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BACKGROUND: Sleep disturbance may impact response to psychological treatment for depression. Understanding how sleep disturbance changes during the course of psychological treatment, and identifying the risk factors for sleep disturbance response may inform clinical decision-making. METHOD: This analysis included 18,915 patients receiving high-intensity psychological therapy for depression from one of eight London-based Improving Access to Psychological Therapies (IAPT) services between 2011 and 2020. Distinct trajectories of change in sleep disturbance were identified using growth mixture modelling. The study also investigated associations between identified trajectory classes, pre-treatment patient characteristics, and eventual treatment outcomes from combined PHQ-9 and GAD-7 metrics used by the services. RESULTS: Six distinct trajectories of sleep disturbance were identified: two demonstrated improvement, while one showed initial deterioration and the other three groups displayed only limited change in sleep disturbance, each with varying baseline sleep disturbance. Associations with trajectory class membership were found based on: gender, ethnicity, unemployment status, antidepressant medication use, long-term health condition status, severity of depressive symptom, and functional impairment. Groups that showed improvement in sleep had the best eventual outcomes from depression treatment, followed by groups that consistently slept well. LIMITATION: Single item on sleep disturbance used, no data on treatment adherence. CONCLUSIONS: These findings reveal heterogeneity in the course of sleep disturbance during psychological treatment for depression. Closer monitoring of changes in sleep disturbance during treatment might inform treatment planning. This includes decisions about when to incorporate sleep management interventions, and whether to change or augment therapy with interventions to reduce sleep disturbance.
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Objective: To explore the clinical characteristics and predictive factors for plastic bronchitis (PB) in children with severe Mycoplasma pneumoniae pneumonia (SMPP). Methods: A retrospective cohort enrolled children with a clinical diagnosis of SMPP who were treated at the Department of Respiratory Medicine of Tianjin Children's Hospital Machang District from January 1, 2018, to October 31, 2023. According to the bronchoscopy and pathological examination results, the patients were divided into 142 cases in the PB group and 274 cases in the non-PB group. The clinical manifestations, laboratory data, imaging findings, and treatments were analyzed.Mann-Whitney U test and Chi-square test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the risk factors. The receiver operating characteristic (ROC) curve was used to explore the predictive value of PB in SMPP. Results: Among 416 SMPP children, there were 197 males and 219 females; PB group 142 cases, non-PB group 274 cases, the age of disease onset was (6.9±2.9) years and (6.6±2.8) years in the PB group and the non-PB group respectively. The incidence of wheezing symptoms, hypoxemia, heat peak >40 â, the duration of fever, neutrophil-lymphocyte ratio, mean platelet volume, C-reactive protein, procalcitonin, interleukin-6, alanine transaminase, aspartate aminotransferase and ferritin were higher in the PB group (16 cases (11.3%) vs. 15 cases (5.5%), 14 cases (9.9%) vs. 12 cases (4.4%), 57 cases (40.1%) vs. 67 cases (24.5%), 10 (8, 12) vs. 9 (8, 12) d, 6.1 (4.1, 13.1)×109 vs. 5.0 (3.7, 6.8)×109/L, 10.2 (9.6, 10.8) vs. 9.4 (8.9, 10.1) fl, 33.4 (16.0, 67.5) vs. 23.0 (10.4, 56.1) mg/L, 0.24 (0.12, 0.48) vs. 0.16 (0.09, 0.31) µg/L, 39.9 (25.1, 81.4) vs. 31.3 (18.3, 59.3) ng/L, 16.0 (12.0, 29.0) vs. 14.0 (10.0, 24.3) U/L, 38.5 (28.0, 52.5) vs. 33.0 (25.0, 44.0) U/L, 233 (136, 488) vs. 156 (110, 293) µg/L, χ2=4.55, 4.79, 11.00, Z=2.25, 4.00, 6.64, 2.76, 2.98, 3.09, 2.22, 2.62, 4.18, all P<0.05). Multivariate Logistic regression analysis showed that the dyspnea (OR=2.97, 95%CI 1.35-6.55, P=0.007), the diminution of respiration (OR=2.40, 95%CI 1.27-4.52, P=0.006), neutrophil-lymphocyte ratio (NLR) (OR=2.07, 95%CI 1.71-2.51, P<0.001), lactate dehydrogenase (LDH) (OR=1.01, 95%CI 1.00-1.01, P<0.001), mean platelet volume/platelet count (MPV/PLT) (OR=1.39, 95%CI 1.13-1.71, P=0.002), pleural effusion (OR=2.23, 95%CI 1.21-4.13, P=0.011),≥2/3 lobe consolidation (OR=1.84, 95%CI 1.04-3.00, P=0.039) and atelectasis (OR=1.98, 95%CI 1.02-3.48, P=0.044) were independent predictors of PB in children with SMPP. ROC curve analysis showed that the cut-off values for NLR, LDH and MPV/PLT in the diagnosis of PB were 2.79 (sensitivity 0.89, specificity 0.69, area under the curve (AUC)=0.86, P<0.001), 474 U/L (sensitivity 0.63, specificity 0.65, AUC=0.70, P=0.003) and 0.04 (sensitivity 0.75, specificity 0.53, AUC=0.68, P=0.005) respectively. Children in the PB group had longer hospital stays and corticosteroid treatment course than those in the non-PB group, the proportion of children in the PB group who received bronchoscopy treatment twice or more was higher (9 (8, 12) vs. 8 (6, 10) d, 7 (5, 8) vs. 6 (5, 7) d, 128 cases (90.1%) vs. 218 cases (79.6%), 106 cases (74.7%) vs. 54 cases (19.7%), Z=6.70, 5.06, χ2=7.48, 119.27, all P<0.05). Conclusions: The dyspnea, respiration diminution, NLR level elevation (>2.79) and pleural effusion were predictive factors for PB in children with SMPP. This provides a basis for the early identification of PB in children with SMPP.
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Objective: To develop and validate clinical and radiomics models based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI of dual-phenotype hepatocellular carcinoma (DPHCC) for preoperative differential diagnosis. Methods: Two hundred and fifty inpatients of hepatocellular carcinoma (HCC) confirmed by postoperative pathology, who underwent Gd-EOB-DTPA-enhanced MRI were retrospectively included. A total of 172 inpatients (72 DPHCC and 100 non-DPHCC) were included in Institution 1 (the First Affiliated Hospital of Soochow University) as a training cohort (between January 2020 and July 2023) and 78 inpatients (44 DPHCC and 34 non-DPHCC) were included in Institution 2 (the Third People's Hospital of Nantong) as an external validation cohort(between January 2019 and July 2023). The regions of interest of the tumor were delineated layer by layer in noncontrast phase, arterial phase (AP), portal venous phase (PP) and hepatobiliary phase (HBP) images. The software of FAE was used to extract the radiomics features of the images. Pearson correlation analysis and recursive feature elimination were used for feature selection. Each phase and combined radiomics models were established using logistic regression, linear discriminant analysis and support vector machine. Receiver operating characteristic curve and the areas under the curve (AUC) were used to evaluate and select the dominant radiomics model. The dominant radiomics model was combined with clinically independent predictors to construct a clinical radiomics model. Delong test was used to compare the performance of the models. Results: The age of the training cohort was (59.6±10.4) years, in which there were 135 men (78.5%). In the external validation cohort, the age was (57.8±9.2) years, including 56 men (71.8%). The maximum diameters of the lesions [M (Q1, Q3), 4.7 (2.6, 7.5) vs 2.7 (1.8, 4.4) cm, P<0.001] and the proportion of the multiple lesions (39.5% vs 16.7%, P<0.001) in the training cohort were higher than those in the external validation cohort. In the training group, the proportion of patients with hepatitis B virus (HBV) infection in the DPHCC subgroup (66.7%,48/172) was higher than that in non-DPHCC subgroup (49.0%,49/78,P=0.021). In the external validation cohort, the AUC (95%CI) of the PP [0.835 (0.733-0.937)] and combined radiomics models [0.786 (0.681-0.891)] were significantly higher than that of noncontrast phase [0.451 (0.319-0.584)], AP [0.566 (0.435-0.696)] and HBP models [0.496 (0.363-0.629)] (all P<0.05). There was no significant difference in AUC between PP radiomics model and combined radiomics model (P=0.189). The AUC between the radiomics models and clinical-radiomics models, which were brought into clinically independent variable HBV, showed no significant difference (all P>0.05). Conclusion: Gd-EOB-DTPA-enhanced MRI radiomics model based on portal venous phase may be available for discriminating DPHCC from non-DPHCC before operation.
Subject(s)
Carcinoma, Hepatocellular , Gadolinium DTPA , Liver Neoplasms , Magnetic Resonance Imaging , Humans , Liver Neoplasms/diagnostic imaging , Carcinoma, Hepatocellular/diagnostic imaging , Magnetic Resonance Imaging/methods , Retrospective Studies , Phenotype , Contrast Media , Male , RadiomicsABSTRACT
AIM: The objective of this study was to create and authenticate a prognostic model for lymph node metastasis (LNM) in colorectal cancer (CRC) that integrates clinical, radiomics, and deep transfer learning features. MATERIALS AND METHODS: In this study, we analyzed data from 119 CRC patients who underwent F18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning. The patient cohort was divided into training and validation subsets in an 8:2 ratio, with an additional 33 external data points for testing. Initially, we conducted univariate analysis to screen clinical parameters. Radiomics features were extracted from manually drawn images using pyradiomics, and deep-learning features, radiomics features, and clinical features were selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression and Spearman correlation coefficient. We then constructed a model by training a support vector machine (SVM), and evaluated the performance of the prediction model by comparing the area under the curve (AUC), sensitivity, and specificity. Finally, we developed nomograms combining clinical and radiological features for interpretation and analysis. RESULTS: The deep learning radiomics (DLR) nomogram model, which was developed by integrating deep learning, radiomics, and clinical features, exhibited excellent performance. The area under the curve was (AUC = 0.934, 95% confidence interval [CI]: 0.884-0.983) in the training cohort, (AUC = 0.902, 95% CI: 0.769-1.000) in the validation cohort, and (AUC = 0.836, 95% CI: 0.673-0.998) in the test cohort. CONCLUSION: We developed a preoperative predictive machine-learning model using deep transfer learning, radiomics, and clinical features to differentiate LNM status in CRC, aiding in treatment decision-making for patients.
Subject(s)
Colorectal Neoplasms , Deep Learning , Fluorodeoxyglucose F18 , Lymphatic Metastasis , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Humans , Positron Emission Tomography Computed Tomography/methods , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Male , Female , Lymphatic Metastasis/diagnostic imaging , Middle Aged , Aged , Retrospective Studies , Predictive Value of Tests , Adult , Sensitivity and Specificity , Nomograms , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathologyABSTRACT
BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.
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Objective: To investigate the effect of increased cardiac output induced by dobutamine on cerebral blood flow (CBF) in healthy volunteers using magnetic resonance 3D-pseudo-continuous arterial spin labeling technology. Methods: A prospective study was conducted on 48 healthy volunteers recruited by handy sampling from June 2021 to January 2022. Physiological parameters before (at rest state) and after (under stress state) dobutamine-induced increase in cardiac output were analyzed. Quantitative CBF maps were generated by using arterial spin labeling difference imaging and proton density weighted reference image processing, and CBF changes under the rest and stress states were compared. Multivariable logistic regression model was used to analyze factors associated with reduced CBF. Results: A total of 48 subjects were included, with an age [M (Q1, Q3)] of 25.0 (24.0, 28.0) years, including 43 men and 5 women. Compared with the rest state, the CBF in the anterior cerebral artery [(36.2±6.9) vs (34.5±6.5) ml·(100 g)-1·min-1, P=0.006] and the middle cerebral artery perfusion area [(35.8±6.5) vs (34.1±6.4) ml·(100 g)-1·min-1, P=0.006] decreased under the stress state, however there was no statistically significant change in CBF in the posterior cerebral artery and the vertebral-basilar artery perfusion area (all P>0.05). Logistic regression analysis showed that the decrease in CBF in the anterior cerebral artery and middle cerebral artery supply regions during the stress state were correlated with an increase in diastolic blood pressure [OR (95%CI): 0.887 (0.796-0.989) and 0.895 (0.805-0.994), both P<0.05]. Conclusions: Dobutamine-induced increase in cardiac output leads to a decrease in CBF in anterior cerebral circulation but has no effect on posterior circulation. The increase in diastolic blood pressure is associated with decreased CBF under the stress state. Changes in CBF should be considered in the context of increased cardiac output.
Subject(s)
Cardiac Output , Cerebrovascular Circulation , Dobutamine , Magnetic Resonance Imaging , Humans , Male , Female , Cerebrovascular Circulation/drug effects , Dobutamine/pharmacology , Adult , Magnetic Resonance Imaging/methods , Prospective Studies , Young AdultABSTRACT
Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.
Subject(s)
Inflammation , Macrophages , Proto-Oncogene Protein c-ets-2 , Female , Humans , Male , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Cells, Cultured , Chromosomes, Human, Pair 21/genetics , Databases, Factual , Gene Expression Regulation , Genome-Wide Association Study , Genomics , Haplotypes/genetics , Inflammation/genetics , Inflammatory Bowel Diseases/genetics , Macrophages/immunology , Macrophages/metabolism , Macrophages/pathology , Proto-Oncogene Protein c-ets-2/genetics , Proto-Oncogene Protein c-ets-2/metabolism , Reproducibility of Results , Tumor Necrosis Factors/metabolism , Interleukin-23/metabolismABSTRACT
OBJECTIVE: To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma. METHODS: We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January, 2013 to December, 2021. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs group, n=111), chemotherapy (CT group, n=108) and clinical observation (CO group, n=434). RESULTS: In TKIs, CT, and CO groups, the 5-year DFS rates were 92.8%, 80.7%, and 81.7%, respectively, significantly higher in TKIs group than in CO group (P < 0.01). The 3-year OS rates of the 3 groups were 96.8%, 97.1%, and 91.7%, respectively. Subgroup analysis showed that in TKIs, CT, and CO groups, the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%, 84.0%, and 81.4%, respectively, significantly higher in TKIs group than in CO group (P < 0.05); the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%, 71.4%, and 83.5%, respectively. Multivariate COX regression analysis showed that age (P < 0.05; HR=0.631, 95% CI: 0.401-0.993), solid nodules (P < 0.01; HR=7.620, 95% CI: 3.037-19.121), micropapillary or solid component (P < 0.05; HR= 1.776, 95% CI: 1.010-3.122), lymphovascular invasion (P < 0.05; HR=2.981, 95% CI: 1.198-7.419), and adjuvant therapy (P < 0.01) were independent predictors of DFS. The most common adverse effects included rashes, paronychia, and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy, and TKIs were associated with a higher incidence of grade 3 or above adverse effects (44.4% vs 9.0%). CONCLUSION: Adjuvant therapy with TKIs helps improve DFS in patients with stage IB (T3-4cmN0M0) lung adenocarcinoma but not in patients with T2ViscPlN0M0. Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Neoplasm Staging , Humans , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/surgery , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/drug therapy , Female , Male , Chemotherapy, Adjuvant , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Disease-Free Survival , Survival Rate , Postoperative Period , ErbB Receptors/antagonists & inhibitors , AgedABSTRACT
OBJECTIVE: To investigate the prevalence of Echinococcus infections in small rodents around human residential areas in Yushu City, Qinghai Province in 2023, so as to provide insights into precision echinococcosis control. METHODS: One or two quadrats, each measuring 50 m × 50 m, were randomly assigned in Shanglaxiu Township and Longbao Township, Yushu City, Qinghai Province on June 2023, respectively, and 300 plate-type mouse traps, each measuring 12.0 cm × 6.5 cm, were assigned in each quadrat. Small rodents were captured during the period between 10 : 00 and 18 : 00 each day for 4 days. Then, all captured small rodents were identified and dissected, and liver specimens with suspected Echinococcus infections were subjected to pathological examinations. The Echinococcus cytochrome c oxidase 1 (cox1) gene was amplified using PCR assay, and the sequence of the amplified product was aligned to that was recorded in the GenBank to characterize the parasite species. In addition, a phylogenetic tree of Echinococcus was generated based on the cox1 gene sequence using the neighbor-joining method. RESULTS: A total of 236 small rodents were captured in Shanglaxiu and Longbao townships, Yushu City, including 65 Qinghai voles and 51 plateau pikas in Shanglaxiu Township, and 62 Qinghai voles and 58 plateau pikas in Longbao Township, and there was no significant difference in the constituent ratio of small rodents between the two townships (χ2 = 0.294, P > 0.05). Seven plateau pikas and 12 Qinghai voles were suspected to be infected with Echinococcus by dissection, and pathological examinations showed unclear structure of hepatic lobules and disordered hepatocyte arrangement in livers of small rodents suspected of Echinococcus infections. PCR assay identified E. shiquicus DNA in 7 Qinghai voles, which were all captured from Shanglaxiu Township. Phylogenetic analysis showed that the cox1 gene sequence of Echinococcus in small rodents was highly homologous to the E. shiquicus cox1 gene sequence reported previously. CONCLUSIONS: Plateau pika and Qinghai vole were predominant small rodents around human residential areas in Yushu City, Qinghai Province in 2023, and E. shiquicus infection was detected in Qinghai voles.
Subject(s)
Echinococcosis , Echinococcus , Phylogeny , Rodentia , Animals , Echinococcosis/epidemiology , Echinococcosis/veterinary , Echinococcosis/parasitology , China/epidemiology , Echinococcus/genetics , Echinococcus/isolation & purification , Echinococcus/classification , Rodentia/parasitology , Prevalence , HumansABSTRACT
Chronic hepatitis B virus (HBV) infection is one of the major public health issues of ongoing global concern. Due to inadequate understanding of the HBV life cycle, there is a lack of effective drugs to cure chronic hepatitis B. During HBV replication, covalently closed circular DNA (cccDNA) serves as the template for viral replication and can be transcribed to produce five viral RNAs of 3.5, 2.4, 2.1 kb and 0.7 kb in length, which are translated to produce HBeAg, core protein, polymerase (P) protein, HBsAg and HBx proteins, respectively. Among them, the 3.5 kb pregenomic RNA (pgRNA) is also the template for viral reverse transcription. Polymerase protein recognizes and binds to the capsid assembly signal on the pgRNA to initiate capsid assembly and reverse transcription. Recent studies have revealed that the processes of splicing, nuclear export, stability, translation, and pgRNA encapsidation of HBV RNAs are regulated by a post-transcriptional regulatory network within the host cell and depend on unique post-transcriptional regulatory elements in the HBV RNA structure. The aim of this review is to overview the post-transcriptional regulatory mechanisms of HBV RNA and their applications in the study of HBV antiviral therapeutics, with the aim of providing new ideas for the development of new drugs targeting HBV RNA.
Subject(s)
Hepatitis B virus , RNA, Viral , Virus Replication , Hepatitis B virus/genetics , Hepatitis B virus/physiology , RNA, Viral/metabolism , Humans , Antiviral Agents/pharmacology , Gene Expression Regulation, Viral , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/drug therapy , RNA Processing, Post-TranscriptionalABSTRACT
Interventions targeting the gut microbiota, such as fecal microbiota transplantation, prove effective in repairing the intestinal barrier and facilitating the recovery of its function and metabolism. However, the regulatory mechanisms governing the remodeling of rumen epithelial morphology and function, rumen metabolism, and host metabolism in cows of subacute ruminal acidosis (SARA) remain poorly understood. Here, we explored the changes in rumen epithelial morphology and transcriptome, rumen metabolome, and blood biochemical parameters in SARA cows following rumen content transplantation (RCT). The entire experiment consisted of 2 periods: the SARA induction period and the RCT period. During the SARA induction period, 12 ruminally cannulated lactating Holstein cows were randomly allocated into 2 groups, fed either a conventional diet [CON; n = 4; 40% concentrate, dry matter (DM) basis] or a high-grain diet (HG; n = 8; 60% concentrate, DM basis). Following the SARA induction period, the RCT period started. The HG cows were randomly assigned to 2 groups: the donor-recipient (DR) group and the self-recipient (SR) group. Rumen contents were entirely removed from both groups before RCT. For the DR group, cows were administered 70% rumen content from the CON cows, paired based on comparable body weight; for the SR group, each cow received 70% self-derived rumen content. The results revealed no significant differences in the thicknesses of the stratum corneum, granulosum, and spinosum/basale layers, as well as the total depth of the epithelium between the SR and DR groups. All these measurements exhibited a decreasing trend and fluctuations over time after the transfer. Notably, these fluctuations tended to stabilize at 13 or 16 d after RCT in the SR group, whereas they tended to stabilize after 8 or 13 d of transfer for the DR group. Transcriptome sequencing revealed that a total of 277 differentially expressed genes (DEGs) were identified between the 2 groups. Enrichment analysis showed that the DEGs were significantly enriched in 11 Gene Ontology biological processes and 14 KEGG pathways. The DEGs corresponding to almost any of these 11 biological process terms and 14 pathways showed mixed up- or downregulation following RCT. Metabolomics analysis indicated that a total of 33 differential metabolites were detected between the SR and DR groups, mainly enriched in 5 key metabolic pathways, including plant polysaccharides and starch degradation, lipid metabolism, amino sugar and nucleotide metabolism, purine metabolism, and Krebs cycle. Among them, the levels of differential metabolites associated with the degradation of plant polysaccharides and starches, metabolism of amino sugars and nucleotides, and purine metabolism pathways were significantly elevated in the DR cows. The results of blood biochemical parameters showed that the triglyceride concentration of the DR cows was increased than that of the SR cows, comparable to the level observed in the CON cows during the SARA induction period. Generally, our findings indicated that RCT facilitated the recovery of rumen epithelial morphological structure but did not promote its function recovery. Moreover, RCT enhanced rumen plant polysaccharide and starch degradation, amino sugar and nucleotide sugar metabolism, as well as purine metabolism. Additionally, it further promoted the recovery of plasma metabolites related to lipid metabolism.
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Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, Pï¼0.001; 77.78% vs 16.84% for bone metastasis, Pï¼0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCsï¼111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant (P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups (P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCsï¼111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage (HR=2.806, 95%CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH (HR=1.841, 95%CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS (HR=2.538, 95%CI:1.169-5.512, P=0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.
Subject(s)
Bone Marrow , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Small Cell Lung Carcinoma/pathology , Lung Neoplasms/pathology , Prognosis , Bone Marrow/pathology , Prospective Studies , Female , Male , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Bone Neoplasms/secondary , Middle Aged , Bone Marrow Neoplasms/secondary , Survival Rate , Bone Marrow Cells , Aged , Thrombocytopenia , Proportional Hazards Models , Kaplan-Meier Estimate , Clinical RelevanceABSTRACT
An elderly woman with a 1-year history of pulmonary shadows was admitted because of intermittent cough and sputum production for 2 months. Chest computed tomography (CT) scans showed bilateral consolidations and ground-glass opacities, with areas of low attenuation inside consolidative opacities on the mediastinal window. Previous history of radiotherapy for nasopharyngeal carcinoma and long-term use of a compound menthol nasal drops provided were important clues to the diagnosis. CT scan-guided needle lung biopsy and bronchoalveolar lavage were performed, and lipid-laden macrophages were confirmed in both bronchoalveolar lavage and lung tissue. Final diagnosis of exogenous lipoid pneumonia was made on the basis of her risk factors for aspiration, history of oil exposure, and classic radiological and histopathological features. Symptoms improved after discontinuation of causative exposure. It is important for clinicians to raise awareness of exogenous lipoid pneumonia and other aspiration lung diseases.
Subject(s)
Pneumonia, Lipid , Humans , Female , Aged , Pneumonia, Lipid/diagnosis , Tomography, X-Ray Computed , Lung/diagnostic imaging , Lung/pathologyABSTRACT
1. The Kaijiang duck is a native Chinese breed known for its excellent egg laying performance, killing-out percentage (88.57%), and disease resistance. The assessment of population genetic structure is the basis for understanding the genetics of indigenous breeds and for their protection and management.2. In this study, whole-genome sequencing was performed on 60 Kaijiang ducks to identify genetic variations and investigate the population structure. Homozygosity (ROH) analysis was conducted to assess inbreeding levels in the population.3. The study revealed a moderate level of inbreeding, indicated by an average inbreeding coefficient of 0.1043. This may impact the overall genetic diversity.4. Genomic Regions of Interest identified included 168 genomic regions exhibiting high levels of autozygosity. These regions were associated with processes including muscle growth, pigmentation, neuromodulation, and growth and reproduction.5. The significance of these pathways indicated their potential role in shaping the desirable traits of the Kaijiang duck. These findings provide insights into the genetic basis of the Kaijiang duck's desirable traits and can inform future breeding and conservation efforts.
Subject(s)
Ducks , Animals , Ducks/genetics , Ducks/physiology , Genetic Variation , Inbreeding , Whole Genome Sequencing/veterinary , Conservation of Natural Resources , Female , Male , China , Genome , BreedingABSTRACT
To find a way to control the electron-bunching process and the bunch-emitting directions when an ultraintense, linearly polarized laser pulse interacts with a nanoscale target, we explored the mechanisms for the periodical generation of relativistic attosecond electron bunches. By comparing the simulation results of three different target geometries, the results show that for nanofoil target, limiting the transverse target size to a small value and increasing the longitudinal size to a certain extent is an effective way to improve the total electron quantity in a single bunch. Then the subfemtosecond electronic dynamics when an ultrashort ultraintense laser grazing propagates along a nanofoil target was analyzed through particle-in-cell simulations and semiclassical analyses, which shows the detailed dynamics of the electron acceleration, radiation, and bunching process in the laser field. The analyses also show that the charge separation field produced by the ions plays a key role in the generation of electron bunches, which can be used to control the quantity of the corresponding attosecond radiation bunches by adjusting the length of the nanofoil target.
ABSTRACT
Objective: To investigate the feasibility and accuracy of computer vision-based artificial intelligence technology in detecting and recognizing instruments and organs in the scenario of radical laparoscopic gastrectomy for gastric cancer. Methods: Eight complete laparoscopic distal radical gastrectomy surgery videos were collected from four large tertiary hospitals in China (First Medical Center of Chinese PLA General Hospital [three cases], Liaoning Cancer Hospital [two cases], Liyang Branch of Jiangsu Province People's Hospital [two cases], and Fudan University Shanghai Cancer Center [one case]). PR software was used to extract frames every 5-10 seconds and convert them into image frames. To ensure quality, deduplication was performed manually to remove obvious duplication and blurred image frames. After conversion and deduplication, there were 3369 frame images with a resolution of 1,920×1,080 PPI. LabelMe was used for instance segmentation of the images into the following 23 categories: veins, arteries, sutures, needle holders, ultrasonic knives, suction devices, bleeding, colon, forceps, gallbladder, small gauze, Hem-o-lok, Hem-o-lok appliers, electrocautery hooks, small intestine, hepatogastric ligaments, liver, omentum, pancreas, spleen, surgical staplers, stomach, and trocars. The frame images were randomly allocated to training and validation sets in a 9:1 ratio. The YOLOv8 deep learning framework was used for model training and validation. Precision, recall, average precision (AP), and mean average precision (mAP) were used to evaluate detection and recognition accuracy. Results: The training set contained 3032 frame images comprising 30 895 instance segmentation counts across 23 categories. The validation set contained 337 frame images comprising 3407 instance segmentation counts. The YOLOv8m model was used for training. The loss curve of the training set showed a smooth gradual decrease in loss value as the number of iteration calculations increased. In the training set, the AP values of all 23 categories were above 0.90, with a mAP of 0.99, whereas in the validation set, the mAP of the 23 categories was 0.82. As to individual categories, the AP values for ultrasonic knives, needle holders, forceps, gallbladders, small pieces of gauze, and surgical staplers were 0.96, 0.94, 0.91, 0.91, 0.91, and 0.91, respectively. The model successfully inferred and applied to a 5-minutes video segment of laparoscopic gastroenterostomy suturing. Conclusion: The primary finding of this multicenter study is that computer vision can efficiently, accurately, and in real-time detect organs and instruments in various scenarios of radical laparoscopic gastrectomy for gastric cancer.
Subject(s)
Artificial Intelligence , Gastrectomy , Laparoscopy , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Laparoscopy/methods , Gastrectomy/methods , Image Processing, Computer-Assisted/methodsABSTRACT
OBJECTIVE: To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. METHODS: Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson's trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. RESULTS: Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson's trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/µm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/µm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). CONCLUSIONS: E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.
Subject(s)
Echinococcosis , Endothelial Cells , Mice , Animals , Endothelial Cells/metabolism , Endothelial Cells/pathology , Mice, Inbred C57BL , Liver/pathology , Liver Cirrhosis/pathology , Echinococcosis/pathology , RNA, Messenger/metabolism , Collagen/adverse effects , Collagen/metabolismABSTRACT
In order to decelerate the growth of myopia in children and adolescents and reduce the risks of associated eye complications, extensive research has been conducted on preventive measures, including optical, behavioral, and pharmaceutical interventions. Spectacle lenses, due to their safety, convenience, and high patient compliance, stand out as the most common method for correcting refractive errors compared to other interventions. As far as we know, various forms of spectacle lenses are currently used in clinical practice, including bifocal lenses, progressive multifocal lenses, peripheral defocus lenses, defocus incorporated multiple segments (DIMS) lenses, highly aspherical lenslets, diffusion optics technology lenses, and violet light transmission (VL) glasses. However, a systematic and comprehensive overview of myopia-controlling spectacle lenses is still lacking. Therefore, this article summarizes the latest research progress on the myopia prevention and control technology of spectacle lenses at home and abroad, providing theoretical support for the myopia prevention and control effect of different spectacle lens technologies, promoting the application of related technologies in clinical work, and offering new ideas for myopia prevention and control.