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1.
Artículo en Inglés | MEDLINE | ID: mdl-38743898

RESUMEN

Objective: To explore and analyze the effect of targeted nursing combined with psychological intervention on chemotherapy for gastric carcinoma and its influence on patient compliance. Methods: The study subjects were 88 patients diagnosed with gastric cancer and treated with chemotherapy from December 2019 to May 2021. Results: The Self-Rating Anxiety Scale and Hamilton Depression Cale scores of the study group were significantly lower than those of the control group (33.45±6.11 vs. 44.17±5.76; 35.14±5.44 vs. 46.87±5.23, respectively; P < .05); In the Morisky scale, patients in the study group scored higher than those in the control group in terms of weight control, medication compliance, appropriate exercise, and diet control; the study group had more cases of Grade 0 nausea and vomiting and significantly fewer cases of Grades I, II, III, and IV nausea and vomiting than the control group compliance (P < .05); patients in the study group gave higher scores than those in the control group on the nursing care quality, from the aspects of the quality of nursing staff. These findings highlight the significant improvements in psychological well-being, adherence to health-related behaviors, reduced nausea and vomiting, and overall satisfaction with nursing care in patients receiving targeted nursing and psychological intervention. Conclusion: The utilization of targeted nursing in tandem with psychological counseling has demonstrated a notably positive impact on chemotherapy outcomes for stomach malignancy. The amalgamation of targeted nursing and psychological intervention not only enhances patient compliance during gastric carcinoma chemotherapy but also leads to a reduction in negative emotions, decreased instances of nausea and vomiting, and higher scores for nursing quality. These findings have significant implications for clinical practice, suggesting that the integration of targeted nursing and psychological support could be a valuable approach in optimizing patient care for gastric carcinoma. The observed improvements underscore the potential for widespread adoption of this combined intervention strategy in clinical settings, potentially leading to enhanced treatment outcomes and overall patient well-being.

2.
IEEE Trans Med Imaging ; PP2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739508

RESUMEN

Segmenting peripancreatic vessels in CT, including the superior mesenteric artery (SMA), the coeliac artery (CA), and the partial portal venous system (PPVS), is crucial for preoperative resectability analysis in pancreatic cancer. However, the clinical applicability of vessel segmentation methods is impeded by the low generalizability on multi-center data, mainly attributed to the wide variations in image appearance, namely the spurious correlation factor. Therefore, we propose a causal-invariance-driven generalizable segmentation model for peripancreatic vessels. It incorporates interventions at both image and feature levels to guide the model to capture causal information by enforcing consistency across datasets, thus enhancing the generalization performance. Specifically, firstly, a contrast-driven image intervention strategy is proposed to construct image-level interventions by generating images with various contrast-related appearances and seeking invariant causal features. Secondly, the feature intervention strategy is designed, where various patterns of feature bias across different centers are simulated to pursue invariant prediction. The proposed model achieved high DSC scores (79.69%, 82.62%, and 83.10%) for the three vessels on a cross-validation set containing 134 cases. Its generalizability was further confirmed on three independent test sets of 233 cases. Overall, the proposed method provides an accurate and generalizable segmentation model for peripancreatic vessels and offers a promising paradigm for increasing the generalizability of segmentation models from a causality perspective. Our source codes will be released at https://github.com/SJTUBME-QianLab/PC_VesselSeg.

3.
Microb Pathog ; 191: 106678, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38718954

RESUMEN

A conditionally pathogenic bacterium called Bibersteinia trehalosi inhabits the upper respiratory tract of ruminants and is becoming a significant cause of pneumonia, especially in goats. In this study, we identified a gram-negative bacteria strain isolated from dead goat's lungs, which was named M01. By integrating the outcomes of its morphological and biochemical characterization with the investigation of the 16S rRNA gene sequence analysis, the isolate was identified as B. trehalosi. Based on antibiotic susceptibility tests, the isolate was shown to be resistant to ß-lactams, tetracyclines, and amphenicols. Its genome was discovered to comprise 2115 encoded genes and a circular chromosome measuring 2,345,568 bp using whole genome sequencing. Annotation of the VFBD database revealed that isolate M01 had four virulence genes encoding three virulence factors. The CARD database revealed that its genome has two antibiotic-resistance genes. Based on pathogenicity testing, isolate M01 was highly pathogenic to mice, primarily causing pneumonia, with an LD50 of 1.31 × 107 CFU/ml. Moreover, histopathology showed loss of alveolar structure and infiltration of lung inflammatory cells. Hence, the current study could provide sufficient information for prevention and control strategies for future epidemics of B. trehalosi in goat species.

4.
Virus Res ; : 199396, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38763299

RESUMEN

Porcine circovirus type 2 (PCV2) infection leads to multi-system inflammation in pigs, and this effect can be achieved by upregulating host miR-21. The underlying mechanism of miR-21 regulates PCV2-induced inflammation is already known, however, how PCV2 regulates miR-21 levels and function using both autonomic and host factors remains to be further revealed. Here we present the first evidence that PCV2 ORF5 induces an inflammatory response by up-regulating miR-21 level through targeting nuclear miR-30d. In this study, we found that overexpression of ORF5 significantly increased miR-21 level and promoted the expression of inflammatory cytokines and activation of the NF-κB pathway, while ORF5 mutation had the opposite effect. Moreover, the differential expression of miR-21 could significantly change the pro-inflammatory effect of ORF5, indicating that ORF5 promotes inflammatory response by up-regulating miR-21. Bioinformatics analysis and clinical detection found that nuclear miR-30d was significantly down-regulated after ORF5 overexpression and PCV2 infection, and targeted pri-miR-21 and PCV2 ORF5. Functionally, we found that miR-30d inhibited the levels of miR-21 and inflammatory cytokines in cells. Mechanistically, we demonstrated that ORF5 inhibits miR-30d expression levels through direct binding but not via the circRNA pathway, and miR-30d inhibits miR-21 levels by targeting pri-miR-21. In summary, the present study revealed the molecular mechanism of ORF5 upregulation of miR-21, further refined the molecular chain of PCV2-induced inflammatory response and elucidated the role of miRNAs in it.

5.
Res Sq ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38746323

RESUMEN

Most Epstein-Barr virus-associated gastric carcinoma (EBVaGC) harbor non-silent mutations that activate phosphoinositide 3 kinase (PI3K) to drive downstream metabolic signaling. To gain insights into PI3K/mTOR pathway dysregulation in this context, we performed a human genome-wide CRISPR/Cas9 screen for hits that synergistically blocked EBVaGC proliferation together with the PI3K antagonist alpelisib. Multiple subunits of carboxy terminal to LisH (CTLH) E3 ligase, including the catalytic MAEA subunit, were among top screen hits. CTLH negatively regulates gluconeogenesis in yeast, but not in higher organisms. Instead, we identified that the CTLH substrates MKLN1 and ZMYND19, which highly accumulated upon MAEA knockout, associated with one another and with lysosomes to inhibit mTORC1. ZMYND19/MKLN1 bound Raptor and RagA/C, but rather than perturbing mTORC1 lysosomal recruitment, instead blocked a late stage of its activation, independently of the tuberous sclerosis complex. Thus, CTLH enables cells to rapidly tune mTORC1 activity at the lysosomal membrane via the ubiquitin/proteasome pathway.

6.
Phys Rev E ; 109(4-1): 044143, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38755904

RESUMEN

The dynamic behaviors, specifically trapping and sorting, of active particles interacting with periodic substrates have garnered significant attention. This study investigates numerically the trapping of soft, deformable particles on a periodic potential substrate, which can be experimentally verified through optical tweezers. The research demonstrates that multiple factors, including the relative size of traps, self-propelled velocity, shape parameters, ratio of particles to traps, and translational diffusion, can influence the trapping effect. Within certain parameter boundaries, it is shown that all particles can be consistently trapped. The research reveals that stable trapping typically occurs at median values of the relative trap size. An increase in the self-propelled velocity, the shape parameter, and the translational diffusion coefficient tends to facilitate the escapement of the particles from the traps. It is noteworthy that particles with larger shape parameters can escape even when the restoring force exceeds the self-propelled force. In addition, as the ratio of particles to traps grows, the fraction of trapped particles steadily reduces. Notably, rigid particles are consistently divided and trapped by traps closely approximating an integer multiple of the particles' area, up until the ratio reaches the aforesaid integer value. These findings can potentially enhance the understanding of the interactive effects between active deformable particles and periodic substrates. Moreover, this work suggests a different experimental approach to sort active particles based on rigidity disparities.

8.
ACS Appl Bio Mater ; 7(5): 3295-3305, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38701399

RESUMEN

Physicochemical properties of nanoparticles, such as particle size, surface charge, and particle shape, have a significant impact on cell activities. However, the effects of surface functionalization of nanoparticles with small chemical groups on stem cell behavior and function remain understudied. Herein, we incorporated different chemical functional groups (amino, DETA, hydroxyl, phosphate, and sulfonate with charges of +9.5, + 21.7, -14.1, -25.6, and -37.7, respectively) to the surface of inorganic silica nanoparticles. To trace their effects on mesenchymal stem cells (MSCs) of rat bone marrow, these functionalized silica nanoparticles were used to encapsulate Rhodamine B fluorophore dye. We found that surface functionalization with positively charged and short-chain chemical groups facilitates cell internalization and retention of nanoparticles in MSCs. The endocytic pathway differed among functionalized nanoparticles when tested with ion-channel inhibitors. Negatively charged nanoparticles mainly use lysosomal exocytosis to exit cells, while positively charged nanoparticles can undergo endosomal escape to avoid scavenging. The cytotoxic profiles of these functionalized silica nanoparticles are still within acceptable limits and tolerable. They exerted subtle effects on the actin cytoskeleton and migration ability. Last, phosphate-functionalized nanoparticles upregulate osteogenesis-related genes and induce osteoblast-like morphology, implying that it can direct MSCs lineage specification for bone tissue engineering. Our study provides insights into the rational design of biomaterials for effective drug delivery and regenerative medicine.


Asunto(s)
Materiales Biocompatibles , Ensayo de Materiales , Células Madre Mesenquimatosas , Nanopartículas , Tamaño de la Partícula , Dióxido de Silicio , Propiedades de Superficie , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Nanopartículas/química , Animales , Ratas , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Osteogénesis/efectos de los fármacos
9.
J Hazard Mater ; 472: 134474, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38696961

RESUMEN

Body size is a key life-history trait of organisms, which has important ecological functions. However, the relationship between soil antibiotic resistance gene (ARG) distribution and organisms' body size has not been systematically reported so far. Herein, the impact of organic fertilizer on the soil ARGs and organisms (bacteria, fungi, and nematode) at the aggregate level was analyzed. The results showed that the smaller the soil aggregate size, the greater the abundance of ARGs, and the larger the body size of bacteria and nematodes. Further analysis revealed significant positive correlations of ARG abundance with the body sizes of bacteria, fungi, and nematodes, respectively. Additionally, the structural equation model demonstrated that changes in soil fertility mainly regulate the ARG abundance by affecting bacterial body size. The random forest model revealed that total phosphorus was the primary soil fertility factor influencing the body size of organisms. Therefore, these findings proposed that excessive application of phosphate fertilizers could increase the risk of soil ARG transmission by increasing the body size of soil organisms. This study highlights the significance of organisms' body size in determining the distribution of soil ARGs and proposes a new disadvantage of excessive fertilization from the perspective of ARGs.

10.
Cell Death Discov ; 10(1): 209, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697957

RESUMEN

Hematopoiesis ensures tissue oxygenation, and remodeling as well as immune protection in vertebrates. During embryogenesis, hemangioblasts are the source of all blood cells. Gata1a and pu.1 are co-expressed in hemangioblasts before hemangioblasts are differentiated into blood cells. However, the genes that determine the differentiation of hemangioblasts into myeloid or erythroid cell lineages have not been fully uncovered. Here we showed that miRNA-7145, a miRNA with previously unknown function, was enriched in erythrocytes at the definitive wave, but not expressed in myeloid cells. Overexpression and loss-of-function analysis of miRNA-7145 revealed that miRNA-7145 functions as a strong inhibitor for myeloid progenitor cell differentiation while driving erythropoiesis during the primitive wave. Furthermore, we confirmed that cuedc2 is one of miRNA-7145 targeted-genes. Overexpression or knock-down of cuedc2 partially rescues the phenotype caused by miRNA-7145 overexpression or loss-of-function. As well, overexpression and loss-of-function analysis of cuedc2 showed that cuedc2 is required for myelopoiesis at the expense of erythropoiesis. Finally, we found that overexpression of zebrafish cuedc2 in 293 T cell inhibits the JAK1/STAT3 signaling pathway. Collectively, our results uncover a previously unknown miRNA-7145-cuedc2 axis, which regulate hematopoiesis through inhibiting the JAK1/STAT3 signaling pathway.

12.
Biomacromolecules ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38717062

RESUMEN

Unlike naturally derived peptides, computationally designed sequences offer programmed self-assembly and charge display. Herein, new tetrameric, coiled coil-forming peptides were computationally designed ranging from 8 to 29 amino acids in length. Experimental investigations revealed that only the sequences having three or more heptads (i.e., 21 or more amino acids) exhibited coiled coil behavior. The shortest stable coiled coil sequence had a melting temperature (Tm) of approximately 58 ± 1 °C, making it ideal for thermoreversible assembly over moderate temperatures. Effects of pH and monovalent salt were examined, revealing structural stability over a pH range of 4 to 11 and an enhancement in Tm with the addition of salt. The incorporation of the coiled coil as a hydrogel cross-linker results in a thermally and mechanically reversible hydrogel. A subsequent demonstration of the hydrogel printed through a syringe illustrated one of many potential uses from 3D printing to injectable hydrogel drug delivery.

13.
Int J Med Microbiol ; 315: 151621, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38759506

RESUMEN

Preterm infants face a high risk of various complications, and their gut microbiota plays a pivotal role in health. Delivery modes have been reported to affect the development of gut microbiota in term infants, but its impact on preterm infants remains unclear. Here, we collected fecal samples from 30 preterm infants at five-time points within the first four weeks of life. Employing 16 S rRNA sequencing, principal coordinates analysis, the analysis of similarities, and the Wilcoxon rank-sum test, we examined the top dominant phyla and genera, the temporal changes in specific taxa abundance, and their relationship with delivery modes, such as Escherichia-Shigella and Enterococcus based on vaginal delivery and Pluralibacter related to cesarean section. Moreover, we identified particular bacteria, such as Taonella, Patulibacter, and others, whose proportions fluctuated among preterm infants born via different delivery modes at varying time points, as well as the microbiota types and functions. These results indicated the influence of delivery mode on the composition and function of the preterm infant gut microbiota. Importantly, these effects are time-dependent during the early stages of life. These insights shed light on the pivotal role of delivery mode in shaping the gut microbiota of preterm infants and have significant clinical implications for their care and management.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38761288

RESUMEN

To investigate the correlation between quantitative plaque parameters, the perivascular fat attenuation index, and myocardial ischaemia caused by haemodynamic impairment. Patients with stable angina who had invasive flow reserve fraction (FFR) assessment and coronary artery computed tomography (CT) angiography were retrospectively enrolled. A total of 138 patients were included in this study, which were categorized into the FFR < 0.75 group (n = 43), 0.75 ≤ FFR ≤ 0.8 group (n = 37), and FFR > 0.8 group (n = 58), depending on the range of FFR values. The perivascular FAI and CTA-derived parameters, including plaque length (PL), total plaque volume (TPV), minimum lumen area (MLA), and narrowest degree (ND), were recorded for the lesions. An FFR < 0.75 was defined as myocardial-specific ischaemia. The relationships between myocardial ischaemia and parameters such as the PL, TPV, MLA, ND, and FAI were analysed using a logistic regression model and receiver operating characteristic (ROC) curves to compare the diagnostic accuracy of various indicators for myocardial ischaemia. The PL, TPV, ND, and FAI were greater in the FFR < 0.75 group than in the grey area group and the FFR > 0.80 group (all p < 0.05). The MLA in the FFR < 0.75 group was lower than that in the grey area group and the FFR > 0.80 group (both P < 0.05). There were no significant differences in the PL, TPV, or ND between the grey area and the FFR > 0.80 group, but there was a significant difference in the FAI. The coronary artery lesions with FFRs ≤ 0.75 had the greatest FAI values. Multivariate analysis revealed that the perivascular FAI and PL density are significant predictors of myocardial ischaemia. The FAI has some predictive value for myocardial ischaemia (AUC = 0.781). After building a combination model using the FAI and plaque length, the predictive power increased (AUC, 0.781 vs. 0.918), and the change was statistically significant (P < 0.001). The combined model of PL + FAI demonstrated great diagnostic efficacy in identifying myocardial ischaemia caused by haemodynamic impairment; the lower the FFR was, the greater the FAI. Thus, the PL + FAI could be a combined measure to securely rule out myocardial ischaemia.

15.
Nat Commun ; 15(1): 4156, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755141

RESUMEN

Epstein-Barr virus (EBV) uses a biphasic lifecycle of latency and lytic reactivation to infect >95% of adults worldwide. Despite its central role in EBV persistence and oncogenesis, much remains unknown about how EBV latency is maintained. We used a human genome-wide CRISPR/Cas9 screen to identify that the nuclear protein SFPQ was critical for latency. SFPQ supported expression of linker histone H1, which stabilizes nucleosomes and regulates nuclear architecture, but has not been previously implicated in EBV gene regulation. H1 occupied latent EBV genomes, including the immediate early gene BZLF1 promoter. Upon reactivation, SFPQ was sequestered into sub-nuclear puncta, and EBV genomic H1 occupancy diminished. Enforced H1 expression blocked EBV reactivation upon SFPQ knockout, confirming it as necessary downstream of SFPQ. SFPQ knockout triggered reactivation of EBV in B and epithelial cells, as well as of Kaposi's sarcoma-associated herpesvirus in B cells, suggesting a conserved gamma-herpesvirus role. These findings highlight SFPQ as a major regulator of H1 expression and EBV latency.


Asunto(s)
Herpesvirus Humano 4 , Histonas , Factor de Empalme Asociado a PTB , Activación Viral , Latencia del Virus , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiología , Humanos , Histonas/metabolismo , Activación Viral/genética , Latencia del Virus/genética , Factor de Empalme Asociado a PTB/metabolismo , Factor de Empalme Asociado a PTB/genética , Regulación Viral de la Expresión Génica , Linfocitos B/virología , Linfocitos B/metabolismo , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/metabolismo , Sistemas CRISPR-Cas , Regiones Promotoras Genéticas/genética , Transactivadores/metabolismo , Transactivadores/genética , Genoma Viral
17.
Magn Reson Med ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38726772

RESUMEN

PURPOSE: This study aims to develop and evaluate a novel cardiovascular MR sequence, MyoFold, designed for the simultaneous quantifications of myocardial tissue composition and wall motion. METHODS: MyoFold is designed as a 2D single breathing-holding sequence, integrating joint T1/T2 mapping and cine imaging. The sequence uses a 2-fold accelerated balanced SSFP (bSSFP) for data readout and incorporates electrocardiogram synchronization to align with the cardiac cycle. MyoFold initially acquires six single-shot inversion-recovery images, completed during the diastole of six successive heartbeats. T2 preparation (T2-prep) is applied to introduce T2 weightings for the last three images. Subsequently, over the following six heartbeats, segmented bSSFP is performed for the movie of the entire cardiac cycle, synchronized with an electrocardiogram. A neural network trained using numerical simulations of MyoFold is used for T1 and T2 calculations. MyoFold was validated through phantom and in vivo experiments, with comparisons made against MOLLI, SASHA, T2-prep bSSFP, and the conventional cine. RESULTS: In phantom studies, MyoFold exhibited a 10% overestimation in T1 measurements, whereas T2 measurements demonstrated high accuracy. In vivo experiments revealed that MyoFold T1 had comparable accuracy to SASHA and precision similar to MOLLI. MyoFold demonstrated good agreement with T2-prep bSSFP in myocardial T2 measurements. No significant differences were observed in the quantification of left-ventricle wall thickness and function between MyoFold and the conventional cine. CONCLUSION: MyoFold presents as a rapid, simple, and multitasking approach for quantitative cardiovascular MR examinations, offering simultaneous assessment of tissue composition and wall motion. The sequence's multitasking capabilities make it a promising tool for comprehensive cardiac evaluations in clinical settings.

18.
Sci Data ; 11(1): 463, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714688

RESUMEN

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.


Asunto(s)
Encéfalo , Desarrollo Infantil , Niño , Preescolar , Humanos , Encéfalo/crecimiento & desarrollo , Encéfalo/diagnóstico por imagen , China , Cognición , Bases de Datos Factuales , Neuroimagen
19.
Mol Neurobiol ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565785

RESUMEN

The relationship of single nucleotide polymorphisms (SNPs) in COL4A2 gene with risk and outcome of primary intracerebral hemorrhage (ICH) in the Chinese Han population remains unclear, which was investigated in this study. Primary ICH patients and non-stroke controls of Chinese Han ethnicity were enrolled. The genotypes of 8 tag-SNPs were determined using a custom-by-design 48-Plex SNPscan Kit. Poor 3-month outcome was defined as modified Rankin Scale score 4-6. Logistic regression was employed to examine association between COL4A2 variants and risk and poor outcome of primary ICH. 323 patients with primary ICH and 376 stroke-free controls were included. Compared to controls, the rs1049931 G and rs1049906 C alleles were associated with increased ICH risk (p = 0.027 and 0.033), and these two allele counts increased this risk after adjustments respectively (additive model: adjusted OR [aOR] 1.41, 95% CI 1.03-1.94, corrected p = 0.043; aOR 1.37, 95% CI 1.01-1.86, corrected p = 0.043). The rs1049931 AG/GG and rs1049906 CT/CC genotypes showed increased susceptibility to non-lobar hemorrhage (aOR 1.63, 95% CI 1.06-2.50, p = 0.025; aOR 1.63, 95% CI 1.07-2.47, p = 0.022). Haplotype analysis revealed an association between rs1049906-rs1049931 haplotype CG and ICH risk (OR 1.36, 95% CI 1.05-1.78, p = 0.021). Regarding clinical outcome, the rs3803230 C allele (dominant model: aOR 1.94, 95% CI 1.04-3.63, p = 0.037) and haplotype AC of rs7990214-rs3803230 (OR 1.98, 95% CI 1.13-3.46, p = 0.015) contributed to 3-month poor outcome. The COL4A2 polymorphisms are associated with an increased risk of primary ICH, mainly non-lobar hemorrhage, and with long-term poor outcome after ICH in Chinese Han population.

20.
J Nucl Med ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38604764

RESUMEN

68Ga-labeled nanobody (68Ga-NC-BCH) is a single-domain antibody-based PET imaging agent. We conducted a first-in-humans study of 68Ga-NC-BCH for PET to determine its in vivo biodistribution, metabolism, radiation dosimetry, safety, and potential for quantifying claudin-18 isoform 2 (CLDN18.2) expression in gastrointestinal cancer patients. Methods: Initially, we synthesized the probe 68Ga-NC-BCH and performed preclinical evaluations on human gastric adenocarcinoma cell lines and xenograft mouse models. Next, we performed a translational study with a pilot cohort of patients with advanced gastrointestinal cancer on a total-body PET/CT scanner. Radiopharmaceutical biodistribution, radiation dosimetry, and the relationship between tumor uptake and CLDN18.2 expression were evaluated. Results: 68Ga-NC-BCH was stably prepared and demonstrated good radiochemical properties. According to preclinical evaluation,68Ga-NC-BCH exhibited rapid blood clearance, high affinity for CLDN18.2, and high specific uptake in CLDN18.2-positive cells and xenograft mouse models. 68Ga-NC-BCH displayed high uptake in the stomach and kidney and slight uptake in the pancreas. Compared with 18F-FDG, 68Ga-NC-BCH showed significant differences in uptake in lesions with different levels of CLDN18.2 expression. Conclusion: A clear correlation was detected between PET SUV and CLDN18.2 expression, suggesting that 68Ga-NC-BCH PET could be used as a companion diagnostic tool for optimizing treatments that target CLDN18.2 in tumors.

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