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.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Objective: To investigate the epidemiological characteristics and influencing factors for hand, foot, and mouth disease (HFMD) incidence in Binzhou City, Shandong Province, so as to provide the evidence for developing HFMD prevention and control strategies. Methods: Data on HFMD cases in Binzhou City from 2017 to 2023 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. Meteorological data during the same period were collected from the fifth-generation European Centre for Medium-Range Weather Forecasts. The incidence of HFMD was calculated, and the temporal, population, and regional distribution characteristics of HFMD were analyzed descriptively. Bayesian spatiotemporal model was used to analyze the influencing factors for HFMD incidence Results: From 2017 to 2023, a total of 17 314 HFMD cases were reported in Binzhou City, with an annual average reported incidence of 62.57/105. The incidence peak was from June to September, and a secondary peak appeared from October to November in some years. The annual average reported incidences were higher in Bincheng District and Yangxin County, which were 107.41/105 and 72.95/105, respectively. There were 10 461 males and 6 853 females, with a male-to-female ratio of 1.53∶1. The age was mainly 1-3 years, with 11 713 cases accounting for 67.65%. Bayesian spatiotemporal model analysis showed that the risk of HFMD incidence had obvious seasonality and regionality. From 2017 to 2019 and in 2021, the peaks occurred in weeks 24-27 and 44-47 each year, with RR values of 1.771-6.747. From 2022 to 2023, it showed a single peak distribution. The RR values were all >1 in Bincheng District, Yangxin County, and Huimin County. Average temperature (RR=1.092, 95%CI: 1.080-1.105) and average relative humidity (RR=1.015, 95%CI: 1.008-1.022) were positively correlated with the risk of HFMD incidence, while average wind speed (RR=0.749, 95%CI: 0.655-0.856) was negatively correlated with the risk of HFMD incidence. Conclusions HFMD in Binzhou City mainly occurs in summer and in central areas. Males and children aged 1-3 years are high-risk populations. The risk of HFMD incidence increases with the increase of average temperature and average relative humidity, and decreases with the increase of average wind speed.

AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

The major components of Olaflur raw material were characterized using ultra performance liquid chromatography-quadrupole time-of-flight-mass spectrometry(UPLC-Q-TOF/MS).The results revealed that cetyl amine fluoride(C16-AmF),octadecene amine fluoride(C18:1-AmF),and octadecyl amine fluoride(Olaflur)were the main components.The contents of C16-AmF,C18:1-AmF,and Olaflur in oral care products were determined via ultra performance liquid chromatography-charged aerosol detector coupled with solid-phase extraction(SPE-UPLC-CAD).The oral care sample was dispersed evenly with a 50%ethanol aqueous solution,and then vortexed with ethanol.The supernatant was collected by centrifugation,concentrated to near dryness,and redissolved with ultrapure water.The re-dissolved sample was loaded onto a Poly-Sery HLB Pro SPE column for purification and elution.The acetonitrile eluate was collected and concentrated to 1.0 mL.Finally,a prepared test solution was separated on a Thermo Acclaim Surfactant Plus chromatographic column(2.1 mm×150 mm,3 μm).Acetonitrile and 100 mmol/L acetic acid-ammonium acetate aqueous solution(pH=4.8)were used as the mobile phases for gradient elution.The flow rate was 0.3 mL/min and cloumn temperature was maintained at 40℃.The sample was detected using a charged aerosol detector,and quantified using an external standard method.The experimental results indicated that the three organic fluorinated amines showed good linear relationship in their respective concentration ranges.The correlation coefficients(r)were greater than 0.99.The limit of detection(LOD)and the limit of quantification(LOQ)of C16-AmF were 2.0 and 8.0 μg/mL,respectively.The LOD and LOQ of C18:1-AmF were 2.0 and 8.0 μg/mL,respectively.The LOD and LOQ of Olaflur were 3.0 μg/mL and 10.0 μg/mL,respectively.The spiked recoveries of the three organic fluorinated amines were 84.3%-104.2%,with relative standard deviations(RSDs)of 4.93%-5.82%.The 28 batches of commercial oral care samples were detected by this method and the results indicated that three organic fluorinated amines were detected in 18 samples and the total content were 22.2-11477.8 μg/g.This method had high sensitivity and good reproducibility.It was suitable for verifying the authenticity of the claims of oral care products promoted with Olaflur as the main efficacy ingredient and selling point,and provided a valuable reference for establishing and improving the standard analytical method for Olaflur.

Objective To explore the correlation between the actual age and the pulp chamber volume(PCV)and pulp dentinal index(PDI)of the right first molars based on cone beam computed tomog-raphy(CBCT)technology,and to construct an accurate and convenient model for age estimation.Methods CBCT image data of 1 857 Han adults(883 males and 974 females)from the Department of Stomatology,Affiliated Hospital of North Sichuan Medical College were collected.The data were di-vided into training and validation sets at a ratio of 8∶2.A total of 1 485 training samples were used to construct the age estimation model,and 372 samples were used to validate the accuracy of the model.The Mimics 21.0 software was used to measure the PCV and calculate the PDI of the right first molars.Their correlations with age and the differences between different sexes and tooth positions were analyzed.Results Both the PCV and the PDI of the first molars showed strong negative correla-tions with the actual age(r values ranged from 0.82 to 0.89).The differences in PCV and PDI be-tween different sexes and tooth positions were statistically significant(P<0.05).The age estimation model based on PDI was superior to that based on PCV.The model based on the PDI values of the two right first molars(y=73.72-44.15 x3-28.27 x4,where x3 and x4 are the PDI values of the right maxil-lary and mandibular first molars,respectively)was the best,with the R2 of 0.79 and the mean abso-lute error of 4.90 years.Conclusion Both PCV and PDI of the first molars are effective indicators for age estimation.The age estimation model based on the PDI is more convenient and accurate than that based on the PCV,providing a more effective method for age estimation in forensic practice.

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

AIM:To observe the effect of continuous light on the structure and differential metabolites of gut microbiota in mice.METHODS:The mice were randomly divided into normal light(light/dark,LD)group and 24-hour continuous light(light/light,LL)group.The body weight,fasting blood glucose,serum free fatty acids,serum triacylglycerol and serum total cholesterol levels of each group of mice were measured after 10 weeks.Fresh feces were collected,and 16S rRNA sequencing technology was used to study the effect of continuous light on the diversity,structure,and species composition of gut microbiota in mice.Additionally,liquid chromatography-mass spectrometry(LC-MS)analysis was per-formed to observe the effect of continuous light on the metabolites in mice.RESULTS:Compared with the LD group,the body weight,fasting blood glucose and lipid levels of the LL group were increased(P＜0.05).At the phylum level,the proportion of Firmicutes in the LL group increased,while the proportion of Bacteroidetes decreased.At the class level,the abundance of norank_f_Muribaculaceae and Prevotellaceae_UCG-001 in the LL group decreased significantly,while the abundance of Lactobacillus,Turicibacter and Odoribacter increased significantly.Non-targeted metabolomics analysis iden-tified 65 and 73 differential metabolites under positive and negative modes,involving six major metabolic pathways,in-cluding ABC transporters,purine metabolism,pyrimidine metabolism,secondary bile acid biosynthesis,protein digestion and absorption,and choline metabolism in cancer.CONCLUSION:The structure and metabolites of gut microbiota in mice exposed to continuous light are relatively specific,and inosine may be a key biomarker and potential therapeutic tar-get for biological clock disorders.

Objective To evaluate the advantages of a real-time computer endoscopy-assisted system(EndoAngel)for colorectal lesions detection in colonoscopy.Methods 2 000 patients who underwent EndoAngel assisted colonoscopy and conventional colonoscopy were selected for the study in a single-center,self-controlled study.According to different examination methods,the patients were divided into artificial intelligence(AI)group and traditional colonoscopy group,each with 1 000 cases.The results were statistically analyzed and compared with the polyp detection rate and adenoma detection rate of the two groups using pathological diagnosis as the gold standard.Further subgroup analysis will be conducted based on the seniority of the operating physicians.Results AI group's polyp detection rate was higher(39.3％)than conventional colonoscopy group polyp detection rate(29.0％),with statistically significant difference(x2=23.59,P=0.000).Of these,the detection rates of hyperplastic polyps and adenomatous polyps were 19.1％and 25.2％,which were significantly higher than those of 12.4％and 20.8％in the conventional colonoscopy group,and the differences were statistically significant(x2=16.92,P=0.000;x2=5.46,P=0.019).Further subgroup analysis of the two groups by physician seniority,the polyp detection rate of AI low seniority group(36.6％)was higher than that of conventional colonoscopy low seniority group(20.40％),with a statistically significant difference(x2=32.20,P=0.000).Among them,the detection rates of hyperplastic polyp(17.8％)and adenomatous polyp(23.6％)in AI low seniority group were higher than those in the conventional colonoscopy low seniority group(12.8％vs 13.6％),and the differences were significant(x2=4.82,P=0.028;x2=16.51,P=0.000).There were no significant differences in adenomatous polyp detection rates between the two groups of senior physicians.Conclusion EndoAngel assisted system can improve the polyp detection rate of colonoscopy,especially for the effect of low seniority physicians is more significant.