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Abstract Variable renewable generation and load fluctuations induce significant balancing cost in power system operation. To overcome this issue, this paper proposes a control architecture that leverages inherent regulation capabilities of wind turbines to minimize the system‐wide balancing costs. Instead of handling wind power fluctuations via power filtering algorithms that are agnostic to system‐wide power imbalance, this paper aims to optimize the wind power generation profile from system perspective. In the proposed method, wind turbines are modelled as semi‐dispatchable units, where the dispatch command is dynamically generated at every automatic generation control cycle by considering mileage payments as an indicator of system‐wide imbalance. As a result, local resources of wind turbines are optimally leveraged in real‐time to mitigate system‐wide power imbalances. The proposed strategy and state‐of‐the‐art techniques are compared in comprehensive high‐fidelity case studies. Our simulation results demonstrate that the proposed system‐aware regulation scheme can alleviate system balancing costs without investments into energy storage systems.

With the increasing share of wind power, it is expected that wind turbines would provide frequency regulation ancillary service. However, the complex wake effect intensifies the difficulty in controlling wind turbines and evaluating the frequency regulation potential from the wind farm. We propose a novel frequency control scheme for doubly-fed induction generator (DFIG)-based wind turbines, in which the wake effect is considered. The proposed control scheme is developed by incorporating the virtual inertia control and primary frequency control in a holistic way. To facilitate frequency regulation in time-varying operation status, the control gains are adaptively adjusted according to wind turbine operation status in the proposed controller. Besides, different kinds of power reserve control approaches are explicitly investigated. Finally, extensive case studies are conducted and simulation results verify that the frequency behavior is significantly improved via the proposed control scheme.

Machine learning approaches have diverse applications in forecasting electrical energy consumption using smart meter data. Various classification techniques and clustering methods analyze smart meter data for accurately forecasting the electrical appliance consumption and peak demand. Electrical appliance forecasting and peak demand forecasting play a vital and key role in planning, maintenance and automation development for electrical power system. However, there is always a variation between electrical appliance consumption and appliance energy demand due to certain parameters including losses in lines and appliance and mismanagement of appliance energy demand. Detail scrutiny of smart meter data is required to identify the decisive attributes and major cause of variation between electrical appliance consumption and customers’ peak demand. This paper proposed a hybrid method based on Machine learning for forecasting appliance consumption and peak demand. We have deployed faster k-medoids clustering, support vector machine and artificial neural network for forecasting appliance consumption and customers’ peak demand. The proposed algorithm achieves 99.2% accuracy in forecasting electrical appliance consumption which is much better compared to state-of-the-art in same field. Experimental results validate the effectiveness of the proposed method in forecasting the electrical appliance consumption using smart meter data.

As an emerging paradigm in distributed power systems, microgrids provide promising solutions to local renewable energy generation and load demand satisfaction. However, the intermittency of renewables and temporal uncertainty in electrical load create great challenges to energy scheduling, especially for small-scale microgrids. Instead of deploying stochastic models to cope with such challenges, this paper presents a retroactive approach to real-time energy scheduling, which is prediction-independent and computationally efficient. Extensive case studies were conducted using 3-year-long real-life system data, and the results of simulations show that the cost difference between the proposed retroactive approach and perfect dispatch is less than 11% on average, which suggests better performance than model predictive control with the cost difference at 30% compared to the perfect dispatch.

Due to the critical nature of the ramp-up phase of an efficient steam-assisted gravity drainage (SAGD) process, it is important to understand the physics of the steam chamber ramp-up phase in order to improve SAGD production performance. In conventional numerical simulation models, the dynamics of the steam chamber ramp-up phase are not fully resolved because of unclear steam–oil–water interactions during the vertical growth of the steam chamber and how its state changes as the reservoir parameters vary. This work provides an efficient approach for the numerical modeling of the steam chamber ramp-up phase in an SAGD operation. The steam chamber ramp-up phase was fully examined through the consideration of the effects of the temperature-dependent oil–water–gas multiphase flow system and the vertical countercurrent flow. The simulation results revealed that for the large temperature gradient of the mobile oil zone at the edge of the steam chamber, a delicate temperature-dependent multiphase flow system was essential for the reliable estimation of the SAGD ramp-up phase. The vertical countercurrent flows of oil–gas and oil–condensate were the dominant mechanisms over cocurrent flow, which significantly impacted the steam chamber ramp-up rate. The numerical model physically predicted the steam chamber ramp-up phase and could be used to efficiently compute a field-scale simulation using a dynamic gridding function that was based on a fine grid model.

Reflex seizures are evoked by a specific afferent stimulus or by activity of the patient and are divided into those characterized by generalized seizures and those principally manifested by focal seizures. Reflex epilepsies are syndromes in which all epileptic seizures are precipitated by sensory stimuli. Three categories of reflex seizures encountered clinically include pure reflex epilepsies, reflex seizures that occur in generalized or focal epilepsy syndromes that are also associated with spontaneous seizures, and isolated reflex seizures occurring in situations that do not necessarily require a diagnosis of epilepsy. Generalized reflex seizures are precipitated by visual light stimulation, thinking, and decision making. These seizures usually respond to valproate treatment. Numerous triggers can induce focal reflex seizures. The triggers include reading, writing, other language functions, startle, somatosensory stimulation, proprioception, auditory stimuli, immersion in hot water, eating, and vestibular stimulation. The classification and characteristics of reflex seizures and epilepsies are described in this review. Findings on EEG and advanced neuroimaging in the reflex seizures and epilepsies, treatment and preventive options, and animal models and mechanisms are also discussed. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical value of multiparameteric quantitative ultrasound combined with a non-invasive prediction model for assessing high-risk steatohepatitis. Methods: One hundred and ninety-four cases with metabolic-associated fatty liver disease (MAFLD) who underwent liver biopsy in Huashan Hospital, Fudan University, from June 2021 to September 2022 were selected. Shear wave elastography (SWE), shear wave dispersion (SWD) imaging, and attenuation imaging (ATI) examinations were conducted in all patients before biopsy. High-risk steatohepatitis was defined as a total activity score of ≥4 in patients with steatohepatitis, hepatocellular ballooning, and liver lobular inflammation based on pathological hepatic steatosis, inflammatory activity, and fibrosis scoring system (SAF), and fibrosis stage≥F2. Binary logistic regression analysis was used to identify the factors influencing high-risk steatohepatitis. A predictive model for diagnosing high-risk steatohepatitis was constructed using R language. The DeLong test was used to compare the area under the curve between groups. Measurement data was compared between groups using the t-test or rank-sum test, and count data were compared between groups using the χ 2 test. Results: There were 46 cases (23.7%) with high-risk steatohepatitis. The quantitative ultrasound parameters included elastic modulus ( OR =2.958, 95% CI : 1.889-4.883, P <0.001), dispersion coefficient ( OR =1.786, 95% CI : 1.424-2.292, P <0.001) and attenuation coefficient ( OR =42.642, 95% CI : 3.463-640.451, P =0.004). Serological indexes of fasting blood glucose ( OR =1.196, 95% CI : 1.048-1.392, P =0.011), alanine aminotransferase ( OR =1.012, 95% CI : 1.006-1.019, P <0.001), aspartate aminotransferase ( OR =1.027, 95% CI : 1.014-1.042, P <0.001), γ-glutamyl transferase ( OR =1.008, 95% CI : 1.001-1.017, P =0.041) and HDL cholesterol ( OR =0.087, 95% CI : 0.016-0.404, P =0.003) were the factors influencing its progression. The AUCs of elastic modulus, dispersion coefficient, attenuation coefficient, multiparametric ultrasound model, serological index model, and ultrasound combined with serology model for the diagnosis of high-risk steatohepatitis were 0.764, 0.758, 0.634, 0.786, 0.773 and 0.825, respectively. The results of the DeLong test showed that the ultrasound combined with the serological model was significantly better than the serological index model and the elastic modulus, dispersion coefficient, and attenuation coefficient alone ( P =0.024, 0.027, 0.038 and <0.001). Conclusion: The combination of multiparametric quantitative ultrasound is helpful for the non-invasive diagnosis of high-risk steatohepatitis and possesses great clinical significance.

Leukocyte-derived chemotaxin-2 (LECT2) is a multifunctional immunoregulator that plays several pivotal roles in the host's defense against pathogens. This study aimed to elucidate the specific functions and mechanisms of LECT2 (CaLECT2) in the northern snakehead (Channa argus) during infections with pathogens such as Nocardia seriolae (N. seriolae). We identified CaLECT2 in the northern snakehead, demonstrating its participation in the immune response to N. seriolae infection. CaLECT2 contains an open reading frame (ORF) of 459 bp, encoding a peptide of 152 amino acids featuring a conserved peptidase M23 domain. The CaLECT2 protein shares 62%-84 % identities with proteins from various other fish species. Transcriptional expression analysis revealed that CaLECT2 was constitutively expressed in all examined tissues, with the highest expression observed in the liver. Following intraperitoneal infection with N. seriolae, CaLECT2 transcription increased in the spleen, trunk kidney, and liver. In vivo challenge experiments showed that injecting recombinant CaLECT2 (rCaLECT2) could protect the snakehead against N. seriolae infection by reducing bacterial load, enhancing serum antibacterial activity and antioxidant capacity, and minimizing tissue damage. Moreover, in vitro analysis indicated that rCaLECT2 significantly enhanced the migration, respiratory burst, and microbicidal activity of the head kidney-derived phagocytes. These findings provide new insights into the role of LECT2 in the antibacterial immunity of fish., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Liver stiffness (LS) measurement with two-dimensional shear wave elastography (2D-SWE) correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve. The size of the spleen increases due to tissue proliferation, fibrosis, and portal vein congestion, which can indirectly reflect the situation of liver fibrosis/cirrhosis. It was reported that the size of the spleen was related to posthepatectomy liver failure (PHLF). So far, there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF. This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area (SPA) for the prediction of PHLF in hepatocellular carcinoma (HCC) patients and to develop a risk prediction model., Aim: To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model., Methods: This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022. Within 1 wk before partial hepatectomy, ultrasound examination was performed to measure LS and SPA, and blood was drawn to evaluate the patient's liver function and other conditions. Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram. Nomogram performance was validated further. The diagnostic performance of the nomogram was evaluated with receiver operating characteristic curve compared with the conventional models, including the model for end-stage liver disease (MELD) score and the albumin-bilirubin (ALBI) score., Results: A total of 562 HCC patients undergoing hepatectomy (500 in the training cohort and 62 in the validation cohort) were enrolled in this study. The independent predictors of PHLF were LS, SPA, range of resection, blood loss, international normalized ratio, and total bilirubin. Better diagnostic performance of the nomogram was obtained in the training [area under receiver operating characteristic curve (AUC): 0.833; 95% confidence interval (95%CI): 0.792-0.873; sensitivity: 83.1%; specificity: 73.5%] and validation (AUC: 0.802; 95%CI: 0.684-0.920; sensitivity: 95.5%; specificity: 52.5%) cohorts compared with the MELD score and the ALBI score., Conclusion: This PHLF nomogram, mainly based on LS by 2D-SWE and SPA, was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The prevalence of hypertensive heart disease (HHD) is high and there is currently no easy way to detect early HHD. Explore the application of radiomics using cardiac magnetic resonance (CMR) non-enhanced cine sequences in diagnosing HHD and latent cardiac changes caused by hypertension., Methods: 132 patients who underwent CMR scanning were divided into groups: HHD (42), hypertension with normal cardiac structure and function (HWN) group (46), and normal control (NOR) group (44). Myocardial regions of the end-diastolic (ED) and end-systolic (ES) phases of the CMR short-axis cine sequence images were segmented into regions of interest (ROI). Three feature subsets (ED, ES, and ED combined with ES) were established after radiomic least absolute shrinkage and selection operator feature selection. Nine radiomic models were built using random forest (RF), support vector machine (SVM), and naive Bayes. Model performance was analyzed using receiver operating characteristic curves, and metrics like accuracy, area under the curve (AUC), precision, recall, and specificity., Results: The feature subsets included first-order, shape, and texture features. SVM of ED combined with ES achieved the highest accuracy (0.833), with a macro-average AUC of 0.941. AUCs for HHD, HWN, and NOR identification were 0.967, 0.876, and 0.963, respectively. Precisions were 0.972, 0.740, and 0.826; recalls were 0.833, 0.804, and 0.863, respectively; and specificities were 0.989, 0.863, and 0.909, respectively., Conclusions: Radiomics technology using CMR non-enhanced cine sequences can detect early cardiac changes due to hypertension. It holds promise for future use in screening for latent cardiac damage in early HHD., (© 2024. The Author(s).)

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary Endoscopic submucosal dissection (ESD) is becoming more and more widespread for removal of submucosal lesions of the GI tract. Although gastric ESD is generally considered less technically challenging than ESD in other areas of the GI tract, including the small bowel, esophagus, and right side of the colon, certain areas of the stomach can still pose challenges. In this case, the target lesion was in the fundus of the stomach, requiring the ESD to be done in retroflexion. To overcome this challenge, the authors suctioned the lesion into the transparent cap attached to allow dissection of the surrounding area in back-and-forth movements. As ESD continues to become more widespread and demand for it increases, novel techniques like this to overcome challenging endoscopic positions will be paramount to success. Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Endometrial carcinoma (EC) risk stratification prior to surgery is crucial for clinical treatment. In this study, we intend to evaluate the predictive value of radiomics models based on magnetic resonance imaging (MRI) for risk stratification and staging of early-stage EC. The study included 155 patients who underwent MRI examinations prior to surgery and were pathologically diagnosed with early-stage EC between January, 2020, and September, 2022. Three-dimensional radiomics features were extracted from segmented tumor images captured by MRI scans (including T2WI, CE-T1WI delayed phase, and ADC), with 1521 features extracted from each of the three modalities. Then, using five-fold cross-validation and a multilayer perceptron algorithm, these features were filtered using Pearson's correlation coefficient to develop a prediction model for risk stratification and staging of EC. The performance of each model was assessed by analyzing ROC curves and calculating the AUC, accuracy, sensitivity, and specificity. In terms of risk stratification, the CE-T1 sequence demonstrated the highest predictive accuracy of 0.858 ± 0.025 and an AUC of 0.878 ± 0.042 among the three sequences. However, combining all three sequences resulted in enhanced predictive accuracy, reaching 0.881 ± 0.040, with a corresponding increase in the AUC to 0.862 ± 0.069. In the context of staging, the utilization of a combination involving T2WI with CE-T1WI led to a notably elevated predictive accuracy of 0.956 ± 0.020, surpassing the accuracy achieved when employing any singular feature. Correspondingly, the AUC was 0.979 ± 0.022. When incorporating all three sequences concurrently, the predictive accuracy reached 0.956 ± 0.000, accompanied by an AUC of 0.986 ± 0.007. It is noteworthy that this level of accuracy surpassed that of the radiologist, which stood at 0.832. The MRI radiomics model has the potential to accurately predict the risk stratification and early staging of EC., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Objective: To investigate the magnetic resonance imaging (MRI) radiomics models in evaluating the human epidermal growth factor receptor 2(HER2) expression in breast cancer., Materials and Methods: The MRI data of 161 patients with invasive ductal carcinoma (non-special type) of breast cancer were retrospectively collected, and the MRI radiomics models were established based on the MRI imaging features of the fat suppression T2 weighted image (T2WI) sequence, dynamic contrast-enhanced (DCE)-T1WIsequence and joint sequences. The T-test and the least absolute shrinkage and selection operator (LASSO) algorithm were used for feature dimensionality reduction and screening, respectively, and the random forest (RF) algorithm was used to construct the classification model., Results: The model established by the LASSO-RF algorithm was used in the ROC curve analysis. In predicting the low expression state of HER2 in breast cancer, the radiomics models of the fat suppression T2WI sequence, DCE-T1WI sequence, and the combination of the two sequences showed better predictive efficiency. In the receiver operating characteristic (ROC) curve analysis for the verification set of low, negative, and positive HER2 expression, the area under the ROC curve (AUC) value was 0.81, 0.72, and 0.62 for the DCE-T1WI sequence model, 0.79, 0.65 and 0.77 for the T2WI sequence model, and 0.84, 0.73 and 0.66 for the joint sequence model, respectively. The joint sequence model had the highest AUC value., Conclusions: The MRI radiomics models can be used to effectively predict the HER2 expression in breast cancer and provide a non-invasive and early assistant method for clinicians to formulate individualized and accurate treatment plans

To validate a radiomics model based on multi-sequence magnetic resonance imaging (MRI) in predicting the ki-67 expression levels in early-stage endometrial cancer, 131 patients with early endometrial cancer who had undergone pathological examination and preoperative MRI scan were retrospectively enrolled and divided into two groups based on the ki-67 expression levels. The radiomics features were extracted from the T2 weighted imaging (T2WI), dynamic contrast enhanced T1 weighted imaging (DCE-T1WI), and apparent diffusion coefficient (ADC) map and screened using the Pearson correlation coefficients (PCC). A multi-layer perceptual machine and fivefold cross-validation were used to construct the radiomics model. The receiver operating characteristic (ROC) curves analysis, calibration curves, and decision curve analysis (DCA) were used to assess the models. The combined multi-sequence radiomics model of T2WI, DCE-T1WI, and ADC map showed better discriminatory powers than those using only one sequence. The combined radiomics models with multi-sequence fusions achieved the highest area under the ROC curve (AUC). The AUC value of the validation set was 0.852, with an accuracy of 0.827, sensitivity of 0.844, specificity of 0.773, and precision of 0.799. In conclusion, the combined multi-sequence MRI based radiomics model enables preoperative noninvasive prediction of the ki-67 expression levels in early endometrial cancer. This provides an objective imaging basis for clinical diagnosis and treatment., (© 2023. The Author(s).)

Objective: To establish a machine learning-based radiomics model to differentiate between glioma and solitary brain metastasis from lung cancer and its subtypes, thereby achieving accurate preoperative classification., Materials and Methods: A retrospective analysis was conducted on MRI T1WI-enhanced images of 105 patients with glioma and 172 patients with solitary brain metastasis from lung cancer, which were confirmed pathologically. The patients were divided into the training group and validation group in an 8:2 ratio for image segmentation, extraction, and filtering; multiple layer perceptron (MLP), support vector machine (SVM), random forest (RF), and logistic regression (LR) were used for modeling; fivefold cross-validation was used to train the model; the validation group was used to evaluate and assess the predictive performance of the model, ROC curve was used to calculate the accuracy, sensitivity, and specificity of the model, and the area under curve (AUC) was used to assess the predictive performance of the model., Results: The accuracy and AUC of the MLP differentiation model for high-grade glioma and solitary brain metastasis in the validation group was 0.992, 1.000, respectively, while the sensitivity and specificity were 1.000, 0.968, respectively. The accuracy and AUC for the MLP and SVM differentiation model for high-grade glioma and small cell lung cancer brain metastasis in the validation group was 0.966, 1.000, respectively, while the sensitivity and specificity were 1.000, 0.929, respectively. The accuracy and AUC for the MLP differentiation model for high-grade glioma and non-small cell lung cancer brain metastasis in the validation group was 0.982, 0.999, respectively, while the sensitivity and specificity were 0.958, 1.000, respectively., Conclusion: The application of machine learning-based radiomics has a certain clinical value in differentiating glioma from solitary brain metastasis from lung cancer and its subtypes. In the HGG/SBM and HGG/NSCLC SBM validation groups, the MLP model had the best diagnostic performance, while in the HGG/SCLC SBM validation group, the MLP and SVM models had the best diagnostic performance., (© 2023. The Author(s).)

Aims: To build machine learning-based radiomics models to discriminate between high- (HGGs) and low-grade gliomas (LGGs) and to compare the effectiveness of three-dimensional arterial spin labelling (3D-ASL) to evaluate which is a better method., Materials and Methods: We retrospectively analysed the magnetic resonance imaging T1WI-enhanced images of 105 patients with gliomas that were pathologically confirmed in our hospital. We divided the patients into a training group and a verification group at a ratio of 8:2; 200 patients from the Brain Tumour Segmentation Challenge 2020 were selected as the test group for image segmentation, feature extraction and screening. We constructed models using multilayer perceptron (MLP), support vector machine, random forest and logistic regression and evaluated their predictive performance. We obtained the mean maximum relative cerebral blood flow (rCBFmax) value from 3D-ASL of 105 patients from the hospital to evaluate its efficacy in discriminating between HGGs and LGGs., Results: In machine learning, the MLP classifier model exhibited the best performance in discriminating between HGGs and LGGs; the areas under the curve obtained by MLP and rCBFmax were 0.968 versus 0.815 (verification group) and 0.981 versus 0.815 (test group), respectively. The machine learning-based MLP classifier model performed better in discriminating between HGGs and LGGs than 3D-ASL., Conclusion: In our study, we found that machine learning-based radiomics models and 3D-ASL were valuable in discriminating between HGGs and LGGs and between them, the machine learning-based MLP model had better diagnostic performance., (Copyright © 2023. Published by Elsevier Ltd.)

In recent years, immunotherapy represented by immune checkpoint inhibitors programmed death 1 (PD-1) has made great progress in the treatment of esophageal cancer and is rewriting the global paradigm for the treatment of esophageal cancer. According to current data, only a small number of patients with esophageal cancer could benefit from immunotherapy. Therefore, it is a challenge to screen the potential beneficiaries of PD-1 inhibitors. Studies have shown that the expression level of programmed death-ligand 1 (PD-L1) in esophageal cancer is closely associated with the efficacy of PD-1 inhibitors, and PD-L1 is the most important predictive biomarker of the efficacy of PD-1 inhibitors. With the clinical application of different PD-1 inhibitors and PD-L1 protein expression detection platforms, clarifying the clinical significance and timing of detection of PD-L1 protein expression in esophageal cancer, and establishing a standardized PD-L1 testing procedure, are of great significance to improve the accuracy of detection and reduce the difference between laboratories, so as to maximize the therapeutic benefits for patients. This consensus was finally reached, based on the combination of literature, expert experience, and internal discussion and voting of committee members, to provide an accurate and reliable evidence for clinicians to make decisions.

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history ( OR =3.090, 95% CI: 1.165-8.200; P <0.05), The AB type of intrapapillary capillary loop (IPCL) ( OR =11.215, 95% CI: 3.955-31.797; P <0.05) were the independent risk factors for the depth of invasion. The smoking history ( OR =5.824, 95% CI: 1.704-19.899; P <0.05), the presence of avascular area (AVA) ( OR =3.393, 95% CI: 1.285-12.072; P <0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Objective: To explore the feasibility and application value of intraoperative direct immunohistochemical (IHC) staining in improving the diagnosis accuracy in difficult cases of bronchiolar adenoma (BA). Methods: Nineteen cases with single or multiple pulmonary ground-glass nodules or solid nodules indicated by imaging in Cancer Hospital of Chinese Academy of Medical Sciences from January to July 2021 and with difficulty in differential diagnosis at frozen HE sections were selected. In the experimental group, direct IHC staining of cytokeratin 5/6 (CK5/6) and p63 was performed on frozen sections to assist the differentiation of BA from in situ/micro-invasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the control group, two pathologists performed routine frozen HE section diagnosis on these 19 cases. The diagnostic results of paraffin sections were used as the gold standard. The sensitivity and specificity of BA diagnosis, consistency with paraffin diagnosis and time used for frozen diagnosis were compared between the experimental group and the control group. Results: The basal cells of BA were highlighted by CK5/6 and p63 staining. There were no basal cells in the in situ/microinvasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the experimental group, the sensitivity and specificity with aid of direct IHC staining for BA were 100% and 86.7%, respectively, and the Kappa value of frozen and paraffin diagnosis was 0.732, and these were significantly higher than those in the control group ( P <0.05). The average time consumption in the experimental group (32.4 min) was only 7 min longer than that in the control group (25.4 min). Conclusions: Direct IHC staining can improve the accuracy of BA diagnosis intraoperatively and reduce the risk of misdiagnosis, but require significantly longer time. Thus frozen direct IHC staining should be restricted to cases with difficulty in differentiating benign from malignant diseases, especially when the surgical modalities differ based on the frozen diagnosis.

Non-specific cytotoxic cells (NCCs) are essential to the cytotoxic cell-mediated immune response in teleost. The fish non-specific cytotoxic cell receptor protein 1 (NCCRP1) plays an important role as a membrane protein in the recognition of target cells and the activation of NCC. However, the roles of fish NCCs during pathogen infection require comprehensive studies. In this study, the coding sequence of northern snakehead (Channa argus) nccrp1 (Canccrp1) was cloned. Canccrp1 contains an open reading frame of 690 bp, encoding a peptide of 229 amino acids with a conserved F-box-associated domain (FBA) and proline-rich motifs (PRMs). Transcriptional expression analysis revealed that the constitutive expression of Canccrp1 was higher in the immune-related organs, such as liver, kidneys, and spleen. Moreover, mRNA and protein expression of Canccrp1 gradually increased in the spleen at 1-6 days post infection (dpi) with Nocardia seriolae, in addition to reaching peak expression in both the kidneys and liver at 2 dpi. A polyclonal antibody prepared against recombinant CaNCCRP1 effectively labeled NCCs in peripheral blood and different tissues. Then, immunofluorescence (IF) staining showed that the number of NCCs was significantly increased and showed a scattered distribution in the early stages of N. seriolae infection (2 and 4 dpi) before the forming of granulomas. At the late stages of N. seriolae infection (6 dpi), more NCCs migrated to preexisting granulomas, showing significant coaccumulation with N. seriolae. All these results clearly indicate the expression changes of CaNCCRP1, and the number and localization changes of NCCs post-N. seriolae infection, implying potential roles for fish NCCs in the antimicrobial infection process in fish., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Superior mesenteric vein (SMV) thrombosis is a rare intestinal ischemic disease. The clinical manifestations of patients differ, and most experience gastrointestinal symptoms., Case Summary: A 45-year-old female patient presented with persistent abdominal pain and abnormal vaginal bleeding for 7 days. A physical examination revealed significant abdominal tenderness with positive rebound tenderness. A laboratory examination revealed a white blood cell count of 27 × 10 9 /l, hemoglobin level of 52 g/L, and D-dimer of 4.54 mg/l. Enhanced computed tomography revealed a thickening and swelling of the jejunum and ileum in the left upper quadrant and portal vein. Filling defects in the main lumen and branch lumen suggested the possibility of portal vein and superior mesenteric vein thrombosis. Symptoms improved after treatment with low-molecular-weight heparin and warfarin. One month later, the patient developed occasional dull pain in the left lower quadrant, with long strips of discharge. An electronic colonoscopy revealed avascular necrosis and tissue exfoliation of the intestinal mucosa. After the continuation of warfarin therapy, the abdominal pain resolved. Five months later, the patient experienced recurrent abdominal pain and vomiting. A physical examination revealed a blood pressure of 75/49 mm Hg. An incomplete ileus with the portal and superior mesenteric vein thrombosis was diagnosed, partial jejunectomy and gastrointestinal bypass anastomosis were performed, and warfarin was continued postoperatively., Conclusion: The intestinal mucosal shedding observed, in this case, was caused by SMV thrombosis, which enriched the clinical manifestations of the disease and provided a new basis for the clinical diagnosis of SMV thrombosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Lin, Zhang, Xue, Ye, Tang, Yang, Luo, Gao and Fang.)

Background: Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits unique histological characteristics within the immune-cell-rich microenvironment, but the role of tertiary lymphoid structure (TLS) in EBVaGC is not yet fully understood., Methods: We retrospectively identified EBVaGC from 8517 consecutive GC cases from the two top cancer centers in China. Furthermore, we evaluated the prognostic value of TLS in 148 EBVaGC patients from our institute and then validated it in an external cohort (76 patients). TLS was quantified and its relationships with overall survival (OS) and therapeutic response were further analyzed. Multiplex immunofluorescence staining and targeted sequencing were used to characterize the composition of TLS and the genomic landscape, respectively., Results: In our study, EBVaGC was observed in 4.3% (190/4436) and 2.6% (109/4081) of GCs in the training and validation cohorts, respectively. TLS was identified in the intratumor (94.6%) and peritumor (77.0%) tissues with lymphoid aggregates, primary and secondary (i.e., mature TLSs) follicles in EBVaGC. Kaplan-Meier analysis showed that mature TLS in intratumoral tissues was associated with a favorable OS in the training and validation cohorts (p < 0.0001; p = 0.0108). Multivariate analyses demonstrated that intratumoral TLS maturation, pTNM, and PD-L1 expression were independent prognostic factors for OS (p < 0.05). Furthermore, the mature TLS was significantly associated with a good response to treatment in EBVaGC patients. Interestingly, the mutation frequency of SMARCA4 was significantly lower in the mature TLS groups., Conclusions: Intratumoral mature TLS was associated with a favorable prognosis and good therapeutic response, suggesting that it is a potential prognostic biomarker and predicts a good therapeutic response in EBVaGC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yin, Ling, Wei, He, Wang, Hu, Lin, Nie, Chen, Lin, Zhou, Xie, Yun, Xie, Xue and Cai.)

Background: Currently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC., Methods: Of 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors., Results: After adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P<0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P<0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P<0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062)., Conclusion: For patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Wei, Li, Yang, Yu, Li, Xie, Yang, Jing, Wang, Kang, Zhang, Qin, Xue, Bi, Chen and Li.)

Background: The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil (5-FU) in advanced-stage gastric cancer is still unelucidated., Aim: To explore the long-term survival benefit of using sustained-release 5-FU implants in stage II and stage III gastric cancer patients., Methods: Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release (SR) chemotherapy with 5-FU was used or not (NSR). The primary end-point was 5-year overall survival. Kaplan-Meier method with log-rank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients., Results: In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219 (70.9%) were men, with an average age of 58.25 years. Furthermore, 56 (18.1%) received neoadjuvant chemotherapy, and 191 (61.8%) were in TNM stage III. In addition, 158 patients received intraoperative sustained-release chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate ( P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival., Conclusion: Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer., Competing Interests: Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Northern snakehead (Channa argus) is an indigenous fish species and is one of popularly cultured snakeheads in China and other Asian countries. Unfortunately, Nocardia seriolae infections have caused considerable losses in the snakehead aquaculture industry. However, the infectivity and the immune response induced by N. seriolae in snakehead are unclear. In order to better understand the immune response of Northern snakehead in a series of time points after N. seriolae challenge, we conducted the transcriptomic comparison in snakehead spleen at 48, 96, and 144 h after the challenge of N. seriola against their control counterparts. Gene annotation and pathway analysis of differentially expressed genes (DEGs) were carried out to understand the functions of the DEGs. Additionally, protein-protein interaction networks were conducted to obtain the interaction relationships of immune-related DEGs. These results revealed the expression changes of multiple DEGs and signaling pathways involved in immunity during N. seriolae infection, which will facilitate our comprehensive understanding of the mechanisms involved in the immune response to bacterial infection in the northern snakehead., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: We evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center randomized phase II trial., Methods: Patients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate., Results: We enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively., Conclusions: S-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT., Trial Registration: ClinicalTrial.gov NCT02301481., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhao, Yang, Chi, Zhao, Jiang, Jiang, Tang, Li, Liu, Dou, Zou, Xue, Ren, Tian, Che, Guo, Bai, Sun, Wang, Song, Liu, Fang, Li and Jin.)

Reactive force field (ReaxFF) is a powerful computational tool for exploring material properties. In this work, we proposed an enhanced reactive force field model, which uses message passing neural networks (MPNN) to compute the bond order and bond energies. MPNN are a variation of graph neural networks (GNN), which are derived from graph theory. In MPNN or GNN, molecular structures are treated as a graph and atoms and chemical bonds are represented by nodes and edges. The edge states correspond to the bond order in ReaxFF and are updated by message functions according to the message passing algorithms. The results are very encouraging; the investigation of the potential, such as the potential energy surface, reaction energies and equation of state, are greatly improved by this simple improvement. The new potential model, called reactive force field with message passing neural networks (ReaxFF-MPNN), is provided as an interface in an atomic simulation environment (ASE) with which the original ReaxFF and ReaxFF-MPNN potential models can do MD simulations and geometry optimizations within the ASE. Furthermore, machine learning, based on an active learning algorithm and gradient optimizer, is designed to train the model. We found that the active learning machine not only saves the manual work to collect the training data but is also much more effective than the general optimizer.

The aromatase inhibitor letrozole can be found in rivers, effluents, and even drinking water. Studies have demonstrated that letrozole affects various metabolic pathways and may cause reproductive toxicity, especially in fish exposed during development. However, studies on the effect of a low concentration of letrozole at the whole-gonad transcriptomic level in the early stage of fish sexual development have not been investigated. The aim of our study was to explore the potential effects of a low concentration of letrozole on the gonad transcriptome of Nile tilapia at an early stage of sexual development. In this study, 9 dpf (days postfertilization) Nile tilapia were exposed to trace letrozole for 12 days. Letrozole exposure from 9 dpf to 21 dpf persistently altered phenotypic sex development and induced the male-biased sex ratio. The transcriptome results showed that 1173 differentially expressed genes (DEGs) were present in the female control vs 1.5 μg/L letrozole-treated female comparison group and that 1576 DEGs were present in the 1.5 μg/L letrozole-treated female vs male control comparison group. Differentially expressed gene enrichment analysis revealed several crucial pathways, including the drug metabolism-cytochrome P450 pathway, the ErbB-PI3K/Akt/mTOR pathway, and the calcium signalling pathway. Further analysis of these identified DEGs indicated that some key genes correlated with metabolism and epigenetic regulation were significantly affected by letrozole, such as UDP-glucuronosyltransferase (Ugt), glutathione S-transferase omega-1 (Gsto1), lysine-specific demethylase 6bb (Kdm6bb, original name is Kdm6a), jumonji and AT-rich interaction domain containing 2 (Jarid2b, original name is Jarid2), growth arrest and DNA damage inducible gamma (Gadd45g), and chromobox protein 7 (Cbx7). The qRT-PCR validation results for twelve DEGs showed that the Pearson's correlation of the log 10 fold change values between the qPCR and RNA-Seq results was 0.90, indicating the accuracy and reliability of the RNA-Seq results. Our study is the first to report the effect of letrozole on the transcriptome of gonads from fish during early-stage sexual development. These findings will be useful for understanding the toxic effects and molecular mechanisms of letrozole exposure at the early stage of gonad development on the sexual development of aquatic organisms., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Endoscopic submucosal dissection (ESD) of undifferentiated early gastric cancer (UD-EGC) remains controversial due to high positive rate of horizontal and vertical resection margins and the risk of lymph node metastasis. The purpose of this study was to compare long-term outcomes of patients with UD-EGC undergoing ESD versus surgery. Methods: This study was a retrospective cohort study. Inclusion criteria: (1) patients with early gastric cancer undergoing ESD or surgical resection; (2) histological types included poorly differentiated adenocarcinoma, poorly differentiated adenocarcima with signet ring cell carcinoma, and signet ring cell carcinoma; (3) no lymph node metastasis or distant metastasis was confirmed by preoperative CT and endoscopic ultrasonography. Exclusion criteria: (1) previous surgical treatment for gastric cancer; (2) synchronous tumors; (3) death with unknown cause; (4) additional surgical treatment was performed within 1 month after ESD. According to the above criteria, clinical data of patients with UD-EGC who received ESD or surgery treatment in Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2016 were collected. After further comparing the clinical outcomes between the two groups by 1:1 propensity score matching, 61 patients in the ESD group and 61 patients in the surgery group were finally included in this study. The disease-free and overall survivals were analyzed by Kaplan-Meier method. Results: All patients in the two groups completed operations successfully. In the ESD group, the median operation time was 46.3 (26.5, 102.3) minutes, 61 cases (100%) were en-bloc resection, and 57 cases (93.4%) were complete resection. Positive margin was found in 4 (6.6%) patients, of whom 2 were positive in horizontal margin and 2 were positive both in horizontal and vertical margins. In the surgery group, only 1 case had positive horizontal margin and no positive vertical margin was observed. There was no significant difference in the positive rate of margin between the two groups ( P >0.05). Median follow-up time was 59.8 (3.0, 131.5) months. The follow-up rate of ESD group and surgery group was 82.0% (50/61) and 95.1% (58/61), respectively. The 5-year disease-free survival rate in ESD group and surgery group was 98.2% and 96.7%, respectively ( P =0.641), and the 5-year overall survival rate was 98.2% and 96.6%, respectively ( P =0.680). In the ESD group, 1 patient (1.6%) had lymph node recurrence, without local recurrence or distant metastasis. In the surgery group, 1 case (1.6%) had anastomotic recurrence and 1 (1.6%) had distant metastasis. Conclusion: ESD has a sinilar long-term efficacy to surgery in the treatment of UD-EGC.

Objective: To analyze the pathologic features of responses to neoadjuvant immunotherapy of squamous cell carcinoma (SCC) of the lung. Methods: The study included 31 patients with resected lung SCC post neoadjuvant immunotherapy. All patients were recruited from the neoadjuvant anti-PD-1 (Sintilimab) phase Ⅰb clinical trial (ChiCTR-OIC-17013726). The histopathological morphology and different degrees of pathologic response to immunotherapy were evaluated basing on irPRC standard. Results: According to the percentage of residual viable tumor (% RVT), pathologic responses of complete pathologic response (cPR), major pathologic response (MPR) and non-MPR were noted in 19% ( n =6), 29% ( n =9), and 52% ( n =16) of patients respectively. In addition, extensive immune activation phenomena (immune cell infiltration, including infiltration of lymphocytes, plasma cells, foamy macrophages, lymphocyte aggregation and tertiary lymphoid structures formation) and tissue repair features (giant cells, granuloma formation, proliferative fibrosis and neovascularization) were observed in tumor regression bed. Conclusions: Neoadjuvant immunotherapy has favorable effect on lung SCC. Pathologic assessment of resected lung cancer specimens after neoadjuvant immunotherapy shows unique histopathological features consistent with its mechanism.

Objective: To discuss the efficacy and safety of endoscopic papillectomy of major duodenal papilla neoplasms. Methods: The clinical-pathological data of 21 patients who were admitted to the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences and underwent endoscopic papillectomy of major duodenal papilla neoplasms from January 2014 to January 2020 were retrospectively studied, their postoperative outcomes and complication were also analyzed. Results: Tweenty-one patients were successfully performed endoscopic papillectomy of major duodenal papilla neoplasms. The resected lesions varied between 0.5-2.8 cm. Completed lesion was resected in 19 cases and lesion blocks in 2 cases. The incidence of postoperative complication was 52.4% (11/21), including 8 cases of postoperative bleeding (38.1%). Five patients stopped bleeding after endoscopic hemostasis and 3 patients stopped after interventional embolization. Two patients experienced perforation (9.5%) and recovered after conservative treatment including anti-inflammatory treatment and abdominal drainage. Five patients had pancreatitis (23.8%) and recovered after treatment with pre-somatostatin and anti-inflammatory rectal suppository. Preoperative pathological results of 21 patients suggested that 11 were high-grade intraepithelial neoplasia and 8 were low-grade intraepithelial neoplasia, and 2 were chronic inflammation. Postoperative pathological results suggested that 4 were adenocarcinoma, and the rest 17 were adenoma. The coincidence rate of preoperative biopsy results and postoperative pathology was 38.1%(8/21), and underestimate of the pathological stage occurred in 11 patients (52.4%) during the preoperative biopsy, overestimate occurred in two patients (9.5%). Four cases had a positive incisal margin. All patients had good prognoses and no death event occurred during the follow-up period. Conclusions: Early-stage major duodenal papilla neoplasms should be treated with aggressive resection. Endoscopic papillectomy of duodenal papilla neoplasms is safe, effective, and can be recommended as the preferred procedure for major duodenal papilla neoplasms.

Background: Positive peritoneal wash cytology with no peritoneal metastasis (CY1P0) is a special type of distant gastric cancer metastasis, which describes a patient with positive peritoneal lavage cytology, but no definitive peritoneal metastasis, and there are no widely accepted treatment guidelines. We enrolled 48 primary CY1P0 gastric cancer patients treated by radical gastrectomy in this study. Our study illustrated the efficacy of radical gastrectomy for CY1P0 gastric cancer patients, and suggested that the pathological N factor and vascular invasion were significant independent risk factors for overall survival (OS)., Aim: To assess the survival of CY1P0 gastric cancer patient post-radical gastrectomy, and to identify factors associated with long-term prognosis., Methods: Our study included 48 patients with primary CY1P0 gastric cancer who had radical gastrectomies at the Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China between 2013 and 2018. R0 resection was achieved in all 48 patients. Twelve patients received neoadjuvant chemotherapy. Thirty patients received adjuvant chemotherapy and four received adjuvant chemoradiotherapy. OS statistics were available for 48 patients. Follow-up continued through March 2020. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify prognostic factors., Results: Median OS was 22.0 mo (95% confidence interval: 13.366-30.634 mo) post-surgery. Univariate analyses demonstrated that tumor site ( P = 0.021), pathological N factor ( P = 0.001), pathological T factor ( P = 0.028), vascular invasion ( P = 0.046), and the level of CA199 prior to initiating therapy ( P = 0.002) were significant risk factors for OS. Multivariate analyses demonstrated that pathological N factor ( P = 0.001) and vascular invasion ( P = 0.031) were significant independent risk factors for OS., Conclusion: This study suggested that radical gastrectomy may be efficient for CY1P0 gastric cancer patient post-radical gastrectomy and the pathological N factor and vascular invasion are significant independent risk factors for OS., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate regional distribution and clinicopathological features of Epstein-Barr virus associated gastric cancer (EBVaGC). Methods: Epstein-Barr virus encoded RNA (EBER)was detected in 4 081 cases of gastric adenocarcinoma in Cancer Hospital, Chinese Academy of Medical Sciences by using in situ hybridization. EBVaGCs were identified and their proportions in different provinces, autonomous regions and municipalities were compared. The correlation between EBVaGC and clinicopathological features was also analyzed. Results: A total of 3.0% (123/4 081) patients with gastric adenocarcinoma are EBVaGCs. Among the areas with cases more than 90, the highest proportion of EBVaGC was found in Jilin province, accounting for 7.6%, and then followed by 5.4% in Liaoning province, 4.1% in Anhui province, 3.9% in Beijing, 3.7% in Inner Mongolia Autonomous Region, 3.4% in Shanxi province, 3.0% in Heilongjiang province, 2.1% in Shandong province, 1.6% in Hebei province, and no EBVaGC was found in Henan province. EBVaGC proportions are significantly different in these provinces, autonomous regions and municipalities ( P <0.05). Multivariate analysis of logistic regression revealed that gender ( OR =2.231, 95% CI: 1.290~3.858), WHO classification ( OR =2.338, 95% CI: 2.051~2.664) and N stage ( OR =0.420, 95% CI: 0.284~0.621) were independent impact factors for EBVaGC. The proportion of EBVaGC was higher in males, gastric carcinomas accompanied with lymphoid stroma and patients without lymph node metastasis. Conclusions: The proportion of EBVaGC in gastric adenocarcinoma displays area distribution disparity in China. The gender, WHO classification and N stage are closely associated with EBVaGC.

Objective: To investigate the value of two-dimensional shear wave elastography (2D SWE) combined with clinical biochemical data in predicting posthepatoectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). Methods: A total of 274 HCC patients who underwent hepatectomy in Zhongshan Hospital Fudan University from January 2015 to January 2016 were retrospectively collected, including 235 males and 39 females, age 19-80 (56±11) years. All patients were confirmed to be HCC by postoperative pathology. The preoperative 2D SWE examination, laboratory examination results and intraoperative indicators were analyzed. According to the occurrence of PHLF after surgery, single factor analysis and multiple logistic regression analysis were performed on the above indicators to obtain a binary logistic regression model, and evaluate the diagnostic effect of the model on PHLF. In addition, 103 HCC patients from October 2019 to January 2020 were retrospectively collected as an external validation set, including 89 males and 14 females, age 23-80 (55±11) years old. Results: The liver stiffness measurement (LSM) obtained from 2D SWE, INR and Laminin (LN) were independent predictors of PHLF. The formula of prediction model PM=-15.451+0.095×LSM+11.7×INR+0.012×LN was obtained by combining above three factors. The area under the curve (AUC) of PHLF was 0.82, which was higher than that of end-stage liver disease model (MELD) score and Child-Pugh grading diagnosis of PHLF. The AUC of PHLF predicted by PM in the external validation group was 0.81. Conclusion: 2D SWE is helpful for clinicians to evaluate liver reserve function preoperatively and to predict the occurrence of PHLF in patients with HCC.

Introduction: Henoch-Schönlein purpura (HSP) is an extremely rare condition in patients with pulmonary tuberculosis, with only a few reported cases. Compared to patients with typical clinical symptoms, it is difficult to make a definitive diagnosis when HSP presents as an initial manifestation in pulmonary tuberculosis patients. Herein, a case of pulmonary tuberculosis that showed HSP at first was reported, and the related literatures were reviewed., Patient Concerns: A 24-year-old man presented with palpable purpura on the extremities, accompanied by abdominal pain, bloody stools, and knee pain., Diagnoses: The patient was diagnosed with pulmonary tuberculosis based on the results of interferon gamma release assays, purified protein derivative test, and computed tomography., Interventions: The patient was treated with vitamin C and chlorpheniramine for 2 weeks, and the above-mentioned symptoms were relieved. However, 3 weeks later, the purpura recurred with high-grade fever and chest pain during the inspiratory phase. The patient was then treated with anti-tuberculosis drugs, and the purpura as well as the high fever disappeared., Outcomes: The patient recovered well and remained free of symptoms during the follow-up examination., Conclusion: Pulmonary tuberculosis presenting with HSP as an initial manifestation is not common. Therefore, it is difficult to clinically diagnose and treat this disease. When an adult patient shows HSP, it is important to consider the possibility of tuberculosis to avoid misdiagnosis and delayed treatment.

Objective: To analyze the long-term therapeutic effect of endoscopic submucosal dissection (ESD) on the treatment of early gastric cancer (EGC). Methods: We retrospectively reviewed EGC patients who underwent ESD at Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), from January 2009 to December 2016. The incidence rates of local recurrence, synchronous cancer and heterogeneous cancer were analyzed. Kaplan-Meier method was used to analyze 5-years recurrence free survival (RFS) and 5-years disease special survival (DSS) of all patients. Results: A total of 255 EGC patients were enrolled in this study, included 175 differentiated early gastric cancer (D-EGC) patients and 80 undifferentiated early gastric cancer (UD-EGC) patients. Among them, 171 patients within the extended indication of ESD while 84 patients beyond the extended indication of ESD. Among the 225 patients, the incidence rates of local recurrence, synchronous cancer and heterogeneous cancer were 2.0%, 2.0% and 2.4%, respectively. The local recurrence rates of D-EGC group and UD-EGC group was 1.7% and 2.5%, respectively, without significant difference ( χ (2)=0.176, P =0.675). The incidence rates of synchronous and heterogenous cancer in the D-EGC group were 2.3% and 3.4%, higher than 1.2% and 0 of UD-EGC group, although there was no significant difference ( χ (2)=0.306, P =0.580 vs χ (2)=2.809, P =0.094). There were no significant differences in 5-years RFS (91.3% vs 95.9%, P =0.236) and 5-years DSS (100% vs 98.6%, P =0.156) between D-EGC group and UD-EGC group. Conclusions: The long-term outcome of ESD in the treatment of EGS is good. More attention should be paid to the occurrence of local recurrence and heterogeneous cancer in EGC patients undergo ESD. These patients still have a good long-tern outcome even undergoing ESD for more than once.

Brain matrix metalloproteinases (MMPs) have been recently implicated in alcohol addiction; however, the molecular mechanisms remain poorly understood. Matrix metalloproteinase-9 (MMP-9), an extrasynaptic protease, is the best described MMP that is thought to regulate addictive behavior. In the present study, the effect of MMP-9 overexpression on hippocampal neuron plasticity and alcoholic behavior was assessed in spontaneous alcohol drinking mice. Two-bottle choice model showed that the overexpression of MMP-9 in the hippocampus developed by adeno-associated virus (AAV) could decrease alcohol consumption and preference, but did not affect taste preference, which was tested using saccharin or quinine solutions. Dendritic spines number of hippocampal neurons was observed by Golgi staining. Compared with the alcohol treatment group, the density of dendritic spines in the hippocampus of alcohol drinking mice was decreased in alcohol + MMP-9 group. Western blot analysis indicated that GluN1 expression in the hippocampus of alcohol drinking group was lower than that in the control group, while the expression of GluN1 was increased in MMP-9 overexpressing mice. MMP-9 also regulated the depolymerization of actin filaments, which induced behavioral changes in mice. Taken together, overexpression of MMP-9 in the hippocampal neurons of mice resulted in decreased dendritic spine density and F-actin/G-actin ratio, which might be the crucial reason for the significant decrease in alcohol consumption in alcohol drinking mice. MMP-9 might be considered as a novel target studying the molecular mechanism of alcohol drinking.

Objective: To evaluate the association of p53 protein expression with clinicopathological features and prognosis in esophageal spindle cell carcinoma. Methods: A total of 4 439 esophageal squamous cell carcinoma (ESCC) patients who underwent radical esophagectomy without neoadjuvant therapy between May 2010 and May 2019 were included. The HE slides and clinicopathological parameters were reviewed. Among these, there were 63 cases of esophageal spindle cell carcinoma; p53 protein expression was evaluated by immunohistochemistry (IHC) and its correlation with clinicopathological parameters and patients' outcome was analyzed. Results: The 63 esophageal spindle cell carcinoma accounted for 1.4% (63/4 439) of all ESCC. Of the 63 patients there were 55 males and 8 females, male to female ratio was 7∶1. The p53 protein mutation expression rate was 77.8% (49/63), including 14 cases with wild-type expression, 22 with nonsense mutation expression, and 27 with missense mutation expression. The concordance rate of p53 protein expression between carcinoma components and spindle cell components was 100%. Survival analysis showed that p53 protein mutation expression was significantly correlated with overall survival (OS, P= 0.044), patients with p53 protein mutation expression had poorer OS. Conclusion: p53 protein expression is highly concordant in the squamous cell carcinoma components and spindle cell components of esophageal spindle cell carcinoma; its mutation expression is associated with poor outcome of the patients.

Introduction: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines., Methods: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models., Results: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women., Discussion: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.

Objective: To assess the diagnostic accuracy of liver and spleen stiffness measured by two dimensional shear wave elastography (2D-SWE) in hepatitis B-related cirrhosis. Methods: The clinical data of fifty-eight hepatitis B-related cirrhosis patients were collected in Zhongshan Hospital, Fudan University from September 2017 to April 2018. Pearson's correlation analyses were used to assess the relationship between liver/spleen stiffness (L-SWE and S-SWE) and hepatic venous pressure gradient (HVPG), as well as the comparison with serological model. The SWE diagnostic performances of Liver (L-SWE), Spleen (S-SWE) were also evaluated. Results: Of all 58 patients, 47 were found HVPG ≥10 mmHg, diagnosed as clinically significant portal hypertension (CSPH) and severe portal hypertension (SPH), which patients are at increased risk of developing complications. Thirty-four patients were found HVPG≥12 mmHg, diagnosed as SPH, which patients were at increased risk of variceal bleeding. Moderate positive correlation was found between L-SWE and HVPG ( r= 0.42, P< 0.01), and S-SWE were significantly correlated with HVPG ( r= 0.68, P< 0.01), while serological models and HVPG were slightly correlated ( r= 0.36 and 0.28, all P< 0.01). The area under the receiver operating characteristic curves of L-SWE, S-SWE and the combination for CSPH were 0.78, 0.88 and 0.89. When L-SWE was>12.86 kPa or S-SWE was>35.73 kPa, patients were at increased risk of developing complications. The area under the receiver operating characteristic curves for SPH were 0.68, 0.81 and 0.77 and the S-SWE had the highest specificity, so when S-SWE was>41.5 kPa, patients were at increased risk of variceal bleeding. Conclusion: L-SWE and S-SWE are reliable and promising non-invasive parameters to assess CSPH and SPH.

Ventilator-associated pneumonia (VAP) is a major complication among critically ill patients who depend on mechanical ventilation. Few reports have focused on intracerebral hemorrhage patients with VAP. Our main objective was to investigate the bacteria distribution characteristics and the impact of ventilator-associated pneumonia mortality in critical cerebral hemorrhage patients. This retrospective study included 89 cases of cerebral hemorrhage patients with VAP admitted to the ICU of Huashan Hospital. We used the chi-square test to compare qualitative variables and Student's t-test to compare means between groups of normally distributed quantitative variables. Multiple logistic regression analysis was used to assess mortality-independent predictors in the ICU. A total of 42% patients with cerebral hemorrhage were diagnosed with VAP in the ICU during the study period, and the mortality rate was 18%. Acinetobacter baumannii (n=58), Klebsiella pneumoniae (n=52), and Pseudomonas aeruginosa (n=21) were the most common pathogenic bacteria. Blood volume >30ml, tracheal ventilation mode and head of bed elevation were independent factors associated with increased mortality. Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the time from bleeding to intubation were other potentially important factors. While the number of infecting bacteria may not be directly related to death, it can increase antibiotic consumption and length of intensive care unit (ICU) stays. Blood volume >30ml, tracheal ventilation mode and head of bed elevation were directly related to the death of critical cerebral hemorrhage patients with ventilator-associated pneumonia., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)

Objectives: To propose a transfer learning (TL) radiomics model that efficiently combines the information from gray scale and elastogram ultrasound images for accurate liver fibrosis grading., Methods: Totally 466 patients undergoing partial hepatectomy were enrolled, including 401 with chronic hepatitis B and 65 without fibrosis pathologically. All patients received elastography and got liver stiffness measurement (LSM) 2-3 days before surgery. We proposed a deep convolutional neural network by TL to analyze images of gray scale modality (GM) and elastogram modality (EM). The TL process was used for liver fibrosis classification by Inception-V3 network which pretrained on ImageNet. The diagnostic performance of TL and non-TL was compared. The value of single modalities, including GM and EM alone, and multimodalities, including GM + LSM and GM + EM, was evaluated and compared with that of LSM and serological indexes. Receiver operating characteristic curve analysis was performed to calculate the optimal area under the curve (AUC) for classifying fibrosis of S4, ≥ S3, and ≥ S2., Results: TL in GM and EM demonstrated higher diagnostic accuracy than non-TL, with significantly higher AUCs (all p < .01). Single-modal GM and EM both performed better than LSM and serum indexes (all p < .001). Multimodal GM + EM was the most accurate prediction model (AUCs are 0.950, 0.932, and 0.930 for classifying S4, ≥ S3, and ≥ S2, respectively) compared with GM + LSM, GM and EM alone, LSM, and biomarkers (all p < .05)., Conclusions: Liver fibrosis can be staged by a transfer learning modal based on the combination of gray scale and elastogram ultrasound images, with excellent performance., Key Points: • Transfer learning consists in applying to a specific deep learning algorithm that pretrained on another relevant problem, expected to reduce the risk of overfitting due to insufficient medical images. • Liver fibrosis can be staged by transfer learning radiomics with excellent performance. • The most accurate prediction model of transfer learning by Inception-V3 network is the combination of gray scale and elastogram ultrasound images.

Background: The benefit of neoadjuvant chemotherapy for patients with signet-ring cell carcinoma of the stomach is controversial., Aim: To evaluate the perioperative and long-term outcomes of neoadjuvant chemotherapy for locally advanced gastric signet-ring cell carcinoma., Methods: This retrospective study identified patients with locally advanced signet-ring cell carcinomas of the stomach (cT3/4 and cN any) diagnosed from January 2012 to December 2017 by using the clinical Tumor-Node-Metastasis (cTNM) staging system. We performed 1:1 propensity score matching (PSM) to reduce bias in patient selection. The histologic and prognostic effects of neoadjuvant chemotherapy were assessed. The overall survival rates were used as the outcome measure to compare the efficacy of neoadjuvant chemotherapy vs surgery-first treatment in the selected patients., Results: Of the 144 patients eligible for this study, 36 received neoadjuvant chemotherapy, and 108 received initial surgery after diagnosis. After adjustment by PSM, 36 pairs of patients were generated, and baseline characteristics, including age, sex, American Society of Anesthesiologists score, tumor location, and cTNM stage, were similar between the two groups. The R0 resection rates were 88.9% and 86.1% in the surgery-first and neoadjuvant chemotherapy groups after PSM, respectively ( P = 1.000). The median follow-up period was 46.4 mo. The 5-year overall survival rates of the neoadjuvant chemotherapy group and surgery-first group were 50.0% and 65.0% ( P = 0.235), respectively, before PSM and 50% and 64.7% ( P = 0.192), respectively, after PSM. Multivariate analyses conducted before and after PSM showed that NAC was not a prognostic factor., Conclusion: Neoadjuvant chemotherapy provides no survival benefit in patients with locally advanced gastric signet-ring cell carcinoma. For resectable gastric signet-ring cell carcinoma, upfront surgery should be the primary therapy., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)