A survey of skin failure perceptions amongst pressure injury management staff in China: A cross-sectional study.

This study sought to evaluate the perceptions of pressure injury (PI) management staff regarding skin failure (SF). Additionally, an analysis of influencing factors based on the collected data was conducted to establish a foundation for targeted SF training. A descriptive, cross-sectional survey was undertaken in October-November 2023, utilising a convenience sampling method involving selected management staff of PI from 16 provinces in China. A total of 501 nursing participants were included, exhibiting an overall perception level that was moderately low. Although the majority were aware of the possibility of SF (n = 417, 83.23%), only 60% reported an understanding of the fundamentals of SF, with the lowest level of comprehension observed in differentiating between SF and PI (n = 212, 42.31%). Overall attitudes were generally positive. Regarding behaviour, active learning was more prevalent (n = 340, 67.86%), but training is less (n = 287, 57.29%). Family education (n = 401, 80.04%) and nursing record monitoring (n = 426, 85.03%) demonstrated better behaviour. Further analysis revealed that training (t = 13.937, p < 0.001) and professional title (F = 4.681, p = 0.010) had a significant effect on participants' perceptions. These findings underscore that there remains a substantial lack of perception about SF amongst participants. Overall, participants exhibited a positive attitude towards SF, highlighting the need for future improvements in SF training.

Deep Learning For Automatic Gross Tumor Volumes Contouring in Esophageal Cancer Based on Contrast-Enhanced Computed Tomography Images: A Multi-Institutional Study.

PURPOSE: To develop and externally validate an automatic artificial intelligence (AI) tool for delineating gross tumor volume (GTV) in patients with esophageal squamous cell carcinoma (ESCC), which can assist in neo-adjuvant or radical radiation therapy treatment planning. METHODS AND MATERIALS: In this multi-institutional study, contrast-enhanced CT images from 580 eligible ESCC patients were retrospectively collected. The GTV contours delineated by 2 experts via consensus were used as ground truth. A 3-dimensional deep learning model was developed for GTV contouring in the training cohort and internally and externally validated in 3 validation cohorts. The AI tool was compared against 12 board-certified experts in 25 patients randomly selected from the external validation cohort to evaluate its assistance in improving contouring performance and reducing variation. Contouring performance was measured using dice similarity coefficient (DSC) and average surface distance. Additionally, our previously established radiomics model for predicting pathologic complete response was used to compare AI-generated and ground truth contours, to assess the potential of the AI contouring tool in radiomics analysis. RESULTS: The AI tool demonstrated good GTV contouring performance in multicenter validation cohorts, with median DSC values of 0.865, 0.876, and 0.866 and median average surface distance values of 0.939, 0.789, and 0.875 mm, respectively. Furthermore, the AI tool significantly improved contouring performance for half of 12 board-certified experts (DSC values, 0.794-0.835 vs 0.856-0.881, P = .003-0.048), reduced the intra- and interobserver variations by 37.4% and 55.2%, respectively, and saved contouring time by 77.6%. In the radiomics analysis, 88.7% of radiomic features from ground truth and AI-generated contours demonstrated stable reproducibility, and similar pathologic complete response prediction performance for these contours (P = .430) was observed. CONCLUSIONS: Our AI contouring tool can improve GTV contouring performance and facilitate radiomics analysis in ESCC patients, which indicates its potential for GTV contouring during radiation therapy treatment planning and radiomics studies.

Risk Factors of Enternal Nutrition Intolerance in Septic Patients: A Case-control Study.

OBJECTIVE: This study aimed to investigate the incidence of enteral nutrition intolerance (ENI) in patients with sepsis and explore potential risk factors. METHODS: A case-control study was conducted in patients with sepsis who were receiving enteral nutrition (EN) at a tertiary hospital in China. The included patients were divided into the ENI group and the non-ENI group. Univariate and multivariate analyses were performed to identify the risk factors for ENI. RESULTS: A total of 859 patients were included in the study. Among them, 288 (33.53%) patients experienced symptoms of ENI, including diarrhea, vomiting, bloating, and gastric retention. Logistic regression analysis revealed that the Acute Physiology and Chronic Health Evaluation H (APACHE H) score, thoracocentesis, and usage of cardiotonic drugs (namely, inotropes) were independent predictors of the ENI. CONCLUSION: The incidence of ENI is relatively high in patients with sepsis, especially in those who have higher APACHE H scores, have undergone thoracocentesis, and have received inotropes.

Posttraumatic growth of medical staff during COVID-19 pandemic: A scoping review.

BACKGROUND: The COVID-19 pandemic has imposed unprecedented stress and challenges upon medical staff, potentially resulting in posttraumatic growth (PTG). This scoping review aims to synthesize the existing knowledge on PTG among medical staff during the pandemic by identifying its current status and potential influencing factors. The findings may provide a foundation for future research and interventions to enhance the medical staff's psychological resilience and well-being. METHODS: Literature was systematically searched on PTG among medical staff during the COVID-19 pandemic from 01 January 2020 to 31 December 2022. The following databases were searched: PubMed, Web of Science, Embase, CINAHL, PsycINFO, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Service System (SinoMed), and Wanfang Data. Eligibility criteria included: (1) medical staff as research subjects; (2) a focus on "posttraumatic growth" or "alternative posttraumatic growth" related to the COVID-19 outbreak and pandemic; (3) discussion of the situation and influencing factors of PTG; and (4) study types, such as qualitative, quantitative, and mixed methods. Two researchers independently selected and extracted study characteristics (study design, study population, region, measurement instruments, and primary outcomes) from the included literature. The data were synthesized qualitatively and descriptively. RESULTS: Thirty-six papers from 12 countries met the inclusion criteria. Moderate PTG levels were observed among healthcare workers during the COVID-19 pandemic, with emphasis on "interpersonal relationships," "changes in life philosophy," and "growth in personal competence." Influencing factors included trauma exposure, sociodemographics, psychological characteristics (resilience and positive qualities), coping, and social support. CONCLUSIONS: This review discovered moderate PTG levels among medical staff during the COVID-19 pandemic, with critical areas in interpersonal relationships, life philosophy, and personal competence. The identified influencing factors can inform future research and interventions to enhance healthcare workers' psychological resilience and well-being.

[A Review on Automatic Detection Algorithm for Patient-Ventilator Asynchrony during Mechanical Ventilation].

This study summarizes the application of automatic recognition technologies for patient-ventilator asynchrony (PVA) during mechanical ventilation. In the early stages, the method of setting rules and thresholds relied on manual interpretation of ventilator parameters and waveforms. While these methods were intuitive and easy to operate, they were relatively sensitive in threshold setting and rule selection and could not adapt well to minor changes in patient status. Subsequently, machine learning and deep learning technologies began to emerge and develop. These technologies automatically extract and learn data characteristics through algorithms, making PVA detection more robust and universal. Among them, logistic regression, support vector machines, random forest, hidden Markov models, convolutional autoencoders, long short-term memory networks, one-dimensional convolutional neural networks, etc., have all been successfully used for PVA recognition. Despite the significant advancements in feature extraction through deep learning methods, their demand for labelled data is high, potentially consuming significant medical resources. Therefore, the combination of reinforcement learning and self-supervised learning may be a viable solution. In addition, most algorithm validations are based on a single dataset, so the need for cross-dataset validation in the future will be an important and challenging direction for development.

The Use of Intraosseous Infusion in the Early Resuscitation of Patients With Extremely Severe Burns.

According to research, shock, the most common complication of extremely severe burns, is also the leading cause of mortality among patients with such burns. The case fatality rate reaches 83.45% when the total burn area exceeds 90%. The American Heart Association in 2020 recommended the intraosseous (IO) access after the peripheral access and prior to the central venous access when venous cannulation is either difficult or delayed. The use and experience with intraosseous infusion in extremely severe burns are still limited. We report efficacy and safety results from 19 burn patients treated with IO infusion between June 2020 and December 2022. In these patients, the mean injury time of burns was 1.55 ± 1.10 hours, the mean burn surface area was 86.24% ± 11.33%, the mean catheterization time was 49.68 ± 10.11 seconds, and the mean emergency retention time was 2.75 ± 1.74 hours, the mean actual fluid supplement amount was 5,533.68 ± 3,077.19 mL, the mean hourly urine volume of the patient was 93.31 ± 60.94 mL, the mean emergency detention time was 4.16 ± 2.97 hours, and the mean duration of hospitalization was 34.50 ± 25.38 days. The results demonstrated a clinically meaningful improvement and higher response rate vs peripheral venous cannulation and an acceptable safety profile in those patients.

Variation in the physiological response of adult worker bees of different ages (Apis mellifera L.) to pyraclostrobin stress.

The social division of labor within the honeybee colony is closely related to the age of the bees, and the age structure is essential to the development and survival of the colony. Differences in tolerance to pesticides and other external stresses among worker bees of different ages may be related to their social division of labor and corresponding physiological states. Pyraclostrobin was widely used to control the fungal diseases of nectar and pollen plants, though it was not friend to honey bees and other pollinators. This work aimed to determine the effects of field recommended concentrations of pyraclostrobin on the activities of protective and detoxifying enzymes, on the expression of genes involved in nutrient metabolism, and immune response in worker bees of different ages determined to investigate the physiological and biochemical differences in sensitivity to pyraclostrobin among different age of worker bees. The result demonstrates that the tolerance of adult worker bees to pyraclostrobin was negatively correlated with their age, and the significantly reduced survival rate of forager bees (21 day-old) with continued fungicide exposure. The activities of protective enzymes (CAT and SOD) and detoxifying enzymes (CarE, GSTs and CYP450) in different ages of adult worker bees were significantly altered, indicating the physiological response and the regulatory capacity of worker bees of different ages to fungicide stress was variation. Compared with 1 and 8 day-old worker bees, the expression of nutrient-related genes (ilp1 and ilp2) and immunity-related genes (apidaecin and defensin1) in forager bees (21 day-old) was gradually downregulated with increasing pyraclostrobin concentrations. Moreover, the expression of vitellogenin and hymenoptaecin in forager bees (21 day-old) was also decreased in high concentration treatment groups (250 and 313 mg/L). The present study confirmed the findings of the chronic toxicity of pyraclostrobin on the physiology and biochemistry of worker bees of different ages, especially to forager bees (21 day-old). These results would provide important physiological and biochemical insight for better understanding the potential risks of pyraclostrobin on honeybees and other non-target pollinators.

Association between Red Blood Cell Distribution Width and Short-Term Mortality in Patients with Paralytic Intestinal Obstruction: Retrospective Data Analysis Based on the MIMIC-III Database.

Objective: Elevated red cell distribution (RDW) has been reported to be associated with mortality in patients with acute pancreatitis and cholecystitis admitted to the intensive care unit (ICU). However, evidence for the relationship between RDW and paralytic intestinal obstruction is lacking. Therefore, the article aims to investigate the relationship between RDW and 28-day mortality of the patients with paralytic intestinal obstruction. Patients and Methods. This is a single-center retrospective study. Based on a particular screening criterion, 773 patients with paralytic intestinal obstruction were selected from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Indicators of the first 24 h into the ICU were used to analyze the relationship between RDW and 28-day death from paralytic intestinal obstruction by Kaplan-Meier (K-M) analysis, logistic regression analysis, and stratification analysis. Results: The curve fitting exhibited a nonlinear relationship. The K-M curve showed that groups with higher RDW values had lower survival rates. The logistic regression analysis revealed that RDW increased with 28-day mortality in patients with paralytic intestinal obstruction in the fully adjusted model. In the fully adjusted model, OR value and 95% CI from the second to the third quantiles compared to the first quartile (reference group) were 1.89 (1.04, 3.44) and 3.29 (1.82, 5.93), respectively. The results of stratified analysis of each layer had the same trend as those of regression analysis, and the interaction results were not significant. Conclusion: Elevated RDW was associated with increased 28-day mortality from paralytic intestinal obstruction in the ICU. This study can help to further explore the relationship between RDW and death in patients with paralytic intestinal obstruction.

Preclinical evaluation of a novel EGFR&c-Met bispecific near infrared probe for visualization of esophageal cancer and metastatic lymph nodes.

PURPOSE: This study aimed to establish a near infrared fluorescent (NIRF) probe based on an EGFR&c-Met bispecific antibody for visualization of esophageal cancer (EC) and metastatic lymph nodes (mLNs). METHODS: EGFR and c-Met expression were assessed by immunohistochemistry. EGFR&c-Met bispecific antibody EMB01 was labeled with IRDye800cw. The binding of EMB01-IR800 was assessed by enzyme linked immunosorbent assay, flow cytometry, and immunofluorescence. Subcutaneous tumors, orthotopic tumors, and patient-derived xenograft (PDX) were established for in vivo fluorescent imaging. PDX models using lymph nodes with or without metastasis were constructed to assess the performance of EMB01-IR800 in differential diagnosis of lymph nodes. RESULTS: The prevalence of overexpressing EGFR or c-Met was significantly higher than single marker either in EC or corresponding mLNs. The bispecific probe EMB01-IR800 was successfully synthesized, with strong binding affinity. EMB01-IR800 showed strong cellular binding to both Kyse30 (EGFR overexpressing) and OE33 (c-Met overexpressing) cells. In vivo fluorescent imaging showed prominent EMB01-IR800 uptake in either Kyse30 or OE33 subcutaneous tumors. Likewise, EMB01-IR800 exhibited superior tumor enrichment in both thoracic orthotopic esophageal squamous cell carcinoma and abdominal orthotopic esophageal adenocarcinoma models. Moreover, EMB01-IR800 produced significantly higher fluorescence in patient-derived mLNs than in benign lymph nodes. CONCLUSION: This study demonstrated the complementary overexpression of EGFR and c-Met in EC. Compared to single-target probes, the EGFR&c-Met bispecific NIRF probe can efficiently depict heterogeneous esophageal tumors and mLNs, which greatly increased the sensitivity of tumor and mLN identification.

High Temperature Self-Regenerative Granular Hydrogels for Fracture Treatments During Subsurface Energy Recovery.

The uses of granular hydrogels to assemble macroscopic bulk hydrogels display numerous distinct advantages. However, prior assembly of bulk hydrogels is accomplished by interparticle linking strategy, which compromised mechanical property and thermal stability under hostile conditions. To expand their applications as engineering soft materials, self-regenerative granular hydrogels via a seamless integrating approach to regenerate bulk hydrogels is highly desirable. Herein, covalent regenerative granular hydrogels (CRHs) are prepared at low-temperature synthetic conditions and re-construct bulk seamless hydrogels at high-temperature aqueous environments. The re-formed bulk hydrogels display rubber-like viscoelastic behaviors over a wide range of temperatures from 90 to 150 °C, where the covalent re-crosslinking reactions homogeneously occurr along the periphery and in the matrix of granular hydrogels, accounting for the increased structural integrity at high temperatures. The bulk hydrogel shows increased elasticity and long-term thermal integrity at 150 °C for more than six months in the confined fractures. Moreover, regenerative granular CRH-based bulk hydrogels significantly improve mechanical robustness under destructive pressure. Thus, high temperature water induced regenerative granular hydrogels present the paradigm to treat engineering scenarios such as large fractures for hydraulic fracturing, drilling operation, and disproportionate permeability reduction under extremely hostile conditions during subsurface energy recovery.

Nosocomial infections in adult patients receiving extracorporeal membrane oxygenation in China: A retrospective cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been increasingly used in China, but nosocomial infections (NI) in patients receiving ECMO remain poorly characterized. Thus, this study aimed to investigate the incidence rate, causative was pathogens, and risk factors of NIs in ECMO patients. METHODS: A retrospective cohort study of patients receiving ECMO between January 2015 and October 2021 was conducted in a tertiary hospital. General demographics and clinical data of the included patients were collected from the electronic medical record system and the real-time NI surveillance system. RESULTS: A total of 86 infected patients with 110 episodes of NIs were identified in 196 patients receiving ECMO. The incidence of NI was 59.2/1000 ECMO days. The median time for the first NI in ECMO patients was 5 days (interquartile range: 2-8 days). Hospital-acquired pneumonia and bloodstream infections were common types of NIs in ECMO patients, and the main pathogens were gram-negative bacteria. Pre-ECMO invasive mechanical ventilation (OR = 2.40, 95% CI:1.12-5.15) and prolonged duration of ECMO (OR = 1.26, 95% CI:1.15-1.39) were risk factors for NIs during ECMO support. DISCUSSION: This study identified the main infection sites and pathogens of NIs in ECMO patients. Although NIs may not affect successful ECMO weaning, additional measures should be implemented to reduce the incidence of NI during ECMO support.

Field recommended concentrations of pyraclostrobin exposure disturb the development and immune response of worker bees (Apis mellifera L.) larvae and pupae.

The strobilurin fungicide pyraclostrobin is widely used to prevent and control the fungal diseases of various nectar and pollen plants. Honeybees also directly or indirectly contact this fungicide with a long-term exposure period. However, the effects of pyraclostrobin on the development and physiology of Apis mellifera larvae and pupae during continuous exposure have been rarely known. To investigate the effects of field-realistic concentrations of pyraclostrobin on honeybee survival and development, the 2-day-old larvae were continuously fed with different pyraclostrobin solutions (100 mg/L and 83.3 mg/L), and the expression of development-, nutrient-, and immune-related genes in larvae and pupae were examined. The results showed that two field-realistic concentrations of pyraclostrobin (100 and 83.3 mg/L) significantly decreased the survival and capped rate of larvae, the weight of pupae and newly emerged adults, and such decrease was a positive correlation to the treatment concentrations. qPCR results showed that pyraclostrobin could induce the expression of Usp, ILP2, Vg, Defensin1, and Hymenoptaecin, decrease the expression of Hex100, Apidaecin, and Abaecin in larvae, could increase the expression of Ecr, Usp, Hex70b, Vg, Apidaecin, and Hymenoptaecin, and decreased the expression of ILP1, Hex100 and Defensin1in pupae. These results reflect pyraclostrobin could decrease nutrient metabolism, immune competence and seriously affect the development of honeybees. It should be used cautiously in agricultural practices, especially in the process of bee pollination.

Highly Robust Nanogels from Thermal-Responsive Nanoparticles with Controlled Swelling for Engineering Deployments.

Regular nanogels have been demonstrated their inefficiency for subterranean oil recovery due to their intrinsic drawbacks of fast swelling within minutes, thermal instability, and salinity vulnerability. Prior deployment of swelling delayed nanogels mainly depended on the reservoirs at a relatively higher temperature. To address the issues encountered during engineering deployment, hereinwe devised an integrative approach to in situ form swelling delayed robust nanogels by introducing radically active monomers with thermally sensitive moieties. The nanoparticles with hydrophobic cores in brine in response to thermal input in situ generated well-dispersed hydrophilic nanogels, which showed a pronounced delayed swelling of a week compared to traditional nanogels showing swelling kinetics within minutes. Furthermore, the formation of swelling-delayed nanogels could occur at ambient temperature. This behavior was radically different from that of temperature-controlled labile cross-linkers containing nanogels, requiring temperatures greater than 50 °C for volume increase thanks to ester hydrolysis. In addition, the in-situ formed nanogels displayed long-term thermal stability and salinity tolerance under hostile media at temperatures up to 130 °C. The release of an acidic proton under aqueous conditions has been demonstrated to control the microenvironment for various scenarios. The nanotechnology of converting hydrophobic nanoparticles to hydrophilic nanogels could be applied in a wide range of practical applications such as plugging materials and foaming stabilizers for in-depth conformance control during water and CO2 flooding.

CT and MRI features of hepatic epithelioid haemangioendothelioma: a multi-institutional retrospective analysis of 15 cases and a literature review.

OBJECTIVE: To improve the current imaging understanding of MRI or CT for hepatic epithelioid haemangioendothelioma (HEHE) to aid in its successful preoperative diagnosis. METHODS: The imaging features of 15 patients (median age 38.6, range 20-71; 7 M/8 F) from eight institutions with pathologically confirmed HEHE were retrospectively analysed. Additionally, the CT/MR imaging features of 180 patients in 15 literature publications were collected, analysed and compared with our case series. RESULTS: Fifteen patients underwent CT and MRI (n = 2), CT (n = 9) or MR (n = 8) scans. A total of 92.9% (13/14) of the patients were initially diagnosed with other lesions on imaging. A total of 86.7% (13/15) were multifocal. Nodules (11/15, 73.3%) were predominantly peripheral in distribution (12/15, 80.0%). Some cases were associated with hepatic capsular retraction (13/15, 86.7%), "target signs" (8/15, 53.3%) and "lollipop signs" (5/15, 33.3%). Peripheral enhancement of various shapes in the early phase with a progressive centripetal filling was the most common pattern of enhancement (12/15, 80.0%). Abnormal vascularity was seen in 50.7% (6/15) of the patients. Suspicious tumour thromboses in the inferior vena cava were seen in 3 (20.0%) of the patients. Two of the 15 patients (13.3%) had a history of smoking. CONCLUSIONS: HEHEs have common distinctive features, including multifocal lesions that are predominantly peripheral, "target signs", "lollipop signs", hepatic capsular retraction and peripheral enhancement of various shapes in the early phase with progressive centripetal filling. Additional aggressive imaging features that may be valuable clues to the diagnosis can be identified by CT or MRI.

Association between dietary phosphorus intake and chronic constipation in adults: evidence from the National Health and Nutrition Examination Survey.

BACKGROUND: Several studies suggest a link between micronutrients and constipation. However, the relationship between constipation and phosphorus has rarely been examined. The main aim of this study was to investigate the association between changes in the prevalence of chronic constipation and dietary phosphorus intake among adult respondents of the National Health and Nutritional Examination Survey (NHANES). METHODS: Data were extracted from the NHANES database for the years 2005-2010. A total of 13,948 people were included in the analysis. Dietary information was collected using the respondents' 24-h dietary records. We conducted multiple logistic regression analyses to examine the correlation between phosphorus intake and poor bowel movement. The primary and secondary outcomes was constipation defined by stool consistency and stool frequency, respectively. RESULTS: Following multi-variate adjustment in model III, a significant association between chronic constipation and each additional 0.1-g intake of dietary phosphorus (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95, 1.00; P = 0.034 for stool consistency vs. OR, 0.94; 95% CI, 0.90, 0.99; P = 0.027 for stool frequency) was observed. Following multi-variate adjustment in model III, OR values and 95% CI from the second to fourth quartiles compared to the first quartile (reference group) were 0.92 (0.66, 1.27), 0.73 (0.47, 1.13), and 0.39 (0.20, 0.76), respectively, using the stool frequency definition. CONCLUSIONS: This study revealed a negative correlation between phosphorus intake and chronic constipation. This may be due to the fact that dietary phosphorus intake is associated with softer stools and increased stool frequency. Further studies in different settings should be considered to verify these findings.

Exploration and validation of a combined immune and metabolism gene signature for prognosis prediction of colorectal cancer.

Background: Colorectal cancer (CRC) is still one of the most frequently diagnosed malignancy around the world. The complex etiology and high heterogeneity of CRC necessitates the identification of new reliable signature to identify different tumor prognosis, which may help more precise understanding of the molecular properties of CRC and identify the appropriate treatment for CRC patients. In this study, we aimed to identify a combined immune and metabolism gene signature for prognosis prediction of CRC from large volume of CRC transcriptional data. Methods: Gene expression profiling and clinical data of HCC samples was retrieved from the from public datasets. IRGs and MRGs were identified from differential expression analysis. Univariate and multivariate Cox regression analysis were applied to establish the prognostic metabolism-immune status-related signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curves were generated for diagnostic efficacy estimation. Real-time polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry (IHC) was conducted to verified the expression of key genes in CRC cells and tissues. Results: A gene signature comprising four genes (including two IRGs and two MRGs) were identified and verified, with superior predictive performance in discriminating the overall survival (OS) of high-risk and low-risk compared to existing signatures. A prognostic nomogram based on the four-gene signature exhibited a best predictive performance, which enabled the prognosis prediction of CRC patients. The hub gene ESM1 related to CRC were selected via the machine learning and prognostic analysis. RT-PCR, Western blot and IHC indicated that ESM1 was high expressed in tumor than normal with superior predictive performance of CRC survival. Conclusions: A novel combined MRGs and IRGs-related prognostic signature that could stratify CRC patients into low-and high- risk groups of unfavorable outcomes for survival, was identified and verified. This might help, to some extent, to individualized treatment and prognosis assessment of CRC patients. Similarly, the mining of key genes provides a new perspective to explore the molecular mechanisms and targeted therapies of CRC.

Identification of an IGF2BP2-Targeted Peptide for Near-Infrared Imaging of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies globally. Peptide-based tumor-targeted imaging is critical for ESCC imaging. In this study, we aim to identify a peptide-targeting IGF2BP2 that specifically binds to human ESCC for near-infrared imaging of esophageal cancer. Applying phage display techniques, we identified a peptide target for IGF2BP2 which was confirmed to be highly expressed in ESCC cell lines or tumor tissue and may serve as an imaging target for ESCC. We conjugated the peptide to the NIRF group, Cy5, and further evaluated the targeting efficacy of the probe at a cellular level and in animal tumor models. The Cy5 conjugated peptide (P12-Cy5) showed a high binding affinity to human ESCC cells in vitro. In vivo, optical imaging also validated the tumor-targeting ability of P12-Cy5 in KYSE-30-bearing subcutaneous ESCC tumor models. Furthermore, the results of biodistribution showed a significantly higher fluorescence intensity in tumors compared to scrambled peptide, which is consistent with in vivo observations. In summary, an IGF2BP2-targeted peptide was successfully identified. In vitro and in vivo experiments confirmed that P12-Cy5 has high affinity, specificity and tumor-targeting properties. Thus, P12-Cy5 is a prospective NIR probe for the imaging of ESCC.

Lu3+-based nanoprobe for virtual non-contrast CT imaging of hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE), the mainstream treatment for hepatocellular carcinoma (HCC), is a method of blocking tumor blood vessels with a mixture of lipiodol and chemotherapeutics. And the contrast-enhanced computed tomography (CT) is the commonly used way for follow-up of HCC after TACE. However, it is noteworthy that when lipiodol deposition plays an embolic effect, it also produces high-density artifacts in CT images. These artifacts usually conceal the enhancement effect of iodine contrast agents. As a result, the residual region is difficult to be visualized. To overcome this obstacle, we developed one kind of Lu3+/Gd3+ doped fluoride nanoprobe modified with Dp-PEG2000 to realize CT/MRI dual-modality imaging of HCC. Compared with lipiodol or ioversol, the obtained PEGylated product LG-PEG demonstrated a greater density value in high keV CT images. In vitro experiments showed the lipiodol artifacts can be removed in virtual non-contrast (VNC) imaging, but the density of ioversol was also removed at the same time. However, the LG-PEG synthesized in this work can still maintain a high density in VNC imaging, which indicates that LG-PEG can exploit its advantages to the full in VNC imaging. Furthermore, LG-PEG successfully exerted tumor enhancement effects in the in vivo VNC images of HCC with lipiodol deposition. In addition, LG-PEG exhibited a strong T2 enhancement effect with low biological toxicity and less side-effect on the main organ and blood. Thus, the LG-PEG reported in this research can serve as an effective and safe VNC contrast agent for HCC imaging after TACE.

NIR-II Navigation with an EGFR-Targeted Probe Improves Imaging Resolution and Sensitivity of Detecting Micrometastases in Esophageal Squamous Cell Carcinoma Xenograft Models.

The survival rate of esophageal squamous carcinoma (ESCC) after surgical resection is estimated to be only 30.3% due to the difficulty in identifying microinfiltration and subtle metastases. In this study, we explored the value of near-infrared fluorescence in the second window (NIR-II) using an epidermal growth factor receptor (EGFR)-targeted probe (cetuximab-IR800) for the intraoperative navigation of ESCC in xenograft mouse models. Immunohistochemical results showed that EGFR was aberrantly expressed in 94.49% (120/127) of ESCC tissues and 90.63% (58/64) of metastatic lymph nodes. Western blot results demonstrated that EGFR protein was highly expressed in ESCC cell lines. Flow cytometry data revealed that cetuximab-IR800 showed a stronger binding specificity in EGFR-positive KYSE-30 cells than in A2780 control cells (P < 0.01). In vivo imaging data showed that the ratio of mean fluorescent intensity (MFI) and tumor to background (TBR) was significantly higher in KYSE-30 subcutaneous tumors with the infusion of cetuximab-IR800 than in those with the infusion of IgG1-IR800 (P < 0.05). Surgical navigation with NIR-II imaging showed that the TBR in orthotopic ESCC was significantly higher than that of NIR in the first window (NIR-I) (2.11 ± 0.46 vs 1.58 ± 0.31, P < 0.05), and NIR-II was more sensitive than NIR-I in detecting subcentimeter metastases (94.87% (37/39) vs 58.97% (23/39), P < 0.001). In conclusion, cetuximab-IR800 with high specificity for ESCC was first used in NIR-II surgical navigation. This probe showed better imaging resolution and higher sensitivity in detecting subtle metastases derived from an orthotopic ESCC model than NIR-I, which indicates that NIR-II has promise in guiding precise surgery for ESCC patients.

Polysaccharides derived from Chinese medicinal herbs: A promising choice of vaccine adjuvants.

Adjuvants have been used in vaccines for a long time to promote the body's immune response, reducing vaccine dosage and production costs. Although many vaccine adjuvants are developed, the use in human vaccines is limited because of either limited action or side effects. Therefore, the development of new vaccine adjuvants is required. Many studies have found that natural polysaccharides derived from Traditional Chinese medicine (TCM) possess good immune promoting effects and simultaneously improve humoral, cellular and mucosal immunity. Recently polysaccharide adjuvants have attracted much attention in vaccine preparation because of their intrinsic characteristics: immunomodulation, biocompatibility, biodegradability, low toxicity and safety. This review article systematically analysed the literature on polysaccharides possessing vaccine adjuvant activity from TCM plants, such as Astragalus polysaccharide (APS), Rehmannia glutinosa polysaccharide (RGP), Isatis indigotica root polysaccharides (IRPS), etc. and their derivatives. We believe that polysaccharide adjuvants can be used to prepare the vaccines for clinical use provided their mechanisms of action are studied in detail.