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Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.
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This study investigates the role of autophagy regulation in modulating neuroinflammation and cognitive function in an Alzheimer's disease (AD) mouse model with chronic cerebral hypoperfusion (CCH). Using the APP23/PS1 mice plus CCH model, we examined the impact of autophagy regulation on cognitive function, neuroinflammation, and autophagic activity. Our results demonstrate significant cognitive impairments in AD mice, exacerbated by CCH, but mitigated by treatment with the autophagy inhibitor 3-methyladenine (3-MA). Dysregulation of autophagy-related proteins, accentuated by CCH, underscores the intricate relationship between cerebral blood flow and autophagy dysfunction in AD pathology. While 3-MA restored autophagic balance, rapamycin (RAPA) treatment did not induce significant changes, suggesting alternative therapeutic approaches are necessary. Dysregulated microglial polarization and neuroinflammation in AD+CCH were linked to cognitive decline, with 3-MA attenuating neuroinflammation. Furthermore, alterations in M2 microglial polarization and the levels of inflammatory markers NLRP3 and MCP1 were observed, with 3-MA treatment exhibiting potential anti-inflammatory effects. Our findings shed light on the crosstalk between autophagy and neuroinflammation in AD+CCH and suggest targeting autophagy as a promising strategy for mitigating neuroinflammation and cognitive decline in AD+CCH.
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PURPOSE: To develop a deep learning (DL) model for differentiating between benign and malignant ovarian tumors of Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US) Category 4 lesions, and validate its diagnostic performance. METHODS: A retrospective analysis of 1619 US images obtained from three centers from December 2014 to March 2023. DeepLabV3 and YOLOv8 were jointly used to segment, classify, and detect ovarian tumors. Precision and recall and area under the receiver operating characteristic curve (AUC) were employed to assess the model performance. RESULTS: A total of 519 patients (including 269 benign and 250 malignant masses) were enrolled in the study. The number of women included in the training, validation, and test cohorts was 426, 46, and 47, respectively. The detection models exhibited an average precision of 98.68% (95% CI: 0.95-0.99) for benign masses and 96.23% (95% CI: 0.92-0.98) for malignant masses. Moreover, in the training set, the AUC was 0.96 (95% CI: 0.94-0.97), whereas in the validation set, the AUC was 0.93(95% CI: 0.89-0.94) and 0.95 (95% CI: 0.91-0.96) in the test set. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive values for the training set were 0.943,0.957,0.951,0.966, and 0.936, respectively, whereas those for the validation set were 0.905,0.935, 0.935,0.919, and 0.931, respectively. In addition, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for the test set were 0.925, 0.955, 0.941, 0.956, and 0.927, respectively. CONCLUSION: The constructed DL model exhibited high diagnostic performance in distinguishing benign and malignant ovarian tumors in O-RADS US category 4 lesions.
Subject(s)
Deep Learning , Ovarian Neoplasms , Ultrasonography , Humans , Female , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/pathology , Ovarian Neoplasms/diagnosis , Retrospective Studies , Middle Aged , Ultrasonography/methods , Adult , Aged , Young AdultABSTRACT
Traumatic brain injury (TBI) is widely recognized as a global public health crisis, affecting millions of people each year, leading to permanent neurologic, emotional, and occupational disability, and highlighting the urgent need for rapid, sensitive, and early assessment. Here, we design a novel and simple lithography-free method for preparing dual-channel graphene-based field-effect transistors (G-FETs) and integrating them with microfluidic channels for simultaneously multiplexed detection of key blood TBI biomarkers: neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP). The G-FET utilizes an ingenious dual-channel electrode array design, where the source is shared between channels and the drains are independent of each other, which is the key to achieving simultaneous output of dual detection signals. At the same time, the microfluidic chip realizes microscale fluidic control and fast sample response time. This integrated detection system shows excellent sensitivity in biological fluids for the TBI biomarkers with detection limits as low as 55.63 fg/mL for NFL and 144.45 fg/mL for GFAP in phosphate-buffered saline (PBS) buffer, respectively. Finally, the clinical sample analysis shows promising performance for TBI detection, with an area under the curve (AUC) of 0.98 for the two biomarkers. And the combined dual-protein assay is also a good predictor of intracranial injury findings on computed tomography (CT) scans (AUC = 0.907). The integrated microfluidic G-FET device with a dual-signal output strategy has important potential for application in clinical practice, providing more comprehensive information for brain injury assessment.
Subject(s)
Biomarkers , Brain Injuries, Traumatic , Glial Fibrillary Acidic Protein , Brain Injuries, Traumatic/blood , Brain Injuries, Traumatic/diagnosis , Biomarkers/blood , Humans , Glial Fibrillary Acidic Protein/blood , Lab-On-A-Chip Devices , Neurofilament Proteins/blood , Neurofilament Proteins/analysis , Transistors, Electronic , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Graphite/chemistry , Limit of Detection , Biosensing Techniques/methods , Biosensing Techniques/instrumentationABSTRACT
MiR-1246 in breast cancer-derived exosomes was a promising biomarker for early diagnosis of breast cancer(BC). However, the low abundance, high homology and complex background interference make the accurate quantitative detection of miR-1246 facing great challenges. In this study, we developed an electrochemical biosensor based on the subtly combined of CRISPR/Cas12a, double-stranded specific nuclease(DSN) and magnetic nanoparticles(MNPs) for the detection of miR-1246 in BC-derived exosomes. Ascribed to the good synergistic effect of DSN, Cas12a and MNPs, the developed electrochemical biosensor exhibited excellent performance with the linear range from 500 aM to 5 pM, and the detection limit as low down to about 50 aM. The target-specific triggered enzyme-digest activity of DSN and Cas12a system, as well as the powerful separation ability of MNPs ensure the high specificity of developed electrochemical biosensor which can distinguish single base mismatches. In addition, the developed electrochemical biosensor has been successfully applied to detect miR-1246 in blood-derived exosomes and realize distinguishing the BC patients from the healthy individuals. It is expected that the well-designed biosensing platform will open up new avenues for clinical liquid biopsy and early screening of breast cancer, as well as provide deeper insights into clinical oncology treatment.
Subject(s)
Biosensing Techniques , Breast Neoplasms , CRISPR-Cas Systems , Electrochemical Techniques , Exosomes , MicroRNAs , Exosomes/chemistry , Exosomes/metabolism , Humans , Biosensing Techniques/methods , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , MicroRNAs/analysis , MicroRNAs/genetics , Female , Electrochemical Techniques/methods , Limit of Detection , Magnetite Nanoparticles/chemistry , Bacterial Proteins , Endodeoxyribonucleases , CRISPR-Associated ProteinsABSTRACT
OBJECTIVE: To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy. METHODS: After retrospectively screening the data of 742 patients between January 2007 and July 2020, 50 patients aged 13 to 39 years with Enneking stage II disease were included in the study. Serum lipid levels, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-α [Lp(a)], and apolipoprotein A1, B, and E (ApoA1, ApoB, and ApoE), and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy. RESULTS: The mean levels of TC, TG, and ApoB were significantly increased following neoadjuvant chemotherapy (16%, 38%, and 20%, respectively, vs. pretreatment values; P<0.01). The mean levels of LDL-C and ApoE were also 19% and 16% higher, respectively (P<0.05). No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy. An increase in Lp(a) was strongly correlated with the Ki-67 index (R=0.31, P=0.023). Moreover, a trend toward longer disease-free survival (DFS) was observed in patients with decreased TG and increased LDL-C following chemotherapy, although this difference was not statistically significant (P=0.23 and P=0.24, respectively). CONCLUSION: Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma. There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy. The scale of increase in serum Lp(a) might have a potential prognostic role in osteosarcoma. Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.
Subject(s)
Knee Joint , Lipids , Lipoproteins , Neoadjuvant Therapy , Osteosarcoma , Humans , Osteosarcoma/drug therapy , Osteosarcoma/blood , Osteosarcoma/pathology , Male , Female , Retrospective Studies , Adolescent , Adult , Lipids/blood , Young Adult , Knee Joint/pathology , Lipoproteins/blood , Bone Neoplasms/drug therapy , Bone Neoplasms/bloodABSTRACT
OBJECTIVE: The main aim of this study was to determine whether the use of contrast-enhanced ultrasound (CEUS) could improve the categorization of suspicious breast lesions based on the Breast Imaging Reporting and Data System (BI-RADS), thereby reducing the number of benign breast lesions referred for biopsy. METHODS: This prospective study, conducted between January 2017 and December 2018, enrolled consenting patients from eight teaching hospitals in China, who had been diagnosed with solid breast lesions classified as BI-RADS 4 using conventional ultrasound. CEUS was performed within 1 wk of diagnosis for reclassification of breast lesions. Histopathological results obtained from core needle biopsies or surgical excision samples served as the reference standard. The simulated biopsy rate and cancer-to-biopsy yield were used to compare the accuracy of CEUS and conventional ultrasound (US). RESULTS: Among the 1490 lesions diagnosed as BI-RADS 4 with conventional ultrasound, 486 malignant and 1004 benign lesions were confirmed based on histology. Following CEUS, 2, 395, and 211 lesions were reclassified as CEUS-based BI-RADS 2, 3, and 5, respectively, while 882 (59%) remained as BI-RADS 4. The actual cancer-to-biopsy yield based on US was 32.6%, which increased to 43.4% when CEUS-based BI-RADS 4A was used as the cut-off point to recommend biopsy. The simulated biopsy rate decreased to 73.4%. Overall, in this preselected BI-RADS 4 population, only 2.5% (12/486) of malignant lesions would have been miscategorized as BI-RADS 3 using CEUS-based reclassification. The diagnostic accuracy, sensitivity, and specificity of contrast-enhanced ultrasound reclassification were 57.65%, 97.53%, and 38.35%, respectively. CONCLUSION: Our collective findings indicate that CEUS is a valuable tool in further triage of BI-RADS category 4 lesions and facilitates a reduction in the number of biopsies while increasing the cancer-to-biopsy yield.
Subject(s)
Breast Neoplasms , Breast , Contrast Media , Ultrasonography, Mammary , Humans , Female , Prospective Studies , Ultrasonography, Mammary/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Middle Aged , Adult , Breast/diagnostic imaging , Breast/pathology , Aged , Image Enhancement/methods , Young Adult , Reproducibility of Results , ChinaABSTRACT
BACKGROUND: To develop a convenient modality to predict axillary response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this multi-center study, a total of 1019 breast cancer patients with biopsy-proven positive lymph node (LN) receiving NAC were randomly assigned to the training and validation groups at a ratio of 7:3. Clinicopathologic and ultrasound (US) characteristics of both primary tumors and LNs were used to develop corresponding prediction models, and a nomogram integrating clinicopathologic and US predictors was generated to predict the axillary response to NAC. RESULTS: Axillary pathological complete response (pCR) was achieved in 47.79% of the patients. The expression of estrogen receptor, human epidermal growth factor receptor -2, Ki-67 score, and clinical nodal stage were independent predictors for nodal response to NAC. Location and radiological response of primary tumors, cortical thickness and shape of LNs on US were also significantly associated with nodal pCR. In the validation cohort, the discrimination of US model (area under the curve [AUC], 0.76) was superior to clinicopathologic model (AUC, 0.68); the combined model (AUC, 0.85) demonstrates strong discriminatory power in predicting nodal pCR. Calibration curves of the nomogram based on the combined model demonstrated that substantial agreement can be observed between the predictions and observations. This nomogram showed a false-negative rates of 16.67% in all patients and 10.53% in patients with triple negative breast cancer. CONCLUSION: Nomogram incorporating routine clinicopathologic and US characteristics can predict nodal pCR and represents a tool to aid in treatment decisions for the axilla after NAC in breast cancer patients.
Subject(s)
Axilla , Breast Neoplasms , Lymph Nodes , Neoadjuvant Therapy , Nomograms , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Neoadjuvant Therapy/methods , Middle Aged , Adult , Lymph Nodes/pathology , Aged , Lymphatic Metastasis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant/methodsABSTRACT
PURPOSE: The overall survival rate for metastatic osteosarcoma hovers around 20%. Responses to second-line chemotherapy, targeted therapies, and immunotherapies have demonstrated limited efficacy in metastatic osteosarcoma. Our objective is to validate differentially expressed genes and signaling pathways between non-metastatic and metastatic osteosarcoma, employing single-cell RNA sequencing (scRNA-seq) and additional functional investigations. We aim to enhance comprehension of metastatic mechanisms and potentially unveil a therapeutic target. METHODS: scRNA-seq was performed on two primary osteosarcoma lesions (1 non-metastatic and 1 metastatic). Seurat package facilitated dimensionality reduction and cluster identification. Copy number variation (CNV) was predicted using InferCNV. CellChat characterized ligand-receptor-based intercellular communication networks. Differentially expressed genes underwent GO function enrichment analysis and GSEA. Validation was achieved through the GSE152048 dataset, which identified PDGFD-PDGFRB as a common ligand-receptor pair with significant contribution. Immunohistochemistry assessed PDGFD and PDGFRB expression, while multicolor immunofluorescence and flow cytometry provided insight into spatial relationships and the tumor immune microenvironment. Kaplan-Meier survival analysis compared metastasis-free survival and overall survival between high and low levels of PDGFD and PDGFRB. Manipulation of PDGFD expression in primary osteosarcoma cells examined invasion abilities and related markers. RESULTS: Ten clusters encompassing osteoblasts, osteoclasts, osteocytes, fibroblasts, pericytes, endothelial cells, myeloid cells, T cells, B cells, and proliferating cells were identified. Osteoblasts, osteoclasts, and osteocytes exhibited heightened CNV levels. Ligand-receptor-based communication networks exposed significant fibroblast crosstalk with other cell types, and the PDGF signaling pathway was activated in non-metastatic osteosarcoma primary lesion. These results were corroborated by the GSE152048 dataset, confirming the prominence of PDGFD-PDGFRB as a common ligand-receptor pair. Immunohistochemistry demonstrated considerably greater PDGFD expression in non-metastatic osteosarcoma tissues and organoids, correlating with extended metastasis-free and overall survival. PDGFRB expression showed no significant variation between non-metastatic and metastatic osteosarcoma, nor strong correlations with survival times. Multicolor immunofluorescence suggested co-localization of PDGFD with PDGFRB. Flow cytometry unveiled a highly immunosuppressive microenvironment in metastatic osteosarcoma. Manipulating PDGFD expression demonstrated altered invasive abilities and marker expressions in primary osteosarcoma cells from both non-metastatic and metastatic lesions. CONCLUSIONS: scRNA-seq illuminated the activation of the PDGF signaling pathway in primary lesion of non-metastatic osteosarcoma. PDGFD displayed an inhibitory effect on osteosarcoma metastasis, likely through the suppression of the EMT signaling pathway.
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Non-small cell lung cancer (NSCLC) is an aggressive and rapidly expanding lung cancer. Abnormal upregulation or knockdown of PDIA6 expression can predict poor prognosis in various cancers. This study aimed to investigate the biological function of PDIA6 in NSCLC. SOX2 and PDIA6 expression in NSCLC tissues and regulatory relationship between them were analyzed using bioinformatics. GSEA was performed on the enrichment pathway of PDIA6. qRT-PCR was utilized to examine expression of SOX2 and PDIA6 in NSCLC tissues and cells, and dual-luciferase reporter assay and ChIP experiments were performed to validate their regulatory relationship. CCK-8 experiment was conducted to assess cell viability, western blot was to examine levels of stem cell markers and proteins related to aerobic glycolysis pathway in cells. Cell sphere formation assay was used to evaluate efficiency of cell sphere formation. Reagent kits were used to measure glycolysis levels and glycolysis products. High expression of PDIA6 in NSCLC was linked to aerobic glycolysis. Knockdown of PDIA6 reduced cell viability, expression of stem cell surface markers, and cell sphere formation efficiency in NSCLC. Overexpression of PDIA6 could enhance cell viability and promote aerobic glycolysis, but the addition of 2-DG could reverse this result. Bioinformatics predicted the existence of upstream transcription factor SOX2 for PDIA6, and SOX2 was significantly upregulated in NSCLC, and they had a binding relationship. Further experiments revealed that PDIA6 overexpression restored repressive effect of knocking down SOX2 on aerobic glycolysis and cell stemness. This work revealed that the SOX2/PDIA6 axis mediated aerobic glycolysis to promote NSCLC cell stemness, providing new therapeutic strategies for NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Protein Disulfide-Isomerases , SOXB1 Transcription Factors , Humans , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Glycolysis/physiology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Protein Disulfide-Isomerases/metabolism , SOXB1 Transcription Factors/metabolismABSTRACT
Cholesterol is an important lipid compound found in a variety of foods, and its level in human blood is closely related to human health. Therefore, development of rapid and accurate POCT (point-of-care testing) methods for cholesterol detection is crucial for assessing food quality and early diagnosis of diseases, in particular, in a resource-limited environment. In this study, a smartphone-assisted colorimetric biosensor is constructed based on platinum,phosphorus-codoped carbon nitride (PtCNP2) for the rapid detection of cholesterol. Phosphorus-doped carbon nitride is prepared by thermal annealing of urea and NH4PF6, into which platinum is atomically dispersed by thermal refluxing. The obtained PtCNP2 exhibits an excellent peroxidase-like activity under physiological pH, whereby colorless o-phenylenediamine (OPD) is oxidized to colored 2,3-diaminophenazine (DAP) in the presence of hydrogen peroxide (H2O2), which can be produced during the oxidation of cholesterol by cholesterol oxidase. A smartphone-assisted visual sensing system is then constructed based on the color recognition software, and rapid on-site detection of cholesterol is achieved by reading the RGB values. Meanwhile, the generated DAP shows an apparent fluorescence signal and can realize highly sensitive detection of cholesterol by the change of the fluorescence signal intensity. Such a cholesterol sensor exhibits a wide linear detection range of 0.5-600 µg mL-1 and a low detection limit of 59 ng mL-1. The practicality of the sensor is successfully demonstrated in the rapid detection of cholesterol in serum and food.
Subject(s)
Colorimetry , Hydrogen Peroxide , Nitriles , Humans , Platinum , Cholesterol , PhosphorusABSTRACT
Estrogen receptor α (ERα) is an important biomarker in breast cancer diagnosis and treatment. Sensitive and accurate detection of ERα protein expression is crucial in guiding selection of an appropriate therapeutic strategy to improve the effectiveness and prognosis of breast cancer treatment. Herein, we report a liquid-gated graphene field-effect transistor (FET) biosensor that enables rapid, sensitive, and label-free detection of the ERα protein by employing a novel drug molecule as a capture probe. The drug molecule was synthesized and subsequently immobilized onto the sensing surface of the fabricated graphene FET, which was able to distinguish the ERα-positive from the ERα-negative protein. The developed sensor not only demonstrated a low detection limit (LOD: 2.62 fM) but also achieved a fast response to ERα protein samples within 30 min. Moreover, depending on the relationship between the change of dirac point and the ERα protein concentrations, the dissociation constant (Kd) was estimated to be 7.35 ± 0.06 pM, indicating that the drug probe-modified graphene FET had a good affinity with ERα protein. The nanosensor was able to analyze ERα proteins from 36 cell samples lysates. These results show that the graphene FET sensor was able to differentiate between ERα-positive and ERα-negative cells, indicating a promising biosensor for the ultrasensitive and rapid detection of ERα protein without antibody labeling.
Subject(s)
Biosensing Techniques , Graphite , Limit of Detection , Estrogen Receptor alpha , Transistors, Electronic , Biomarkers , Biosensing Techniques/methodsSubject(s)
Cities , Environment , Trees , Urban Health , Humans , Trees/physiology , Urban Health/trends , Urban PopulationABSTRACT
BACKGROUND: Training parents to implement language and communication intervention strategies is an effective approach to promote language development for children with language delay. AIMS: This study introduces an online parent training program conducted in Hubei province, China, which was designed to help parents of language-delayed children with a diagnosis of autism spectrum disorder (ASD), developmental language disorder (DLD) or global developmental delay (GDD) apply language intervention strategies into daily interactions and promote their children's language development at home. METHODS & PROCEDURES: The Bethel Hearing and Speaking Training Center Family Training for Early Communication & Language Development (Bethel Family Training Program, BFT) (Bethel HSTC, 2020) was designed to improve the language and communication skills for children with language delay in a naturalistic way. The caregivers (including parents, grandparents and other main caregivers) participated in an 8-h online program, including lectures on milestones in child language development, common misunderstandings of child language development, and three basic family language intervention strategies ('Looking together, playing together, and talking together') incorporating active learning through video analysis and discussion. Tongji Hospital in Hubei then continued with 3 months of online home intervention monitoring to all the caregivers via weekly online Q&As led by BFT certified speech therapists' team. The Gesell Developmental Schedules (GDS) was carried out before the online parent training program and after the 3-month online home intervention monitoring. OUTCOMES & RESULTS: 146 families whose children aged 12-68 months with language delay participated in the online training program. The results of the GDS assessments conducted before and after the program showed that not only did the developmental quotient (DQ) of language improve, but so did the DQ of social behaviour and adaptive behaviour (p < 0.001). There is no between-group difference in the application of three strategies between the ASD group and the DLD or GDD group (p > 0.05). Furthermore, both caregivers' ability to apply 'looking together, playing together, talking together' strategies and the effective interaction time played important roles in improving the child's language abilities. CONCLUSION & IMPLICATIONS: The online parent training focusing on improving daily interaction with children through speech-language stimulation strategies promoted the development of language skills. It is an economic and practical approach for children with language delay who have limited access to local language intervention programs. WHAT THIS PAPER ADDS: What is already known on the subject Parent-implemented language intervention is an effective approach at improving children's language development. Telepractice is an appropriate model of service delivery for audiologists and speech-language therapists and may be the primary mode of service delivery or may supplement in-person services. What this paper adds to the existing knowledge This paper explores the effectiveness of an online parent training program and provides new evidence that online training on language support strategies (looking together, playing together, talking together) followed by home intervention monitoring works for Mandarin-speaking children and it is equally effective for children with ASD and non-ASD diagnosis. What are the potential or actual clinical implications of this work? Developmental behavioural paediatricians and speech-language therapists in countries and areas that lack sufficient training resource for every child will have the option to deliver parent training and home intervention monitoring online, which will save time and cost considerably while offering convenience.
Subject(s)
Language Development Disorders , Parents , Humans , Language Development Disorders/therapy , China , Male , Female , Child, Preschool , Parents/education , Parents/psychology , Language Therapy/education , Language Therapy/methods , Language Development , Child Language , Infant , Child , Autism Spectrum DisorderABSTRACT
OBJECTIVES: Abdominal palpation is an essential examination to diagnose various digestive system diseases. This study aimed to develop an objective and standardized test based on abdominal palpation simulators, and establish a credible pass/fail standard of basic competency. METHODS: Two tests were designed using the newly developed Jucheng abdominal palpation simulator (test 1) and the AbSim simulator (test 2), respectively. Validity evidence for both tests was gathered according to Messick's contemporary framework by using experts to define test content and then administering the tests in a highly standardized way to participants of different experience. Different simulator setups modified by the built-in software were selected from hepatomegaly, splenomegaly, positive McBurney's sign plus rebound tenderness, gallbladder tenderness (Murphy's sign), pancreas tenderness, and a normal setup without pathologies, with six sets used in test 1 and five sets used in test 2. Different novices and experienced were included in the tests, and test 1 was also administered to an intermediate group. Scores and test time were collected and analyzed statistically. RESULTS: The internal consistency reliability of test 1 and test 2 showed low Cronbach's alphas of 0.35 and -0.41, respectively. Cronbach's alpha for palpation time across cases were 0.65 for test 1 and 0.76 for test 2. There was no statistical difference in total time spent and total scores among the three groups in test 1 (P-values (ANOVA) were 0.53 and 0.35 respectively), nor between novices and experienced groups in test 2 (P-values (t-test) were 0.13 and 1.0 respectively). It was not relevant to try to establish pass/fail standards due to the low reliability and lack of discriminatory ability of the tests. CONCLUSIONS: It was not possible to measure abdominal palpation skills in a valid way using either of the two standardized, simulation-based tests in our study. Assessment of the patient's abdomen using palpation is a challenging clinical skill that is difficult to simulate as it highly relies on tactile sensations and adequate responsiveness from the patients.
Subject(s)
Abdomen , Software , Humans , Reproducibility of Results , Computer Simulation , Clinical Competence , PalpationABSTRACT
BACKGROUND: Cell-based immunotherapy shows the therapeutic potential in sarcomas, in addition to angiogenesis-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI). Multi-antigen stimulated cell therapy-I (MASCT-I) technology is a sequential immune cell therapy for cancer, which composes of multiple antigen-loaded dendritic cell (DC) vaccines followed by the adoptive transfer of anti-tumor effector T-cells. METHODS: In this phase 1 study, we assessed MASCT-I plus camrelizumab (an ICI against PD-1) and apatinib (a highly selective TKI targeting VEGFR2) in patients with unresectable recurrent or metastatic bone and soft-tissue sarcoma after at least one line of prior systemic therapy. One MASCT-I course consisted of 3 DC subcutaneous injections, followed by 3 active T cell infusions administered 18-27 days after each DC injection. In schedule-I group, 3 DC injections were administered with a 28-day interval in all courses; in schedule-II group, 3 DC injections were administered with a 7-day interval in the first course and with a 28-day interval thereafter. All patients received intravenous camrelizumab 200 mg every 3 weeks and oral apatinib 250 mg daily. RESULTS: From October 30, 2019, to August 12, 2021, 19 patients were enrolled and randomly assigned to schedule-I group (n = 9) and schedule-II group (n = 10). Of the 19 patients, 11 (57.9%) experienced grade 3 or 4 treatment-related adverse events. No treatment-related deaths occurred. Patients in schedule-II group showed similar objective response rate (ORR) with those in schedule-I group (30.0% versus 33.3%) but had higher disease control rate (DCR; 90.0% versus 44.4%) and longer median progression-free survival (PFS; 7.7 versus 4.0 months). For the 13 patients with soft-tissue sarcomas, the ORR was 30.8%, DCR was 76.9%, and median PFS was 12.9 months; for the 6 patients with osteosarcomas, the ORR was 33.3%, the DCR was 50.0%, and median PFS was 5.7 months. CONCLUSIONS: Overall, MASCT-I plus camrelizumab and apatinib was safe and showed encouraging efficacy in advanced bone and soft-tissue sarcoma, and schedule-II administration method was recommended. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04074564.
Subject(s)
Sarcoma , Humans , Pilot Projects , Sarcoma/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Introduction: The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection. Methods: Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm, as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67, and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI-RADS categories were further analyzed. Results: A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (p < 0.001) and levels of Ki-67 (p = 0.01) and that poor differentiation (32.7% in LR-M, 12% in LR-5, and 6.2% in LR-4) (p < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5, and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (p > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection. Conclusions: Biological characteristics of HCC, including differentiation and level of Ki-67 expression, could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.
ABSTRACT
OBJECTIVES: To compare the on-site diagnostic performance of contrast-enhanced ultrasound (CEUS), computed tomography (CECT), and magnetic resonance imaging (CEMRI) for hepatocellular carcinoma (HCC) across diverse practice settings. METHODS: Between May 2019 and April 2022, a total of 2085 patients with 2320 pathologically confirmed focal liver lesions (FLLs) were enrolled. Imaging reports were compared with results from pathology analysis. Diagnostic performance was analyzed in defined size, high-risk factors for HCC, and hospital volume categories. RESULTS: Three images achieved similar diagnostic performance in classifying HCC from 16 types of FLLs, including HCC ≤2.0 cm. For HCC diagnosis at low-volume hospitals and HCC with high-risk factors, the accuracy and specificity of CEUS were comparable to CECT and CEMRI, while the sensitivity of CEUS (77.4 and 89.5%, respectively) was inferior to CEMRI (87.0 and 92.8%, respectively). The diagnostic accuracy of CEUS + CEMRI and CEUS + CECT increased by 7.8 and 6.2% for HCC ≤2.0 cm, 8.0 and 5.0% for HCC with high-risk factors, and 7.4 and 5.5% for HCC at low-volume hospitals, respectively, compared with CEMRI/CECT alone. CONCLUSIONS: Compared with CECT and CEMRI, CEUS provides adequate diagnostic performance in clinical first-line applications at high-volume hospitals. Moreover, a higher diagnostic performance for HCC is achieved by combining CEUS with CECT/CEMRI compared with any single imaging technique.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Contrast Media , Ultrasonography/methods , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methodsABSTRACT
To explore the effect of comfort nursing in the perioperative period of free flap transplantation to repair defects of malignant head and neck tumors. This retrospective study included 242 patients with postoperative defects of malignant head and neck tumors repaired using free flap transplantation from December 2017 to December 2022. Among them, 113 patients received routine nursing and were included in the control group, and 129 patients received comfort nursing and were included in the observation group. The perioperative indexes of skin flap transplantation, skin flap necrosis, hospital stay, and cortisol levels were compared. Albumin and pre-albumin levels were compared 1 hour before and 24 hours after surgery. The nursing quality, Self-Rating Depression Scale and Self-Rating Anxiety Scale scores, and nursing satisfaction were compared between the 2 groups. The success rate of skin flap transplantation in the observation group was significantly higher than that in the control group, whereas the rates of skin flap necrosis, length of stay, and cortisol levels were significantly lower in the observation group than in the control group. The Albumin and pre-albumin levels in the observation group were significantly higher than those in the control group 24 hours after surgery. The complication rate was significantly lower in the observation group than in the control group. The Self-Rating Depression Scale and Self-Rating Anxiety Scale scores in the observation group were significantly lower than those in the control group 24 hours after surgery. The satisfaction with nursing was significantly higher in the observation group than in the control group. Comfort nursing improved the success rate of free flap transplantation, reduced complications, reduced stress, improved nutritional, and psychological status of patients during the perioperative period, and improved nursing quality and patient satisfaction with nursing.