Superb microvascular imaging for evaluating the activity of juvenile localised scleroderma: a preliminary study.

OBJECTIVES: To investigate microvascular changes in juvenile localised scleroderma (JLS) lesions using superb microvascular imaging (SMI) and assess SMI's utility in evaluating disease activity. METHODS: This prospective study enroled 16 children (7 males) with pathologically diagnosed JLS between January 2021 and June 2023. Lesions were assessed using Localised Scleroderma Cutaneous Assessment Tools, including the localised scleroderma skin activity index (LoSAI) and localised scleroderma skin damage index (LoSDI). Lesions with LoSAI scores > 0 were classified as active. The thickness and blood flow of the lesions and healthy skin layers of the contralateral site were evaluated using ultrasound. SMI was used to detect microvascular blood flow in the lesions and healthy skin, and the vascular index (VI) was calculated. The difference in VI between active lesions and healthy skin was correlated with LoSAI and total scores. RESULTS: Of 46 lesions, 23 were active and 23 inactive. The skin thickness of the lesion was 0.094 ± 0.024 cm, and that of the healthy site was 0.108 ± 0.026 cm (p < 0.001). The VI of the active lesions and healthy skin were 7.60 (3.60, 12.80)% and 1.10 (0.50, 2.10)%, respectively (p < 0.001). The VI of the inactive lesions and the healthy skin were 0.85 (0.00, 2.20)% and 1.60 (1.00, 3.10)%, respectively (p = 0.011). VI differences between active lesions and healthy skin positively correlated with the LoSAI clinical score (r = 0.625, p = 0.001) and total score (r = 0.842, p < 0.001). CONCLUSION: SMI can quantitatively detect microvascular blood flow changes in JLS skin, indicating lesion activity and severity. CLINICAL RELEVANCE STATEMENT: SMI is a convenient, non-invasive, technique for detecting active JLS lesions and can provide valuable information to guide treatment options. KEY POINTS: Current grading systems of juvenile localised scleroderma rely on subjective clinical information. Superb Microvascular Imaging identified that vascular indexes between active lesions and healthy skin positively correlated with clinical scores. Superb Microvascular Imaging effectively assesses microvascular blood flow, aiding juvenile localised scleroderma lesion activity evaluation.

Interpretable artificial intelligence-based app assists inexperienced radiologists in diagnosing biliary atresia from sonographic gallbladder images.

BACKGROUND: A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model's performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings. METHODS: A new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC). RESULTS: The new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists. CONCLUSIONS: The interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings.

Radiofrequency ablation for pediatric recurrent hepatocellular carcinoma: a single-center experience.

PURPOSE: To summarize our single-center experience with percutaneous ultrasound (US)-guided radiofrequency ablation (RFA) for pediatric recurrent hepatocellular carcinoma (RHCC). METHODS: From September 2007 to September 2021, patients under 18 who underwent percutaneous US-guided RFA for RHCC were retrospectively enrolled in this study. Local effectiveness, complications, local tumor progression (LTP), progression free survival (PFS), and overall survival (OS) were evaluated. RESULTS: A total of 10 patients (9 male and 1 female; mean age, 11.7 ± 4 years ; age range, 6-17 years) with 15 intrahepatic RHCC lesions were enrolled in this study. Complete ablation (CA) was achieved in 14 out of 15 lesions (93.3%) after the first RFA. During the follow-up (mean, 63.1 ± 18 months; range, 5.3-123.3 months), LTP did not occur. Five patients died including three with tumor progression and one with liver failure. The accumulative one- and three-year PFS rates were 30% and 10%, respectively. The accumulative one- and three-year OS rates were 77.8% and 44.4%, respectively. CONCLUSIONS: Our single-center experience suggests the safety and feasibility of percutaneous US-guided RFA for pediatric RHCC.

Percutaneous Ultrasound Cholangiography With Microbubbles in Children With Biliary Diseases.

ABSTRACT: The application of intracavity contrast-enhanced ultrasound in the evaluation of biliary disease has been confirmed valuable among pediatric population. This pictorial essay aims to demonstrate the role of percutaneous ultrasound cholangiography (PUSC) with microbubbles in the diagnosis of different pediatric biliary diseases in our center. The biliary system's morphologic characteristics in PUSC mode of neonatal hepatitis, biliary atresia, choledochal cysts, and biliary complications of hepatobiliary surgery are presented.

Rapid Immunodot AQP4 Assay for Neuromyelitis Optica Spectrum Disorder.

Importance: Immunoglobulin G autoantibodies for aquaporin 4 (AQP4-IgG) serve as diagnostic biomarkers for neuromyelitis optica spectrum disorder (NMOSD), and the most sensitive and specific laboratory tests for their detection are cell-based assays (CBAs). Nevertheless, the limited availability of special instruments limits the widespread use of CBAs in routine laboratories. Objective: To validate an enzyme immunodot assay for simple and rapid detection of AQP4-IgG. Design, Setting, and Participants: This multicenter case-control study, conducted from May 2020 to February 2023, involved 4 medical centers (3 in China and 1 in Korea). The study included patients with AQP4-IgG-positive NMOSD, patients with other immune-related diseases, and healthy control individuals. Participants were excluded if they did not agree to participate or if their serum sample had turbidity. Exposures: Serum AQP4 antibodies measured with immunodot assay. Main Outcomes and Measures: The main outcome was performance of the immunodot assay compared with the gold standard CBA for detecting AQP4-IgG. To examine generalizability, cross-validation in Korea and at a second site in China, validation of patients with other immune-related diseases, and follow-up validation of the original cohort were performed. Results: A total of 836 serum samples were collected; 400 were included in the diagnostic study and 436 in the validation sets. In a head-to-head diagnostic study involving 200 patients with NMOSD with AQP4-IgG (mean [SD] age, 43.1 [13.5] years; 188 [94%] female) and 200 healthy controls, use of an immunodot assay demonstrated antibody detection performance comparable to that of the gold standard (κ = 98.0%). The validation sets included 47 patients with NMOSD and 26 patients with other autoimmune diseases from Korea, 31 patients with NMOSD at a second site in China, 275 patients with other diseases, and 57 patients with NMOSD at follow-up. In the validation study, of 436 cases, 2 (<1%) were false positive and none were false negative. The CBA identified 332 AQP4-IgG-positive samples and 504 negative samples (200 [40%] in controls and 304 [60%] in patients with other diseases); 2 of the positive cases (<1%) were false negative and 4 of the negative cases (<1%) were false positive. The overall sensitivity of the immunodot assay was 99.4% (95% CI, 97.8%-99.9%), and the specificity was 99.2% (95% CI, 98.0%-99.8%). Conclusions and Relevance: This case-control study found that the immunodot assay was comparable to CBA for detecting AQP4-IgG. With its time- and cost-efficient characteristics, the immunodot assay may be a practical option for AQP4-IgG detection.

Predicting Infectious Complications after Percutaneous Thermal Ablation of Liver Malignancies: A 12-year Single-Center Experience.

Background Infectious complications after percutaneous thermal ablation are seldom discussed, but better understanding of risk factors and early prediction is critical. Purpose To estimate the incidence of infectious complications after percutaneous thermal ablation of liver malignancies and to develop prediction models. Materials and Methods This single-center retrospective study reviewed the data of 3167 patients who underwent 7545 percutaneous US-guided thermal ablation procedures of liver malignancies between January 2010 and January 2022. All procedures with infectious complications were included as the case group. For each case, one treatment date-matched control subject without infection was randomly selected following a nested case-control design. Independent factors of overall and hepatobiliary infection were investigated with multivariable logistic regression. Results A total of 80 patients (median age, 59 years; IQR, 51-68 years; 64 men, 16 women) developed infectious complications after 80 ablation procedures; the incidence was 1.1% (80 of 7545 procedures). Of those with infection, 18% (14 of 80 patients) were severe, and 10% (eight of 80 patients) died as a result. Independent risk factors for overall infectious complication included prior biliary intervention (odds ratio [OR], 18.6; 95% CI: 4, 86; P < .001), prior transarterial chemoembolization (TACE) (OR, 2.4; 95% CI: 1.0, 5.8; P = .045), and the largest tumor size (OR, 1.9; 95% CI: 1.3, 2.8; P = .002); on this basis, subcapsular location was an additional risk factor of hepatobiliary infection. Prediction models for overall and hepatobiliary infection had an area under the receiver operating characteristics curve (AUC) of 0.77 and 0.82, respectively, both of which showed better AUC compared with the models, including prior biliary intervention alone (AUC = 0.63 and 0.65, respectively; P = .01 and P = .005, respectively). Conclusion Infectious complications after percutaneous thermal ablation of liver malignancies were uncommon but potentially fatal. Independent predictors were prior biliary intervention, prior transarterial chemoembolization, and the largest tumor size. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ben-Arie and Sosna in this issue.

A Gellan Gum/Sodium Alginate-based gastric-protective hydrogel loaded with a combined herbal extract consisting of Panax notoginseng, Bletilla striata and Dendrobium officinale.

One Chinese herbal combination consisting of Panax notoginseng, Bletilla striata and Dendrobium officinale (PBD) is an effective Traditional Chinese Medicine (TCM) prescription and is widely used in clinics to treat gastric ulcers due to their safety and effectiveness compared with chemical agents, such as aspirin and omeprazole. Herein, an in situ forming gel (ISFG) based on Gellan Gum (GG) and Sodium Alginate (SA) was designed to deliver extracts of PBD prescription (EPBDP). The central composite design optimized prescription dosage was 0.1 % w/v of GG and 0.5 % w/v of SA. Gels prepared with this formulation demonstrated outstanding fluidity and instantaneous gel formation. In vitro release data showed that sustained drug release occurred in the gel, and the gel was pH-sensitive. The rheological tests confirmed the formation of stable gel, which exhibited strong viscosity and elasticity. In vitro adhesion assays revealed that the gel had strong gastric mucosal adhesion, while in vivo residual rate experiments of active ingredients revealed that the gel might greatly improve the gastric retention of active ingredients. Animal studies demonstrated that the gel was effective in treating gastric ulcers. Hence, the results of the study show that EPBDP-ISFG, a highly pH-sensitive sustained-release system, is effective.

Medical text classification based on the discriminative pre-training model and prompt-tuning.

Medical text classification, as a fundamental medical natural language processing task, aims to identify the categories to which a short medical text belongs. Current research has focused on performing the medical text classification task using a pre-training language model through fine-tuning. However, this paradigm introduces additional parameters when training extra classifiers. Recent studies have shown that the "prompt-tuning" paradigm induces better performance in many natural language processing tasks because it bridges the gap between pre-training goals and downstream tasks. The main idea of prompt-tuning is to transform binary or multi-classification tasks into mask prediction tasks by fully exploiting the features learned by pre-training language models. This study explores, for the first time, how to classify medical texts using a discriminative pre-training language model called ERNIE-Health through prompt-tuning. Specifically, we attempt to perform prompt-tuning based on the multi-token selection task, which is a pre-training task of ERNIE-Health. The raw text is wrapped into a new sequence with a template in which the category label is replaced by a [UNK] token. The model is then trained to calculate the probability distribution of the candidate categories. Our method is tested on the KUAKE-Question Intention Classification and CHiP-Clinical Trial Criterion datasets and obtains the accuracy values of 0.866 and 0.861. In addition, the loss values of our model decrease faster throughout the training period compared to the fine-tuning. The experimental results provide valuable insights to the community and suggest that prompt-tuning can be a promising approach to improve the performance of pre-training models in domain-specific tasks.

Effect of Heat Treatment on the Digestive Characteristics of Different Soybean Oil Body Emulsions.

Soybean oil body (SOB) emulsions were prepared using OBs extracted at pH 11.0 and pH 7.0. The pH 11.0-SOB comprised oleosins, whereas pH 7.0-SOB comprised extrinsic proteins and oleosins. All SOB emulsions were heated at 60-100 °C for 15 min. Heating may lead to the release of extrinsic proteins from the surface of pH 7.0-SOB due to heat-induced denaturation. The total proportion of α-helix and ß-sheets gradually decreased from 77 (unheated) to 36.2% (100 °C). During stomach digestion, the extrinsic protein hydrolysis of heated pH 7.0-SOB emulsions was fast between 60 and 80 °C, and it then slowed between 90 and 100 °C; heating inhibited the oleosin hydrolysis of pH 7.0- and 11.0-SOBs. Heat treatment promoted aggregation and coalescence, and it resulted in increased particle sizes for all emulsions. Larger aggregates were found in heated pH 7.0-SOB emulsions, and larger oil droplets were found in heated pH 11.0-SOB emulsions. After intestinal digestion, the droplets of all SOB emulsions gradually dispersed, and particle sizes decreased. Different heating temperatures had lesser effects on particle sizes and microstructures. Lipolysis was affected by the extraction pH and heating. For pH 11.0-SOB emulsions, the FFA release tendency was greatly affected by the heating temperature, and heating to 80 °C resulted in the highest FFA release (74%). However, all pH 7.0-SOB emulsions had similar total FFA releases. In addition, the droplet charges of heated pH 7.0-SOB emulsions were lower than those of unheated pH 7.0-SOB emulsions in both the intestine and stomach phases; however, the charge changes in different pH 11.0-SOB emulsions showed the opposite tendency. This study will offer guidance regarding the application of SOB emulsions in food.

Predictive model containing gene signature and shear wave elastography to predict patient outcomes after Kasai surgery in biliary atresia.

AIMS: Infants with biliary atresia (BA) are treated with Kasai portoenterostomy (KPE) surgery, but many BA patients need subsequent salvage liver transplants. The aim of this study is to develop a comprehensive gene-clinical model based on two-dimensional shear wave elastography (2DSWE), liver gene expression, and other clinical parameters to predict response to KPE for BA patients. METHODS: Differentially expressed gene patterns between liver samples of BA (n = 102) and non-BA control (n = 14) were identified using RNA sequencing analysis. Biliary atresia patients were then randomly assigned to training and validation cohorts. Gene classifier based on the differentially expressed genes was built in the training cohort. Nomogram models with and without gene classifier were further constructed and validated for predicting native liver survival of BA patients. The utility of the nomograms was compared by C-index. RESULTS: Using the least absolute shrinkage and selection operator model, we generated a nine-gene prognostic classifier. The nomogram based on the nine-gene classifier, age, preoperative 2DSWE, and albumin had the better C-index compared to gene classifier alone in the training cohort (0.83 [0.76-0.90] vs. 0.69 [0.61-0.77], p = 0.003) and the validation cohort (0.74 [0.67-0.82] vs. 0.62 [0.55-0.70], p = 0.001). Using risk scores developed from the nomogram, the 12-month survival rates of BA patients with native liver were 35.7% (95% confidence interval [CI], 22.7-56.3) in the high-risk group and 80.8% (95% CI, 63.4-100.0) in the low-risk group in the validation cohort. CONCLUSIONS: The comprehensive genetic-clinical nomogram based on preoperative 2DSWE, liver gene expression, and other clinical parameters can accurately predict response to KPE.

CaCP15 Gene Negatively Regulates Salt and Osmotic Stress Responses in Capsicum annuum L.

Salt and osmotic stress seriously restrict the growth, development, and productivity of horticultural crops in the greenhouse. The papain-like cysteine proteases (PLCPs) participate in multi-stress responses in plants. We previously demonstrated that salt and osmotic stress affect cysteine protease 15 of pepper (Capsicum annuum L.) (CaCP15); however, the role of CaCP15 in salt and osmotic stress responses is unknown. Here, the function of CaCP15 in regulating pepper salt and osmotic stress resistance was explored. Pepper plants were subjected to abiotic (sodium chloride, mannitol, salicylic acid, ethrel, methyl jasmonate, etc.) and biotic stress (Phytophthora capsici inoculation). The CaCP15 was silenced through the virus-induced gene silencing (VIGS) and transiently overexpressed in pepper plants. The full-length CaCP15 fragment is 1568 bp, with an open reading frame of 1032 bp, encoding a 343 amino acid protein. CaCP15 is a senescence-associated gene 12 (SAG12) subfamily member containing two highly conserved domains, Inhibitor 129 and Peptidase_C1. CaCP15 expression was the highest in the stems of pepper plants. The expression was induced by salicylic acid, ethrel, methyl jasmonate, and was infected by Phytophthora capsici inoculation. Furthermore, CaCP15 was upregulated under salt and osmotic stress, and CaCP15 silencing in pepper enhanced salt and mannitol stress resistance. Conversely, transient overexpression of CaCP15 increased the sensitivity to salt and osmotic stress by reducing the antioxidant enzyme activities and negatively regulating the stress-related genes. This study indicates that CaCP15 negatively regulates salt and osmotic stress resistance in pepper via the ROS-scavenging.

Utility of the pediatric liver contrast-enhanced ultrasound criteria in differentiating malignant and benign multifocal lesions.

BACKGROUND: The pediatric liver contrast-enhanced ultrasound (CEUS) criteria were developed to improve the diagnostic performance of CEUS in differentiating pediatric benign and malignant liver lesions. However, the diagnostic performance of CEUS in the evaluation of multiple focal liver lesions in the pediatric population has not yet been fully evaluated. OBJECTIVE: To evaluate the diagnostic performance of the pediatric liver CEUS criteria in differentiating benign and malignant multifocal liver lesions in children. MATERIALS AND METHODS: From April 2017 to September 2022, the CEUS characteristics of multifocal liver lesions in patients < 18 years were analyzed. Lesions classified as CEUS-1, CEUS-2 or CEUS-3 were considered benign and lesions classified as CEUS-4 or CEUS-5 were considered malignant. The diagnostic performance of the pediatric liver CEUS criteria (i.e. sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV] and accuracy) was assessed. RESULTS: After exclusion, 21 patients (median age, 36.0 months; range, 1.0-204 months; 7 boys) were included. There were significant differences in the serum alpha fetoprotein level (P= 0.039) and the presence of washout (P < 0.001) between children with malignant and benign lesions. The sensitivity, specificity, PPV, NPV and accuracy of the pediatric liver CEUS criteria were 100.0% (10/10), 90.9% (10/11), 90.9% (10/11), 100.0% (10/10) and 95.2% (20/21), respectively. CONCLUSION: The pediatric liver CEUS criteria had excellent diagnostic performance in differentiating benign and malignant multifocal liver lesions in children.

Intratumoral erythroblastic islands restrain anti-tumor immunity in hepatoblastoma.

Erythroblastic islands (EBIs) are the specialized structures for erythropoiesis, but they have never been found functional in tumors. As the most common pediatric liver malignancy, hepatoblastoma (HB) requires more effective and safer therapies to prevent progression and the lifelong impact of complications on young children. However, developing such therapies is impeded by a lack of comprehensive understanding of the tumor microenvironment. By single-cell RNA sequencing of 13 treatment-naive HB patients, we discover an immune landscape characterized by aberrant accumulation of EBIs, formed by VCAM1+ macrophages and erythroid cells, which is inversely correlated with survival of HB. Erythroid cells inhibit the function of dendritic cells (DCs) via the LGALS9/TIM3 axis, leading to impaired anti-tumor T cell immune responses. Encouragingly, TIM3 blockades relieve the inhibitory effect of erythroid cells on DCs. Our study provides an immune evasion mechanism mediated by intratumoral EBIs and proposes TIM3 as a promising therapeutic target for HB.

Characteristic gene prognostic model of type 1 diabetes mellitus via machine learning strategy.

The present study was designed to detect possible biomarkers associated with Type 1 diabetes mellitus (T1DM) incidence in an effort to develop novel treatments for this condition. Three mRNA expression datasets of peripheral blood mononuclear cells (PBMCs) were obtained from the GEO database. Differentially expressed genes (DEGs) between T1DM patients and healthy controls were identified by Limma package in R, and using the DEGs to conduct GO and DO pathway enrichment. The LASSO-SVM were used to screen the hub genes. We performed immune correlation analysis of hub genes and established a T1DM prognosis model. CIBERSORT algorithm was used to identify the different immune cells in distribution between T1DM and normal samples. The correlation of the hub genes and immune cells was analyzed by Spearman. ROC curves were used to assess the diagnostic value of genes in T1DM. A total of 60 immune related DEGs were obtained from the T1DM and normal samples. Then, DEGs were further screened to obtain 3 hub genes, ANP32A-IT1, ESCO2 and NBPF1. CIBERSORT analysis revealed the percentage of immune cells in each sample, indicating that there was significant difference in monocytes, T cells CD8+, gamma delta T cells, naive CD4+ T cells and activated memory CD4+ T cells between T1DM and normal samples. The area under curve (AUC) of ESCO2, ANP32A-IT1 and NBPF1 were all greater than 0.8, indicating that these three genes have high diagnostic value for T1DM. Together, the findings of these bioinformatics analyses thus identified key hub genes associated with T1DM development.

Nanodroplet-enhanced sonodynamic therapy potentiates immune checkpoint blockade for systemic suppression of triple-negative breast cancer.

Immune checkpoint blockade (ICB) has shown great promise in treating various advanced malignancies including triple-negative breast cancer (TNBC). However, only limited number of patients could benefit from it due to the low immune response rate caused by insufficient matured dendritic cells (DCs) and inadequate tumor infiltration of cytotoxic T lymphocytes (CTLs). Here, we report a combination therapeutic strategy which integrates STING pathway activation, hypoxia relief and sonodynamic therapy (SDT) with anti-PD-L1 therapy to improve the therapeutic outcome. The synthesized nanodroplet consisted of a O2-filled Perfluorohexane (PFH) core and a lipid membrane carrying sonosensitizer IR-780 and STING agonist Vadimezan (DMXAAs). It released O2 inside the hypoxic tumor tissue, thereby enhancing SDT which relied on O2 to generate cytotoxic reactive oxygen species (ROS). The co-delivered STING agonist DMXAAs promoted the maturation and tumor antigen cross-presenting of DCs for priming of CTLs. Moreover, SDT induced immunogenic cell death (ICD) of tumor to release abundant tumor-associated antigens, which increased tumor immunogenicity to promote tumor infiltration of CTLs. Consequently, not only a robust adaptive immune response was elicited but also the immunologically "cold" TNBC was turned "hot" to enable a potent anti-PD-L1 therapy. The nanodroplet demonstrated strong efficacy to systemically suppress TNBC growth and mimic distant tumor in vivo. STATEMENT OF SIGNIFICANCE: Only a limited number of triple-negative breast cancer (TNBC) patients can benefit from immune checkpoint blockade therapy due to its low immune response rate caused by insufficient matured DCs and inadequate tumor infiltration of cytotoxic T lymphocytes (CTLs). Interestingly, compelling evidence has shown that sonodynamic therapy (SDT) not only directly kills cancer cells but also elicits immunogenic cell death (ICD), which promotes tumor infiltration of cytotoxic T lymphocytes to transform an immunosuppressive "cold" tumor into a "hot" one. However, the hypoxic tumor microenvironment severely restricts the therapeutic efficiency of SDT, wherein, oxygen is indispensable in the process of ROS generation. Here, we report an O2-filled nanodroplet-enhanced sonodynamic therapy that significantly potentiated immune checkpoint blockade for systemic suppression of TNBC.

Increased Expression of the p-STAT3/IL-17 Signaling pathway in patients with Dermatomyositis.

OBJECTIVE: To explored the roles of phosphorylated signal transduction and activator of transcription 3 (p-STAT3) and IL (interleukin) -17 in patients with dermatomyositis (DM). METHODS: A total of 20 DM patients and 12 healthy controls were enrolled. The Flow cytometry combined with counting was used to detect the numbers of Th17 cells. Western blotting and immunohistochemistry was used to examine the muscle levels of p-STAT3 and IL-17, and serum levels of IL-17 were measured by enzyme-linked immunosorbent assays. RESULTS: Muscle p-STAT3 and IL-17 levels, the numbers of Th17 cells, and serum IL-17 levels were markedly increased in DM. p-STAT3 and IL-17 were co-expressed in the muscle of DM patients. The p-STAT3 levels correlated with the number of Th17 cells as well as muscle and serum IL-17 levels. The correlations of the p-STAT3 level with elevated levels of transaminases, myocardial enzymes, and the health assessment questionnaire score were significantly positive, while the correlation with manual muscle testing-8 was significantly negative. A receiver operating characteristic curve indicated good predictive value of p-STAT3 for the occurrence of DM. CONCLUSION: The increased p-STAT3/IL-17 signaling pathway activation in DM patients may induce muscle inflammation and necrosis, and it may be a potential target for DM.

A nomogram model based on preoperative grey-scale US features and routine serum biomarkers to predict the outcome of infants with biliary atresia after Kasai portoenterostomy.

Objective: To establish a nomogram to predict the outcome of biliary atresia (BA) infants 3-months post- Kasai portoenterostomy (KPE). Methods: BA Infants who underwent KPE from two hospitals were included in the training (n = 161) and validation cohorts (n = 64). A logistic regression equation (Equation A) for predicting the serum total bilirubin (TBIL) level 3-month post-KPE was established in the training cohort. Then, a nomogram was developed based on Equation A in the training cohort and validated in the validation cohort. Moreover, a new equation (Equation B) was generated based on the nomogram and the size of the enlarged hilar lymph nodes (LNs) in the validation cohort. The predictive performance of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and by calculating the area under the ROC curve (AUC), sensitivity, specificity, and positive (PPV) and negative (NPV) prediction values. Results: A nomogram based on gallbladder morphology and serum levels of TBIL and total protein (TP) was established with AUC (95%CI) of 0.673 (0.595, 0.745) and 0.647 (0.518, 0.763), sensitivity (95%CI) of 71.4% (62.1%,79.6%) and 81.8% (59.7%,94.8%), specificity (95%CI) of 63.3% (48.3%,76.6%) and 47.6% (32.0%,63.6%), PPV (95%CI) of 81.6% (72.5%,88.9%) and 45.0% (29.3%,61.5%), and NPV (95%CI) 49.2% (36.4%,62.1%) and 83.3% (62.6%,95.3%), respectively, in the training and validation cohorts. Furthermore, in the validation cohort, the AUC (95%CI) of Equation B was 0.798 (95%CI: 0.679, 0.888), which was significantly higher than that of the nomogram (P = 0.042). Conclusion: A nomogram based on the pre-KPE gallbladder morphology, TBIL, and TP to predict the outcome of BA 3-months post-KPE is established. Moreover, the addition of the size of the enlarged hilar LNs into the nomogram further improves its predictive value.

Clinical and genetic analysis of familial neuromyelitis optica spectrum disorder in Chinese: associated with ubiquitin-specific peptidase USP18 gene variants.

BACKGROUND: Familial clustering of neuromyelitis optica spectrum disorder (NMOSD) was present in Chinese. This study was to investigate the clinical characteristics and genetic background of familial NMOSD. METHODS: Through questionnaires in four medical centres in 2016-2020, we identified 10 families with NMOSD aggregation. The statistical differences of clinical characteristics between familial and sporadic NMOSD (22 cases and 459 cases) were summarised. The whole-exome sequencing (WES) for seven families (13 cases and 13 controls) was analysed, compared with our previous WES data for sporadic NMOSD (228 cases and 1 400 controls). The family-based and population-based association and linkage analysis were conducted to identify the pathogenetic genes, the variant impacts were predicted. RESULTS: The familial occurrence was 0.87% in Chinese. Familial patients had higher expanded disability status scale score than sporadic patients (p=0.03). The single-nucleotide polymorphism (SNP) rs2252257 in the promoter and enhancer of ubiquitin-specific peptidase USP18 was linked to familial NMOSD (p=7.8E-05, logarithm of the odds (LOD)=3.1), SNPs rs361553, rs2252257 and rs5746523 were related to sporadic NMOSD (p=1.29E-10, 3.45E-07 and 2.01E-09, respectively). Patients with the SNP rs361553 T/T genotype had higher recurrence rate than C/T or C/C genotype (1.22±0.85 vs 0.69±0.57 and 0.81±0.65, p=0.003 and 0.001, respectively). SNPs rs361553 and rs2252257 altered USP18 expression in brain and nerve tissues. CONCLUSION: Most clinical characteristics of familial NMOSD were indistinguishable from sporadic NMOSD except for the worst episodes severity. USP18 with impaired intronic regulatory function contributed to the pathogenesis of NMOSD.

Neutrophil Nanovesicle Protects against Experimental Autoimmune Encephalomyelitis through Enhancing Myelin Clearance by Microglia.

Timely clearance of myelin debris is the premise of neuroinflammation termination and tissue regeneration in multiple sclerosis (MS). Microglia are the main scavengers of myelin debris in MS lesions, but its phagocytic capability is limited in MS patients. Here, we develop neutrophil-derived nanovesicles (NNVs) to enhance the efficiency of myelin debris clearance in microglia for MS therapy. RNA sequencing (RNAseq) results demonstrate that NNVs treatment ameliorates lesional neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Consequently, EAE mice exhibit favorable neurological functions and white matter integrity after NNVs treatment. Specifically, NNVs treatment upregulates the expression of nuclear factor E2-related factor 2 (NRF2) in microglia, as revealed by Assay for Transposase Accessible Chromatin using sequencing (ATACseq). We also demonstrate that NRF2 can activate the transcription of RUBCN (RUN domain and cysteine-rich domain containing Beclin 1-interacting protein), which in turn enhances LC3-associated phagocytosis (LAP) in microglia. As a result, myelin debris engulfed by microglia can be efficiently catabolized in NNVs-treated EAE mice without obvious side effects. Together, this study proves that NNVs can modulate neuroinflammation by clearing myelin debris and is a promising MS treatment strategy.

Prevalence of multiple sclerosis in Guangzhou, China: A population-based case-finding prospective study.

BACKGROUND: Multiple sclerosis (MS) is rare in China, and the prevalence previously reported may be biased. Currently, few studies that have investigated the prevalence of MS in China based on the latest diagnostic criteria. METHODS: Through a population-based survey from August 8, 2021 to December 31, 2021, we calculated the prevalence of multiple sclerosis in 18,676,605 residents of Guangzhou, China. MS patients were identified through the health insurance system of the Guangzhou Health Insurance Bureau, and we surveyed 17 large tertiary hospitals using a case-finding approach. All MS patients were diagnosed according to the 2017 McDonald criteria. RESULTS: A total of 143 patients in the resident population of Guangzhou were diagnosed with MS, with a crude prevalence of 0.77 per 100,000 (95% confidence interval (CI): 0.65-0.90), and the prevalence was higher in in females (1.14/100,000) than in males (0.44/100,000). The age-adjusted prevalence was 0.92 per 100,000 (95% CI: 0.77-1.10). The prevalence peaked at the age of 25-29 years (2.86/100,000) for both males and females (1.44/100,000 and 4.42/100,000, respectively). CONCLUSIONS: This is the first study to report the prevalence of MS in Guangzhou, China, according to the criteria. Our study shows that the prevalence of MS in Guangzhou is lower than that in other cities in China.