Quercetin ameliorates ulcerative colitis by restoring the balance of M2/M1 and repairing the intestinal barrier via downregulating cGAS‒STING pathway.

Macrophage polarization is closely associated with the pathogenesis of ulcerative colitis (UC). Quercetin, a flavonoid, has shown promise as a treatment for inflammatory diseases, but its specific mechanism of action remains unclear. This study investigates whether quercetin can regulate intestinal macrophage polarization and promote intestinal tissue repair via the cGAS-STING pathway for the treatment of UC. In vivo, mice with 3% DSS-induced UC were intraperitoneally injected with quercetin and RU.521 for 7 days, following which their general conditions and corresponding therapeutic effects were assessed. The impact of interferon-stimulated DNA (ISD) and quercetin on macrophage polarization and the cGAS-STING pathway was investigated using RAW264.7 cells and bone marrow-derived macrophages (BMDMs) in vitro. The results demonstrated that ISD induced M1 macrophage polarization and activated the cGAS-STING pathway in vitro, while quercetin reversed ISD's inflammatory effects. In vivo, quercetin suppressed the cGAS-STING pathway in the intestinal macrophages of DSS-induced UC mice, which reduced M1 macrophage polarization, increased M2 polarization, and facilitated intestinal barrier repair in UC. Taken together, these findings provide new insights into the mechanisms via which quercetin could be used to treat UC.

A new resorcylic acid lactone from the endophytic fungus Chaetosphaeronema sp.

A new 14-membered resorcylic acid lactone (RAL14), chaetolactone A (1), along with three known ones (2-4), was obtained from the fermentation of the soil-derived fungus Chaetosphaeronema sp. SSJZ001. Their structures were established based on extensive spectroscopic data analyses (UV, IR, HRESIMS, 1D, and 2D NMR),13C NMR chemical shifts calculations coupled with the DP4+ probability method, theoretical calculations of ECD spectra, as well as X-ray diffraction analysis. All compounds were evaluated for their cytotoxic effects against A549, HO-8910, and MCF-7 cell lines.

Compound sophora decoction alleviates ulcerative colitis by regulating macrophage polarization through cGAS inhibition: network pharmacology and experimental validation.

INTRODUCTION: Ulcerative colitis (UC) is a refractory disease with complex pathogenesis, and its pathogenesis is not clear. The present study aimed to investigate the potential target and related mechanism of Compound Sophora Decoction (CSD) in treating UC. METHODS: A network pharmacology approach predicted the components and targets of CSD to treat UC, and cell and animal experiments confirmed the findings of the approach and a new target for CSD treatment of UC. RESULTS: A total of 155 potential targets were identified for CSD treatment of UC, with some related to macrophage polarization, such as nitric oxide synthase (NOS2), also known as inducible nitric oxide synthase (iNOS). GO and KEGG enrichment analysis indicated that oxidative stress response and multiple inflammatory signaling pathways such as TNF-α may play a significant role. In vitro experiments revealed that Interferon-stimulated DNA (ISD) interference can cause polarization imbalances in Raw 264.7 and bone marrow-derived macrophages (BMDMs). Flow cytometry demonstrated that polarization of macrophages in the intestine, spleen, and lymph nodes in vivo was also unbalanced after dextran sulfate sodium (DSS) modeling with pathological intestinal injury. Both in vitro and in vivo studies indicated that after inducing inflammation, the levels of macrophage polarization-related markers (iNOS and Arg1) and inflammation-related factors (CCL17, IL10, TNF-α, and CXCL10) changed, accompanied by increased expression of cGAS. However, CSD treatment based on inflammation can inhibit the expression of cGAS protein and mRNA, lower the level of inflammatory factors, promote the expression of anti-inflammatory factors, and regulate macrophage polarization. CONCLUSION: We concluded that CSD alleviated DSS-induced UC by inhibiting cGAS, thus regulating macrophage polarization.

Oleanane and 30-noroleanane triterpenoids from the roots of Paeonia lactiflora.

An investigation of EtOAc extract from the roots of Paeonia lactiflora yielded three new 30-noroleanane triterpenoids paeonenoides L-N (1-3) and one new oleanane triterpenoid paeonenoide O (4) together with 7 known compounds (5-11). Extensive spectrographic experiments were applied to identify the structures of 1-4, and their absolute configurations were unambiguously determined by theoretical calculations of ECD spectra, as well as the single-crystal X-ray diffraction analysis. Compounds 8, 9 and 10 were isolated from the Paeonia genus for the first time. Moreover, compounds 8, 9 and 11 showed inhibitory activities against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages with the IC50 values of 72. 17 ± 4.74, 30.02 ± 2.03 and 28.34 ± 1.85 µM, respectively.

Ultrathin Cu9S5 Nanosheets with Sulfur Vacancy for Multimodal Tumor Therapy.

Multimodal tumor therapy with nanotechnology is an effective and integrative strategy to overcome the limitations of therapeutic efficacy and possible side effects associated with monotherapy. However, the construction of multimodal treatment nanoplatforms often involves various functional components, leading to certain challenges, such as time-consuming synthesis processes, low product yield, and inadequate biocompatibility. To address these issues, we have developed a straightforward method for preparing ultrathin Cu9S5 nanosheets (NSs) with surface defects for photothermal/photodynamic/chemodynamic therapy. The ultrathin morphology of the Cu9S5 NSs (with 2-3 nm) not only confers excellent biocompatibility but also enables broad-spectrum absorption with a remarkable photothermal conversion efficiency (58.96%) under 1064 nm laser irradiation. Moreover, due to the presence of a S vacancy, these Cu9S5 NSs exhibit favorable enzyme-like properties, including reactive oxygen species generation and glutathione consumption, particularly under laser irradiation. The efficacy of related tumor therapy and antibacterial treatment is significantly enhanced by the synergistic activation of photothermal/photodynamic/chemodynamic therapy through 1064 nm laser irradiation, as demonstrated by both in vitro and in vivo experiments. This study presents a novel strategy for multimodal tumor therapy with the prepared ultrathin Cu9S5 NSs, which holds promising pathways for photodynamic therapy in the NIR-II region.

Knowledge-Driven Experimental Discovery of Ce-Based Metal Oxide Composites for Selective Catalytic Reduction of NOx with NH3 through Interpretable Machine Learning.

Mining the scientific literature, combined with data-driven methods, may assist in the identification of optimized catalysts. In this paper, we employed interpretable machine learning to discover ternary metal oxides capable of selective catalytic reduction of nitrogen oxides with ammonia (NH3-SCR). Specifically, we devised a machine learning framework utilizing extreme gradient boosting (XGB), identified for its optimal performance, and SHapley Additive exPlanations (SHAP) to evaluate a curated database of 5654 distinct metal oxide composite catalytic systems containing cerium (Ce) element, with records of catalyst composition and preparation and reaction conditions. By virtual screening, this framework precisely pinpointed a CeO2-MoO3-Fe2O3 catalyst with superior NOx conversion, N2 selectivity, and resistance to H2O and SO2, as confirmed by empirical evaluations. Subsequent characterization affirmed its favorable structural, chemical bulk properties and reaction mechanism. Demonstrating the efficacy of combining knowledge-driven techniques with experimental validation and analysis, our strategy charts a course for analogous catalyst discoveries.

Development and validation of a nomogram model based on pretreatment ultrasound and contrast-enhanced ultrasound to predict the efficacy of neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer.

OBJECTIVES: To develop a nomogram using pretreatment ultrasound (US) and contrast-enhanced ultrasound (CEUS) to predict the clinical response of neoadjuvant chemotherapy (NAC) in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC). METHODS: A total of 111 patients with pancreatic ductal adenocarcinoma (PDAC) treated with NAC between October 2017 and February 2022 were retrospectively enrolled. The patients were randomly divided (7:3) into training and validation cohorts. The pretreatment US and CEUS features were reviewed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of clinical response in the training cohort. Then a prediction nomogram model based on the independent predictors was constructed. The area under the curve (AUC), calibration plot, C-index and decision curve analysis (DCA) were used to assess the nomogram's performance, calibration, discrimination and clinical benefit. RESULTS: The multivariate logistic regression analysis showed that the taller-than-wide shape in the longitudinal plane (odds ratio [OR]:0.20, p = 0.01), time from injection of contrast agent to peak enhancement (OR:3.64; p = 0.05) and Peaktumor/ Peaknormal (OR:1.51; p = 0.03) were independent predictors of clinical response to NAC. The predictive nomogram developed based on the above imaging features showed AUCs were 0.852 and 0.854 in the primary and validation cohorts, respectively. Good calibration was achieved in the training datasets, with C-index of 0.852. DCA verified the clinical usefulness of the nomogram. CONCLUSIONS: The nomogram based on pretreatment US and CEUS can effectively predict the clinical response of NAC in patients with BRPC and LAPC; it may help guide personalized treatment.

Deep learning-based automatic scoring models for the disease activity of rheumatoid arthritis based on multimodal ultrasound images.

OBJECTIVES: We aimed to investigate the value of deep learning (DL) models based on multimodal ultrasonographic (US) images to quantify RA activity. METHODS: Static greyscale (SGS), dynamic greyscale (DGS), static power Doppler (SPD) and dynamic power Doppler (DPD) US images were collected and evaluated by two expert radiologists according to the EULAR-OMERACT Synovitis Scoring system. Four DL models were developed based on the ResNet-type structure, evaluated on two separate test cohorts, and finally compared with the performance of 12 radiologists with different levels of experience. RESULTS: In total, 1244 images were used for the model training, and 152 and 354 for testing (cohort 1 and 2, respectively). The best-performing models for the scores of 0/1/2/3 were the DPD, SGS, DGS and SPD models, respectively (Area Under the receiver operating characteristic Curve [AUC] = 0.87/0.95/0.74/0.95; no significant differences). All the DL models provided results comparable to the experienced radiologists on a per-image basis (intraclass correlation coefficient: 0.239-0.756, P < 0.05). The SPD model performed better than the SGS one on test cohort 1 (score of 0/2/3: AUC = 0.82/0.67/0.95 vs 0.66/0.66/0.75, respectively) and test cohort 2 (score of 0: AUC = 0.89 vs 0.81). The dynamic DL models performed better than the static ones in most of the scoring processes and were more accurate than the most of senior radiologists, especially the DPD model. CONCLUSION: DL models based on multimodal US images allow a quantitative and objective assessment of RA activity. Dynamic DL models in particular have potential value in assisting radiologists to improve the accuracy of RA US-based grading.

[Comprehensive identification of metabolites and metabolic characteristics of luteolin and kaempferol in Simiao Yong'an Decoction in rats by UHPLC-LTQ-Orbitrap MS/MS].

Simiao Yong'an Decoction is a classic prescription for treating gangrene. Modern medical evidence has proven that Si-miao Yong'an Decoction has therapeutic effects on atherosclerosis(AS), vascular occlusion angeitides, and hypertension, while its pharmacodynamic mechanism remains unclear. The evidence of network pharmacology, molecular docking, literature review, and our previous study suggests that luteolin and kaempferol are two major flavonoids in Simiao Yong'an Decoction and can inhibit macrophage inflammation and exert anti-AS effects. However, due to lack of the metabolism studies in vivo, little is known about the metabolic characteristics of luteolin and kaempferol. This study employed ultra-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS/MS) and relevant software to identify the metabolites and metabolic pathways of luteolin and kaempferol in rat plasma, urine, and feces, after oral administration of luteolin and kaempferol, respectively. After the administration of luteolin, 10, 11, and 3 metabolites of luteolin were detected in the plasma, urine, and feces, respectively. After the administration of kaempferol, 9, 3, and 1 metabolites of kaempferol were detected in the plasma, urine, and feces, respectively. The metabolic pathways mainly involved methylation, glucuronidation, and sulfation. This study enriches the knowledge about the pharmacological mechanism of luteolin and kaempferol and supplies a reference for revealing the metabolic process of other flavonoids in Simiao Yong'an Decoction, which is of great significance for elucidating the pharmacological effects and effective substances of this decoction in vivo.

Association between cumulative duration of deep anesthesia and postoperative acute kidney injury after noncardiac surgeries: a retrospective observational study.

BACKGROUND: Bispectral index (BIS) is a processed electroencephalography monitoring tool and is widely used in anesthetic depth monitoring. Deep anesthesia exposure may be associated with multiple adverse outcomes. However, the relationship between anesthetic depth and postoperative acute kidney injury (AKI) remains unclear. We sought to determine the effect of BIS-based deep anesthesia duration on postoperative AKI following noncardiac surgery. METHODS: This retrospective study used data from the Vital Signs DataBase, including patients undergoing noncardiac surgeries with BIS monitoring. The BIS values were collected every second during anesthesia. Restricted cubic splines and logistic regression were used to assess the association between the cumulative duration of deep anesthesia and postoperative AKI. RESULTS: 4774 patients were eligible, and 129 (2.7%) experienced postoperative AKI. Restricted cubic splines showed that a cumulative duration of BIS < 45 was nonlinearly associated with postoperative AKI (P-overall = 0.033 and P-non-linear = 0.023). Using the group with the duration of BIS < 45 less than 15 min as the reference, ORs of postoperative AKI were 2.59 (95% confidence interval [CI]:0.60 to 11.09, p = 0.200) in the 15-100 min group, and 4.04 (95%CI:0.92 to 17.76, p = 0.064) in the ≥ 100 min group after adjusting for preoperative and intraoperative covariates in multivariable logistic regression. CONCLUSIONS: The cumulative duration of BIS < 45 was independently and nonlinearly associated with the risk of postoperative AKI in patients undergoing noncardiac surgery.

Relationship between weight-adjusted waist circumference index and prevalence of gallstones in U.S. adults: a study based on the NHANES 2017-2020.

Objective: We aimed to assess the association between weight-adjusted waist circumference index (WWI) and gallstone prevalence in US adults. Methods: We selected individuals from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2020 and used logistic regression analyses, subgroup analyses, and dose-response curves to assess the association between WWI and gallbladder stone prevalence and age, sex, and ethnicity. Results: A total of 7971 participants aged ≥20 years were enrolled in our study; 828 patients had a self-reported history of gallstones. After correcting for confounders, for each unit of WWI after Ln conversion, the prevalence of gallbladder stones increased by 34% (OR=1.34, 95% CI:1.20, 1.50). Dose-response curves showed a positive correlation between WWI and gallbladder stone prevalence.According to the subgroup analysis, the positive association between TyG index and high-frequency HI was more significant in males(OR=1.34, 95% CI:1.07, 1.69), <40 years old(OR=1.42, 95% CI:1.18, 1.71), white people Americans(OR=1.35, 95% CI:1.08, 1.68) and other races(OR= 1.56, 95% CI:1.13, 2.14). Conclusion: Higher WWI was positively associated with the prevalence of gallbladder stones and was associated with gender, age, and ethnicity. This is noteworthy, although a causal relationship could not be established.

Synthesis and Capacitive Properties of Mesoporous Tungsten Oxide Films Prepared by Ultrasonic Spray Deposition.

Mesoporous tungsten trioxide (WO3) films are prepared by the combination of the template-assisted sol-gel method and ultrasonic spraying deposition (USD) for supercapacitors, and then the surface morphology and electrochemical performance of the films are studied. Compared to WO3 prepared by the traditional hydrothermal synthesis and spin coating method, the films obtained by USD exhibit advantages such as low cost, minimal material usage, and suitability for large-area in-line manufacturing. Additionally, the mesoporous structure of USD-produced films is also supportive of ion transportation. Due to the high specific surface area of WO3 films deposited by USD, it is a material capable of use in a high-performance energy storage device. Through the control of spray coats, the film thickness and specific capacitance can be effectively controlled. Electrochemical measurements show that the mesoporous WO3 films possess excellent electrochemical performance with a maximum specific capacitance of 109.15 F/g at 0.5 A/g. The cycling performance up to 5000 cycles of mesoporous WO3 films is due to the stable nature of nanocrystalline produced by the combination of USD and sol-gel chemistry.

Antifungal and elicitor activities of p-hydroxybenzoic acid for the control of aflatoxigenic Aspergillus flavus in kiwifruit.

Aspergillus flavus not only reduces kiwifruit production but also synthesizes carcinogenic aflatoxins, resulting in a relevant threat to human health. p-Hydroxybenzoic acid (pHBA) is one of the most abundant phenolics in kiwifruit. In this study, pHBA was found to reduce A. flavus mycelial growth by blocking the fungal mitotic exit network (MEN) and cytokinesis and to inhibit the biosynthesis of aflatoxins B1 and B2. The application of pHBA promoted the accumulation of endogenous pHBA and induced oxidative stress in A. flavus-infected kiwifruit, resulting in an increase in H2O2 content and catalase (CAT) and superoxide dismutase (SOD) activities. Preventive and curative treatments with 5 mM pHBA reduced A. flavus advancement by 46.1% and 68.0%, respectively. Collectively, the antifungal and elicitor properties of pHBA were examined for the first time, revealing new insights into the role of pHBA in the defense response of kiwifruit against A. flavus infection.

Evaluation of the diagnostic efficacy of liquid-based cytology obtained via percutaneous ultrasound-guided fine-needle aspiration for pancreatic masses: a large tertiary center's 8-year experience.

PURPOSE: There were limited data on the diagnostic efficacy of liquid-based cytology (LBC) for pancreatic tissues acquired by percutaneous ultrasound-guided fine-needle aspiration (US-FNA). This study aimed to evaluate the diagnostic value of LBC acquired via percutaneous US-FNA for pancreatic tumors compared with LBC combined with smear cytology (SC). METHODS: A retrospective database search (January 2014 and February 2022) was performed for patients who underwent percutaneous US-FNA with both LBC and SC. Clinical and pathological data were collected from 298 patients; eventually, 251 cases met the inclusion criteria. Diagnostic accuracy, sensitivity (SEN), specificity (SPE), positive predictive value (PPV) and negative predictive value (NPV) were compared. Rapid on-site evaluation (ROSE) was not available in all cases. RESULTS: Based on the pancreaticobiliary cytology guidelines published by the Papanicolaou Society of Cytopathology, 224 (89.2%), 13 (5.2%) and 14 (5.6%) cases were diagnosed as malignant, pre-malignant and benign lesions, respectively. The diagnostic accuracy of the LBC + SC (88.5%) was better than that of LBC (87.3%) but without statistical significance (P = 0.125). The SEN, SPE, PPV and NPV were 87.5%, 85.2%, 98.0% and 45.1%, respectively, in the LBC group and 88.8%, 85.2%, 98.0% and 47.9%, respectively, in the LBC + SC group. According to univariate and multivariate analyses, there were no factors have significant association with the diagnostic sensitivity of LBC. CONCLUSIONS: LBC obtained via percutaneous US-FNA provides good diagnostic value for pancreatic lesions and there was no significant difference between the diagnostic accuracy of LBC and LBC + SC when ROSE was unavailable.

Relationship between uric acid to albumin ratio and in-stent restenosis in patients with coronary artery disease undergoing drug-eluting stenting.

BACKGROUND: In-stent restenosis (ISR) in patients undergoing percutaneous coronary intervention (PCI) to treat coronary artery disease (CAD) is an urgent issue in clinical practice. Recent studies have highlighted uric acid-albumin ratio (UAR) as a new marker for evaluating inflammation and oxidative stress, capable of predicting cardiovascular ailments. We aimed to examine the correlation between UAR levels and ISR in patients who underwent drug-eluting stent (DES) implantation. METHODS: We included 503 patients with CAD who underwent initial DES implantation and angiography during the follow-up period. Based on coronary angiographic findings, the patients were categorized into ISR (n = 73) and non-ISR groups (n = 430). Before angiography, laboratory parameters were measured for all enrolled patients. To ascertain the influential factors linked to ISR, multivariate logistic regression analysis was performed. The predictive capability of UAR in determining ISR was assessed using receiver operating characteristic (ROC) curve analysis. Statistical significance was set at P  < 0.05. RESULTS: Multivariate logistic regression analysis revealed that diabetes mellitus, stent length, UAR, albumin levels, and C-reactive protein levels independently predicted ISR. ROC curve analysis revealed that UAR had an area under the curve of 0.767 (95% CI: 0.709 - 0.826) for predicting ISR and demonstrated that UAR outperformed the individual predictive abilities of uric acid and albumin for ISR. CONCLUSION: UAR was associated with ISR in patients with CAD undergoing PCI with DES implantation. Moreover, ROC curve analysis demonstrated that UAR exhibited superior predictive accuracy for ISR compared with evaluating uric acid and albumin levels separately.

Safety and outcome of early enteral nutrition in patients receiving extracorporeal membrane oxygenation.

OBJECTIVE: To explore the benefits and risks of early enteral nutrition (EN) in patients receiving extracorporeal membrane oxygenation (ECMO). METHODS: A single center retrospective review was performed including patients receiving ECMO for more than 24 h from May 2014 to July 2021. RESULTS: A total of sixty-five patients were enrolled, of which thirty-six patients (55.4%) received early EN. On ECMO day 3rd, 7th and 14th, the median energy intake through EN in the early EN group was 500 kcal (IQR:300, 880), 1000 kcal (IQR: 500, 1500) and 1000 kcal (500, 1500), representing 29.7%, 66.7% and 66.7% of energy target, respectively. Thirteen (36.1%) patients had EN intolerance in the early EN group, which is significantly lower than that in the delayed EN group (82.8%, P < 0.001). The most common reasons for EN intolerance were abdominal distention (22.2%), followed by elevated gastric residual volume (8.3%) in the early EN group. Forty-three (66.1%) patients successfully weaned off ECMO, with higher rate in the early EN group than in the delayed EN group (80.6% vs 48.3%, p = 0.006). Nineteen patients (52.8%) survived in the early EN group, which is also significantly higher than that in the delayed EN group (20.7%, P = 0.008). Patients receiving early enteral nutrition significantly reduced the mortality rate and the adjusted mortality hazard ratio was 0.22 (95%CI:0.10, 0.47). CONCLUSION: Early EN was safe and well-tolerated and can reduce the in-hospital mortality of patients receiving ECMO. For patients receiving ECMO, EN started with hypocaloric doses within 48 h of ECMO initiation is recommend.

Stigma toward mental disorders and associated factors among community mental health workers in Wuhan, China.

BACKGROUND: Stigma toward mental disorders (STMD) is a significant barrier to mental health service delivery. To improve the provision of mental health services for community-dwelling residents in China, this study investigated STMD and its associated factors in community mental health workers (CMHWs) in Wuhan, China. METHODS: In this cross-sectional study, a total of 3869 CMHWs (22.9% men and 37.1 ± 8.4 years old) were randomly selected through multistage sampling and invited to participate in this survey. The perceived devaluation-discrimination scale (PDD) and the National Mental Health Literacy Questionnaire (NMHLQ) were used to assess STMD and mental health knowledge, respectively. The presence of STMD was indicated by a mean item score of 3.0 or higher on the PDD. Multiple logistic regression was used to identify factors associated with STMD. RESULTS: Of the CMHWs, 41.9% had poor mental health knowledge (NMHLQ score < 80), and 18.5% exhibited STMD. In multiple regression analysis, factors significantly associated with STMD were social workers (vs. primary care physicians, OR = 1.44, p < .001), poor self-rated capacity to handle common mental health problems (vs. good, OR = 1.57, p < .001), and poor mental health knowledge (vs. NMHLQ score ≥ 80, OR = 1.46, p < .001). CONCLUSION: STMD is common among Chinese CMHWs. To reduce STMD among CMHWs, training programs in mental health care skills and mental health education may be necessary.

Predicting the Efficacy of Neoadjuvant Chemotherapy for Pancreatic Cancer Using Deep Learning of Contrast-Enhanced Ultrasound Videos.

Contrast-enhanced ultrasound (CEUS) is a promising imaging modality in predicting the efficacy of neoadjuvant chemotherapy for pancreatic cancer, a tumor with high mortality. In this study, we proposed a deep-learning-based strategy for analyzing CEUS videos to predict the prognosis of pancreatic cancer neoadjuvant chemotherapy. Pre-trained convolutional neural network (CNN) models were used for binary classification of the chemotherapy as effective or ineffective, with CEUS videos collected before chemotherapy as the model input, and with the efficacy after chemotherapy as the reference standard. We proposed two deep learning models. The first CNN model used videos of ultrasound (US) and CEUS (US+CEUS), while the second CNN model only used videos of selected regions of interest (ROIs) within CEUS (CEUS-ROI). A total of 38 patients with strict restriction of clinical factors were enrolled, with 76 original CEUS videos collected. After data augmentation, 760 and 720 videos were included for the two CNN models, respectively. Seventy-six-fold and 72-fold cross-validations were performed to validate the classification performance of the two CNN models. The areas under the curve were 0.892 and 0.908 for the two models. The accuracy, recall, precision and F1 score were 0.829, 0.759, 0.786, and 0.772 for the first model. Those were 0.864, 0.930, 0.866, and 0.897 for the second model. A total of 38.2% and 40.3% of the original videos could be clearly distinguished by the deep learning models when the naked eye made an inaccurate classification. This study is the first to demonstrate the feasibility and potential of deep learning models based on pre-chemotherapy CEUS videos in predicting the efficacy of neoadjuvant chemotherapy for pancreas cancer.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

Single cell landscape of parietal epithelial cells in healthy and diseased states.

The biology and diversity of glomerular parietal epithelial cells (PECs) are important for understanding podocyte regeneration and crescent formation. Although protein markers have revealed the morphological heterogeneity of PECs, the molecular characteristics of PEC subpopulations remain largely unknown. Here, we performed a comprehensive analysis of PECs using single-cell RNA sequencing (scRNA-seq) data. Our analysis identified five distinct PEC subpopulations: PEC-A1, PEC-A2, PEC-A3, PEC-A4 and PEC-B. Among these subpopulations, PEC- A1 and PEC-A2 were characterized as podocyte progenitors while PEC-A4 represented tubular progenitors. Further dynamic signaling network analysis indicated that activation of PEC-A4 and the proliferation of PEC-A3 played pivotal roles in crescent formation. Analyses suggested that upstream signals released by podocytes, immune cells, endothelial cells and mesangial cells serve as pathogenic signals and may be promising intervention targets in crescentic glomerulonephritis. Pharmacological blockade of two such pathogenic signaling targets, proteins Mif and Csf1r, reduced hyperplasia of the PECs and crescent formation in anti-glomerular basement membrane glomerulonephritis murine models. Thus, our study demonstrates that scRNA-seq-based analysis provided valuable insights into the pathology and therapeutic strategies for crescentic glomerulonephritis.