Objective Maintain a sable differential pressure inside the Underwater Positive Pressure Protective Suit(UPPPS)to ensure normal breathing and safe underwater operations for the diver.Methods Utilize a pressure regulator as the UPPPS's pressure control valve to automatically maintain the differential pressure inside the suit.Results By establishing a physical model,the relationship between the steady-state differential pressure with the ventilation flow rate and the ambient pressure was obtained.(1)The ventilation flow rate is positively correlated with the steady-state differential pressure,the higher the ventilation flow rate,the greater the steady-state differential pressure.(2)At the same ventilation flow rate,the larger the ambient pressure is,the smaller the steady-state differential pressure is.Underwater unmanned and manned experiments using the UWT suit were conducted.The expermental results are in agreement with the theoretical analysis.Conclusion The performance of pressure regulator has been verified by the underwater experiments,it effectively stabilizes the differential pressure within the UPPPS.

Obsessive-compulsive disorder （OCD） is a highly disabling mental disorder that impairs patients' social function and quality of life， and impose a substantial economic burden. Intolerance of uncertainty （IU） refers to a cognitive bias in perceiving， interpreting and responding to uncertain situations or events. IU is closely associated with the cognitive patterns of OCD patients. Based on magnetic resonance imaging （MRI）， this paper discusses the research progress of the relationship between IU and psychopathological characteristics of OCD， and put forward the research direction， aims to provide evidence-based references for the development of optimized therapeutic interventions for OCD.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective To analyze changes in sleep,mood state,and brain function in healthy populations living in near-sea-level environments before and after exposure to high-altitude environment,and to explore the correlations between regional brain functional changes and variations in sleep and mood states.Methods A total of 45 healthy volunteers were enrolled.The participants came from regions of near-sea-level altitudes and were exposed to the high-altitude environment for a short period of time.The Pittsburgh Sleep Quality Index(PSQI),Zung Self-Rating Depression Scale(SDS),Patient Health Questionnaire-9(PHQ-9),Zung Self-Rating Anxiety Scale(SAS),and Generalized Anxiety Disorder-7(GAD-7)were administered to assess sleep quality as well as depressive and anxiety symptoms at 4 time points—prior to high-altitude exposure,immediately after exposure,one month after returning to low-altitude regions,and three months after returning to low-altitude regions.Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected before and after high-altitude exposure,and regional brain functional parameters,including the amplitude of low-frequency fluctuations(ALFF)and functional connectivity strength,were analyzed.Statistical analyses were performed,including a linear mixed-effects model to evaluate longitudinal changes in scale scores,paired-sample t-tests to compare brain function differences before and after exposure,and Pearson correlation analyses to examine the relationship between brain functional changes and alterations in sleep and mood states.Results Compared with the pre-exposure findings,the participants exhibited significantly increased PSQI scores(8.89±4.41 vs.5.08±2.69,P<0.05)and PHQ-9 scores(3.60±4.19 vs.1.54±2.30,P<0.05)immediately after high-altitude exposure.One month after returning to the low-altitude environment,both sleep and depression scores decreased relative to the findings immediately after exposure(PSQI:3.88±2.13 vs.8.89±4.41,P<0.05;PHQ-9:1.50±2.25 vs.3.60±4.19,P<0.05)and showed no statistically significant difference compared with the pre-exposure findings(P>0.05).Three months after returning to near-sea-level environment,sleep,depression,and anxiety scores were all reduced compared with the findings immediately after exposure(PSQI:3.76±2.31 vs.8.89±4.41,P<0.05;PHQ-9:1.24±2.13 vs.3.60±4.19,P<0.05;SAS:23.84±5.93 vs.27.93±7.05,P<0.05),also showing no significant difference compared with the pre-exposure levels(P>0.05).Brain function analysis revealed that,relative to the pre-exposure levels,ALFF in the bilateral superior temporal gyrus,insula,and dorsolateral prefrontal cortex(DLPFC)increased after high-altitude exposure(P<0.05),and that functional connectivity strength in the DLPFC was also elevated(P<0.05).Furthermore,changes in DLPFC functional connectivity strength were positively correlated with changes in sleep and mood scores(P<0.05).Conclusion High-altitude exposure has a significant impact on the sleep,mood states,and brain function of populations from near-sea-level regions,and DLPFC,in particular,is closely associated with changes in sleep and mood states.The findings of this study provide a theoretical basis for health management and intervention strategies in high-altitude environments.

Objective To investigate the role of exosomal microRNA(miRNA)miR-210-3p in chemoresistance and stem cell property formation in cervical cancer,and to elucidate its underlying mechanism through targeting of F-box protein 31(FBXO31).Methods Exosomes were isolated from cisplatin-sensitive HeLa cells and cisplatin-resistant HeLa/DDP cells via ultracentrifugation,and their uptake by HeLa/DDP cells was verified using the PKH26 red fluorescent labeling method.HeLa cells were transfected with NC inhibitor,miR-210-3p inhibitor alone,or in combination with si-NC and si-FBXO31.After 24 hours of transfection,exosomes were extracted and co-cultured with HeLa/DDP cells for 48 hours.Consequently,HeLa/DDP cells were divided into five groups:the Ctrl group(PBS blank control),the NC inhibitor group,the miR-210-3p inhibitor group,the miR-210-3p inhibitor+si-NC group and the miR-210-3p inhibitor+si-FBXO31 group.RT-qPCR was used to measure miR-210-3p and FBXO31 expression levels.The half-maximal inhibitory concentration(IC50)of cisplatin was determined using the MTT assay.Stem cell properties were assessed via tumor sphere formation assays.Western blot analysis was performed to detect the protein expression of FBXO31 and stem cell markers(e.g.,SOX2,OCT4,NANOG).The targeting relationship between miR-210-3p and FBXO31 was validated using dual-luciferase reporter assays.The effect of exosomal miR-210-3p on the metastasis of cervical cancer in vivo was evaluated by nude mice xenograft tumor.Resuts Compared with human normal cervical epithelial cells(HCeEpiC),miR-210-3p expression was significantly upregulated in cervical cancer cell lines(HeLa,HT3,C33A,and CaSki),while FBXO31 expression was significantly downregulated(P<0.05).HeLa/DDP cells(cisplatin-resistant)exhibited significantly higher miR-210-3p expression levels and IC50 values for cisplatin compared with parental HeLa cells(P<0.05),and HeLa exosomes were efficiently taken up by HeLa/DDP cells.Compared with the NC inhibitor groupThe miR-210-3p inhibitor group showed significantly reduced expression levels of miR-210-3p,OCT4,SOX2,and NANOG,as well as a significantly lower IC50(P<0.05),while FBXO31 expression was significantly increased(P<0.05).Compared with the miR-210-3p inhibitor+si-NC group,the miR-210-3p inhibitor+si-FBXO31 group exhibited significantly decreased FBXO31 expression(P<0.05)and increased IC50,Oct-4,SOX2,and NANOG expression(P<0.05).Compared with the control group and the empty vector group,the tumor weight and volume were significantly lower in the miR-210-3p than in the control and empty vector groups(P<0.05).Conclusion Exosomal miR-210-3p promotes chemoresistance to DDP and enhances stem cell-like properties in CC cells by directly targeting and inhibiting FBXO31.

β-Thalassemia is a single-gene disease caused by mutations in β-globin and has a distinct geographical characteristics. Current treatment for patients with moderate to severe thalassemia has mainly relied on long-term blood transfusion and/or hematopoietic stem cell transplantation. B cell lymphoma/leukemia 11A (BCL11A) as a transcriptional repressor plays a vital role in monitoring γ/β hemoglobin switching, maintaining the normal function of hematopoietic stem cells, and regulating erythrocyte differentiation and lymphocyte development. With the rapid progress in gene editing technology, the BCL11A as a therapeutic target for β-thalassemia has shown promising results. This article has systematically summarized the regulatory mechanism and therapeutic potential of the BCL11A, with an aim to provide new ideas for the treatment of β-thalassemia.

Objective:To investigate the genetic and evolutionary characteristics of hemagglutinin (HA) and neuraminidase (NA) genes of influenza B/Victoria (BV) virus in Xi′an city from 2019 to 2023.Methods:Twenty-five BV strains isolated from the Xi′an influenza surveillance network laboratory between 2019 and 2023 were collected. The HA and NA genes were sequenced using MiniSeq high-throughput sequencing platform. An evolutionary tree was constructed using bioinformatics software to analyze homology and mutation sites, and to predict N-glycosylation sites online. The antigenicity of the strains was analyzed through hemagglutination inhibition tests.Results:The BV influenza in Xi′an exhibited a distinct seasonal transmission pattern from 2019 to 2023, with peak prevalence occurring during the winter and spring seasons. The evolutionary analysis of the HA genes shows that the strains from Xi′an in 2019 belong to the V1A.3 branch, and the strains from 2021 to 2023 belong to the V1A.3a.2 branch. Analysis of antigenic sites showed that there were variations in 6 sites of 3 antigenic determinants in the HA proteins of the BV strains from 2021-2022 compared to 2019, and 2 sites of 1 antigenic determinant changed in the HA proteins in 2023 compared to 2021-2022. The evolutionary analysis of the NA genes indicates that the BV strains from Xi′an in 2019 belong to the A. 1.1 branch. By 2021 and 2022, it had evolved into the A. 1.2 clade, and by 2023, it had further evolved into the B clade and its derivatives, with no strains showing mutations associated with resistance to NA inhibitors. Antigenic analysis indicated that the majority of BV strains in Xi′an were similar to the strains included in the vaccine composition. Furthermore, glycosylation analysis showed that the potential N-glycosylation sites in the HA proteins of BV strains from 2021-2023 were reduced by one compared to those from 2019, and only a few strains from 2023 displayed alterations in the potential N-glycosylation sites of the NA proteins.Conclusions:The HA and NA genes of the BV strains from 2019 to 2023 are continuously mutating and evolving into new branches. Since 2021, V1A.3a.2 has become the dominant evolutionary branch of the HA genes, while the evolutionary branches of the NA genes from 2019 to 2023 have been continuously changing.

Evoked Potentials ; Social Isolation ; Attention ; Humans

Objective To investigate the clinicopathological characteristics and the factors affecting the prognosis of patients with resectable sarcomatoid carcinoma of the bladder(SCB).Methods A retrospective analysis was conducted with the clinical data of patients with resectable SCB treated at the Second Hospital of Tianjin Medical University between September 2008 and December 2023.The patients were divided into two groups,a bladder-preserving surgery(BPS)group and a radical cystectomy(RC)group,according to the specific surgical approach used for each patient.Kaplan-Meier survival curves were used to evaluate overall survival(OS)in both groups,and Cox regression models were employed to identify risk factors affecting survival.Results A total of 77 patients with resectable SCB were included.Among them,35 patients(45.5％)underwent BPS,while 42 patients(54.5％)underwent RC.Ki-67 expression≥30％was observed in 91.7％of the patients.A total of 92.2％of the patients was tested positive for cytokeratin(CK)and 98.1％for vimentin.In addition,62.5％and 37.5％of patients had the human epidermal growth factor receptor 2(Her-2)scores of 0 and 1+,respectively.The median follow-up time was 23.2 months(ranging from 0.4 to 164.7 months).The 1-year,3-year,and 5-year survival rates for the BPS group and the RC group were as follows,76.2％vs.84.9％,46.7％vs.61.1％,and 35.6％vs.43.2％,respectively.Multivariate Cox regression analysis revealed that in the RC group,age ≥ 75 years old(hazard ratio[HR]=3.836,95％confidence interval[CI]:1.168-12.595,P=0.027),tumor multiplicity(HR=3.439,95％CI:1.235-9.574,P=0.018),and lack of adjuvant therapy(HR=3.164,95％CI:1.015-9.862,P=0.047)were independent risk factors affecting survival.In the BPS group,female sex was identified as an independent risk factor for survival(HR=3.601,95％CI:1.200-10.804,P=0.022).Conclusion Ki-67,CK,and vimentin are significantly overexpressed in SCB patients,while Her-2 is either unexpressed or expressed at low levels.In the RC group,tumor multiplicity,age ≥75 years,and lack of postoperative adjuvant therapy are independent risk factors for overall survival.Female sex is an independent risk factor affecting prognosis in the BPS group.