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.

Structural optimization of lead compounds is a crucial step in drug discovery.One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties.One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules,thereby accelerating the molecular optimization process.Deep molecular diffusion generative models simulate a gradual process that creates novel,chemically feasible molecules from noise.However,the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules,leading to challenges in modifying the scaffold-based molecular structures,and creates limitations in the stability and diversity of the generated molecules.To address these challenges,we propose a deep molecular diffusion generative model,the three-dimensional(3D)equivariant diffusion-driven molecular generation(3D-EDiffMG)model.The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder(dual-SWLEE)is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions.Addi-tionally,a gate multilayer perceptron(gMLP)block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies.The experimental results show that 3D-EDiffMG effectively generates unique,novel,stable,and diverse drug-like molecules,highlighting its potential for lead optimization and accelerating drug discovery.

Refinement and standardisation of the management of clinical diagnostic and treatment operations is a key aspect of achieving high-quality development in hospitals.By analysing the management status quo of clinical diagnosis and treatment operations in hospitals,it combed the problems existing in this field.Based on the closed-loop management model,it proposed measures and recommendations to promote the continuous optimisation of the management of clinical diagnostic operations in hospitals.Hospitals should establish hospital-level operation catalog and conduct classified management,authorize operators and dynamically adjust them,carry out operation quality management,pay attention to information management of operation management,and combine operation management with physician performance management.

Objective:To explore the feasibility of using low-dose computed tomography(LDCT)with deep learning reconstruction(DLR)on the chest for the screening of lung nodules,and to compare the image quality and detection rate of nodules between LDCT and routine dose CT(RDCT)-DLR.Methods:A total of 104 overweight or obese patients[body mass index(BMI)≥25 kg/m2]who received CT examination on chest due to pulmonary nodule screening from September to December 2023 were included to conduct prospective study.All patients underwent respectively RDCT(120 kV)and LDCT(100 kV)scans,all of the two scans used the modulation of automatic tube current,and adopted deep learning AI algorithm ClearInfinity to conduct reconstruction(RDCT:CI 40%,LDCT:CI 50%).Radiation dose and nodules number of them were recorded.At the T8 vertebral level,CT values(Hounsfield Units,HU)of mediastinal fat and lung parenchyma in the right lower lobe were measured,along with image noise(standard deviation,SD).The signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were subsequently calculated.Two radiologists independently performed subjective evaluations of image quality and pulmonary nodules using a Likert 4-point scale.Paired t-tests or Wilcoxon rank-sum test were employed to compare differences in radiation dose,objective image noise,and subjective scores between LDCT and RDCT.Results:A total of 104 patients were enrolled,including 54 males and 50 females,with a mean age of 52±13 years and a BMI of(27.77±2.64)kg/m2.The effective radiation dose of LDCT demonstrated a statistically significant reduction compared to RDCT(Z=-8.853,P<0.001),with a mean effective radiation dose reduction of 77.86%.The differences in lung CT value,lung noise,fat noise,lung parenchyma SNR,fat SNR and CNR of images between two groups were significant(Z=-3.022,-2.327,-4.785,-2.059,-3.765,-4.013,P<0.05),while there were not significant differences in the comparisons for fat CT value and lung parenchyma SNR(P>0.05).The image contrast,image noise,and subjective score for image quality of lung nodule of LDCT were lower than those of RDCT(t=2.877,2.387,5.096,P<0.05),but all subjective scores of that were>3,which can meet the requirements of clinical diagnosis.In terms of nodule detection,RDCT found out about 418 nodules,while LDCT found out about 421,the false positive rate of LDCT only was 0.72%.Conclusion:In overweight or obese patients,LDCT that combined with DLR algorithm on chest is equivalent to RDCT on image quality and the detection rate of lung nodule,and it significantly reduce radiation exposure on patients at the same time.

OBJECTIVE:Premature ovarian failure has manifested a trend of younger,and stem cell therapy has been progressively implemented in clinical practice in recent years.Nevertheless,given the extensive range of sources and variegated existence of stem cells in diverse tissues,certain disparities prevail in their biological characteristics and functions.In this paper,the therapeutic efficacies of dissimilar sources of mesenchymal stem cells on animal models of premature ovarian failure were contrasted,with the aim of providing a basis for the clinical application of stem cells.METHODS:The animal model experiments of mesenchymal stem cell therapy for premature ovarian failure were retrieved from PubMed,The Cochrane Library,and EMbase,as well as Chinese databases such as CNKI,WanFang,VIP,and China Biomedical Literature Service.The search period extended from the inception to December 31,2023.Two researchers independently screened the literature,extracted and analyzed the data.The quality of the included studies was evaluated by means of the SYRCLE animal experiment bias risk assessment table.Main outcome measures:Follicle stimulating hormone,estradiol,luteinizing hormone,the quantity of follicles at all levels.Secondary outcome measure:Pregnancy rate.Network meta-analysis,mapping,and tabulation were executed using Stata 17.0 software after assessing the risk of bias in the included studies.RESULTS:Totally 24 animal experiment studies were incorporated,and the overall quality of the literature was mediocre,encompassing 7 distinct sources of mesenchymal stem cells.They were umbilical cord-derived mesenchymal stem cells,menstrual blood-derived mesenchymal stem cells,placenta-derived mesenchymal stem cells,human cord blood-derived mesenchymal stem cells,bone marrow-derived mesenchymal stem cells,adipose-derived mesenchymal stem cells,and amnio-derived mesenchymal stem cells.The network meta-analysis demonstrated that(1)in contrast to the blank group,mesenchymal stem cells from various sources were effective in enhancing the pregnancy rate and estradiol,reducing follicle-stimulating hormone and luteinizing hormone,augmenting the number of follicles at all levels,and diminishing the number of atretic follicles.(2)According to the area map under the cumulative sequencing curve,the three stem cells with the most prominent efficacy in improving estradiol levels were umbilical cord-derived mesenchymal stem cells(72.7％)＞adipose-derived mesenchymal stem cells(72.6％)＞menstrual blood-derived mesenchymal stem cells(71.7％).(3)The three kinds of stem cells with the highest efficacy in reducing follicle-stimulating hormone levels were the adipose-derived mesenchymal stem cells(96.3％)＞human cord blood-derived mesenchymal stem cells(65.4％)＞umbilical cord-derived mesenchymal stem cells(63.9％).(4)The three kinds of stem cells with the highest efficacy in reducing luteinizing hormone levels were adipose-derived mesenchymal stem cells(100.0％)＞umbilical cord-derived mesenchymal stem cells(51.6％)＞human cord blood-derived mesenchymal stem cells(46.8％).(5)The top three kinds of stem cells for increasing the number of primordial follicles were human cord blood-derived mesenchymal stem cells(76.3％)＞umbilical cord-derived mesenchymal stem cells(75.5％)＞menstrual blood-derived mesenchymal stem cells(57.5％).(6)The top three kinds of stem cells for increasing the number of primary follicles were umbilical cord-derived mesenchymal stem cells(75.3％)＞adipose-derived mesenchymal stem cells(53.0％)＞the placenta-derived mesenchymal stem cells(51.7％).(7)The top three kinds of stem cells for increasing the number of secondary follicles were adipose-derived mesenchymal stem cells(76.1％)＞menstrual blood-derived mesenchymal stem cells(66.8％)＞umbilical cord-derived mesenchymal stem cells(66.5％).(8)The top three kinds of stem cells in reducing the number of atretic follicles were adipose-derived mesenchymal stem cells(99.9％)＞bone marrow-derived mesenchymal stem cells(68.1％)＞umbilical cord-derived mesenchymal stem cells(53.4％).CONCLUSION:(1)For animal models of premature ovarian failure,the results of the network meta-analysis disclosed that various stem cell transplantation treatments were preponderant over the blank or placebo group to varying extents,and the efficacies were comparable.(2)The results indicated that umbilical cord-derived mesenchymal stem cells were the most frequently utilized and adipose-derived mesenchymal stem cells were the most potent.More high-quality experimental study data are requisite in the future for further validation.

Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Objective:To investigate the levels of diphtheria-specific binding antibodies and neutralizing antibodies in mice immunized with pneumococcal polysaccharide conjugate vaccine using diphtheria toxoid as a carrier.Methods:NIH mice were immunized with one batch of diphtheria, tetanus and acellular pertussis combined vaccine, absorbed (DTaP-1) or three different batches of 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13, containing diphtheria toxoid vector) at three dilutions (5-, 10- and 20-fold dilution). Serum samples were collected to test for diphtheria-specific antibody titers and diphtheria potencies of the vaccines. Another three batches of DTaP vaccine and three batches of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis combined vaccine (Tdap) were used to immunize NIH mice. Serum samples were collected and the diphtheria potencies were detected. Statistical analysis was performed using one-way analysis of variance.Results:At the 5-fold and 10-fold dilutions, the titers of diphtheria-specific antibodies induced by three batches of PCV13 vaccine were all lower than those by DTaP-1 vaccine (all P<0.001), while there was no statistically significant difference at the 20-fold dilution ( P>0.05). The diphtheria potencies of the DTaP-1 vaccine and the three batches of PCV13 vaccine were 100.5, 76.2, 64.5, and 62.0 IU/ml, respectively. The diphtheria potencies of another three batches of DTaP vaccine were 82.5, 83.6, and 79.9 IU/ml, respectively, and those of three batches of Tdap vaccine were 10.3, 12.2, and 12.9 IU/ml, respectively. There was no statistically significant difference in diphtheria potency between DTaP vaccine and PCV13 vaccine( P>0.05), while there was a statistically significant difference between Tdap vaccine and the PCV13 vaccine ( P<0.001). Conclusions:The pneumococcal polysaccharide conjugate vaccine with diphtheria toxoid has good diphtheria immunogenicity and can induce the production of higher levels of diphtheria-specific binding antibodies and protective neutralizing antibodies in vivo. Pneumococcal capsular polysaccharide exerts an immune enhancement effect on diphtheria toxoid. The relevant results provide valuable guidance for determining carrier protein dosage in bacterial polysaccharide conjugate vaccines, planning vaccine co-administration, and selecting the dosage of diphtheria toxoid antigen in the research and development of combined vaccines.

Objective:To explore the degree of change in anteversion angle and related risk factors after intramedullary nail fixation of intertrochanteric femur fracture in the elderly.Methods:The data of 256 elderly patients who underwent intramedullary nail fixation for intertrochanteric fractures of the femur at Tianjin Hospital of Tianjin University from March 2020 to March 2023 were selected, including 114 males and 142 females, with an age of 75.40±10.69 years (range, 65-94 years). The degree of change in the anteversion angle of the affected hip before and after the surgery was measured by CT scan of the hip, the Receiver Operating Characteristic Curve (ROC) was plotted, the area under the ROC curve was analyzed, and the optimal degree of grouping was determined by calculating the Youden Index, then all the patients were divided into two groups. The correlation between various risk factors (age, sex, type of internal fixation, fracture AO type, quality of reduction, fracture medial cortical defect or not, cusp distance) and the change of anterior tilt angle was screened by univariate and multivariate logistic regression analyses.Results:All 256 patients were followed up for 20.7±2.1 months (range, 18-23 months). Anteversion on the healthy side was 12.68°±5.10° (range, 5°-28°); postoperative anteversion on the affected side was 15.04°±7.67° (range, 9°-36°). By comparing the difference in the anterior tilt angle between the affected side and the healthy side, it was found that the anterior tilt angle of 67 patients was completely restored to the healthy side level after the operation. The anteversion angle was enlarged in 131 cases, of which the mildly increased angle (1°-9°) was found in 106 cases, moderately increased (10°-15°) was found in 17 cases, and significantly increased (>15°) was found in 8 cases; 58 patients showed anteversion angle reduction, of which 45 cases were mildly reduced (1°-9°), 13 cases were moderately reduced (10°-14°). The area under the ROC curve for the patient's anteversion angle and its 95% CI were 0.714(0.559, 0.867), and the maximum value of its Youden Index was 0.221, which corresponded to the optimal critical angle of 4°. There was no statistically significant difference in age, gender, reduction quality or fracture AO classification between the group with an anteversion angle>4° and the group with an anteversion angle≤4° ( P>0.05). The types of internal fixation, medial cortical defect and insufficient tip apex distance (TAD) were included in the binary variable logistic regression analysis. The results showed that single-nail internal fixation [ OR=0.412, 95% CI(0.244, 0.695), P=0.007], medial cortical defect [ OR=0.471, 95% CI(0.279, 0.793), P=0.009] and TAD>25 mm [ OR=0.367, 95% CI(0.207, 0.651), P=0.003] are independent risk factors for changes in anteversion angle after intramedullary nail fixation of intertrochanteric femur fractures in elderly. Conclusion:Single-nail internal fixation, medial cortical defect and TAD >25 mm are independent risk factors for the change of anteversion angle after intramedullary nail internal fixation of intertrochanteric fractures in the elderly.