Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

BackgroundMigrant children face many challenges in the process of social change and adaptation to a new environment， especially in school adaptation. Studies have shown that peer attachment plays a vital role in the social adaptation of children and adolescents， while psychological resilience and sense of security， as important psychological resources， also play a moderating and mediating role in individuals' coping with environmental changes. However， there is a lack of systematic research on how peer attachment affects the school adaptation of migrant children through psychological resilience and whether this process is moderated by sense of security. ObjectiveTo explore the relationship between peer attachment and school adaptation of migrant children and to examine the path of psychological resilience and sense of security in it， so as to provide references for improving the school adaptation of migrant children. MethodsUsing cluster sampling method， 695 migrant children in grades 4 to 6 of a primary school in an urban-rural fringe area of Sichuan Province were selected from April 1 to 30， 2022. Assessments were conducted using Revised Inventory for Parent and Peer Attachment （IPPA-R）， Resilience Scale for Chinese Adolescents （RSCA）， Scale of Sense of Security of Children Left Behind （SSSCLB） and Scale of School Adjustment of Student （SSAS）. Process 4.1 was used to examine the role of psychological resilience and sense of security. ResultsA total of 631 （90.79%） valid questionnaires were gathered. There were significant positive correlations among IPPA-R peer attachment subscale score， RSCA score， SSSCLB score and SSAS score （r=0.160~0.600， P<0.01）. Peer attachment had a significant positive predictive effect on the school adaptation （β=0.178， P<0.01） and psychological resilience （β=0.518， P<0.01） of migrant children. Psychological resilience had positive predictive effect on the school adaptation （β=0.467， P<0.01）. Psychological resilience played a partial mediating role in the relationship between peer attachment and school adaptation， with the mediating effect value was 0.242 （95% CI： 0.184~0.302）， accounting for 57.62% of the total effect. Moreover， the interaction term between psychological resilience and sense of security had a significant predictive effect on school adaptation （β=0.103， P<0.01）. ConclusionThe psychological resilience of migrant children plays a partial mediating role in the relationship between peer attachment and school adaptation， and the status of sense of security can moderate the relationship between psychological resilience and school adaptation of migrant children.

Objective To explore the feasibility of applying artificial intelligence (AI) technology in chromosomal aberration (CA) analysis for occupational health surveillance of radiation workers and in biological dose estimation during nuclear emergency responses. Methods Peripheral blood samples from healthy volunteers were irradiated in vitro with X-rays and cobalt-60 (⁶⁰Co) γ rays. Chromosome slides were prepared using an automated harvesting and dropping device. The data training and outcome evaluation of CA analysis was performed on the AI software using chromosome images from occupational medical examination of radiation workers from the current lab or chromosome slides from blood samples irradiated with X-rays. The trained AI software was then used to assist in CA analysis and biological dose estimation among occupational medical examination of radiation workers, with results compared with manual reading and actual exposure doses. Results The trained AI software achieved a CA recognition accuracy of 95.11%. In the occupational health examination of radiation workers, the positive CA detection rate using AI + manual review was 2.25% higher than that in manual reviewing alone. The errors in biological dose estimation for ⁶⁰Co γ rays and X-rays using AI + manual review analysis were 11.86% and 7.33%, respectively, both within the acceptable 20.00% error margin. Conclusion AI + manual review can be effectively applied in CA analysis for occupational health examination and biological dose estimation during nuclear emergencies, significantly improving analysis efficiency.

OBJECTIVES: Neurodegenerative diseases are closely associated with myelin loss, and the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) are crucial to remyelination. However, the regulatory mechanisms involved remain incompletely understood. This study aims to investigate how astrocytes (ASTs) regulate the secretion of chitinase-3-like protein 1 (CHI3L1) via connexin 47 (Cx47)-mediated exosome signaling, and its subsequent effect on OPC proliferation. METHODS: Primary cells were isolated from postnatal day 1 Sprague-Dawley (P1SD) rats to establish 3 culture conditions: OPCs alone (Group O), OPCs in direct contact with ASTs (Group C), and OPCs cultured with AST-conditioned medium (Group A). Cellular morphology and proliferation were assessed using optical microscopy, 5-ethynyl-2'- deoxyuridine (EdU) incorporation, and flow cytometry. RNA sequencing (RNA-Seq) and bioinformatics analysis (BA) were conducted to identify differentially expressed genes (DEGs) among groups. Protein expression and cell cycle distribution were analyzed by Western blotting (WB) and flow cytometry. Exosomes were isolated and purified via differential centrifugation, characterized by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), and CHI3L1 expression in exosomes was verified via WB. Cx47 was silenced using small interfering RNA (siRNA) to evaluate its effect on OPC proliferation and exosome secretion. Artificial exosomes were constructed by encapsulating CHI3L1 in single unilamellar vesicles (SUVs), whose structure and size were validated by NTA and TEM. Following Cx47 knockdown, artificial exosomes were added back, and OPC proliferation was assessed via flow cytometry and EdU assay. RESULTS: Direct co-cultured with ASTs (Group C) resulted in significantly enhanced OPC proliferation compared to the Group O and Group A (P<0.05). RNA-Seq and WB analyses revealed that ASTs promote OPC proliferation and exosome secretion enriched in CHI3L1 through Cx47. Cx47 knockdown by siRNA led to significant decreases in OPC proliferation and exosome release (P<0.05). The inhibitory effect of Cx47 silencing on OPC proliferation was partially reversed by supplementation with either isolated exosomes or exogenous CHI3L1. CONCLUSIONS This study reveals a novel mechanism by which ASTs regulate OPC proliferation: Through direct contact, ASTs enhance the secretion of CHI3L1-rich exosomes via Cx47, thereby converting intercellular contact signals into secretory signals that promote OPC proliferation. As a key exosomal molecule, CHI3L1 may play an important role in neural function and remyelination and warrants further investigation.
Animals ; Exosomes/metabolism* ; Cell Proliferation ; Rats, Sprague-Dawley ; Rats ; Connexins/genetics* ; Oligodendrocyte Precursor Cells/metabolism* ; Astrocytes/metabolism* ; Chitinase-3-Like Protein 1/metabolism* ; Cells, Cultured ; Cell Differentiation

Renal tubular acidosis（RTA）in children is mainly primary，with a low incidence rate and often an insidious onset. It exhibits strong clinical heterogeneity，and the related complications include growth retardation，abnormal bone metabolism，and renal dysfunction，which seriously affect the life quality of children. Currently，clinical attention to RTA remains insufficient，and its genetic mechanisms have not been fully clarified. The metabolic control rate and patient compliance need to be improved. This article reviews important research advances in the field of primary RTA，summarizes progress in classification，etiology，diagnostic and therapeutic strategies，prognosis and long-term disease management. It emphasizes that the precise diagnosis and treatment of children with primary RTA require the integration of molecular genetic technologies，individualized treatment regimens，and long-term monitoring and follow-up. In the future，efforts should focus on enhancing epidemiological studies and establishing evidence-based guidelines，further elucidating the pathogenesis of RTA，developing better-tolerated medications suitable for long-term use，and advancing parallel strategies for the prevention and management of primary RTA.

Objective To analyze the economic cost of self-monitoring of gestational diabetes mellitus, and provide a basis for measuring the economic burden of gestational diabetes mellitus, and to provide a reference for the formulation of intervention development and the adjustment of resource allocation. Methods The individual economic cost of self-monitoring for gestational diabetes mellitus was measured based on a decision tree model, and the total economic cost of self-monitoring for gestational diabetes mellitus in Beijing was estimated. The uncertainty of the model parameters was analyzed using one-way sensitivity analysis. Results The average individual economic cost of gestational diabetes self-monitoring was 1184 RMB, and the individual cost incurred by choosing different types of blood glucose meters ranged from 403 to 18 000 RMB. The average individual economic cost of finger-stick blood glucose monitoring was 606 RMB and the average individual economic cost of continuous glucose monitoring was 2 374 RMB. The total economic cost of gestational diabetes self-monitoring in Beijing was 23.818 0 million RMB, and the total economic cost incurred by choosing different types of blood glucose meters ranged from 0.292 5 to 9.027 9 million RMB. The proportion of the finger-stick blood glucose monitoring had the greatest impact on the robustness of the results. Conclusion Finger-stick blood glucose monitoring is still the dominant self-monitoring method and is less costly than continuous glucose monitoring. Self-monitoring of pregnant women with gestational diabetes mellitus incurs certain economic cost and causes an economic burden on society.