The occurrence and progression of diseases constitute a complex dynamic process, and cross-sectional data from a single time point are insufficient to fully characterize their evolutionary patterns. In contrast, longitudinal time-series data can capture the dynamic evolution of diseases over time, which is key to achieving precise disease prediction. In recent years, breakthroughs in deep learning have driven significant progress in intelligent predictive models based on longitudinal time-series data. However, challenges inherent to such data-including irregular sampling, high missing rates, and heterogeneity-also impose specific requirements on model design. This paper provides a systematic review of research advances in intelligent models for disease prediction based on time-series data. We conduct an in-depth analysis from three perspectives: data processing and representation, representative model architectures, and time-series modeling strategies, aiming to provide a reference for building more efficient and robust longitudinal disease prediction models.

The mechanistic target of rapamycin （mTOR） is an important signaling functions as a central regulator of cell growth, proliferation and metabolism. Dysregulated mTOR signaling has been implicated in various inflammatory and hyperproliferative skin conditions. Emerging data suggest that mTOR signaling is tightly associated with acne pathogenesis. The regulatory mechanisms of the mTOR signaling pathway in the pathogenesis of acne were summarized and the current progress of therapeutic targeting mTOR pathway for acne were discussed in this paper.

Objective: To analyze the association between alcohol consumption and lumbar disc herniation (LDH), so as to provide a reference for the development of prevention and treatment strategies for LDH. Methods: From May to July 2022, permanent residents aged ≥18 years from eight counties (cities/districts) in Gansu Province were selected using a multistage stratified random sampling method. Data on basic characteristics, alcohol consumption in the past 30 days, hypertension, and diabetes mellitus were collected through questionnaire surveys. LDH was determined based on imaging findings, combined with disease history or clinical symptoms. Multivariable logistic regression model was used to analyze the association between alcohol consumption and LDH, with subgroup analyses conducted by gender, age, ethnicity, and altitude of residence. Propensity score matching (PSM) was utilized for sensitivity analysis. Results: A total of 4 545 individuals were surveyed. There were 2 026 (44.58%) males and 2 519 (55.42%) females. The mean age was (44.82±15.33) years. The study participants were predominantly of Han ethnicity, with 2 598 persons accounting for 57.17%. The altitude of residence was mainly above 3 500 m, with 1 941 persons accounting for 42.71%. There were 574 alcohol drinkers, accounting for 12.63%. LDH was detected in 1 035 cases, with a detection rate of 22.77%. Multivariable logistic regression analysis showed that after adjusting for gender, age, physical activity, and hypertension, compared to non-drinking residents, alcohol-consuming residents exhibited a 27.6% reduction in the risk of LDH (OR=0.724, 95%CI: 0.544-0.963). No significant interaction effects on LDH risk were observed between alcohol consumption and gender, age, ethnicity, or altitude of residence (all Pfor interaction >0.05). The results of the sensitivity analysis indicated that compared to non-drinking residents, alcohol-consuming residents exhibited a 38.8% reduction in the risk of LDH (OR=0.612, 95%CI: 0.382-0.976). Conclusion Alcohol consumption was statistically associated with a lower risk of LDH.

Objective:To investigate the clinical features and prognostic factors of newly-treated elderly acute myeloid leukemia (AML) patients with intermediate-risk karyotype.Methods:A retrospective case series study was conducted. A total of 87 newly-treated elderly AML patients with intermediate-risk karyotype in the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2013 to December 2023 were selected. The clinical characteristics were summarized. The Kaplan-Meier method was used for survival analysis and Cox proportional hazards model was used to make univariate and multivariate analyses of prognostic factors.Results:The median age [ M ( Q1, Q3)] of 87 patients was 69 (60, 87) years. The patients with normal karyotype and abnormal karyotype accounted for 77.1% (67/87), 22.9% (20/87), respectively. A total of 74 patients (85.1%) had 1 or more gene mutations, of which FLT3-ITD, NPM1 mutation, CEBPA mutation and WT1 high expression accounted for 29.9% (26/87), 26.4% (23/87), 19.5% (17/87), and 65.5% (57/87), respectively; additionally, 44.7% (39/87) of patients had 2 or more gene mutations. The objective response rate of patients after induction therapy was 47.7% (41/87), while the relapse rate was 73.2% (30/41). The median progression-free survival (PFS) time was 7.8 months, and the median overall survival (OS) time was 12.1 months. Univariate analysis result revealed that age, FLT3-ITD, hypomethylating agents, and minimal residual disease complete remission (MDR-CR) were factors influencing the OS of newly-treated elderly AML patients with intermediate-risk karyotype (all P < 0.05). Multivariate analysis indicated that MDR-CR was an independent risk factor for OS (yes vs. no: HR = 0.27, 95% CI: 0.14-0.51, P < 0.001). Conclusions:Newly-treated elderly AML patients with intermediate-risk karyotype have a high relapse rate and poor prognosis, and MDR-CR is identified as an independent influencing factor for the prognosis of these patients.

Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70％of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66％antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

This study aims to simultaneously detect three antibiotic resistance genes(blaNDM,mcr-1 and cfr).A triplex fluorescence quantitative PCR method was established.Plasmids,primers and probes were designed and optimized.The method could specifically detect blaNDM,mcr-1 and cfr,but not other antibiotic resistance genes.The R2 of the standard curves of the three antibiotic re-sistance genes were all greater than 0.999,and the coefficients of variation were all lower than 1％.The lowest detection limits of the plasmids were 1 × 102 copies/μL.This method was used to de-tect 800 bacterial samples.The results showed that 32 samples contained mcr-1 gene,40 samples contained blaNDM gene,2 samples contained cfr gene,8 samples contained both mcr-1 and blaNDM genes.There were no samples carrying three antibiotic resistance genes detected.The results indica-ted that the triplex fluorescence quantitative PCR method established in this experiment had the advantages of high sensitivity,specificity and stability.It was suitable for rapid detection of blaNDM,mcr-1 and cfr antibiotic resistance genes in clinical practice.It provided a convenient and quick method basis for the detection of antibiotic resistance genes.

Background and Aims:In recent years,with the continuous progress of systemic therapy,hepatic arterial infusion chemotherapy(HAIC)combined with immune checkpoint inhibitors and anti-angiogenic agents has demonstrated significant efficacy in the treatment of advanced hepatocellular carcinoma(HCC).However,direct comparisons between different immunotherapeutic targets,such as PD-1 and PD-L1 inhibitors,in terms of clinical benefit and safety remain limited.This study aimed to compare the efficacy and safety of HAIC plus bevacizumab and sintilimab(HAIC-BP1)versus HAIC plus bevacizumab and atezolizumab(HAIC-BPL)in advanced HCC.Methods:A retrospective analysis was conducted on 88 patients with advanced HCC who received first-line HAIC-BP1or HAIC-BPL at Sun Yat-sen University Cancer Center between January 2020 and December 2022.Progression-free survival(PFS),overall survival(OS),objective response rate(ORR),disease control rate(DCR),and adverse events(AEs)were compared between the two groups.Cox regression analysis was performed to identify prognostic factors affecting PFS.Results:A total of 47 patients were included in the HAIC-BP1 group and 41 patients in the HAIC-BPL group,with no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The ORR(59.6%vs.65.9%)and DCR(72.3%vs.80.5%)did not significantly differ between the HAIC-BP1 group and the HAIC-BPL group(both P>0.05).After a median follow-up of 16.3 months,there were no significant differences in median OS(21.3 months vs.22.4 months)or median PFS(6.7 months vs.6.2 months)between the HAIC-BP1 group and the HAIC-BPL group(both P>0.05).The incidence of AEs was similar,and no treatment-related deaths occurred.Multivariate Cox regression analysis identified tumor diameter>10 cm as an independent adverse prognostic factor for PFS(HR=0.48,95%CI=0.27-0.83,P=0.009).Conclusion:Both HAIC-BP1 and HAIC-BPL demonstrated comparable efficacy and favorable safety profiles as first-line treatment options for advanced HCC.Tumor diameter>10 cm was an independent unfavorable prognostic factor for PFS,underscoring the importance of patient stratification in clinical decision-making.

Objective The three UGT genes involved in the synthesis of flavonoid glycosides in the wild chrysanthemum were cloned,fused and expressed in prokaryotic system,which provided a basis for further study of the functions of these genes in the synthesis of flavonoid compounds.Methods three candidate UDP-glycosyltransferase(UGT)family genes were successfully cloned from flower tissue cDNA of diploid Chrysanthemum indicum.L in Hubei,namely:CiUGT1(1425 bp),CiUGT2(1311 bp)and CiUGT3(1314 bp)encoded opal fraction of 51.72,48.08 and 48.28 kDa,respectively.After the physical and chemical properties of the protein were analyzed,the recombinant plasmid was constructed by seamless Klon technology,and the recombinant proteins of CiUGT2 and CiUGT3 were successfully expressed in Escherichia coli.Results SDS-PAGE analysis showed that the purified CiUGT2 and CiUGT3 protein samples were about 0.2 mg/mL and 1.4 mg/mL,respectively.Conclusion Two candidate UGTs were obtained to catalyze the synthesis of flavonoid 7-O-glucosides in Chrysanthemum indicum.L,which provide the theoretical basis for the molecular mechanism of flavonoid glycosides biosynthesis in the capitulum of Chrysanthemum indicum.L.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective To explore the necessity,significance,and implementation forms of integrating tumor health sci-ence popularization education and communication practice into clinical undergraduate oncology teaching.Methods Science pop-ularization education was conducted among clinical undergraduate oncology students at Guangzhou Medical University who partici-pated in science communication activities.Before and after the activities,online questionnaires were distributed via Wenjuanxing.Student questionnaires were collected within the deadline,while two different versions of questionnaires were randomly distributed to 30 parents and 20 faculty members involved in oncology teaching to assess their views and attitudes toward the necessity of pub-lic cancer prevention science communication,as well as the integration of science popularization education and communication practice into oncology teaching,and to evaluate its educational significance.Results The analysis of the questionnaires showed that nearly all or the vast majority of students,parents,and teachers highly recognized the necessity of public cancer prevention science education and awareness-raising,as well as the importance of medical students disseminating tumor health knowledge.They also strongly supported the inclusion of science popularization education in oncology teaching.Most students felt that their knowledge level improved significantly after the education sessions.Conclusion The integration of tumor science popularization education and communication practice into oncology teaching is highly necessary and meaningful.It significantly enhances students' health science literacy,sense of mission,and responsibility.It is recommended to incorporate such content into oncolo-gy teaching.