Patients with rare disease are a vulnerable group in healthcare who urgently need more attention from the government and society. Despite their overall number, they face challenges such as limited diagnosis and treatment options, poor access to medications, and heavy financial burdens. Providing better protection for this group is not only essential for public well-being, but also an important indicator of societal progress. This paper analyzes the current status and challenges of rare disease protection in China, with a focus on building diagnostic and treatment networks, optimizing the multitiered social security system, and improving pharmaceutical access mechanisms. It highlights issues such as incomplete health insurance coverage, unequal resource allocation, and insufficient incentives for drug development. To address these challenges, we suggest strengthening policies, improving the multitiered social security system, encouraging social support, and promoting medical and pharmaceutical innovation to provide comprehensive care for rare disease patients.

Objective:To analyze the evolution of ceftazidime/avibactam (CZA) resistance phenotyes and clinical features of 11 ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates carrying bla KPC. Methods:Eleven CRKP isolates, designated K01 to K11, obtained from infected liver transplant patients from June to September 2024 were retrospectively studied. Broth microdilution method, whole genome sequencing (WGS) and plasmid conjugation assays were employed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural characteristics of these CRKP isolates. Clinical data were simultaneously collected and organized to analyze the correlation between bla KPC gene mutations and the clinical efficacy of antimicrobial therapy. Results:All eleven isolates of CRKP exhibited multidrug resistance phenotypes. Among them, K01-K09 and K11 were sensitive to CZA and resistant to carbapenems, while K10 was resistant to CZA and displayed sensitivity or intermediate resistance to carbapenems. WGS analysis showed that all 11 CRKP isolates belonged to the ST11-KL64 clonal type. Among these isolates, the K01-K09 and K11 isolates carry the bla KPC-2 gene, whereas the K10 isolate carries the bla KPC-33 gene. A single nucleotide mutation in bla KPC-2 (G532T) resulted in a substitution of tyrosine (Y) for aspartic acid (D) at Ambler position 179 (D179Y), causing resistance of CRKP to CZA and reduced sensitivity to Imipenem and Meropenem. The conjugative plasmid was successfully constructed, and compared to the parental strain, its minimum inhibitory concentration (MIC) to CZA increased 32 folds. Clinical data revealed that the patient developed the bla KPC-33 mutation after 51 days of CZA treatment. Conclusions:The bla KPC-33 mutation following CZA treatment for CRKP infection exhibits a considerable delay. It is essential to dynamically monitor the evolution of CRKP resistance to ensure timely adjustment of therapeutic strategies in case of the occurrence of mutations such as bla KPC-33.

Objective·To fabricate a 3D-printed dental crown and bridge resin slurry using digital light processing(DLP)technology,investigate the influence of different printing parameters on its mechanical properties,determine the optimal printing parameters,and optimize the composition ratio of DLP-printed crown and bridge resin.Methods·Based on the viscosity characteristics of the mixture,the optimal ratio of urethane dimethacrylate(UDMA)to poly(propylene glycol)dimethacrylate(PPGDMA)was explored.After silanizing silicon dioxide(SiO2),it was mixed with UDMA,PPGDMA,and 2,4,6-trimethylbenzoyl bis(p-tolyl)phosphine oxide(TMO)to prepare DLP-printed dental crown and bridge resin slurries with different solid contents,and their rheological properties were tested.The Beer-Lambert equation was used to calculate the light penetration depth and critical exposure energy of the printing slurry.Based on these values,different exposure intensities,exposure times,post-curing times,and layer thicknesses were set respectively to carry out a series of printing experiments.By comparing and analyzing the flexural strength of the products under different printing parameters,the optimal printing parameter combination was screened out.Results·Viscosity tests showed that the optimal UDMA-to-PPGDMA ratio was 6∶4.The rheological behavior of printing slurries with different solid contents was tested,and the results showed that the DLP-printed dental crown and bridge resin with a solid content of 22%exhibited the best printing performance.According to the Beer-Lambert analysis,the light penetration depth Dp of the printing slurry was 119.79 μm,and the critical exposure energy Ec was 25.54 mJ/cm2.When the exposure intensity was 20 mW/cm2,the flexural strength reached a maximum of(132.39±8.92)MPa,and the difference was statistically significant(P<0.05).The flexural results of different exposure times showed that the flexural strength could reach(131.73±9.43)MPa when the single-layer exposure time was 3.0 s,and there was no significant difference when the exposure time was further increased.The flexural results of different post-curing times showed that when the post-curing time reached 30 min,there was no significant relationship between the flexural strength value and the increase in post-curing time.Regarding the influence of different layer thicknesses on the flexural performance,the test results showed that when the layer thickness was 50 μm,the result was the best,and the difference was statistically significant(P<0.001).Conclusion·Based on viscosity and rheological tests,a DLP-printable crown and bridge resin slurry was successfully developed.The optimal printing parameters were determined through statistical analysis of flexural strength:exposure intensity of 20 mW/cm2,exposure time of 3.0 s,post-curing time of 30 min,and a layer thickness of 50 μm.

Objective:To explore the dual mediating effects of health belief and depression among health knowledge, social support, and health behaviors based on the capacity, opportunity, motivation-behavior (COM-B) model, and analyze the influencing factors of health behaviors in patients with ischemic stroke.Methods:This multi-center cluster sampling research recruited ischemic stroke patients ( n=1 696) who were hospitalized in neurology departments of five tertiary hospitals in Henan Province from October 2023 to October 2024. A cross-sectional investigation was conducted using the general information questionnaire, social support rating scale (SSRS), stroke prevention knowledge questionnaire(SPKQ), short form health belief model scale(SF-HBMS), health promoting lifestyle profile-Ⅱ (HPLP-Ⅱ), and patient health questionnaire-9(PHQ-9) to ultimately reveal the pathways and effect sizes among variables. Partial correlation analysis and multiple linear stepwise regression analysis were conducted to examine the relationships among social support, health knowledge, health belief, health behaviors, and depression in stroke patients by SPSS 26.0 software. Structural equation modeling was constructed using AMOS 28.0 software, and the mediating effect was tested using the Bootstrap method. Results:The scores of social support, health knowledge, health belief, and health behaviors among ischemic stroke patients were (37.46±9.94), (26.56±6.84), (75.62±12.62) and (130.79±26.27), respectively. The score of depression was 5.00 (2.00, 8.00). Health behaviors were positively correlated with health knowledge, social support, and health belief( r=0.333, 0.246, 0.267, all P<0.05), while negatively correlated with depression ( r=-0.146, P<0.05). Multiple linear stepwise regression analysis showed that health knowledge, social support, health belief, and depression were all influencing factors of health behaviors in ischemic stroke patients (all P<0.05). Health belief (effect value=0.068, 95% CI=0.048-0.093) and depression (effect value=0.009, 95% CI=0.003-0.018) both played partial mediating roles between health knowledge and health behaviors, accounting for 17.3%(0.077/0.446) of the total effect. Meanwhile, health belief (effect value=0.045, 95% CI=0.029-0.063) and depression (effect value=0.016, 95% CI=0.008-0.027) both played partial mediating roles between social support and health behaviors, accounting for 26.5%(0.061/0.230) of the total effect. Conclusion:Health knowledge and social support can not only directly influence health behaviors but also indirectly affect them through health belief and depression in patients with ischemic stroke.

Objective·To fabricate a 3D-printed dental crown and bridge resin slurry using digital light processing(DLP)technology,investigate the influence of different printing parameters on its mechanical properties,determine the optimal printing parameters,and optimize the composition ratio of DLP-printed crown and bridge resin.Methods·Based on the viscosity characteristics of the mixture,the optimal ratio of urethane dimethacrylate(UDMA)to poly(propylene glycol)dimethacrylate(PPGDMA)was explored.After silanizing silicon dioxide(SiO2),it was mixed with UDMA,PPGDMA,and 2,4,6-trimethylbenzoyl bis(p-tolyl)phosphine oxide(TMO)to prepare DLP-printed dental crown and bridge resin slurries with different solid contents,and their rheological properties were tested.The Beer-Lambert equation was used to calculate the light penetration depth and critical exposure energy of the printing slurry.Based on these values,different exposure intensities,exposure times,post-curing times,and layer thicknesses were set respectively to carry out a series of printing experiments.By comparing and analyzing the flexural strength of the products under different printing parameters,the optimal printing parameter combination was screened out.Results·Viscosity tests showed that the optimal UDMA-to-PPGDMA ratio was 6∶4.The rheological behavior of printing slurries with different solid contents was tested,and the results showed that the DLP-printed dental crown and bridge resin with a solid content of 22%exhibited the best printing performance.According to the Beer-Lambert analysis,the light penetration depth Dp of the printing slurry was 119.79 μm,and the critical exposure energy Ec was 25.54 mJ/cm2.When the exposure intensity was 20 mW/cm2,the flexural strength reached a maximum of(132.39±8.92)MPa,and the difference was statistically significant(P<0.05).The flexural results of different exposure times showed that the flexural strength could reach(131.73±9.43)MPa when the single-layer exposure time was 3.0 s,and there was no significant difference when the exposure time was further increased.The flexural results of different post-curing times showed that when the post-curing time reached 30 min,there was no significant relationship between the flexural strength value and the increase in post-curing time.Regarding the influence of different layer thicknesses on the flexural performance,the test results showed that when the layer thickness was 50 μm,the result was the best,and the difference was statistically significant(P<0.001).Conclusion·Based on viscosity and rheological tests,a DLP-printable crown and bridge resin slurry was successfully developed.The optimal printing parameters were determined through statistical analysis of flexural strength:exposure intensity of 20 mW/cm2,exposure time of 3.0 s,post-curing time of 30 min,and a layer thickness of 50 μm.

Objective:To analyze the research trends and hotspots of artificial intelligence (AI) in four top-tier large hospitals in the United States based on bibliometrics, for references for hospitals in China.Methods:From the Web of Science Core Collections database, AI research papers published by researchers affiliated with four major hospitals in the United States (Mayo Clinic, Cleveland Clinic, The Johns Hopkins Hospital, and Massachusetts General Hospital) from 1991 to 2023 were retrieved. Bibliometric analysis, co-occurrence network analysis and thematic analysis were adopted to analyze the annual number of published papers, number of literature citations, high-frequency author collaboration networks, high-frequency keywords, and research hotspots.Results:A total of 509 English-language literatures were included, and the number of published papers showed explosive growth starting from 2021, with the highest number of publications (153 papers) in 2023. Massachusetts General Hospital had the largest number of papers, totaling 191. 10 papers had more than 240 citations. From the perspective of high-frequency author collaboration networks, two large research teams and five small research teams have been formed, and cross team collaboration has emerged. 45 high-frequency keywords (frequency≥4 times) shaped three clusters, inluding artificial intelligence technology, cardiovascular disease, and medical imaging. The research hotspots had shifted from traditional technology development to multi scenario applications driven by machine learning and deep learning.Conclusions:In recent years, AI related research in four large hospitals in the United States had been in a period of rapid growth, with the number of papers increasing year by year. Mature research teams had been formed, and research trends were rapidly in line with advances in AI technology. Chinese hospitals could learn from their developmental experiences, increase cross institutional cooperation research efforts, strengthen the clinical translation and application of medical AI technology, and continuously promote the high-quality development of medical AI research in China.

Objective To explore current status and potential subtypes of elderly stroke patients' medication literacy among,and to analyze related influencing factors of different subtypes.Methods A total of 285 elderly stroke patients admitted in the First Affiliated Hospital of Zhengzhou University from November 2023 to June 2024 were selected as subjects.General Information questionnaire,medication literacy scale for elderly patients with chronic diseases,and perceived social support scale were conducted.Latent profile analysis(LPA)of elderly stroke patients' medication literacy was conducted,and Logistic regression analysis was used to explore influencing factors of different profiles.Results Score of medication literacy scale for elderly stroke patients was(48.26±12.51)points.Medication literacy among elderly stroke patients can be divided into 3 profiles,namely proactive-high literacy type(51.9％),balanced-medium literacy type(34.0％),and dependent-low literacy type(14.1％).Logistic regression analysis showed that recent medication types,current place of residence,educational level,diabetes,and social support were the influencing factors of elderly stroke patients' medication literacy(P＜0.05).Conclusion The level of medication literacy among elderly stroke patients is medium,which is characterized by 3 categories.Medical staffs targeted intervention should be adopted according to different category characteristics,so as to accurately meet their nursing needs,finally improve the level of elderly stroke patients' medication literacy.

Objective:To explore the dual mediating effects of health belief and depression among health knowledge, social support, and health behaviors based on the capacity, opportunity, motivation-behavior (COM-B) model, and analyze the influencing factors of health behaviors in patients with ischemic stroke.Methods:This multi-center cluster sampling research recruited ischemic stroke patients ( n=1 696) who were hospitalized in neurology departments of five tertiary hospitals in Henan Province from October 2023 to October 2024. A cross-sectional investigation was conducted using the general information questionnaire, social support rating scale (SSRS), stroke prevention knowledge questionnaire(SPKQ), short form health belief model scale(SF-HBMS), health promoting lifestyle profile-Ⅱ (HPLP-Ⅱ), and patient health questionnaire-9(PHQ-9) to ultimately reveal the pathways and effect sizes among variables. Partial correlation analysis and multiple linear stepwise regression analysis were conducted to examine the relationships among social support, health knowledge, health belief, health behaviors, and depression in stroke patients by SPSS 26.0 software. Structural equation modeling was constructed using AMOS 28.0 software, and the mediating effect was tested using the Bootstrap method. Results:The scores of social support, health knowledge, health belief, and health behaviors among ischemic stroke patients were (37.46±9.94), (26.56±6.84), (75.62±12.62) and (130.79±26.27), respectively. The score of depression was 5.00 (2.00, 8.00). Health behaviors were positively correlated with health knowledge, social support, and health belief( r=0.333, 0.246, 0.267, all P<0.05), while negatively correlated with depression ( r=-0.146, P<0.05). Multiple linear stepwise regression analysis showed that health knowledge, social support, health belief, and depression were all influencing factors of health behaviors in ischemic stroke patients (all P<0.05). Health belief (effect value=0.068, 95% CI=0.048-0.093) and depression (effect value=0.009, 95% CI=0.003-0.018) both played partial mediating roles between health knowledge and health behaviors, accounting for 17.3%(0.077/0.446) of the total effect. Meanwhile, health belief (effect value=0.045, 95% CI=0.029-0.063) and depression (effect value=0.016, 95% CI=0.008-0.027) both played partial mediating roles between social support and health behaviors, accounting for 26.5%(0.061/0.230) of the total effect. Conclusion:Health knowledge and social support can not only directly influence health behaviors but also indirectly affect them through health belief and depression in patients with ischemic stroke.

Objective The effects of stachydrine(STA)on the proliferation,apoptosis and radiosensitivity of acute myeloid leukemia(AML)cells by regulating the transcription factor forkhead box protein O3(FOXO3)-forkhead box protein M1(FOXM1)signaling axis.Methods Human AML cells(HL-60)were treated with STA at a concentration of 50～1 600 μmol/L,and the activity of HL-60 cells was detected using the cell counting kit-8(CCK-8)method to screen for the optimal drug concentration;HL-60 cells were separated into Control group,low,medium,and high concentration STA groups(STA-L group,STA-M group,STA-H group),STA+lentivirus transfection control group(STA-H+LV-NC group),and high-concentration STA+FOXO3 overexpression lentiviral group(STA-H+LV-FOXO3 group).5-ethyny1-2'-deoxyuridine(Edu)was applied to detect HL-60 cell proliferation;flow cytometry(FCM)was applied to detect cell apoptosis;cell cloning experiments were applied to detect the radiotherapy sensitivity of cells;Western blot was applied to detect the expression of cell proliferation antigen markers(Ki67),Cyclin D1,Caspase-3,B-cell lymphoma2 assaciated X protein(Bax),FOXO3,and FOXM1 proteins.Results STA concentrations of 100,200 and 400 μmol/L were selected for subsequent experiments.Compared with the control group,the positive rate of Ki67,Cyclin D1,Edu,FOXO3 and FOXM1 expression levels in the STA-L,STA-M,and STA-H groups decreased sequentially(tSTA-L=2.169～5.879,tSTA-M=3.089～11.284,tSTA-H=4.572～11.502),Caspase-3 and Bax expression levels,the apoptosis rate,increased sequentially(tSTA-L=9.171,10.082,20.144;tSTA-M=5.435,7.530,7.450;tSTA-H=4.138,4.159,5.956)and the differences were statistically significant(all P<0.05),respectively.Compared with the STA-H+LV-NC group,the positive rate of Edu and the expression levels of Ki67,Cyclin D1,FOXO3 and FOXM1 were obviously increased in the STA-H+LV-FOXO3 group(t=10.055～16.267),Caspase-3 and Bax expression levels,the apoptosis rate were obviously reduced(t=5.736,5.433,8.933),and the differences were statistically significant(all P<0.05),respectively.The colony formation rate of HL-60 cells in the radiotherapy group and STA+radiotherapy group decreased with the increase of radiotherapy dose,and the differences were statistically significant(F=78.630,137.843,all P<0.05),and the colony formation rate of HL-60 cells in the STA+radiotherapy group was lower than that in the radiotherapy group at the same dose(t=1.480～11.301,all P<0.05).Conclusion Stachydrine inhibits AML cell proliferation,induces apoptosis,and enhances radiotherapy sensitivity by inhibiting the FOXO3-FOXM1 signaling axis.

Objective The effects of stachydrine(STA)on the proliferation,apoptosis and radiosensitivity of acute myeloid leukemia(AML)cells by regulating the transcription factor forkhead box protein O3(FOXO3)-forkhead box protein M1(FOXM1)signaling axis.Methods Human AML cells(HL-60)were treated with STA at a concentration of 50～1 600 μmol/L,and the activity of HL-60 cells was detected using the cell counting kit-8(CCK-8)method to screen for the optimal drug concentration;HL-60 cells were separated into Control group,low,medium,and high concentration STA groups(STA-L group,STA-M group,STA-H group),STA+lentivirus transfection control group(STA-H+LV-NC group),and high-concentration STA+FOXO3 overexpression lentiviral group(STA-H+LV-FOXO3 group).5-ethyny1-2'-deoxyuridine(Edu)was applied to detect HL-60 cell proliferation;flow cytometry(FCM)was applied to detect cell apoptosis;cell cloning experiments were applied to detect the radiotherapy sensitivity of cells;Western blot was applied to detect the expression of cell proliferation antigen markers(Ki67),Cyclin D1,Caspase-3,B-cell lymphoma2 assaciated X protein(Bax),FOXO3,and FOXM1 proteins.Results STA concentrations of 100,200 and 400 μmol/L were selected for subsequent experiments.Compared with the control group,the positive rate of Ki67,Cyclin D1,Edu,FOXO3 and FOXM1 expression levels in the STA-L,STA-M,and STA-H groups decreased sequentially(tSTA-L=2.169～5.879,tSTA-M=3.089～11.284,tSTA-H=4.572～11.502),Caspase-3 and Bax expression levels,the apoptosis rate,increased sequentially(tSTA-L=9.171,10.082,20.144;tSTA-M=5.435,7.530,7.450;tSTA-H=4.138,4.159,5.956)and the differences were statistically significant(all P<0.05),respectively.Compared with the STA-H+LV-NC group,the positive rate of Edu and the expression levels of Ki67,Cyclin D1,FOXO3 and FOXM1 were obviously increased in the STA-H+LV-FOXO3 group(t=10.055～16.267),Caspase-3 and Bax expression levels,the apoptosis rate were obviously reduced(t=5.736,5.433,8.933),and the differences were statistically significant(all P<0.05),respectively.The colony formation rate of HL-60 cells in the radiotherapy group and STA+radiotherapy group decreased with the increase of radiotherapy dose,and the differences were statistically significant(F=78.630,137.843,all P<0.05),and the colony formation rate of HL-60 cells in the STA+radiotherapy group was lower than that in the radiotherapy group at the same dose(t=1.480～11.301,all P<0.05).Conclusion Stachydrine inhibits AML cell proliferation,induces apoptosis,and enhances radiotherapy sensitivity by inhibiting the FOXO3-FOXM1 signaling axis.