Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

Post-stroke cognitive impairment(PSCI) is one of the common complications in stroke patients, mainly manifested as impairments in memory, attention, and orientation. Adenosine monophosphate-activated protein kinase(AMPK), as a crucial intracellular energy sensor, has attracted extensive research attention in the field of PSCI in recent years. This paper provides a comprehensive review of the research progress on AMPK-related signaling pathways and their roles in PSCI, with a focus on exploring action mechanisms of AMPK in processes such as oxidative stress, neuroinflammation, autophagy, and apoptosis. Additionally, it summarizes the prospects and challenges of AMPK as a potential target for improving PSCI, aiming to offer new theoretical foundations for the clinical prevention and treatment of PSCI.

Objective:To explore the role of retinoic acid-related orphan receptor α (RORα) in cognitive impairment induced by chronic alcohol consumption in mice.Methods:(1)The SPF grade RORαflox/flox transgenic mice aged 8 weeks were generated, and 22 transgenic mice were evenly divided into two groups by the method of matching body mass, which were the control group (Con group) and the alcohol group (EtOH group), with 11 mice in each group.(2)Emx1-Cre transgenic mice were used to selectively knock out the RORα gene in the forebrain of RORαflox/flox transgenic mice, producing conditional knockout mice (cKO mice) with the genotype RORαflox/flox-Emx1-Cre+ /+. Fourteen cKO mice were further split into two groups by the method of matching body mass, which were the conditional knockout group (cKO group) and the conditional knockout + alcohol group (cKO + EtOH group), with 7 mice in each group. A chronic alcohol use cognitive impairment model was developed in the EtOH group and cKO + EtOH group through the two-bottle free-choice method, while the Con group and cKO group were given two bottles of water for the same period. Cognitive abilities of mice in all groups were evaluated using behavioral novel object recognition test and Y-maze test.RORα mRNA and protein expression levels in the hippocampus of the Con group and EtOH group were assessed by RT-qPCR and Western blot, respectively.The GraphPad Prism 9.0 software was used for data analysis.One-way ANOVA was used for the comparison of multiple groups and Tukey test was used for further pairwise comparisons.Results:(1) Comparison between Con group and EtOH group: the relative levels of ROR α protein (0.63±0.04) and mRNA (0.78±0.03) in the hippocampus of mice in the EtOH group were significantly lower than those in the Con group((1.00±0.06), (1.00±0.05), both P<0.05). The duration of the EtOH group in the Y maze was significantly lower than that of the Con group ((212.30±32.05) s, (129.30±21.50) s, P<0.05), and the new object recognition index of the EtOH group was lower than that of the Con group ((14.73±25.49)% vs (-15.55±27.88)%, P=0.08). (2)Comparison between Con group and cKO group: the frequency and duration of entering the Y maze of mice in the cKO group ((7.43±2.30) times, (124.10±13.95) s) were lower than those in the Con group ((14.90±3.65) times, (212.30±32.05) s, both P<0.05). There was no statistically significant difference in the new object recognition index between the cKO group and the Con group ( P>0.05). (3) Comparison between the cKO+ EtOH group and the cKO group: the frequency ((2.71±1.11)times) and duration ((161.70±17.95) s) of entering the new heteroarm of Y maze in the KO+ EtOH group were lower than those in the cKO group ((7.43±2.30) times, (124.10±13.95) s, both P<0.05), and there was no statistically significant difference in the new object recognition index ( P>0.05). (4) Comparison between the cKO+ EtOH group and the EtOH group: the frequency of entering new heteroarm of the Y maze in the cKO+ EtOH group ((2.71±1.11)times) was significantly lower than that in the EtOH group (12.18±4.49) ( P<0.05), while there was no statistically significant difference in other behavioral results between the two groups ( P>0.05). Conclusion:Chronic alcohol consumption leads to cognitive impairment through the downregulation of RORα in the hippocampus of mice. Specific knockout of RORα in the forebrain exacerbates cognitive impairment induced by chronic alcohol use. RORα may represent a potential therapeutic target for cognitive impairment resulting from chronic alcohol consumption.

Objective:To present an evaluation indicator system for access to cancer screening services.Methods:The evaluation indicator pool was constructed through a scoping review. The theoretical framework was constructed based on the multi-source indicators, and the qualitative expert consultation method was employed to form the initial version of the three-level evaluation indicator system. Delphi expert consultation method was conducted in two rounds to evaluate the relevance, importance, and availability of the proposed evaluation indicator system. The expert positive coefficient, authority coefficient, coordination degree of expert opinions, and concentration of expert opinions were subjected to analysis. Subsequently, the three-level evaluation indicator system for access to cancer screening services was adjusted and determined based on the boundary value method and the open opinions of experts. Finally, the combination weight method was employed to determine the weight.Results:The initial version of the indicator system comprised 3 primary (first-level) indicators, 11 secondary (second-level) indicators, and 46 tertiary (third-level) indicators. Delphi expert consultation was conducted for the initial version, and 17 experts ultimately completed it, exhibiting a positive coefficient of 100% and an authority coefficient of 0.87. In comparison to the initial round of consultation, Kendall's W coefficient ranges (0.15-0.43, all P<0.05) of relevance, importance, and availability scores for each tertiary indicator in the second round exhibited an improvement. The analysis of the importance dimension indicates that expert opinions are also more concentrated, as evidenced by an increase of 8.5% and 7.0% in the proportion of the tertiary indicators with an arithmetic mean above 8 and a full mark ratio above 0.5, respectively. The final evaluation indicator system comprises three primary indicators, with the weights of structure evaluation, process evaluation, and outcome evaluation being 0.338, 0.378, and 0.285, respectively. It also comprises 11 secondary indicators and 45 tertiary indicators. Conclusions:The evaluation indicator system developed in this article can be an effective evaluation tool for quantitative comparison of access to cancer screening services across different populations, cancer types, and before and after intervention. Furthermore, it is recommended that the system undergo continuous optimization concerning its application.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

OBJECTIVES: To evaluate the regulatory effects of lncRNA LINC00261 on proliferation, invasion, and metastasis of esophageal squamous cell carcinoma (ESCC) cells. METHODS: The differentially expressed RNAs in ESCC were identified using the GSE149612 dataset from the GEO database. PCR was used to detect LINC00261 expression levels in clinical ESCC and normal esophageal tissue samples and in multiple ESCC cell lines and normal esophageal epithelial cells (HEEC). In ESCC cells, the effects of overexpression of LINC00261 on cell proliferation, invasion, metastasis and apoptosis were analyzed using CCK-8 assay, clone formation assay, Transwell assay and flow cytometry. The potential targets of LINC00261 were predicted using bioinformatics tools including ENCORI and verified using dual-luciferase reporter assay and Western blotting. The effects of LINC00261 overexpression on ESCC were confirmed in a nude mouse model bearing ESCC xenograft. RESULTS: Analysis of the GSE149612 dataset revealed significantly lower LINC00261 expression in ESCC tissues and cell lines. In cultured ESCC cells, LINC00261 overexpression markedly suppressed cell proliferation, invasion, and metastasis and promoted cell apoptosis. Dual-luciferase reporter assays confirmed that LINC00261 targets the miR-23a-3p/ZNF292 axis. In the tumor-bearing mouse model, LINC00261 overexpression significantly inhibited ESCC xenograft proliferation and metastasis. CONCLUSIONS LINC00261 suppresses ESCC progression by targeting the miR-23a-3p/ZNF292 axis, suggesting a potential therapeutic strategy for ESCC treatment.
Humans ; MicroRNAs/genetics* ; Cell Proliferation ; Esophageal Neoplasms/genetics* ; Animals ; Esophageal Squamous Cell Carcinoma ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Cell Line, Tumor ; Neoplasm Invasiveness ; Mice ; Carcinoma, Squamous Cell/genetics* ; Apoptosis ; Gene Expression Regulation, Neoplastic ; Neoplasm Metastasis

Objective To compare regression models for age estimation constructed based on the Pulp Dentinal Index(PDI)of the first permanent molars and explore a more accurate and applicable novel method.Methods A total of 900 Cone Beam Computed Tomography(CBCT)image datasets from adult Han Chinese individuals(455 males and 445 females)residing in Sichuan province,China,were collected from the Affiliated Hospital of North Sichuan Medical College.The PDI of the first permanent molars were measured using Mimics software.Regression analysis was performed with age as the dependent variable and PDI as the independent variable to establish and validate the optimal mathematical model for age estimation.Results Strong correlations were observed between the PDI of all four first permanent molars and age,with the correlation being stronger for maxillary teeth compared to mandibular teeth,and the highest correlation found in the left maxillary first molar among females(r=0.881).Significant differences in PDI were identified between maxillary and mandibular positions as well as between genders(P＜0.05),but not between left and right positions(P＞0.05).Among the 11 mathematical models constructed,the cubic regression model outperformed others,with the left maxillary first molar model demonstrating the best performance(Age=73.93-70.79x-68.75x2+94.33x3),yielding a mean absolute error(MAE)of 4.88 years.Conclusion Among the 11 regression models constructed in this study based on CBCT-measured PDI values of the first permanent molars,the cubic regression model exhibited the highest accuracy,with an MAE of 4.88 years.

Objective:To investigate the supervisor-student relationship experience of nursing postgraduates from the perspective of humanistic care, identify the influencing factors for students' care experience, and provide a reference for building a good supervisor-student relationship pattern with humanistic care.Methods:Objective sampling was used to enroll 15 nursing postgraduates from colleges and universities in Wuhan, Hubei Province, Beijing, and Guangzhou, Guangdong Province. A semi-structured interview was then conducted in the students. Nvivo 12 software and the Colaizzi seven-step analysis method were used for sorting and analysis of the interview data.Results:Five themes and 15 sub-themes (namely, daily interpersonal interaction, academic interaction, emotional communication, internal growth, and professional literacy) were extracted. Among these themes, equal communication and mental health care were of particular concern to the students. The nursing postgraduates also expected their tutors to provide care in their daily life and help them develop three essential values.Conclusions:The supervisor-student relationship from the perspective of humanistic care is becoming more individualized and diversified. The tutors should provide multidimensional care to nursing postgraduates based on the students' personal characteristics. Meanwhile, they should focus on developing students' humanistic care abilities to cultivate high-level nursing professionals with a high humanistic care foundation.

Purpose To investigate the feasibility of a deep learning framework to automatically analyze echocardiographic color Doppler videos in detecting valvular regurgitation.Materials and Methods This study retrospectively collected echocardiographic images of 1 109 patients with valvular regurgitation in the Fourth Medical Center of PLA General Hospital,from June 2015 to September 2019 as the training and validation sets.A prospective continuous collection of 1 562 echocardiography images was used as the test set in the Fourth Medical Center of PLA General Hospital from May 13 to June 13,2023,including 378 cases of mitral regurgitation and 223 cases of aortic regurgitation.This study developed deep learning networks to establish view classification model and valvular regurgitation recognition model,including the efficiency of section classification of deep learning models.Results The deep learning view classification model in this study could automatically identify two views for diagnosing mitral regurgitation and aortic regurgitation.The recognition accuracy for the parasternal long axis color Doppler view and the apical four chamber mitral color Doppler view was 1.00 and 0.93,respectively.The sensitivity,specificity,accuracy and area under the curve of the deep learning model for diagnosing mitral regurgitation were 0.847,0.852,0.849 and 0.930,respectively.The sensitivity,specificity,accuracy and area under the curve of the deep learning model in diagnosing aortic regurgitation were 0.857,0.861,0.859 and 0.940,respectively.Conclusion Deep learning algorithms can automatically identify valvular regurgitation and have the potential to become a screening tool for valvular heart disease.