Zinc finger BED-type containing 3 promotes hepatic steatosis by interacting with polypyrimidine tract-binding protein 1.

AIMS/HYPOTHESIS: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD. METHODS: Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c). RESULTS: In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing. CONCLUSIONS/INTERPRETATION: This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD. DATA AVAILABILITY: RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).

Preparation of Pueraria lobata Root-Derived Exosome-Like Nanovesicles and Evaluation of Their Effects on Mitigating Alcoholic Intoxication and Promoting Alcohol Metabolism in Mice.

Purpose: Pueraria lobata (P. lobata), a dual-purpose food and medicine, displays limited efficacy in alcohol detoxification and liver protection, with previous research primarily focused on puerarin in its dried roots. In this study, we investigated the potential effects and mechanisms of fresh P. lobata root-derived exosome-like nanovesicles (P-ELNs) for mitigating alcoholic intoxication, promoting alcohol metabolism effects and protecting the liver in C57BL/6J mice. Methods: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pre-treated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers. Results: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (-31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation. Conclusion: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.

The effects of exosomes originating from different cell sources on the differentiation of bone marrow mesenchymal stem cells into schwann cells.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can differentiate into Schwann cells (SCs) during peripheral nerve injury; in our previous research, we showed that SC-derived exosomes (SC-exos) played a direct induction role while fibroblast-derived exosomes (Fb-exos) had no obvious induction role. The induction role of neural stem cell (NSC)-derived exosomes (NSC-exos) has also been widely confirmed. However, no studies have compared the induction effects of these three types of cells at the same time. Therefore, by investigating the effect of these three cell-derived exosomes upon the induction of BMSCs to differentiate into SCs, this study explored the role of different exosomes in promoting the differentiation of stem cells into SCs cells, and conducted a comparison between the two groups by RNA sequencing to further narrow the range of target genes and related gene pathways in order to study their related mechanisms. MATERIALS AND METHODS: We extracted exosomes from SCs, fibroblasts (Fb) and neural stem cells (NSC) and then investigated the ability of these exosomes to induce differentiation into BMSCs under different culture conditions. The expression levels of key proteins and gene markers were detected in induced cells by fluorescence immunoassays, western blotting and polymerase chain reaction (PCR); then, we statistically compared the relative induction effects under different conditions. Finally, we analyzed the three types of exosomes by RNA-seq to predict target genes and related gene pathways. RESULTS: BMSCs were cultured by three media: conventional (no induction), pre-induction or pre-induction + original induction medium (ODM) with exosomes of the same cell origin under different culture conditions. When adding the three different types of exosomes separately, the overall induction of BMSCs to differentiate into SCs was significantly increased (P < 0.05). The induction ability was ranked as follows: pre-induction + ODM + exosome group > pre-induction + exosome group > non-induction + exosome group. Using exosomes from different cell sources under the same culture conditions, we observed the following trends under the three culture conditions: RSC96-exos group ≥ NSC-exos group > Fb-exos group. The overall ability to induce BMSCs into SCs was significantly greater in the RSC96-exos group and the NSC-exos group. Although there was no significant difference in induction efficiency when comparing these two groups, the overall induction ability of the RSC96-exos group was slightly higher than that of the NSC-exos group. By combining the differentiation induction results with the RNA-seq data, the three types of exosomes were divided into three comparative groups: RSC vs. NSC, RSC vs. Fb and NSC vs. Fb. We identified 203 differentially expressed mRNA target genes in these three groups. Two differentially expressed genes were upregulated simultaneously, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). We did not identify any co-upregulated target genes for the miRNAs, but did identify one target gene of the lncRNAs, namely ENSRNOG00000065005. Analysis identified 90 GO terms related to nerves and axons in the mRNAs; in addition, KEGG enrichment and GASA analysis identified 13 common differential expression pathways in the three groups. CONCLUSIONS: Our analysis found that pre-induction + ODM + RSC96/NSC-exos culture conditions were most conducive with regards to induction and differentiation. RSC96-exos and NSC-exos exhibited significantly greater differentiation efficiency of BMSCs into SCs. Although there was no statistical difference, the data indicated a trend for RSC96-exos to be advantageous We identified 203 differentially expressed mRNAs between the three groups and two differentially expressed target mRNAs were upregulated, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). 90 GO terms were related to nerves and axons. Finally, we identified 13 common differentially expressed pathways across our three types of exosomes. It is hoped that the efficiency of BMSCs induction differentiation into SCs can be improved, bringing hope to patients and more options for clinical treatment.

A virtual biopsy study of microsatellite instability in gastric cancer based on deep learning radiomics.

OBJECTIVES: This study aims to develop and validate a virtual biopsy model to predict microsatellite instability (MSI) status in preoperative gastric cancer (GC) patients based on clinical information and the radiomics of deep learning algorithms. METHODS: A total of 223 GC patients with MSI status detected by postoperative immunohistochemical staining (IHC) were retrospectively recruited and randomly assigned to the training (n = 167) and testing (n = 56) sets in a 3:1 ratio. In the training set, 982 high-throughput radiomic features were extracted from preoperative abdominal dynamic contrast-enhanced CT (CECT) and screened. According to the deep learning multilayer perceptron (MLP), 15 optimal features were optimized to establish the radiomic feature score (Rad-score), and LASSO regression was used to screen out clinically independent predictors. Based on logistic regression, the Rad-score and clinically independent predictors were integrated to build the clinical radiomics model and visualized as a nomogram and independently verified in the testing set. The performance and clinical applicability of hybrid model in identifying MSI status were evaluated by the area under the receiver operating characteristic (AUC) curve, calibration curve, and decision curve (DCA). RESULTS: The AUCs of the clinical image model in training set and testing set were 0.883 [95% CI: 0.822-0.945] and 0.802 [95% CI: 0.666-0.937], respectively. This hybrid model showed good consistency in the calibration curve and clinical applicability in the DCA curve, respectively. CONCLUSIONS: Using preoperative imaging and clinical information, we developed a deep-learning-based radiomics model for the non-invasive evaluation of MSI in GC patients. This model maybe can potentially support clinical treatment decision making for GC patients.

Osteoprotegerin deficiency aggravates methionine-choline-deficient diet-induced nonalcoholic steatohepatitis in mice.

Clinical studies have shown that osteoprotegerin (OPG) is reduced in patients with nonalcoholic steatohepatitis (NASH), but the underlying mechanisms are unclear. The current study focuses on the role of OPG in the NASH pathogenesis. OPG knockout mice and wild-type control mice fed a methionine choline-deficient diet (MCD) for 4 weeks resulted in an animal model of NASH. Measurement of triglycerides (TG) in serum and liver to assess steatosis. Hematoxylin eosin (HE), Sirius Red and Masson staining were used to assess the liver damage. Transcriptome sequencing analysis, qPCR and western blot were to analyze changes in lipid metabolism and inflammation-related indicators in the liver. In vivo knockout of OPG resulted in a reduction of TG levels in the liver and a significant increase in serum ALT and AST. The expression of inflammatory factors and fibrosis genes was significantly upregulated in the livers of OPG knockout mice. Transcriptome sequencing analysis showed that OPG knockout significantly enhanced MCD diet-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Mechanistically, OPG may inhibit MAPK signaling pathway activity by upregulating the expression of dual specificity phosphatase 14 (DUSP14), thereby reducing inflammatory injury. OPG could regulate the activity of the MAPK signaling pathway via DUSP14, thus regulating the expression of some inflammatory factors in NASH, it may be a promising target for the treatment of NASH.

Quantitative Radiological Features and Deep Learning for the Non-Invasive Evaluation of Programmed Death Ligand 1 Expression Levels in Gastric Cancer Patients: A Digital Biopsy Study.

RATIONALE AND OBJECTIVES: Programmed Death-Ligand 1 (PD-L1) is an important biomarker for patient selection of immunotherapy in gastric cancer (GC). This study aimed to construct and validate a non-invasive virtual biopsy system based on radiological features and clinical factors to predict the PD-L1 expression level in GC. MATERIALS AND METHODS: 217 patients who received gastrectomy for GC were consecutively enrolled in this study, with 157 patients from center 1 as the training cohort and 60 patients from center 2 as the external validation cohort. 1205 quantitative radiomics features were extracted from preprocessed pre-operative contrast-enhanced CT images of enrolled patients. A radiological signature was computed using a regression random forest model and was integrated with clinical factors in a multilayer perceptron. The performance of the digital biopsy system was evaluated by the receiver operating characteristic (ROC) curve and calibration curve in both the training and validation cohort. RESULTS: 15 features were selected for the construction of radiological signature, which was significantly associated with expression levels of PD-L1 in both the training cohort (p<0.0001) and the external validation cohort (p<0.01). The hybrid deep learning model integrating the radiological signature and clinical factor could accurately distinguish GCs with high PD-L1 expression levels in both the training cohort (AUC = 0.806, 95%CI: 0.736-0.875) and the validation cohort (AUC = 0.784, 95%CI: 0.668-0.901). CONCLUSIONS: Our results indicate that the combination of deep learning and quantitative radiological features are potential approaches for the non-invasive evaluation of PD-L1 expression levels in GC. The digital biopsy system could provide valuable suggestive information for clinical decision-making of immunotherapy in GC.

CircRNA_103948 inhibits autophagy in colorectal cancer in a ceRNA manner.

Circular RNA (circRNA) is implicated in many types of cancer; however, the expression and role of circRNAs in colorectal cancer (CRC) remains poorly understood. In this study, a circRNA microarray assay was performed to detect abnormally expressed circRNAs in CRC, and tissue arrays were used to determine the prognosis for CRC patients. Cell counting kit-8, clone formation, wound healing, and transwell assays were used to evaluate cell functions in vitro, and a mouse subcutaneous tumor model was designed for in vivo analysis. Autophagy was observed using confocal laser scanning and transmission electron microscopy. The expression of circRNA, miRNA, and mRNA was detected using qPCR; western blot, RNA pull-down assay, RNA immunoprecipitation, and dual luciferase assessment were applied for mechanistic studies. We found that circRNA_103948 expression is upregulated in CRC tissues, compared with adjacent normal tissues, and associated with poor prognosis. Knockdown of circRNA_103948 suppressed CRC both in vitro and in vivo. Mechanistically, circRNA_103948 could directly bind to miR-1236-3p and relieve suppression of the target TPT1. Furthermore, circRNA_103948 inhibited autophagy of CRC cells. Taken together, circRNA_103948 knockdown inhibited CRC cell growth by targeting miR-1236-3p/TPT1 axis-mediated autophagy. Thus, the circRNA_103948/miR-1236-3p/TPT1 axis affects CRC progression via modulation of autophagy.

Comparative analysis of clonal evolution among patients with right- and left-sided colon and rectal cancer.

Tumor multiregion sequencing reveals intratumor heterogeneity (ITH) and clonal evolution playing a key role in tumor progression and metastases. Large-scale high-depth multiregional sequencing of colorectal cancer, comparative analysis among patients with right-sided colon cancer (RCC), left-sided colon cancer (LCC), and rectal cancer (RC), as well as the study of lymph node metastasis (LN) with extranodal tumor deposits (ENTDs) from evolutionary perspective remain weakly explored. Here, we recruited 68 patients with RCC (18), LCC (20), and RC (30). We performed high-depth whole-exome sequencing of 206 tumor regions including 176 primary tumors, 19 LN, and 11 ENTD samples. Our results showed ITH with a Darwinian pattern of evolution and the evolution pattern of LCC and RC was more complex and divergent than RCC. Genetic and evolutionary evidences found that both LN and ENTD originated from different clones. Moreover, ENTD was a distinct entity from LN and evolved later.

Clinical characteristics and potential factors for recurrence of positive SARS-CoV-2 RNA in convalescent patients: a retrospective cohort study.

BACKGROUND: The recurrence of positive SARS-CoV-2 RT-PCR is frequently found in discharged COVID-19 patients but its clinical significance remains unclear. The potential cause, clinical characteristics and infectiousness of the recurrent positive RT-PCR patients need to be answered. METHODS: A single-centered, retrospective study of 51 discharged COVID-19 patients was carried out at a designated hospital for COVID-19. The demographic data, clinical records and laboratory findings of 25 patients with recurrent positive RT-PCR from hospitalization to follow-up were collected and compared to 26 patients with negative RT-PCR discharged regularly during the same period. Discharged patients' family members and close contacts were also interviewed by telephone to evaluate patients' potential infectiousness. RESULTS: The titer of both IgG and IgM antibodies was significantly lower (p = 0.027, p = 0.011) in patients with recurrent positive RT-PCR. Median duration of viral shedding significantly prolonged in patients with recurrent positive RT-PCR (36.0 days vs 9.0 days, p = 0.000). There was no significant difference in demographic features, clinical features, lymphocyte subsets count and inflammatory cytokines levels between the two groups of patients. No fatal case was noted in two groups. As of the last day of follow-up, none of the discharged patients' family members or close contact developed any symptoms of COVID-19. CONCLUSIONS: Patients with low levels of IgG and IgM are more likely to have recurrent positive SARS-CoV-2 RT-PCR results and lead to a prolonged viral shedding. The recurrent positive of SARS-CoV-2 RT-PCR may not indicate the recurrence or aggravation of COVID-19. The detection of SARS-CoV-2 by RT-PCR in the patients recovered from COVID-19 is not necessarily correlated with the ability of transmission.

Hypothalamic BMP9 suppresses glucose production by central PI3K/Akt/mTOR pathway.

Bone morphogenetic proteins (BMPs) are secreted ligands that belong to the transforming growth factor-ß (TGF-ß) superfamily. BMP7 has been reported to play a role in reversing obesity and regulating appetite in the hypothalamus. Whether BMP9 plays a central role in regulating glucose metabolism and insulin sensitivity remains unclear. Here, we investigated the impact of central BMP9 signaling and possible route of transmission. We performed intracerebroventricular (ICV) surgery and injected adenovirus expressing BMP9 (Ad-BMP9) into the cerebral ventricle of mice. Metabolic analysis, hyperinsulinemic-euglycemic clamp test, and analysis of phosphatidylinositol 3,4,5-trisphosphate (PIP3) formation were then performed. Real-time PCR and Western blotting were performed to detect gene expression and potential pathways involved. We found that hypothalamic BMP9 expression was downregulated in obese and insulin-resistant mice. Overexpression of BMP9 in the mediobasal hypothalamus reduced food intake, body weight, and blood glucose level, and elevated the energy expenditure in high-fat diet (HFD)-fed mice. Importantly, central treatment with BMP9 improved hepatic insulin resistance (IR) and inhibited hepatic glucose production in HFD-fed mice. ICV BMP9-induced increase in hepatic insulin sensitivity and related metabolic effects were blocked by ICV injection of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) signaling. In addition, ICV BMP9 promoted the ability of insulin to activate the insulin receptor/phosphoinositide 3-kinase (PI3K)/Akt pathway in the hypothalamus. Thus, this study provides insights into the potential mechanism by which central BMP9 ameliorates hepatic glucose metabolism and IR via activating the mTOR/PI3K/Akt pathway in the hypothalamus.

Long-term outcomes of juvenile-onset recurrent respiratory papillomatosis.

OBJECTIVE: To investigate the adult outcomes of children with juvenile-onset recurrent respiratory papillomatosis via long-term follow-up. STUDY DESIGN: Retrospective study. SETTING: Beijing Tongren Hospital. PARTICIPANTS: The study includes 121 patients with recurrent respiratory papillomatosis. MAIN OUTCOME AND MEASURE: We followed up respiratory papillomatosis patients aged least 14 years and analysed their clinical features based on recurrence-free time. RESULTS: In total, 112 (92.6%) patients underwent three or more operations. The age at initial operation was 4.3 ± 2.9 years; 47.9% (58/121) experienced recurrence and underwent surgical treatment after age 14. At follow-up, 5% (6/121) had died, 41.3% (50/121) had been recurrence-free for 5 years or more (cured group), and 53.7% (65/121) had recurrence in the past 5 years (recurrent group). The age at the last operation was 9.2 ± 4.6 years in the cured group. The overall operation frequency was higher in the recurrence group than in the cured group (17.8 ± 11.9 vs 8.7 ± 6.5). Additionally, the human papillomavirus (HPV) infection and tracheal dissemination rates were higher in the recurrence group than in the cured group (90.8% [59/65] vs 54.0% [27/50] and 26.2% [17/65] vs 10% [5/50], respectively). CONCLUSION: The mortality rate for juvenile-onset recurrent respiratory papillomatosis is 5%. Approximately 50% of children experience recurrence and require repeated operations in adulthood. No significant difference in sex, age at initial operation or adjuvant therapy between the cured and recurrent groups was observed; however, significant between-group differences were found in overall operation frequency, aggressive disease, tracheal dissemination of papilloma, and HPV infection.

A deep learning nomogram kit for predicting metastatic lymph nodes in rectal cancer.

BACKGROUND: Preoperative diagnoses of metastatic lymph nodes (LNs) by the most advanced deep learning technology of Faster Region-based Convolutional Neural Network (Faster R-CNN) have not yet been reported. MATERIALS AND METHODS: In total, 545 patients with pathologically confirmed rectal cancer between January 2016 and March 2019 were included and were randomly allocated with a split ratio of 2:1 to the training and validation sets, respectively. The MRI images for metastatic LNs were evaluated by Faster R-CNN. Multivariate regression analyses were used to develop the predictive models. Faster R-CNN nomograms were constructed based on the multivariate analyses in the training sets and were validated in the validation sets. RESULTS: The Faster R-CNN nomogram for predicting metastatic LN status contained predictors of age, metastatic LNs by Faster R-CNN and differentiation degrees of tumors, with areas under the curves (AUCs) of 0.862 (95% CI: 0.816-0.909) and 0.920 (95% CI: 0.876-0.964) in the training and validation sets, respectively. The Faster R-CNN nomogram for predicting LN metastasis degree contained predictors of metastatic LNs by Faster R-CNN and differentiation degrees of tumors, with AUCs of 0.859 (95% CI: 0.804-0.913) and 0.886 (95% CI: 0.822-0.950) in the training and validation sets, respectively. Calibration plots and decision curve analyses demonstrated good calibrations and clinical utilities. The two nomograms were used jointly as a kit for predicting metastatic LNs. CONCLUSION: The Faster R-CNN nomogram kit exhibits excellent performance in discrimination, calibration, and clinical utility and is convenient and reliable for predicting metastatic LNs preoperatively. CLINICAL TRIAL REGISTRATION: ChiCTR-DDD-17013842.

Establishment and Applicability of a Diagnostic System for Advanced Gastric Cancer T Staging Based on a Faster Region-Based Convolutional Neural Network.

Background: The accurate prediction of the tumor infiltration depth in the gastric wall based on enhanced CT images of gastric cancer is crucial for screening gastric cancer diseases and formulating treatment plans. Convolutional neural networks perform well in image segmentation. In this study, a convolutional neural network was used to construct a framework for automatic tumor recognition based on enhanced CT images of gastric cancer for the identification of lesion areas and the analysis and prediction of T staging of gastric cancer. Methods: Enhanced CT venous phase images of 225 patients with advanced gastric cancer from January 2017 to June 2018 were retrospectively collected. Ftable LabelImg software was used to identify the cancerous areas consistent with the postoperative pathological T stage. The training set images were enhanced to train the Faster RCNN detection model. Finally, the accuracy, specificity, recall rate, F1 index, ROC curve, and AUC were used to quantify the classification performance of T staging on this system. Results: The AUC of the Faster RCNN operating system was 0.93, and the recognition accuracies for T2, T3, and T4 were 90, 93, and 95%, respectively. The time required to automatically recognize a single image was 0.2 s, while the interpretation time of an imaging expert was ~10 s. Conclusion: In enhanced CT images of gastric cancer before treatment, the application of Faster RCNN to diagnosis the T stage of gastric cancer has high accuracy and feasibility.

The clinical and immunological features of pediatric COVID-19 patients in China.

In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3-4 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.

Antibody responses to SARS-CoV-2 in patients with COVID-19.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

Differences between COVID-19 and suspected then confirmed SARS-CoV-2-negative pneumonia: A retrospective study from a single center.

Coronavirus disease 2019 (COVID-19) broke out in Wuhan, Hubei, China in December 2019. Tens thousands of people have been infected with the disease. Our aim was to distinguish severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients from SARS-CoV-2-negative patients. We retrospectively compared the data of COVID-19 patients with those of suspected and confirmed SARS-CoV-2-negative patients (control patients). There were 78 COVID-19 patients and 26 control patients, whose median ages were significantly different (P = .001). The percentage of COVID-19 patients admitting exposure to Wuhan was obviously higher than that of control patients (X2 = 29.130; P < .001). Fever and cough appeared more frequently in COVID-19 patients than in the control patients. The routine blood workup parameters of COVID-19 patients did not change much and their mean counts were in the normal range. There were 38.5% of control patients had higher procalcitonin (PCT) levels than 0.5 ng/mL, which was significantly higher than that percentage of COVID-19 patients (X2 = 22.636; P < .05), and COVID-19 patients were also more likely to have decreased or normal urea and creatinine levels than control patients (X2 = 24.930, 8.480; P < .05).Younger age, exposure to Wuhan, fever, cough, and slight changes in routine blood workup parameters, urea and creatinine were important features discriminating COVID-19 from control patients. Slightly increased, but far less than 0.5 ng/mL, PCT levels also differentiated COVID-19 patients from control patients.

Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients.

We explored the relationships between lymphocyte subsets, cytokines, pulmonary inflammation index (PII) and disease evolution in patients with (corona virus disease 2019) COVID-19. A total of 123 patients with COVID-19 were divided into mild and severe groups. Lymphocyte subsets and cytokines were detected on the first day of hospital admission and lung computed tomography results were quantified by PII. Difference analysis and correlation analysis were performed on the two groups. A total of 102 mild and 21 severe patients were included in the analysis. There were significant differences in cluster of differentiation 4 (CD4+ T), cluster of differentiation 8 (CD8+ T), interleukin 6 (IL-6), interleukin 10 (IL-10) and PII between the two groups. There were significant positive correlations between CD4+ T and CD8+ T, IL-6 and IL-10 in the mild group (r2  = 0·694, r 2  = 0·633, respectively; P < 0·01). After 'five-in-one' treatment, all patients were discharged with the exception of the four who died. Higher survival rates occurred in the mild group and in those with IL-6 within normal values. CD4+ T, CD8+ T, IL-6, IL-10 and PII can be used as indicators of disease evolution, and the PII can be used as an independent indicator for disease progression of COVID-19.

Evaluation of Rectal Cancer Circumferential Resection Margin Using Faster Region-Based Convolutional Neural Network in High-Resolution Magnetic Resonance Images.

BACKGROUND: High-resolution MRI is regarded as the best method to evaluate whether there is an involved circumferential resection margin in rectal cancer. OBJECTIVE: We explored the application of the faster region-based convolutional neural network to identify positive circumferential resection margins in high-resolution MRI images. DESIGN: This was a retrospective study. SETTINGS: The study conducted at a single surgical unit of a public university hospital. PATIENTS: We studied 240 patients with rectal cancer in the Affiliated Hospital of Qingdao University from July 2016 to August 2018, who were determined to have a positive circumferential resection margin and who had received a high-resolution MRI. All posttreatment cases were excluded from this study. MAIN OUTCOME MEASURES: The faster region-based convolutional neural network was trained by 12,258 transverse relaxation-weighted (T2-weighted imaging) images of pelvic high-resolution MRI to build an artificial intelligence platform and complete clinical tests. In this network, the proportion of positive and negative circumferential resection margin images was 1:2. In accordance with the test results of the validation group, the metrics of the receiver operating characteristic curves and the area under the curve were applied to compare the diagnostic results of the artificial intelligence platform with those of senior radiology experts. RESULTS: In this artificial intelligence platform, the accuracy, sensitivity, and specificity of the circumferential resection margin status as determined were 0.932, 0.838, and 0.956. The area under the receiver operating characteristic curves was 0.953. The time required to automatically recognize an image was 0.2 seconds. LIMITATIONS: This is a single-center retrospective study with limited data volume and a highly selected patient cohort. CONCLUSIONS: In high-resolution MRI images of rectal cancer before treatment, the application of faster region-based convolutional neural network to segment the positive circumferential resection margin has high accuracy and feasibility. See Video Abstract at http://links.lww.com/DCR/B88. EVALUACIÓN DEL MARGEN DE RESECCIÓN CIRCUNFERENCIAL DEL CÁNCER RECTAL MEDIANTE EL USO DE UNA RED NEURONAL CONVOLUCIONAL MÁS RÁPIDA BASADA EN UNA REGIÓN EN IMÁGENES DE RESONANCIA MAGNÉTICA DE ALTA RESOLUCIÓN: La resonancia magnética de alta resolución se considera el mejor método para evaluar si existe un margen de resección circunferencial involucrado en el cáncer de recto.Se exploró la aplicación de la red neuronal convolucional más rápida basada en una región para identificar márgenes de resección circunferencial positivos en imágenes de resonancia magnética de alta resolución.Este fue un estudio retrospectivo realizado en una única unidad quirúrgica de un hospital universitario público.Estudiamos 240 pacientes con cáncer rectal en el Hospital Afiliado de la Universidad de Qingdao desde el 2 de julio de 2006 hasta el 2 de agosto de 2008, a los que se determinó que tenían un margen de resección circunferencial positivo y que habían recibido una resonancia magnética de alta resolución. Todos los casos posteriores al tratamiento fueron excluidos de este estudio.La red neuronal convolucional más rápida basada en una región recibió capacitación de 12,258 imágenes de RM pélvica de alta resolución con relajación transversal para construir una plataforma de inteligencia artificial y completar pruebas clínicas. En esta red, la proporción de imágenes con margen de resección circunferencial positivo y negativo fue 1: 2. De acuerdo con los resultados de las pruebas del grupo de validación, se aplicaron las métricas de las curvas de las características operativas del receptor y del área bajo la curva para comparar los resultados de diagnóstico de la plataforma de inteligencia artificial con los de expertos de radiología de alto nivel.En esta plataforma de inteligencia artificial, la precisión, sensibilidad y especificidad del estado del margen de resección circunferencial según lo determinado fueron 0.932, 0.838 y 0.956, respectivamente. El área bajo las curvas características de operación del receptor fue de 0.953. El tiempo requerido para reconocer automáticamente una imagen fue de 0.2 segundos.Este es un estudio retrospectivo de centro único con volumen de datos limitado y una cohorte de pacientes altamente seleccionada.En las imágenes de resonancia magnética de alta resolución de cáncer rectal antes del tratamiento, la aplicación de la red neuronal convolucional más rápida basada en una región, para segmentar el margen de resección circunferencial positivo tiene una alta precisión y factibilidad. Consulte Video Resumen en http://links.lww.com/DCR/B88.

Circulating complement-1q tumor necrosis factor-α-related protein isoform 5 levels are low in type 2 diabetes patients and reduced by dapagliflozin.

AIMS/INTRODUCTION: As a member of the tumor necrosis factor-α-related protein family, complement-1q tumor necrosis factor-α-related protein isoform 5 (CTRP5) has been found to be associated with obesity and insulin resistance (IR). Previous studies in humans and animals have reported contradictory results related to the association between CTRP5 and IR. The purpose of the present study was to explore the relationship between CTRP5 and IR through a cross-sectional study and drug intervention study of type 2 diabetes patients. MATERIALS AND METHODS: A cross-sectional study was carried out with 118 newly diagnosed patients with type 2 diabetes and 116 healthy adults. In an interventional study, 78 individuals with newly diagnosed type 2 diabetes received sodium-glucose cotransporter 2 inhibitor (dapagliflozin) treatment for 3 months. Circulating CTRP5 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Serum CTRP5 concentrations were markedly reduced in patients with type 2 diabetes when compared with those of healthy individuals (P < 0.01). When considering the study population as a whole, individuals with IR (homeostasis model of assessment of IR ≥2.78) had lower CTRP5 concentrations than the individuals without IR (homeostasis model of assessment of IR <2.78; P < 0.01). Serum CTRP5 negatively correlated with age, body mass index, waist-to-hip ratio, Systolic blood pressure, triglyceride, total cholesterol, glycated hemoglobin, fasting blood glucose, 2-h blood glucose, fasting insulin and homeostasis model of assessment of IR. After 12 weeks of sodium-glucose cotransporter 2 inhibitor treatment, serum CTRP5 levels in type 2 diabetes patients were significantly reduced accompanied with ameliorated glycometabolism and IR compared with before treatment (P < 0.01). CONCLUSIONS: CTRP5 is likely a marker for type 2 diabetes in humans.