Druggability evaluation is one of the core processes in new drug development, yet the inaccuracy and high cost of existing in vitro liver models have been a major technical bottleneck, leading to an increasing demand from the pharmaceutical industry for reliable in vitro liver models to enhance the efficiency of new drug research and development. Traditional animal models and in vitro 2D culture models have their limitations in simulating in vivo physiological and pathological conditions, making it challenging to accurately predict drug efficacy and safety. With the advancement of microfluidic technology, in vitro cell culture, and biosensor technology, liver-on-a-chip (LOC) has garnered increasing attention in the field of new drug development in recent years, and is expected to become a powerful tool for addressing the challenges in druggability evaluation. While introducing the construction technology of LOC, this article mainly summarizes the research and application of existing LOC from the perspectives of disease model construction, drug metabolism research, and drug safety evaluation. Furthermore, it analyzes the role of LOC in druggability evaluation and discusses the current challenges and prospects in this field.

Objective:To screen the Alzheimer's disease(AD)-related genes and construct its diagnostic model using bioinformatics technology and machine learning(ML)algorithms,to discuss the immunological characteristics of AD patients,and to provide novel biomarkers for AD diagnosis.Methods:The AD-related gene expression dataset GSE125583 was downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified through differential analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses were performed to explore the biological functions and signaling pathways of DEGs.A protein-protein interaction(PPI)network was constructed,and hub genes were screened using Cytoscape software combined with three ML algorithms:Least Absolute Shrinkage and Selection Operator(LASSO),eXtreme Gradient Boosting(XGBoost),and Random Forest(RF).The screened hub genes were utilized to build an AD diagnostic model via RF,followed by feature importance ranking.The model's efficacy and key genes were evaluated using a test set.Single-sample gene set enrichment analysis(ssGSEA)was used for immune cell infiltration analysis between AD group and control group.Results:Differential analysis identified 1 287 DEGs.The GO functional enrichment analysis results revealed that DEGs were primarily involved in biological functions related to neural signaling,synapses,and vesicles.KEGG signaling pathway enrichment analysis indicated significant enrichment of DEGs in ion transport,neurotransmitter,and ligand-gated channel pathways.Nine overlapping hub genes were screened by the three ML algorithms.In the AD diagnostic model,the top four key genes with highest diagnostic performance were adenylate cyclase-activating polypeptide 1(ADCYAP1),brain-derived neurotrophic factor(BDNF),platelet-derived growth factor receptor β(PDGFRB),and C-X-C motif chemokine receptor 4(CXCR4),with corresponding area under the curve(AUC)values of 0.852,0.795,0.820,and 0.756,respectively.The model achieved an AUC of 0.828,accuracy of 81.25%,sensitivity of 84.40%,and specificity of 71.43%.The immune cell infiltration analysis results demonstrated higher infiltration of macrophages,monocytes,natural killer(NK)cells,and lymphocytes in AD tissue.Among these,NK/natural killer T(NKT)cells and plasmacytoid dendritic cells showed significant correlations with the four key genes(P<0.05).Conclusion:The feature genes screened based on bioinformatics and ML exhibit diagnostic potential for AD.Genes such as ADCYAP1 may serve as potential biomarkers for AD diagnosis,offering significant implications for early prevention and treatment.

Objective:Exploring the efficacy and safety of the combination of programmed cell death protein 1 (PD-1) inhibitors with chemotherapy for the treatment of local recurrence at the primary tumor site of esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy.Methods:Seventy-six patients with local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy, who were treated at the Cancer Hospital Affiliated with Nanjing Medical University from January 2019 to January 2024. All patients received treatment with a PD-1 inhibitor combined with chemotherapy, and the short-term efficacy, long-term efficacy, and adverse reactions were observed. Univariate and multivariate Cox regression models were employed to identify the factors influencing overall survival (OS) and after-recurrence survival (ARS).Results:Among the 76 patients, 7 achieved partial response, 35 had stable disease, and 34 experienced progressive disease. The objective response rate was 9.2% (7/76), and the disease control rate was 55.3% (42/76). With a median follow-up time of 23.1 months, 33 out of 76 patients died. The median survival time was 38.5 months (95% CI: 29.6-47.3 months); the 1-year, 2-year, and 3-year OS were 94.5%, 66.6%, and 51.7%, respectively. The median ARS was 14.7 months (95% CI: 10.4-19.1 months); the 6-month, 12-month, and 24-month ARS were 85.8%, 59.6%, and 25.7%, respectively. Univariate analysis showed that the initial radiation dose, the Eastern Cooperative Oncology Group (ECOG) performance status of patients after recurrence, the recurrence-free interval (RFI), and the approach to chemotherapy treatment following local esophageal recurrence were factors affecting OS and ARS ( P＜0.05). Multivariate analysis showed that initial radiotherapy dose ( HR=0.268, 95% CI: 0.100-0.720), the ECOG performance status after recurrence ( HR=4.106, 95% CI: 1.228-13.728), and RFI ( HR=0.248, 95% CI: 0.106-0.582) were independent prognostic factors for OS. Additionally, the initial radiation dose ( HR=0.289, 95% CI: 0.098-0.853) and the ECOG performance status after recurrence ( HR=5.143,95% CI:1.404-18.838) were independent prognostic factors for ARS. The incidence of treatment-related adverse-reactions was 85.5% (65/76). Grade 3 or higher treatment-related adverse reactions primarily included anemia in 4 cases, leukopenia in 8 cases, neutropenia in 9 cases, thrombocytopenia in 2 cases, liver function abnormalities in 4 cases, and elevated troponin T in 2 cases. There were no cases of treatment-related mortality. Conclusions:The combination of PD-1 inhibitors with chemotherapy is safe and effective for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy and can provide survival benefits for patients. This approach can be considered as a therapeutic option for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy.

OBJECTIVE To optimize the venipuncture disinfection procedures for the patients with psoriasis by modifying the skin pretreatment,number of times of disinfection and action time,evaluate the disinfection effects before and after the modification and observe the impact on skin barrier function.METHODS A total of 78 patients with psoriasis who were hospitalized in Air Force Medical Center of Special Medicine from Jan.2024 to Mar.2025 were enrolled in the study and were randomly divided into the control group and the study group,with 39 cases in each group.Both groups were disinfected with povidone iodine swabs.The control group was treated with a single clockwise spiral wipe centered on the puncture site,and the total time of embrocation and drying time was 60 s;the study group was treated with the modified disinfection method'pretreatment-bidirectional disinfec-tion-120-second drying',which was unidirectional wiping of puncture site skin of hand back with sterile swab in-filtrating with normal saline,a single clockwise spiral wipe centered on the puncture site,counter-clockwise wipe for two times,the total time of embrocation and drying 120 s in total.The skin specimens were collected from the puncture sites for culture and identification of pathogens before the disinfection and after the drying,and the trans-epidermal water loss(TEWL)volume was detected by TewameterTM 300 instrument.RESULTS Totally 16 types of pathogens were isolated from the two groups of patients before the disinfection,among which Staphylococcus spp was dominant.The bacterial colony counts were[26.00(8.00,74.00)]CFU/cm2 in the study group before the disinfection,[41.00(13.00,94.00)]CFU/cm2 in the control group,and there was no significant difference(P=0.081).The bacterial colony counts of the two groups were lower after the disinfection and drying than before the disinfection(P＜0.001),and the bacterial colony counts of the study group were[0.00(0.00,1.00)]CFU/cm2,lower than[1.00(0.00,4.00)]CFU/cm2 of the control group(P=0.042).The TEWL value of the two groups was greater after the disinfection than before the disinfection(P＜0.001),however,there was no between-group difference(P=0.933).CONCLUSION The modified disinfection procedure has more advantages in eradicating pathogens without increasing damage to skin barrier,it provides safer disinfection plans for the patients with psoriasis and is worthy to be promoted in the hospital.

Objective:To establish a normal data model of fetal right ventricular size and function using echocardiography，and to explore the clinical value of quantitative assessment of right ventricular size and function in the diagnosis of congenital heart diseases.Methods:（1）A simple random sampling method was employed to collect 1 004 pregnant women with normal singleton pregnancies at 24 to 32 +6 weeks of gestation who underwent fetal cardiac ultrasound examinations at the First Affiliated Hospital of Air Force Medical University from January 2021 to December 2023. Two-dimensional and M-mode echocardiography were used to measure the right ventricular end-diastolic diameter（RVEDD），right ventricular end-diastolic area（RVEDA），tricuspid annular plane systolic excursion（TAPSE）during systole，and the right ventricular fractional area change（RVFAC）was calculated. The correlations between the above parameters and ultrasound gestational age（USGA）were analyzed. Moreover，percentile growth curves for each parameter were plotted. With the above parameters as dependent variables and the USGA as the independent variable，a Z-score model was established through regression analysis.（2）A stratified sampling method was adopted to select 30 fetuses diagnosed with hypoplastic right heart syndrome（HRHS）and 30 fetuses diagnosed with pulmonary stenosis（PS）during the same period as the case group. The model was verified，and the morphological and functional characteristics of the right ventricle were analyzed. Results:The data of RVEDD，RVEDA，TAPSE，and RVFAC in normal fetuses showed a skewed distribution. Each parameter showed good linear correlations with USGA（ r=0.836，0.834，0.846，0.242；all P<0.001）. The constructed percentile curves for each parameter indicated that RVEDD，RVEDA and TAPSE increased significantly with the growth of USGA，while RVFAC showed a slow downward trend. All parameters in the HRHS group and TAPSE and RVFAC in the PS group deviated significantly from the normal reference range（all P<0.001）. Conclusions:By analyzing RVEDD，RVEDA，TAPSE and RVFAC of normal fetuses，the percentile and Z-score normal reference value models of multiple parameters of fetal right ventricular size and function have been established，providing corresponding standards for quantitative analysis.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

OBJECTIVE To optimize the venipuncture disinfection procedures for the patients with psoriasis by modifying the skin pretreatment,number of times of disinfection and action time,evaluate the disinfection effects before and after the modification and observe the impact on skin barrier function.METHODS A total of 78 patients with psoriasis who were hospitalized in Air Force Medical Center of Special Medicine from Jan.2024 to Mar.2025 were enrolled in the study and were randomly divided into the control group and the study group,with 39 cases in each group.Both groups were disinfected with povidone iodine swabs.The control group was treated with a single clockwise spiral wipe centered on the puncture site,and the total time of embrocation and drying time was 60 s;the study group was treated with the modified disinfection method'pretreatment-bidirectional disinfec-tion-120-second drying',which was unidirectional wiping of puncture site skin of hand back with sterile swab in-filtrating with normal saline,a single clockwise spiral wipe centered on the puncture site,counter-clockwise wipe for two times,the total time of embrocation and drying 120 s in total.The skin specimens were collected from the puncture sites for culture and identification of pathogens before the disinfection and after the drying,and the trans-epidermal water loss(TEWL)volume was detected by TewameterTM 300 instrument.RESULTS Totally 16 types of pathogens were isolated from the two groups of patients before the disinfection,among which Staphylococcus spp was dominant.The bacterial colony counts were[26.00(8.00,74.00)]CFU/cm2 in the study group before the disinfection,[41.00(13.00,94.00)]CFU/cm2 in the control group,and there was no significant difference(P=0.081).The bacterial colony counts of the two groups were lower after the disinfection and drying than before the disinfection(P＜0.001),and the bacterial colony counts of the study group were[0.00(0.00,1.00)]CFU/cm2,lower than[1.00(0.00,4.00)]CFU/cm2 of the control group(P=0.042).The TEWL value of the two groups was greater after the disinfection than before the disinfection(P＜0.001),however,there was no between-group difference(P=0.933).CONCLUSION The modified disinfection procedure has more advantages in eradicating pathogens without increasing damage to skin barrier,it provides safer disinfection plans for the patients with psoriasis and is worthy to be promoted in the hospital.

Objective:To establish a normal data model of fetal right ventricular size and function using echocardiography，and to explore the clinical value of quantitative assessment of right ventricular size and function in the diagnosis of congenital heart diseases.Methods:（1）A simple random sampling method was employed to collect 1 004 pregnant women with normal singleton pregnancies at 24 to 32 +6 weeks of gestation who underwent fetal cardiac ultrasound examinations at the First Affiliated Hospital of Air Force Medical University from January 2021 to December 2023. Two-dimensional and M-mode echocardiography were used to measure the right ventricular end-diastolic diameter（RVEDD），right ventricular end-diastolic area（RVEDA），tricuspid annular plane systolic excursion（TAPSE）during systole，and the right ventricular fractional area change（RVFAC）was calculated. The correlations between the above parameters and ultrasound gestational age（USGA）were analyzed. Moreover，percentile growth curves for each parameter were plotted. With the above parameters as dependent variables and the USGA as the independent variable，a Z-score model was established through regression analysis.（2）A stratified sampling method was adopted to select 30 fetuses diagnosed with hypoplastic right heart syndrome（HRHS）and 30 fetuses diagnosed with pulmonary stenosis（PS）during the same period as the case group. The model was verified，and the morphological and functional characteristics of the right ventricle were analyzed. Results:The data of RVEDD，RVEDA，TAPSE，and RVFAC in normal fetuses showed a skewed distribution. Each parameter showed good linear correlations with USGA（ r=0.836，0.834，0.846，0.242；all P<0.001）. The constructed percentile curves for each parameter indicated that RVEDD，RVEDA and TAPSE increased significantly with the growth of USGA，while RVFAC showed a slow downward trend. All parameters in the HRHS group and TAPSE and RVFAC in the PS group deviated significantly from the normal reference range（all P<0.001）. Conclusions:By analyzing RVEDD，RVEDA，TAPSE and RVFAC of normal fetuses，the percentile and Z-score normal reference value models of multiple parameters of fetal right ventricular size and function have been established，providing corresponding standards for quantitative analysis.

Objective:Exploring the efficacy and safety of the combination of programmed cell death protein 1 (PD-1) inhibitors with chemotherapy for the treatment of local recurrence at the primary tumor site of esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy.Methods:Seventy-six patients with local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy, who were treated at the Cancer Hospital Affiliated with Nanjing Medical University from January 2019 to January 2024. All patients received treatment with a PD-1 inhibitor combined with chemotherapy, and the short-term efficacy, long-term efficacy, and adverse reactions were observed. Univariate and multivariate Cox regression models were employed to identify the factors influencing overall survival (OS) and after-recurrence survival (ARS).Results:Among the 76 patients, 7 achieved partial response, 35 had stable disease, and 34 experienced progressive disease. The objective response rate was 9.2% (7/76), and the disease control rate was 55.3% (42/76). With a median follow-up time of 23.1 months, 33 out of 76 patients died. The median survival time was 38.5 months (95% CI: 29.6-47.3 months); the 1-year, 2-year, and 3-year OS were 94.5%, 66.6%, and 51.7%, respectively. The median ARS was 14.7 months (95% CI: 10.4-19.1 months); the 6-month, 12-month, and 24-month ARS were 85.8%, 59.6%, and 25.7%, respectively. Univariate analysis showed that the initial radiation dose, the Eastern Cooperative Oncology Group (ECOG) performance status of patients after recurrence, the recurrence-free interval (RFI), and the approach to chemotherapy treatment following local esophageal recurrence were factors affecting OS and ARS ( P＜0.05). Multivariate analysis showed that initial radiotherapy dose ( HR=0.268, 95% CI: 0.100-0.720), the ECOG performance status after recurrence ( HR=4.106, 95% CI: 1.228-13.728), and RFI ( HR=0.248, 95% CI: 0.106-0.582) were independent prognostic factors for OS. Additionally, the initial radiation dose ( HR=0.289, 95% CI: 0.098-0.853) and the ECOG performance status after recurrence ( HR=5.143,95% CI:1.404-18.838) were independent prognostic factors for ARS. The incidence of treatment-related adverse-reactions was 85.5% (65/76). Grade 3 or higher treatment-related adverse reactions primarily included anemia in 4 cases, leukopenia in 8 cases, neutropenia in 9 cases, thrombocytopenia in 2 cases, liver function abnormalities in 4 cases, and elevated troponin T in 2 cases. There were no cases of treatment-related mortality. Conclusions:The combination of PD-1 inhibitors with chemotherapy is safe and effective for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy and can provide survival benefits for patients. This approach can be considered as a therapeutic option for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy.