The evaluation of blood compatibility of biomaterials is crucial for ensuring the clinical safety of implantable medical devices. To address the limitations of traditional testing methods in real-time monitoring and electrical property analysis, this study developed a portable electrical impedance tomography (EIT) system. The system uses a 16-electrode design, operates within a frequency range of 1 to 500 kHz, achieves a signal to noise ratio (SNR) of 69.54 dB at 50 kHz, and has a data collection speed of 20 frames per second. Experimental results show that the EIT system developed in this study is highly consistent with a microplate reader ( R ²=0.97) in detecting the hemolytic behavior of industrial-grade titanium (TA3) and titanium alloy-titanium 6 aluminum 4 vanadium (TC4) in anticoagulated bovine blood. Additionally, with the support of a multimodal image fusion Gauss-Newton one-step iterative algorithm, the system can accurately locate and monitor in real-time the dynamic changes in blood permeation and coagulation caused by TC4 in vivo. In conclusion, the EIT system developed in this study provides a new and effective method for evaluating the blood compatibility of biomaterials.
Electric Impedance ; Animals ; Tomography/instrumentation* ; Biocompatible Materials ; Materials Testing/instrumentation* ; Cattle ; Titanium ; Alloys ; Prostheses and Implants

Objective:To evaluate preliminary application effects of a provincial-county-township-village four-level network framework which aims at promoting oral health of the elderly, and to conduct preliminary evaluations of the application of this model in the prevention and treatment of oral diseases among the elderly in economically accelerated areas.Methods:Based on the population survey in June 2022, the study focuses on the elderly (≥85 years old) veterans who fought in the Korean War and currently resided in Wuyi County, an old revolutionary base area in Zhejiang Province with accelerated economic development. A four-level network medical service model matrix was constructed, spanning from the provincial level to the county, township, and village. Digital oral health records were established, and in-home dental treatment was provided for elderly individuals who met the inclusion and exclusion criteria. Pre-treatment and 3-months follow-up visits were conducted, and the impact of oral health was recorded using a scale, along with a survey of denture satisfaction.Results:A total of 54 elderly individuals received the geriatric oral healthcare services. After a 3-months follow-up, the mean total score of the oral health impact profile-14 questionnaires was (3.27±3.00), which was significantly lower than the score (32.82±7.15) in pre-treatment ones ( Z=-2.94, P=0.003). Scores in dimensions such as physical pain, functional limitations, psychological discomfort, psychological disorders, and physical disorders were all significantly lower than the pre-treatment scores ( P<0.05). The visual analogue score for denture satisfaction was 48.64±1.21, indicating a satisfaction rate of 100% (11/11). Conclusions:These findings confirm the favorable preliminary application effects of the four-level network framework in improving the prevention and treatment of oral diseases among the elderly in economically accelerated areas.

OBJECTIVE: To investigate the current status and influencing factors of feeding intolerance (FI) during enteral nutrition (EN) in intensive care unit (ICU) patients. METHODS: A retrospective case-control study was conducted, including patients from two ICU wards of a tertiary hospital in Guizhou Province from July 2019 to December 2022. Clinical data were collected using a self-designed data collection form, including general information [age, gender, acute physiology and chronic health evaluation II (APACHE II)], clinical treatment (mechanical ventilation, mild hypothermia therapy), medication use (vasoactive drugs, glucocorticoids, analgesics, sedatives), EN implementation (types of EN fluids, EN methods, tube feeding rate), EN tolerance, and blood glucose status. Patients were divided into EN tolerance and EN intolerance groups based on the FI criteria. Differences in the above-mentioned indicators between the two groups were compared, and statistically significant indicators were included in a binary multivariate Logistic regression analysis to explore the independent influencing factors of FI during EN in ICU patients. RESULTS: A total of 683 ICU patients were included, with 57.10% (390/683) incidence of FI during EN. The most common FI symptom was diarrhea (41.58%), followed by gastric retention, reflux, abdominal distension, nausea, abdominal pain, vomiting, and aspiration, with blood in stool being the least common (3.37%). Compared to the EN tolerance group, the EN intolerance group had significantly higher proportions of patients aged ≥60 years, undergoing mechanical ventilation, receiving analgesic and sedative medications, having hyperglycemia, using short-peptide EN fluids, receiving continuous EN, and having a feeding rate > 40 mL/h (all P < 0.05). The binary multivariate Logistic regression analysis revealed that age ≥60 years [odds ratio (OR) = 1.738, 95% confidence interval (95%CI) was 1.241-2.436, P = 0.001], continuous EN (OR = 0.534, 95%CI was 0.377-0.756, P < 0.001), use of analgesic medications (OR = 1.701, 95%CI was 1.139-2.539, P = 0.009), hyperglycemic state (OR = 2.794, 95%CI was 1.999-3.907, P < 0.001), and tube feeding rate > 40 mL/h (OR = 1.018, 95%CI was 1.009-1.027, P < 0.001) were independent risk factors for FI during EN in ICU patients. CONCLUSIONS The incidence of FI during EN in ICU patients is relatively high and influenced by age, EN methods, analgesic medications, hyperglycemic state, and tube feeding rate. Therefore, healthcare professionals need to accurately identify the risk factors for FI and actively implement effective intervention measures to reduce the incidence of FI and improve patient outcomes.
Humans ; Retrospective Studies ; Enteral Nutrition/methods* ; Intensive Care Units ; Case-Control Studies ; Male ; Female ; APACHE ; Logistic Models ; Diarrhea/epidemiology* ; Respiration, Artificial/adverse effects* ; Middle Aged ; Aged

Humans ; Infant ; Protein-Tyrosine Kinases ; Proto-Oncogene Proteins ; Brain Neoplasms/surgery* ; Glioma/surgery* ; Oncogene Proteins, Fusion/genetics* ; Lung Neoplasms

Objective:To investigate the changes in gray matter volume of the subsystems as well as intra-subsystem and inter-subsystem functional connectivity in the default mode network (DMN) of relapsing-remitting multiple sclerosis (RRMS) patients with preserved cognitive function.Methods:In this prospective study, thirty-seven RRMS patients with preserved cognitive function who were admitted to Huashan Hospital of Fudan University from April 2020 to January 2021 (RRMS group) and 43 healthy volunteers (HC group) were recruited. Patients in the RRMS group received the cognitive assessment using a clinical cognitive functioning scale. Three-dimensional T 1WI and resting-state functional MRI were performed to obtain the brain structural and functional data. The DMN was divided into three subsystems: CORE, dorsal medial prefrontal cortex (DMPFC), and medial temporal lobe (MTL). The gray matter volume of the three subsystems were extracted from the gray matter volume map generated by spatial normalization; 24 regions of interest (ROIs) of the DMN were defined based on Yeo′s 17 networks, and their functional connectivity values were calculated to derive the mean intra-subsystem and inter-subsystem functional connectivity values. Differences in gray matter volume and functional connectivity between the RRMS and HC groups were compared using independent sample t-tests; Spearman′s partial correlation was used to analyze the correlation between subsystems′ gray matter volume and functional connectivity, as well as between subsystems′ functional connectivity and clinical scale scores. Results:Compared to the HC group, the gray matter volume of the three subsystems of the DMN were considerably reduced in the RRMS group ( P<0.05). The functional connectivity within and between the three subsystems were not statistically significantly different between the HC and RRMS groups ( P>0.05). Based on the ROI analysis, patients with RRMS the brain regions with significantly reduced DMN intra-subsystem functional connectivity values were mainly located in the left dorsomedial prefrontal cortex of the DMPFC, the right lateral temporal cortex of the DMPFC, and the left medial temporal cortex of the MTL, as compared with the HC group ( P<0.01). The gray matter volume of DMPFC was positively correlated with the functional connectivity within DMPFC in the control group ( r=0.326, P=0.040). In the RRMS group, the gray matter volume of CORE was positively correlated with the functional connectivity between CORE and DMPFC ( r=0.363, P=0.038), and the functional connectivity within CORE was positively correlated with scores on the memory and executive screening scale ( r=0.430, P=0.036). Conclusions:RRMS patients with preserved cognitive function exhibit gray matter atrophy in all three DMN subsystems. There is no correlation between the structure and function of the DMPFC subsystem. The functional connectivity within CORE subsystem may reflect memory and execution status; DMPFC and CORE may be critical encephalic regions for neurodegeneration and brain functional changes in RRMS patients with preserved cognitive function.

Up-frameshift 1 (UPF1), as the most critical factor in nonsense-mediated messenger RNA (mRNA) decay (NMD), regulates tumor-associated molecular pathways in many cancers. However, the role of UPF1 in lung adenocarcinoma (LUAD) amino acid metabolism remains largely unknown. In this study, we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics. We further confirmed that UPF1 knockdown inhibited activating transcription factor 4 (ATF4) and Ser51 phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), the core proteins in amino acid metabolism reprogramming. In addition, UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells, which depends on the function of ATF4. Clinically, UPF1 mRNA expression is abnormal in LUAD tissues, and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival (OS) in LUAD patients. Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.
Activating Transcription Factor 4/genetics* ; Adenocarcinoma of Lung ; Amino Acids ; Cell Proliferation ; Eukaryotic Initiation Factor-2 ; Humans ; Lung Neoplasms ; RNA Helicases/metabolism* ; RNA, Messenger/metabolism* ; Trans-Activators/metabolism*

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Humans ; Ganglioglioma/pathology* ; Central Nervous System Neoplasms/pathology* ; Central Nervous System/pathology* ; Brain Neoplasms/pathology* ; World Health Organization

Objective:To preliminarily evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for pulmonary oligometastatic tumors from head and neck carcinoma.Methods:Clinical data of 24 patients with pulmonary oligometastasis from head and neck carcinoma undergoing SBRT in Zhejiang Cancer Hospital from January 2014 to May 2019 were retrospectively analyzed. Survival analysis was performed by Kaplan- Meier method. Results:Among the 24 patients, 12 cases were diagnosed with nasopharyngeal origin and 12 cases of non-nasopharyngeal origin. A total of 34 pulmonary metastatic lesions were treated with SBRT. The median follow-up time was 19.5 months. Thirteen cases developed new lesions after SBRT, and 9 of them occurred within 1 year after SBRT treatment. The actual 1-year local control rate was 95%. The median progression-free survival was 15.2 months, and the 1-and 2-year progression-free survival were 59% and 46%, respectively. The 2-and 3-years overall survival rate at were 71% and 51% fter lung metastasis, respectively. Univariate analysis showed that the patients with primary lesions located in nasopharynx and disease-free interval of more than 1 year had survival advantage. No more than grade 3 radiation-induced injury was observed in the whole cohort after SBRT, and the incidence of mild radiation-induced injury was 13%.Conclusions:SBRT is safe and effective in the treatment of pulmonary oligometastatsis from head and neck carcinoma, and it may be more effective for patients with primary tumors located in nasopharynx.