, OR=0.167, 95%CI(0.041, 0.672), P=0.012;<6 months vs.>12 months, OR=0.022, 95%CI(0.004, 0.108), P<0.001 might be risk factors for poor MRI healing degree 1 year postoperatively. CONCLUSION In patients received ACL autograft tendon over-the-top reconstruction, smaller ICNWR, larger posterior lateral tibial slope, larger BMI, and shorter time to return to sports may all be high-risk factors for poor graft healing degree on MRI 1 year postoperatively, and the surgical technique and the postoperative rehabilitation are supposed to be individualized for such patients.
Humans ; Male ; Female ; Adult ; Magnetic Resonance Imaging ; Anterior Cruciate Ligament Reconstruction/methods* ; Middle Aged ; Adolescent ; Young Adult ; Tendons/transplantation* ; Child ; Risk Factors ; Retrospective Studies ; Transplantation, Autologous ; Anterior Cruciate Ligament Injuries/diagnostic imaging* ; Anterior Cruciate Ligament/diagnostic imaging* ; Autografts ; Wound Healing

OBJECTIVE: To evaluate the impact of preoperative cervical sagittal parameters on the loss of cervical lordosis (LCL) after expansive open-door laminoplasty (EOLP) and explore the optimal predictors. METHODS: A retrospective analysis was performed on the clinical data of 94 patients with cervical spondylotic myelopathy who underwent EOLP from January 2019 to January 2021, including 61 males and 33 females, aged 34 to 75 years old with an average age of(53.1±9.7) years old. Preoperative routine anteroposterior, lateral, and dynamic X-ray films of the cervical and thoracic spine were taken to comprehensively assess various cervical sagittal parameters: T₁ slope (T₁S), C₂-C₇ sagittal vertical axis (C₂-C₇ SVA), C₂-C₇ cervical lordosis (CL), T1 slope-cervical lordosis (T₁S-CL), cervical lordosis/T₁ slope (CL/T₁S), C₂-C₇ cervical range of motion (ROM), thoracic kyphosis (TK), cephalad vertebral level undergoing laminoplasty (CVLL), and C_2,3 disc angle. Statistical analysis was conducted to identify the independent risk factors of preoperative sagittal parameters for postoperative LCL. RESULTS: A total of 94 patients meeting the inclusion and exclusion criteria were enrolled, with a postoperative follow-up period of 12 to 24 months. Pearson correlation analysis showed that T₁S, T₁S-CL, CVLL, and C_2,3 disc angle were significantly correlated with postoperative LCL, while C₂-C₇ SVA, CL, CL/T₁S, C₂-C₇ ROM, and TK had no significant correlation with postoperative LCL. Regression analysis further indicated that T₁S (β=0.426, P<0.001), T₁S-CL (β=0.716, P<0.001), C_2,3 disc angle (β=0.351, P<0.001), and CVLL (β=-3.348, P<0.001) were significantly correlated with postoperative LCL. CONCLUSION For patients with cervical spondylotic myelopathy treated with EOLP, T₁S, T₁S-CL, CVLL, and C_2,3 disc angle are important factors for predicting cervical lordosis loss, among which CVLL may be the most critical predictive indicator.
Humans ; Male ; Female ; Middle Aged ; Laminoplasty/methods* ; Aged ; Cervical Vertebrae/physiopathology* ; Retrospective Studies ; Adult ; Lordosis/surgery* ; Spondylosis/surgery*

PURPOSE: The study aimed to examine the pattern of motorization and the mortality rate related to road traffic crashes in Zunyi (a city in northern Guizhou province of China) from 2013 to 2022, and to identify the epidemiological characteristics of these crashes with to provide insights that could help improve road safety. METHODS: Data were obtained from the Zunyi traffic management data platform, and the mortality rates were calculated. We deployed various analytical methods, including descriptive analysis, Chi-square test or Fisher's exact test for categorical variables, circular distribution map analysis, and Rayleigh test to characterize the traits of road traffic crashes in the region. RESULTS: During the 10-year study period, 7488 people died due to road traffic accidents, with males accounting for 70.4% and females 29.6% (χ² = 101.97, p < 0.001). The mortality rate increased from 7.80 deaths per 100,000 people in 2013 to 10.70 deaths per 100,000 people in 2016, but then decreased to 9.54 deaths per 100,000 people in 2019. A notable finding was that the death rate per 10,000 vehicles declined from 16.09 deaths per 10,000 vehicles in 2013 to 5.48 deaths per 10,000 vehicles in 2022. The study also found that vulnerable road users represented nearly half (48.76%) of all accident fatalities, and unlicensed or inexperienced driving contributed significantly to the occurrence of road traffic accidents. CONCLUSION Although the number of road traffic accidents in Zunyi has decreased, there are still some critical issues that need to be addressed, particularly for vulnerable road users and unlicensed drivers. Our results highlight the need for targeted interventions to address the specific risk factors of road traffic crashes, particularly those affecting vulnerable road users and drivers without sufficient experience or license.
Humans ; Accidents, Traffic/statistics & numerical data* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Child

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.