ObjectiveTo analyze the clinicopathological features of patients with comorbidities of chronic hepatitis B （CHB） and steatotic liver disease （SLD）， to investigate the impact of hyperglycemia on the risk of liver fibrosis and end-stage liver diseases （ESLD）， and to provide a basis for the clinical management of such population. MethodsA total of 668 adult patients with CHB-SLD confirmed by liver biopsy in The Fifth Medical Center of Chinese PLA General Hospital from January 2011 to December 2019 were enrolled， and a retrospective cohort was established with the time of liver biopsy as the baseline and the onset of ESLD as the endpoint. All patients were followed up to March 31， 2024. Propensity score matching （PSM） was performed at a ratio of 1∶4 to balance baseline features between groups， resulting in 82 patients in the hyperglycemia group and 281 in the non-hyperglycemia group. The two groups were compared in terms of metabolic profiles， laboratory markers， and histopathological features. The Mann-Whitney U test was used for comparison of non-normally distributed quantitative data between two groups. The chi-square test or Fisher exact test was used for comparison of categorical data between two groups. A multivariate Logistic regression analysis was used to investigate the influencing factors for advanced fibrosis （AF）， and the Kaplan-Meier survival analysis and the Cox proportional-hazards regression model were used to determine the influencing factors for the development of ESLD. ResultsCompared with the non-hyperglycemia group， the hyperglycemia group had a significantly higher number of factors for metabolic disorders， a significantly higher degree of hepatic steatosis， and a significantly higher detection rate of AF （all P<0.05）. The multivariate Logistic regression analysis showed that hyperglycemia was a risk factor for AF （odds ratio = 1.753， 95% confidence interval ［CI］： 1.017　—　3.023， P=0.043）. The survival analysis showed that hyperglycemia increased the risk of ESLD （χ²=4.340， P=0.037）. The multivariate Cox regression analysis confirmed that hyperglycemia was a significant metabolic risk factor for ESLD in patients with AF （adjusted hazard ratio=3.208， 95%CI： 1.201　—　8.568， P=0.020）. ConclusionHyperglycemia can increase the risk of AF and ESLD in CHB-SLD patients. Clinical monitoring and active management should be strengthened for patients who have already developed AF and hyperglycemia.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

Objective To investigate the application value of clinical-radiomics nomogram in predicting the expression of liver kinase B1(LKB1)in non-small cell lung cancer(NSCLC)before surgery.Methods A total of 140 NSCLC patients were randomized into training group(n=106)and validation group(n=34)according to the ratio of 7∶3.The training group was used as the study cohort to screen the clinically independent predictors and radiomics characteristics related to LKB1 expression,and the clinical model,radiomics model and clinical-radiomics nomogram model were constructed,respectively.The predictive performance of the three models was analyzed using the receiver operating characteristic(ROC)curve in the training group,and validated in the validation group.The calibration curve was used to assess the consistency between the predicted results of nomogram model and the actual observations,and the decision curve was used to evaluate the clinical benefit of the nomogram model.Results The clinical model consisted of pathological type and hilal/mediastinal lymphadenopathy,the radiomics model consisted of Radiomics score(Radscore),and the nomogram model consisted of Radscore,pathological type and hilal/mediastinal lymphadenopathy.In the training group,the area under the curve(AUC)of the nomogram model,radiomics model and clinical model was 0.884,0.843 and 0.788,respectively.In the validation group,the AUC of the three models were 0.976,0.851,and 0.912,respectively.The calibration curve analysis showed good consis-tency between the predicted results of nomogram model and the actual observations,and the decision curve showed that the model had good clinical benefit.Conclusion Radiomics combined with clinical risk factors can effectively predict the expression of LKB1 in NSCLC patients before surgery,so as to contribute to the formulation of therapeutic strategies in clinical practice.

In order to establish a competitive chemiluminescent enzyme-linked immunoassay for rapid and quantitative detection of Senecavirus A antibodies,the polystyrene plate was coated with inactivated Senecavirus A antigen,and the monoclonal antibodies against Senecavirus A VP2 and VP3 proteins labeled by horseradish peroxidase(HRP)were used as the competitive enzymic anti-bodies of the antibodies in the serum samples.The standard curve of the calibrator prepared by di-lution of positive serum was drawn to achieve quantitative detection.The successfully established SVA competitive CLEIA reported the result within 45 minutes.The maximum dilution of 1∶2 048 for calibrator serum was still detectable with no cross-reaction with the standard positive serum of other five kinds of virus antigens such as foot-and-mouth disease.The coefficient of variation within batches was less than 10％,and the coefficient of variation between batches was less than 15％,which showed good repeatability and stability.The positive and negative coincidence rates were 95.30％and 97.57％,respectively,and the total coincidence rate was 96.88％,showing high consistency.The SVA competitive CLEIA assay established in this study can be used for the rapid quantitative detection of Senecavirus A antibodies,filling the gap in the domestic rapid quantitative detection of SVA antibodies.

Objective:To explore the effects of fluoride exposure from early life to adulthood on learning and memory abilities of offspring mice and the expression of genes related to the NOTCH signaling pathway in hippocampal tissue.Methods:Thirty 8-week-old (body weight 18 - 24 g) clean-grade C57BL/6J mice, half male and half female, were randomly divided into 3 groups by body weight and then paired 1 ∶ 1 (10 mice per group). Successfully pregnant female mice were given tap water containing 0 (control), 20, or 40 mg/L sodium fluoride (NaF) during gestation and lactation until weaning. Offspring mice were exposed to fluoride until 12 weeks of age after weaning at 21 days, with fluoride exposure doses identical to those of the maternal mice. The 24-hour urine of the offspring mice was collected to determine urine fluoride level using fluoride ion selective electrode method, and Morris water maze was used to evaluate their spatial learning and memory ability. The offspring mice were euthanized under anesthesia, and protein and RNA were extracted from hippocampal tissue. Western blot was used to detect the protein expression levels of postsynaptic density protein 95 (PSD95) and synapsin-1 (SYN-1) in hippocampal tissues. Quantitative real-time PCR and Western blot were used to detect the mRNA and protein expression levels of NOTCH signaling pathway related genes (including NOTCH1, DLL3, HES5) in hippocampal tissue.Results:Compared with the control group [(0.86 ± 0.25) mg/L], the offspring mice of the 20 and 40 mg/L NaF groups had higher urinary fluoride levels [(3.77 ± 0.51), (6.04 ± 1.63) mg/L, P < 0.05]. The Morris water maze results showed that compared with the control group, the offspring mice in the 20 and 40 mg/L NaF groups had longer escape latency (day 5), fewer platform crossings, and shorter target platform dwell time ( P < 0.05). Compared with the control group, the protein expression level of synaptic related protein PSD95 in the hippocampal tissues of the offspring mice in the 40 mg/L NaF group was lower, and the protein expression level of SYN-1 in the 20 and 40 mg/L NaF groups was lower ( P < 0.05). The protein expression level of NOTCH1, a gene related to the NOTCH signaling pathway, was lower in the hippocampal tissue of offspring mice in the 40 mg/L NaF group. The mRNA and protein expression levels of DLL3 and HES5 were also lower in the 20 and 40 mg/L NaF groups, and the mRNA expression level of HES5 in the 40 mg/L NaF group was lower than that in the 20 mg/L NaF group ( P < 0.05). Conclusions:Exposure to fluoride from early life to adulthood can lead to a decline in the learning and memory abilities of offspring mice, as well as a decrease in the expression of synaptic related proteins. The mechanism of action may be related to the inhibition of the NOTCH signaling pathway in hippocampal tissue.

Objective:To explore and evaluate the optimization and application of case-based learning (CBL) in the reform practice for integrated curriculum of the digestive system.Methods:The 174 undergraduate students majoring in eight-year clinical medicine enrolled in 2019 at the Peking University Health Science Center were selected as research objects. CBL was used in the integration and optimization of the digestive system curriculum. These included increasing class hours, selecting disease modules, lesson preparation involving multi-disciplinary teachers, and joint teaching. Upon completion of teaching, a comprehensive evaluation of teaching effectiveness was conducted through questionnaires administrated to teachers and students, feedback from supervision experts, and scores of students. SPSS 21.0 was used for the t-test and a reliability analysis was conducted on the questionnaire results. Results:Teachers, students, and supervision experts were highly satisfied with CBL. More than 95% of teachers believed that joint teaching facilitated the sharing of diverse professional knowledge among teachers, enhanced the in-depth instruction of imaging knowledge, promoted the transformation of teaching ideas, and improved teaching ability. More than 70% of students agreed that joint teaching deepened their understanding of diseases, stimulated learning interest, and established a theoretical foundation for clinical practice. The average score of class performance was (47.60±2.41) points (a total score of 50 points). The answers of students to case-based questions in final exams were satisfactory. The average score of final evaluation was (82.24±8.82) points.Conclusions:The optimization and application of CBL in the integrated curriculum of the digestive system is highly accepted by teachers and students. This method improves the interest of learning and facilitates the establishment of overall medical thinking and clinical thinking in students.

Objective To establish a reversed-phase HPLC method for determining three stereoisomers in baloxavir marboxil and provide a basis for the quality specification of baloxavir marboxil.Methods The chromatographic column was CHIRALPAK IC-3(4.6 mm × 150 mm,3 μm),The mobile phase was acetonitrile-0.1％formic acid aqueous solution-isopropanol(35:50:15).The column temperature was 40 ℃.The flow rate was 0.5 mL·min-1.The injection volume was 10 μL.The detection wavelength was 259 nm.Result The isomer peaks were completely separated from the principal component peak.The detection limits for stereoisomers 1,2 and 3 were 0.024 7,0.038 7,0.038 1 μg·mL-1 respectively.The quantitation limits for stereoisomers 1,2 and 3 were 0.049 4,0.077 3,0.076 1 μg·mL-1 respectively.There were good linear relationships between the concentrations and peak area within the ranges of the study,and the linearity concentration ranges of stereoisomers 1,2 and 3 were 0.049 5-0.989 0 μg·mL-1,0.051 6-1.031 0 μg·mL-1,0.050 8-1.015 0 μg·mL-1 respectively.The linear correlation coefficients were 0.999 4.The recovery was 92.28％-103.90％.The sample solution was stable in 48 h at room temperature.Conclusion The method is accurate and reliable for determining stereoisomers in baloxavir marboxil,and provide a guideline of quality standards of baloxavir marboxil and safety evalution.

Objective To identify potential biomarkers for proliferative diabetic retinopathy(PDR)using proteomics and transcriptomics data.Methods In this study,the proteomics dataset(PXD046630)and two transcriptomics datasets(GSE60436 and GSE102485)were derived from the aqueous humor samples and fibrovascular membranes of PDR patients,respectively.Differentially expressed genes(DEGs)were identified via R software,specifically the limma and edgeR pack-ages.The shared DEGs between PXD046630 and GSE60436 were analyzed via protein-protein interaction(PPI),Gene On-tology(GO)enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.The key DEGs were validated in GSE102485 via receiver operating characteristic(ROC)curve analysis.A quantitative polymerase chain reaction(qPCR)assay was used to confirm the mRNA of these candidate biomarkers in human retinal microvascular endothelial cells(HRMECs)cultured in high glucose and low oxygen conditions.Results A total of 59 shared DEGs and 26 hub genes were identified from the PXD046630 and GSE60436 datasets.KEGG analysis revealed that six pathways,inclu-ding extracellular matrix-receptor interaction,proteoglycans in cancer,and complement and coagulation cascades,were enriched in 12 key DEGs.Fibronectin 1(FN1),tissue inhibitor of metalloproteinase 3(TIMP3),complement factor H(CFH),decorin(DCN),and lipoprotein receptor-related protein-2(LRP2)were identified as potential biomarkers on the basis of their AUC values being greater than 0.900(CI≥95％).The mRNA expression levels of FN1,CFH,and LRP2 were significantly increased in HRMECs cultured in high glucose and low oxygen conditions.Conclusion FN1,CFH,and LRP2 are potential biomarkers for PDR,and further studies are needed to explore their roles and therapeutic potential in PDR.

Ulcerative colitis (UC) is a chronic inflammatory disease of unknown etiology, primarily involving the colon and rectum. Characterized by recurrent episodes and prolonged disease course, UC requires dynamic monitoring and evaluation. Current commonly used methods for disease monitoring and assessment include C-reactive protein (CRP), fecal calprotectin (FC), and colonoscopy. However, CRP lacks specificity, FC fails to effectively differentiate UC from Crohn's disease, while colonoscopy involves complex bowel preparation, is invasive, and suffers from poor patient compliance. Therefore, there is an urgent clinical need to identify non-invasive biological markers with high sensitivity and specificity for the diagnosis and evaluation of UC. Recent studies have demonstrated that anti-integrin αvβ6 autoantibodies hold significant value in the diagnosis, differential diagnosis, and disease assessment of UC, potentially emerging as an important clinical biomarker. This article reviews the research progress of anti-integrin αvβ6 autoantibodies in UC for reference.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.