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Objective: To investigate the value of the pre-operative amide proton transfer-weighted (APTw) MRI to assess the prognostic factors in rectal adenocarcinoma (RA)., Methods: This prospective study ran from January 2022 to September 2023 and consecutively enrolled participants with RA who underwent pre-operative MRI and radical surgery. The APTw signal intensity (SI) values of RA with various tumor (T), node (N) stages, perineural invasion (PNI), and tumor grade were compared by Mann-Whitney U-test or t-test. The receiver operating characteristic curve was used to evaluate the diagnostic performance of the APTw SI values., Results: A total of 51 participants were enrolled (mean age, 58 years ± 10 [standard deviation], 26 men). There were 24 in the T1-T2 stage and 9 with positive PNI. The APTw SI max, 99th, and 95th values were significantly higher in T3-T4 stage tumor than in T1-T2; the median (interquartile range) (M (IQR)) was (4.0% (3.6-4.9%) vs 3.4% (2.9- 4.3%), p = 0.017), (3.7% (3.2-4.1%) vs 3.2% (2.8-3.8%), p = 0.013), and (3.3% (2.8-3.8%) vs 2.9% (2.3-3.5%), p = 0.033), respectively. These indicators also differed significantly between the PNI groups, with the M (IQR) (4.5% (3.6-5.7%) vs 3.7% (3.2-4.2%), p = 0.017), (4.1% (3.4-4.8%) vs 3.3% (3.0-3.9%), p = 0.022), and (3.7% (2.7-4.2%) vs 2.9% (2.6-3.5%), p = 0.045), respectively., Conclusion: Pre-operative APTw MRI has potential value in the assessment of T-staging and PNI determination in RA., Clinical Relevance Statement: Pre-operative amide proton transfer-weighted MRI provides a quantitative method for noninvasive assessment of T-staging and PNI in RA aiding in precision treatment planning., Key Points: The efficacy of APTw MRI in RA needs further investigation. T3-T4 stage and PNI positive APTw signal intensities were higher than T1-T2 and non-PNI, respectively. APTw MRI provides a quantitative method for assessment of T staging and PNI in RA., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

The remediation of heavy metal-contaminated soils necessitated a holistic approach that encompassed water and fertilizer conservation alongside soil property restoration. This study introduced the synthesis of (poly)acrylamide-layered double hydroxide gel spheres (PAM-LDH beads), which were designed to simultaneously immobilize heavy metals, control the release of fertilizers, and enhance soil water retention. Laboratory soil experiments under diverse conditions highlighted the superior performance of PAM-LDH beads in the immobilization of hexavalent chromium (Cr(VI)). The layered double hydroxide (LDH) component was identified as the key player in Cr(VI) immobilization, with anion exchange being the predominant mechanism. Notably, the encapsulated urea within the beads was released independently of environmental influences, governed by a concentration gradient across the beads surface. This release process was characterized by an initial phase of absorptive swelling followed by a diffusive phase. The impact on plant growth was assessed, revealing that PAM-LDH beads significantly curtailed Cr(VI) accumulation and alleviated its phytotoxic effects. Changes in the carbon (C) and nitrogen (N) content of the plants suggested that the urea encapsulated within the beads served as a nutrient source, contributing to soil fertility. Moreover, the water-holding capacity and soil-water characteristic curves of PAM-LDH beads suggested that these superabsorbent beads could delay soil water evaporation. The observed shifts in microbial community structure provided evidence for the enhancement of soil carbon and nitrogen cycles, indicative of improved soil properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Automated breast tumor segmentation on the basis of dynamic contrast-enhancement magnetic resonance imaging (DCE-MRI) has shown great promise in clinical practice, particularly for identifying the presence of breast disease. However, accurate segmentation of breast tumor is a challenging task, often necessitating the development of complex networks. To strike an optimal tradeoff between computational costs and segmentation performance, we propose a hybrid network via the combination of convolution neural network (CNN) and transformer layers. Specifically, the hybrid network consists of a encoder-decoder architecture by stacking convolution and deconvolution layers. Effective 3D transformer layers are then implemented after the encoder subnetworks, to capture global dependencies between the bottleneck features. To improve the efficiency of hybrid network, two parallel encoder sub-networks are designed for the decoder and the transformer layers, respectively. To further enhance the discriminative capability of hybrid network, a prototype learning guided prediction module is proposed, where the category-specified prototypical features are calculated through online clustering. All learned prototypical features are finally combined with the features from decoder for tumor mask prediction. The experimental results on private and public DCE-MRI datasets demonstrate that the proposed hybrid network achieves superior performance than the state-of-the-art (SOTA) methods, while maintaining balance between segmentation accuracy and computation cost. Moreover, we demonstrate that automatically generated tumor masks can be effectively applied to identify HER2-positive subtype from HER2-negative subtype with the similar accuracy to the analysis based on manual tumor segmentation. The source code is available at https://github.com/ZhouL-lab/ PLHN.

Purpose: The interval between neoadjuvant chemotherapy (NAC) and surgery for locally advanced breast cancer (LABC) remains controversial. At the same time, the prognostic effect of delayed surgery in patients with poor responses is currently unclear., Methods: Data was collected from patients who had poor responses to NAC and underwent modified radical surgery from January 2013 to December 2018. The interval from completion of NAC to surgery was divided into two groups: a longer (greater than four weeks) or shorter (four weeks or less) interval. The associations of these interval groups with overall survival (OS) and recurrence-free survival (RFS) were evaluated by multivariable Cox models adjusting for the existing prognostic factors. Propensity score matching (PSM) was used to minimize election bias., Results: A total of 1,229 patients (mean age, 47.2 ± 8.9 years; median follow-up duration, 32.67 [6.57-52.63] months) were included. The 5-year OS rates were 73.2% and 60.8% in the shorter (n = 171) and longer interval group (n = 1,058), respectively, while the 3-year RFS rates were 80.8% and 71.7%, respectively. In multivariate Cox analysis, the longer interval was associated with an increased risk of mortality (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.01-2.02; p = 0.046) and recurrence (HR, 1.50; 95% CI, 1.12-1.99; p = 0.006). There was an interaction between the molecular subtype and the surgery interval for OS ( p interaction = 0.014) and RFS ( p interaction = 0.027). After PSM, no significant difference in OS ( p = 0.180) and RFS ( p = 0.069) was observed between the two groups., Conclusion: Among LABC patients with a poor response, those with a longer interval between NAC and surgery had worse OS and RFS. The results indicate that these patients should receive modified radical surgery timely, which may in turn improve their prognosis., Competing Interests: The authors declare that they have no competing interests., (© 2024 Korean Breast Cancer Society.)

Background: Neoadjuvant chemotherapy has variable efficacy in patients with non-small-cell lung cancer (NSCLC), yet reliable noninvasive predictive markers are lacking. This study aimed to develop a radiomics model predicting pathological complete response and postneoadjuvant chemotherapy survival in NSCLC., Materials and Methods: Retrospective data collection involved 130 patients with NSCLC who underwent neoadjuvant chemotherapy and surgery. Patients were randomly divided into training and independent testing sets. Nine radiomics features from prechemotherapy computed tomography (CT) images were extracted from intratumoral and peritumoral regions. An auto-encoder model was constructed, and its performance was evaluated. X-tile software classified patients into high and low-risk groups based on their predicted probabilities. survival of patients in different risk groups and the role of postoperative adjuvant chemotherapy were examined., Results: The model demonstrated area under the receiver operating characteristic (ROC) curve of 0.874 (training set) and 0.876 (testing set). The larger the area under curve (AUC), the better the model performance. Calibration curve and decision curve analysis indicated excellent model calibration (Hosmer-Lemeshow test, P = .763, the higher the P-value, the better the model fit) and potential clinical applicability. Survival analysis revealed significant differences in overall survival (P = .011) and disease-free survival (P = .017) between different risk groups. Adjuvant chemotherapy significantly improved survival in the low-risk group (P = .041) but not high-risk group (P = 0.56)., Conclusion: This study represents the first successful prediction of pathological complete response achievement after neoadjuvant chemotherapy for NSCLC, as well as the patients' survival, utilizing intratumoral and peritumoral radiomics features., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To investigate the survival benefit of preoperative bone scan in asymptomatic patients with early-stage non-small cell lung cancer (NSCLC)., Methods: This retrospective study included patients with radical resection for stage T1N0M0 NSCLC between March 2013 and December 2018. During postoperative follow-up, we monitored patient survival and the development of bone metastasis. We compared overall survival, bone metastasis-free survival, and recurrence-free survival in patients with or without preoperative bone scan. Propensity score matching and inverse probability of treatment weighting were used to minimize election bias., Results: A total of 868 patients (58.19 ± 9.69 years; 415 men) were included in the study. Of 87.7% (761 of 868) underwent preoperative bone scan. In the multivariable analyses, bone scan did not improve overall survival (hazard ratio [HR] 1.49; 95% confidence intervals [CI] 0.91-2.42; p = 0.113), bone metastasis-free survival (HR 1.18; 95% CI 0.73-1.90; p = 0.551), and recurrence-free survival (HR 0.89; 95% CI 0.58-1.39; p = 0.618). Similar results were obtained after propensity score matching (overall survival [HR 1.28; 95% CI 0.74-2.23; p = 0.379], bone metastasis-free survival [HR 1.00; 95% CI 0.58-1.72; p = 0.997], and recurrence-free survival [HR 0.76; 95% CI 0.46-1.24; p = 0.270]) and inverse probability of treatment weighting., Conclusion: There were no significant differences in overall survival, bone metastasis-free survival, and recurrence-free survival between asymptomatic patients with clinical stage IA NSCLC with or without preoperative bone scan., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

This study aimed to investigate the association between hepatic VNN1 expression and carcass traits in Mahuang chickens as well as to identify polymorphisms in the upstream and downstream regions of VNN1 that could potentially be associated with these carcass traits. The study revealed that VNN1 expression levels in liver correlated with various carcass traits such as dressed weight, eviscerated weight, and abdominal fat weight. A total of 39 polymorphic sites were identified, among which 23 were found to be associated with 15 different carcass traits. These polymorphic sites were organized into three distinct haplotype blocks, with BLOCK2 and BLOCK3 being associated with various eviscerated weight percentages, thigh weight, breast muscle weight, wing weight, and other traits. The study underscores the significant role of VNN1 in influencing the carcass traits of Mahuang chickens and sheds light on the genetic foundations of these traits. The findings provide valuable insights that could inform breeding strategies aimed at optimizing traits relevant to market demands and slaughtering efficiency.

Background: Previous studies have demonstrated the role of N6-methyladenosine (m 6 A) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry., Results: The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential m 6 A modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis., Conclusions: In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis., (© 2024. The Author(s).)

Dunaliella salina is by far the most salt-tolerant organism and contains many active substances, including β-carotene, glycerol, proteins, and vitamins, using in the production of dried biomass or cell extracts for the biofuels, pharmaceutical formulations, food additives, and fine chemicals, especially β-carotene. We report a high-quality genome sequence of D. Salina FACHB435, which has a 472 Mb genome size, with a contig N50 of 458 Kb. A total of 30,752 protein-coding genes were predicted. The annotation results evaluated by BUSCO was shown that completeness was 91.0% and replication was 53.1%. The fragments were 6.3% and the deletions were 2.6%. Phylogenomic and comparative genomic analyses revealed that A. thaliana diverged from Volvocales about 448 million years ago, then Volvocales C. eustigma , D. salina , and other species diverged about 250 million years ago. High light could promote the accumulation of β-carotene in D. salina at a 13 d stage of culture. The enrichment of DEGs in KEGG, it notes that the predicted up-regulated genes of carotenoid metabolic pathway include DsCrtB, DsPDS, DsZ-ISO, DsZDS, DsCRTISO, DsLUT5, DsCrtL-B , and DsCCD8 , while the predicted down-regulated genes include DsCrtF , and DsLUT1 . The four genes that were both up-regulated and down-regulated were DsZEP, DsCrtR-b, DsCruA/P and DsCrtZ 4 . The research results can provide scientific basis for the industrialization practice of D. salina ., 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 © 2024 Chen, Li, Shi, Suen, Zheng, Zhang, Chen and Xue.)

Background and Objective: Spatial interaction between tumor-infiltrating lymphocytes (TILs) and tumor cells is valuable in predicting the effectiveness of immune response and prognosis amongst patients with lung adenocarcinoma (LUAD). Recent evidence suggests that the spatial distance between tumor cells and lymphocytes also influences the immune responses, but the distance analysis based on Hematoxylin and Eosin (H&E) -stained whole-slide images (WSIs) remains insufficient. To address this issue, we aim to explore the relationship between distance and prognosis prediction of patients with LUAD in this study., Methods: We recruited patients with resectable LUAD from three independent cohorts in this multi-center study. We proposed a simple but effective deep learning-driven workflow to automatically segment different cell types in the tumor region using the HoVer-Net model, and quantified the spatial distance (DIST) between tumor cells and lymphocytes based on H&E-stained WSIs. The association of DIST with disease-free survival (DFS) was explored in the discovery set (D1, n = 276) and the two validation sets (V1, n = 139; V2, n = 115)., Results: In multivariable analysis, the low DIST group was associated with significantly better DFS in the discovery set (D1, HR, 0.61; 95 % CI, 0.40-0.94; p = 0.027) and the two validation sets (V1, HR, 0.54; 95 % CI, 0.32-0.91; p = 0.022; V2, HR, 0.44; 95 % CI, 0.24-0.81; p = 0.009). By integrating the DIST with clinicopathological factors, the integrated model (full model) had better discrimination for DFS in the discovery set (C-index, D1, 0.745 vs. 0.723) and the two validation sets (V1, 0.621 vs. 0.596; V2, 0.671 vs. 0.650). Furthermore, the computerized DIST was associated with immune phenotypes such as immune-desert and inflamed phenotypes., Conclusions: The integration of DIST with clinicopathological factors could improve the stratification performance of patients with resectable LUAD, was beneficial for the prognosis prediction of LUAD patients, and was also expected to assist physicians in individualized treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Breast cancer is becoming a significant global health challenge, with millions of fatalities annually. Magnetic Resonance Imaging (MRI) can provide various sequences for characterizing tumor morphology and internal patterns, and becomes an effective tool for detection and diagnosis of breast tumors. However, previous deep-learning based tumor segmentation methods from multi-parametric MRI still have limitations in exploring inter-modality information and focusing task-informative modality/modalities. To address these shortcomings, we propose a Modality-Specific Information Disentanglement (MoSID) framework to extract both inter- and intra-modality attention maps as prior knowledge for guiding tumor segmentation. Specifically, by disentangling modality-specific information, the MoSID framework provides complementary clues for the segmentation task, by generating modality-specific attention maps to guide modality selection and inter-modality evaluation. Our experiments on two 3D breast datasets and one 2D prostate dataset demonstrate that the MoSID framework outperforms other state-of-the-art multi-modality segmentation methods, even in the cases of missing modalities. Based on the segmented lesions, we further train a classifier to predict the patients' response to radiotherapy. The prediction accuracy is comparable to the case of using manually-segmented tumors for treatment outcome prediction, indicating the robustness and effectiveness of the proposed segmentation method. The code is available at https://github.com/Qianqian-Chen/MoSID.

Background: Liver metastasis (LIM) is an important factor in the diagnosis, treatment, follow-up, and prognosis of patients with gastric gastrointestinal stromal tumor (GIST). There is no simple tool to assess the risk of LIM in patients with gastric GIST. Our aim was to develop and validate a nomogram to identify patients with gastric GIST at high risk of LIM., Methods: Patient data diagnosed as having gastric GIST between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training cohort and internal validation cohort in a 7:3 ratio. For external validation, retrospective data collection was performed on patients diagnosed as having gastric GIST at Yunnan Cancer Center (YNCC) between January 2015 and May 2023. Univariate and multivariate logistic regression analyses were used to identify independent risk factors associated with LIM in patients with gastric GIST. An individualized LIM nomogram specific for gastric GIST was formulated based on the multivariate logistic model; its discriminative performance, calibration, and clinical utility were evaluated., Results: In the SEER database, a cohort of 2341 patients with gastric GIST was analyzed, of which 173 cases (7.39%) were found to have LIM; 239 patients with gastric GIST from the YNCC database were included, of which 25 (10.46%) had LIM. Multivariate analysis showed tumor size, tumor site, and sex were independent risk factors for LIM (P < .05). The nomogram based on the basic clinical characteristics of tumor size, tumor site, sex, and age demonstrated significant discrimination, with an area under the curve of 0.753 (95% CI, 0.692-0.814) and 0.836 (95% CI, 0.743-0.930) in the internal and external validation cohort, respectively. The Hosmer-Lemeshow test showed that the nomogram was well calibrated, whereas the decision curve analysis and the clinical impact plot demonstrated its clinical utility., Conclusion: Tumor size, tumor subsite, and sex were significantly correlated with the risk of LIM in gastric GIST. The nomogram for patients with GIST can effectively predict the individualized risk of LIM and contribute to the planning and decision making related to metastasis management in clinical practice., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies of non-small cell lung cancer (NSCLC) focused on CEA measured at a single time point, ignoring serial CEA measurements., Methods: This retrospective cohort included 2959 patients underwent surgery for stage I-III NSCLC. CEA trajectory patterns and long-term cumulative CEA burden were evaluated using the latent class growth mixture model., Results: Four CEA trajectory groups were identified, named as low-stable, decreasing, early-rising and later-rising. Compared with the low-stable group, the adjusted hazard ratios associated with death were 1.27, 4.50, and 3.68 for the other groups. Cumulative CEA burden were positively associated with the risk of death in patients not belonging to the low-stable group. The 5-year overall survival (OS) rates decreased from 62.3% to 33.0% for the first and fourth quantile groups of cumulative CEA burden. Jointly, patients with decreasing CEA trajectory could be further divided into the decreasing & low and decreasing & high group, with 5-year OS rates to be 77.9% and 47.1%. Patients with rising CEA trajectory and high cumulative CEA were found to be more likely to develop bone metastasis., Conclusions: Longitudinal trajectory patterns and long-term cumulative burden of CEA were independent prognostic factors of NSCLC. We recommend CEA in postoperative surveillance of NSCLC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objective: Image segmentation of histopathology of colorectal cancer is a core task of computer aided medical image diagnosis system. Existing convolutional neural networks generally extract multi-scale information in linear flow structures by inserting multi-branch modules, which is difficult to extract heterogeneous semantic information under multi-level and different receptive field and tough to establish context dependency among different receptive field features., Methods: To address these issues, we propose a symmetric spiral progressive feature fusion encoder-decoder network called the Symmetric Conical Network (SC-Net). First, we design a Multi-scale Feature Extraction Block (MFEB) matching with the Symmetric Conical Network to obtain multi-branch heterogeneous semantic information under different receptive fields, so as to enrich the diversity of extracted feature information. The encoder is composed of MFEB through spiral and multi-branch arrangement to enhance context dependence between different information flow. Secondly, the information loss of contour, color and others in high-level semantic information through causally stacking MFEB, the Feature Mapping Layer (FML) is designed to map low-level features to high-level semantic features along the down-sampling branch and solve the problem of insufficient global feature extraction in deep levels., Results: The SC-Net was evaluated on our self-constructed colorectal cancer dataset, a publicly available breast cancer dataset and a polyp dataset. The results revealed that the mDice of segmentation reached 0.8611, 0.7259 and 0.7144. We compare our model with the state-of-art semantic segmentation UNet++, PSPNet, Attention U-Net, R2U-Net and other advanced segmentation networks. The experimental results demonstrate that we achieve the most advanced performance., Conclusions: The results indicate that the proposed SC-Net excels in segmenting H&E stained pathology images, effectively preserving morphological features and spatial information even in scenarios with weak texture, poor contrast, and variations in appearance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated., Methods: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out., Results: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells., Conclusions: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multiphoton microscopy (MPM) enables deep brain imaging. Three optical windows: NIR-I, NIR-II, and NIR-III are widely used. Recently, NIR-IV (the 2200 nm window) has been demonstrated to be the last and longest window for deep tissue MPM. However, so far MPM covers only two optical windows labeled by single fluorescent probe, one for emission and one for excitation. Here we demonstrate in vivo deep brain MPM covering three optical windows, with emission at NIR-I, NIR-II, and excitation at NIR-IV, labeled by ICG. The innovations include: (1) characterizing both 3-photon excitation and emission properties of ICG emitting at both NIR-I and NIR-II, in water, plasma, and circulating blood; (2) a home-built multiphoton microscope with simultaneous dual channel detection, with which we demonstrate deep brain MPM 950 μm (NIR-I) and 850 μm (NIR-II) into the mouse brain in vivo, verifying that multi-optical window MPM is promising for deep brain imaging., (© 2024 Wiley‐VCH GmbH.)

Understanding user behavior via IP addresses is a crucial measure towards numerous pragmatic IP-based applications, including online content delivery, fraud prevention, marketing intelligence, and others. While profiling IP addresses through methods like IP geolocation and anomaly detection has been thoroughly studied, the function of an IP address-e.g., whether it pertains to a private enterprise network or a home broadband-remains underexplored. In this work, we initiate the first attempt to address the IP usage scenario classification problem. We collect data consisting of IP addresses from four large-scale regions. A novel continuous neural tree-based ensemble model is proposed to learn IP assignment rules and complex feature interactions. We conduct extensive experiments to evaluate our model in terms of classification accuracy and generalizability. Our results demonstrate that the proposed model is capable of efficiently uncovering significant higher-order feature interactions that enhance IP usage scenario classification, while also possessing the ability to generalize from the source region to the target one., (© 2024. The Author(s).)

Background: Adjuvant chemotherapy is considered for stage II colorectal cancer (CRC) patients with poor prognostic risk factors. However, current stratification algorithms are still insufficient to identify high-risk patients., Methods: We conducted a screening strategy to define ZNF326 based on quantitative proteomics in 11 paired CRC patients selected by a nested case-control design, and tested the association between ZNF326 expression level with the prognosis of stage II CRC patients and the benefit from adjuvant chemotherapy in public datasets; further investigation was conducted through subgroup analyses., Results: We found that low ZNF326 expression was significantly associated with a lower 5-year overall survival (OS) rate among stage II patients in both the discovery [P=0.008; hazard ratio (HR): 3.13, 95% confidence interval (CI): 1.29-7.58] and validation (P=0.025; HR: 1.98, 95% CI: 1.08-3.65) cohorts. In the Cox multivariable analysis, low ZNF326 expression was both associated with shorter OS after adjustment for age, sex, and adjuvant chemotherapy in the discovery and validation data sets. Subgroup analyses yielded largely similar results. In a pooled database, the rate of 5-year OS was higher among stage II ZNF326 -high tumors who were treated with adjuvant chemotherapy than it was among those who were not treated with adjuvant chemotherapy (P=0.011; HR: 0.28, 95% CI: 0.10-0.80)., Conclusions: ZNF326 has the potential to be used in clinical practice for risk classification. ZNF326 -low expression level identified a subgroup of patients with high-risk stage II CRC who appeared to less benefit from adjuvant chemotherapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-908/coif). The authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: Artificial intelligence (AI) technology represented by deep learning has made remarkable achievements in digital pathology, enhancing the accuracy and reliability of diagnosis and prognosis evaluation. The spatial distribution of CD3 + and CD8 + T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer (CRC). This study aimed to investigate CD3 CT (CD3 + T cells density in the core of the tumor [CT]) prognostic ability in patients with CRC by using AI technology., Methods: The study involved the enrollment of 492 patients from two distinct medical centers, with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort. To facilitate tissue segmentation and T-cells quantification in whole-slide images (WSIs), a fully automated workflow based on deep learning was devised. Upon the completion of tissue segmentation and subsequent cell segmentation, a comprehensive analysis was conducted., Results: The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3 CT and CD3-CD8 (the combination of CD3 + and CD8 + T cells density within the CT and invasive margin) in predicting mortality (C-index in training cohort: 0.65 vs. 0.64; validation cohort: 0.69 vs. 0.69). The CD3 CT was confirmed as an independent prognostic factor, with high CD3 CT density associated with increased overall survival (OS) in the training cohort (hazard ratio [HR] = 0.22, 95% confidence interval [CI]: 0.12-0.38, P <0.001) and validation cohort (HR = 0.21, 95% CI: 0.05-0.92, P = 0.037)., Conclusions: We quantify the spatial distribution of CD3 + and CD8 + T cells within tissue regions in WSIs using AI technology. The CD3 CT confirmed as a stage-independent predictor for OS in CRC patients. Moreover, CD3 CT shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Grasping and twisting motions are vital when manipulating objects due to their fundamental role in enabling precision, adaptability, and effective interaction. However, few studies in soft robotics exploiting artificial muscles have achieved object manipulation in situ through the coordination of twisting and grasping motions akin to our forearm and hand's capabilities. Especially, when using the same artificial muscle module to achieve these two motions will greatly simplify the manufacturing and control complexity. Here, we introduce identical origami artificial muscle modules (OAMMs) subjected to distinct end constraints into the design of the robotic manipulator, allowing it to achieve independent grasping and twisting motions to achieve effective, precise object manipulation. Applying different end constraints to the identical OAMMs yields distinct motions at their ends, where utilizing a fixed end and a sliding end realizes pure translation, while opting for a fixed end and a rotating end enables pure rotation. The differentially constrained OAMMs then serve as soft actuators for the manipulator's torsional mechanism and grasping mechanism to accomplish independent, controllable twisting and grasping motions. The coordination of twisting and grasping motions finally enables the manipulator to complete various tasks, including installing a light bubble, pouring the water from a lidded bottle into a cup, and sorting and stacking puzzle blocks. Our study pioneers the utilization of OAMMs for precise and versatile object manipulation through the coordination of independent twisting and grasping motions.

Objective: Addressing the increasing global health issue of childhood obesity, exacerbated by pervasive food marketing, this study critically evaluated China's food marketing policies in comparison with international best practices, aiming to uncover policy content and implementation gaps and inform policy enhancement strategies., Method: Three key indicators were utilized from the Healthy Food-Environment Policy Index (Food-EPI)'s food promotion domain. A panel of experts ( n = 13) from academic institutions, China Centers for Disease Control and Prevention, and the food industry assessed the Chinese government's policy scores and implementation levels concerning food marketing. Benchmarked against international best practices using the Food-EPI process, this evaluation encompassed context analysis, data collection, evidence-based policy action, government validation, policy rating, scoring, and results translation for government and stakeholders. The three chosen indicators specifically addressed childhood overweight- and obesity-related food marketing in broadcast media (Indicator 1), non-broadcast media (Indicator 2), and child gathering settings (Indicator 3)., Results: Specifically, Indicator 1, the Single Food Marketing Indicator Score was measured at 2.31 ± 0.38, with an accompanying Food Marketing Policy Implementation Percentage of 46.2%, and Low Implementation Level. For non-broadcast mediums (Indicator 2), these metrics were gauged at 1.77 ± 0.27, 35.4%, and Low Implementation Level, respectively. In child gathering settings (Indicator 3), for efforts curbing unhealthy food promotion, a score of 2.77 ± 0.27, an implementation percentage of 55.4%, and Medium Implementation Level was obtained. Cumulatively, the overarching efficacy of food marketing policy enforcement was determined to be suboptimal, with the consolidated figures being Total Food Marketing Score as 2.28 ± 0.97, Total Food Marketing Policy Implementation Percentage as 45.6%, and Total Food Marketing Policy Implementation Level as Low., Conclusion: Like many countries, China's food marketing policies and implementation have room for improvement when compared to international best practices. Recommendations include emphasizing nutritional legislation, fostering stakeholder collaboration, bolstering public health campaigns, and leveraging technology for stringent enforcement.

Objective: The objective of this study was to evaluate the home food environment of the elderly in Beijing and analyze its association with the body mass index (BMI) of the elderly, as well as to provide recommendations for improving the home food environment for the elderly., Methods: This study was conducted in Beijing, China, in 2019. The participants were 1764 elderly individuals aged 65 to 80, recruited from 12 communities through a multistage stratified random sampling method. The study involved the use of questionnaire surveys to gather data on participants' demographics, the availability of various foods in their households, and their living conditions. Socioeconomic status (SES) was evaluated based on their educational level, occupation, and income level. Height and weight measurements were taken to calculate BMI. We conducted both univariate analysis and multiple linear regression analysis to evaluate the relationship between the home food environment and BMI., Results: A total of 1800 questionnaires were distributed, of which 1775 were retrieved, resulting in a questionnaire recovery rate of 98.6%. Among these, 1764 questionnaires were deemed valid, corresponding to a questionnaire validity rate of 99.4%. The participants had a mean age of 69.7 ± 4.3 years old, over 40% of whom were overweight or obese. In terms of low-energy/high-nutrient-density foods, the most readily available items were fresh vegetables (95.6%), followed by coarse grains (94.1%), fresh fruits (90.4%), and dairy products (83.6%). Among high-energy/low-nutrient-density foods, preserved foods were the most available (51.9%), followed by salted snacks (40.6%), sugary beverages (28.2%), and fried foods (9.4%). Approximately 7.3% of participants lived alone. Elderly individuals with higher SES had a lower BMI compared to those with medium to low SES (25.9 vs. 26.5, 25.9 vs. 26.4, p < 0.05). Those living alone had a higher BMI than those who did not (27.2 vs. 26.2, p = 0.001). After controlling for potential confounding variables, older adults with high SES exhibited a BMI reduction of 0.356 kg/m 2 ( p = 0.001), whereas those living alone exhibited an increase in BMI of 1.155 kg/m 2 ( p < 0.001). The presence of preserved foods at home was linked to a BMI increase of 0.442 kg/m 2 ( p = 0.008)., Conclusion: This study underscores the significant impact of family SES, living conditions, and the availability of preserved foods on the BMI of elderly individuals.

3-Photon microscopy (3PM) excited at the 1700 nm window features a smaller tissue attenuation and hence a larger penetration depth in brain imaging compared with other excitation wavelengths in vivo . While the comparison of the penetration depth quantified by effective attenuation length l e with other excitation wavelengths have been extensively investigated, comparison within the 1700 nm window has never been demonstrated. This is mainly due to the lack of a proper excitation laser source and characterization of the in vivo emission properties of fluorescent labels within this window. Herein, we demonstrate detailed measurements and comparison of l e through the 3-photon imaging of the mouse brain in vivo , at different excitation wavelengths (1600 nm, 1700 nm, and 1800 nm). 3PF imaging and in vivo spectrum measurements were performed using AIE nanoparticle labeling. Our results show that l e derived from both 3PF imaging and THG imaging is the largest at 1700 nm, indicating that it enables the deepest penetration in brain imaging in vivo ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background Parenchymal Enhancement (BPE) quantification in Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) plays a pivotal role in clinical breast cancer diagnosis and prognosis. However, the emerging deep learning-based breast fibroglandular tissue segmentation, a crucial step in automated BPE quantification, often suffers from limited training samples with accurate annotations. To address this challenge, we propose a novel iterative cycle-consistent semi-supervised framework to leverage segmentation performance by using a large amount of paired pre-/post-contrast images without annotations. Specifically, we design the reconstruction network, cascaded with the segmentation network, to learn a mapping from the pre-contrast images and segmentation predictions to the post-contrast images. Thus, we can implicitly use the reconstruction task to explore the inter-relationship between these two-phase images, which in return guides the segmentation task. Moreover, the reconstructed post-contrast images across multiple auto-context modeling-based iterations can be viewed as new augmentations, facilitating cycle-consistent constraints across each segmentation output. Extensive experiments on two datasets with various data distributions show great segmentation and BPE quantification accuracy compared with other state-of-the-art semi-supervised methods. Importantly, our method achieves 11.80 times of quantification accuracy improvement along with 10 times faster, compared with clinical physicians, demonstrating its potential for automated BPE quantification. The code is available at https://github.com/ZhangJD-ong/Iterative-Cycle-consistent-Semi-supervised-Learning-for-fibroglandular-tissue-segmentation.

Background: The correlation between the preoperative splenic area measured on CT scans and the overall survival (OS) of early-stage non-small cell lung cancer (NSCLC) patients remains unclear., Methods: A retrospective discovery cohort and validation cohort consisting of consecutive NSCLC patients who underwent resection and preoperative CT scans were created. The patients were divided into two groups based on the measurement of their preoperative splenic area: normal and abnormal. The Cox proportional hazard model was used to analyse the correlation between splenic area and OS., Results: The discovery and validation cohorts included 2532 patients (1374 (54.27%) males; median (IQR) age 59 (52-66) years) and 608 patients (403 (66.28%) males; age 69 (62-76) years), respectively. Patients with a normal splenic area had a 6% higher 5-year OS (n = 727 (80%)) than patients with an abnormal splenic area (n = 1805 (74%)) (p = 0.007) in the discovery cohort. A similar result was obtained in the validation cohort. In the univariable analysis, the OS hazard ratios (HRs) for the patients with abnormal splenic areas were 1.32 (95% confidence interval (CI): 1.08, 1.61) in the discovery cohort and 1.59 (95% CI: 1.01, 2.50) in the validation cohort. Multivariable analysis demonstrated that abnormal splenic area was independent of shorter OS in the discovery (HR: 1.32, 95% CI: 1.08, 1.63) and validation cohorts (HR: 1.84, 95% CI: 1.12, 3.02)., Conclusion: Preoperative CT measurements of the splenic area serve as a prognostic indicator for early-stage NSCLC patients, offering a novel metric with potential implications for personalized therapeutic strategies in top-tier oncology research., (© 2023. The Author(s).)

Numerous patch-based methods have recently been proposed for histological image based breast cancer classification. However, their performance could be highly affected by ignoring spatial contextual information in the whole slide image (WSI). To address this issue, we propose a novel hierarchical Graph V-Net by integrating 1) patch-level pre-training and 2) context-based fine-tuning, with a hierarchical graph network. Specifically, a semi-supervised framework based on knowledge distillation is first developed to pre-train a patch encoder for extracting disease-relevant features. Then, a hierarchical Graph V-Net is designed to construct a hierarchical graph representation from neighboring/similar individual patches for coarse-to-fine classification, where each graph node (corresponding to one patch) is attached with extracted disease-relevant features and its target label during training is the average label of all pixels in the corresponding patch. To evaluate the performance of our proposed hierarchical Graph V-Net, we collect a large WSI dataset of 560 WSIs, with 30 labeled WSIs from the BACH dataset (through our further refinement), 30 labeled WSIs and 500 unlabeled WSIs from Yunnan Cancer Hospital. Those 500 unlabeled WSIs are employed for patch-level pre-training to improve feature representation, while 60 labeled WSIs are used to train and test our proposed hierarchical Graph V-Net. Both comparative assessment and ablation studies demonstrate the superiority of our proposed hierarchical Graph V-Net over state-of-the-art methods in classifying breast cancer from WSIs. The source code and our annotations for the BACH dataset have been released at https://github.com/lyhkevin/Graph-V-Net.

Purpose: To explore the correlation between the initial recurrence site and survival after recurrence (PRS) in non-small cell lung cancer (NSCLC)., Methods: We collected 588 stages I-III NSCLC patients with recurrence after radical resection in Yunnan Cancer Hospital from January 2013 to December 2018. We used Kaplan-Meier survival curves to compare PRS in patients with different site recurrences. The univariate and multivariate Cox proportional hazard models were used to analyze the impact of the initial recurrence site on PRS., Results: The recurrence site included the lung (n = 109), brain (n = 113), bone (n = 79), abdomen (n = 28), pleura (n = 24), lymph node (n = 81), and multisite (n = 154). In the total population, patients with multisite recurrence had substantially worse PRS (24.8 months, 95% confidence interval [CI]: 17.46-32.20) than that of patients without multiple sites recurrence (42.2 months, 95% CI 32.24-52.10) (P = 0.026). However, patients with lung recurrence had better RFS (63.1 months, 95% CI 51.13-74.00) than those who did not (31.0 months, 95% CI 25.10-36.96) (P < 0.001). In adenocarcinoma, patients with pleural recurrence had substantially worse PRS (21.3 months, 95% CI 15.07-27.46) than that of patients without pleural recurrence (46.9 months, 95% CI 35.07-58.80) (P = 0.031). Multivariate Cox proportional hazards regression analysis revealed that lung recurrence (HR 0.58, 95% CI 0.40-0.82; P = 0.003) was independent protective prognostic factor for PRS in the total population, while pleural recurrence (HR 2.18, 95% CI 1.14-4.17; P = 0.018) was independent adverse prognostic factors for PRS in adenocarcinoma patients., Conclusion: The initial recurrence site was associated with PRS in NSCLC patients. Identification of recurrence sites could guide the subsequent treatment., (© 2023. The Author(s).)

Purpose: Adjuvant therapy is recommended to minimize the risk of distant metastasis (DM) and local recurrence (LR) in patients with locally advanced rectal cancer (LARC). However, its role is controversial. We aimed to develop a pretreatment MRI-based deep learning model to predict LR, DM, and overall survival (OS) over 5 years after surgery and to identify patients benefitting from adjuvant chemotherapy (AC)., Materials and Methods: The multi-survival tasks network (MuST) model was developed in a primary cohort (n = 308) and validated using two external cohorts (n = 247, 245). An AC decision tree integrating the MuST-DM score, perineural invasion (PNI), and preoperative carbohydrate antigen 19-9 (CA19-9) was constructed to assess chemotherapy benefits and aid personalized treatment of patients. We also quantified the prognostic improvement of the decision tree., Results: The MuST network demonstrated high prognostic accuracy in the primary and two external cohorts for the prediction of three different survival tasks. Within the stratified analysis and decision tree, patients with CA19-9 levels > 37 U/mL and high MuST-DM scores exhibited favorable chemotherapy efficacy. Similar results were observed in PNI-positive patients with low MuST-DM scores. PNI-negative patients with low MuST-DM scores exhibited poor chemotherapy efficacy. Based on the decision tree, 14 additional patients benefiting from AC and 391 patients who received over-treatment were identified in this retrospective study., Conclusion: The MuST model accurately and non-invasively predicted OS, DM, and LR. A specific and direct tool linking chemotherapy decisions and benefit quantification has also been provided., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The Covid-19 pandemic has dramatically changed how information is shared and processed worldwide. The COVID-19 pandemic has profoundly affected the globalization of information, causing shifts in communication, information dissemination, and technology. This paper investigates the impact of pandemics-related uncertainty on the index of de facto informational globalization (the measure based on high-technology exports, international patents, and used internet bandwidth). The paper uses the panel dataset of 18 Central and Eastern European (CEE) countries from 1990 to 2020. The results indicate that pandemics-related uncertainty negatively affects the informational globalization level in the CEE economies. The findings are robust in utilizing different estimation techniques and considering NATO member CEE countries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objectives: The aim of this study is to evaluate the feasibility of clinicopathological characteristics and computed tomography (CT) morphological features in predicting lymph node metastasis (LNM) for patients with T1 colorectal cancer (CRC)., Methods: A total of 144 patients with T1 CRC who underwent CT scans and surgical resection were retrospectively included in our study. The clinicopathological characteristics and CT morphological features were assessed by two observers. Univariate and multiple logistic regression analyses were used to identify significant LNM predictive variables. Then a model was developed using the independent predictive factors. The predictive model was subjected to bootstrapping validation (1000 bootstrap resamples) to calculate the calibration curve and relative C-index., Results: LNM were found in 30/144 patients (20.83%). Four independent risk factors were determined in the multiple logistic regression analysis, including presence of necrosis (adjusted odds ratio [OR] = 10.32, 95% confidence interval [CI] 1.96-54.3, p = 0.004), irregular outer border (adjusted OR = 5.94, 95% CI 1.39-25.45, p = 0.035), and heterogeneity enhancement (adjusted OR = 7.35, 95% CI 3.11-17.38, p = 0.007), as well as tumor location (adjusted OR right-sided colon  = 0.05 [0.01-0.60], p = 0.018; adjusted OR rectum  = 0.22 [0.06-0.83], p = 0.026). In the internal validation cohort, the model showed good calibration and good discrimination with a C-index of 0.89., Conclusions: There are significant associations between lymphatic metastasis status and tumor location as well as CT morphologic features in T1 CRC, which could help the doctor make decisions for additional surgery after endoscopic resection., Key Points: • LNM more frequently occurs in left-sided T1 colon cancer than in right-sided T1 colon and rectal cancer. • CT morphologic features are risk factors for LNM of T1 CRC, which may be related to fundamental biological behaviors. • The combination of tumor location and CT morphologic features can more effectively assist in predicting LNM in patients with T1 CRC, and decrease the rate of unnecessary extra surgeries after endoscopic resection., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Genotype imputation is a powerful technique employed by next-generation sequencing (NGS) and genotyping arrays, which can significantly enhance the cost-effectiveness and efficiency of genomic selection. The accuracy of imputation is largely determined by the choice of reference panel, with previous studies generally demonstrating that a closely related population as a reference panel leads to greater accuracy than a more distantly related population. Various strategies have been proposed for selecting desirable individuals via targeted resequencing, but their efficiencies need further improvement. In this study, we present a practical broiler selection methodology for a local Chinese chicken line that integrates established methods based on pedigree, genomics, and random sampling, and leverages genotype and pedigree information from the yellow-plumage dwarf chicken line. The efficacy of these selection strategies was assessed by evaluating their ability to accurately impute masked genotypes from data obtained using a 600K chip. Our findings reveal that the pedigree-based method yields superior accuracy in genotype imputation, whereas the haplotype-based method exhibits greater stability. Nonetheless, the impact of these targeted methods for selecting key individuals is slightly different when initiating a new sequencing project in a production context. Overall, this study highlights the advantages of using the pedigree-based approach as the preferred method for optimizing genotype imputation in broiler chickens., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Accurately assessing the risk of recurrence in patients with locally advanced rectal cancer (LARC) before treatment is important for the development of treatment strategies. The purpose of this study is to develop an MRI-based scoring system to predict the risk of recurrence in patients with LARC., Methods: This was a multicenter observational study that enrolled participants who underwent neoadjuvant chemoradiotherapy. To evaluate the risk of recurrence in these patients, we developed the mrDEC scoring system and assessed inter-reader agreement. Additionally, we plotted Kaplan-Meier curves to compare the 3-year disease-free survival (DFS) and 5-year overall survival (OS) rates among patients with different mrDEC scores., Results: A total of 1287 patients with LARC were included in this study. We observed substantial inter-reader agreement for mrDEC. Based on the mrDEC scores ranging from 0 to 3, the patients were categorized into four groups. The 3-year DFS rates for the groups were 91.0%, 79.5%, 65.5%, and 44.0% (P < 0.0001), respectively, and the 5-year OS rates were 92.9%, 87.1%, 74.8%, and 44.5%, respectively (P < 0.0001)., Conclusions: The mrDEC scoring system proved to be an effective tool for predicting the prognosis of patients with LARC and can assist clinicians in clinical decision-making., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: miR-26b-5p actively participates in the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). The database showed that fibroblast growth factor (FGF)-21 is a potential binding site of miR-26b-5p. This study aimed to investigate the molecular osteogenic mechanisms of miR-26b-5p targeting FGF21., Methods: Bone marrow was aspirated from the anterior superior iliac spine during bone marrow puncture. BMSCs were used to establish an in vitro cell model, and BMSCs markers were analyzed by flow cytometry. miR-26b-5p were overexpressed for 48 hours, and then placed in an osteogenic induction medium for osteogenic induction culture, the expression of RNA was detected using RT-qPCR. On day 7 of induction, RT-qPCR was used to measure Runx2, Osterix (Osx), and target gene FGF21 expression levels in each group. RT-qPCR, the dual-luciferase reporter gene system and western blot were used to verify that FGF21 was a direct target of miR-26b-5p., Results: BMSCs were identified according to the antigenic characteristics. miR-26b-5p expression was significantly upregulated after the expression of miR-26b-5p mimics, and FGF21 expression was downregulated; in miR-26b-5p inhibitor, the opposite results were revealed. After overexpression of miR-26b-5p, the alkaline phosphatase activity and nodules of Alizarin red S in the culture medium was increased; the opposite results were revealed in miR-26b-5p inhibitor. The expressions of Runx2 and Osx in the miR-26b-5p group were also significantly higher; in the miR-26b-5p inhibitor group, the opposite results were revealed. Luciferase reporter assays demonstrated that FGF21 was a direct target of miR-26b-5p. The western blotting analysis showed that FGF21 expression was significantly downregulated in the miR-26b-5p overexpressed group. Finally, the expressions of the characteristic osteogenic factors in the miR-26b-5p control + FGF21 group was significantly lower, but then increased significantly in the miR-26b-5p mimics + FGF21 group; the expressions of the characteristic osteogenic factors in the miR-26b-5p control + si-FGF21 group was significantly higher., Conclusions: miR-26b-5p can regulate the osteogenic differentiation of BMSCs and participate in PMOP pathogenesis via suppressing FGF21., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Photoaging is unique to the skin and is accompanied by an increased risk of tumors. To explore the transcriptomic regulatory mechanism of skin photoaging, the epidermis, and dermis of 16 healthy donors (eight exposed and eight non-exposed) were surgically excised and detected using total RNA-Seq. Weighted gene co-expression network analysis (WGCNA) identified the most relevant modules with exposure. The hub genes were identified using correlation, p-value, and enrichment analysis. The critical genes were identified using Support Vector Machine-Recursive Feature Elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression, then enriched using single-gene GSEA. A competitive endogenous RNA (ceRNA) network was constructed and validated using qRT-PCR. Compared with non-exposed sites, 430 mRNAs, 168 lncRNAs, and 136 miRNAs were differentially expressed in the exposed skin. WGCNA identified the module MEthistle and 12 intersecting genes from the 71 genes in this module. The enriched pathways were related to muscle. The critical genes were KLHL41, MYBPC2, and ERAP2. Single-gene GSEA identified the Hippo signaling pathway, basal cell carcinoma, cell adhesion molecules, and other pathways. Six miRNAs and 18 lncRNAs related to the critical genes constituted the ceRNA network and were verified using qPCR. The differential expression of KLHL41, MYBPC2, and ERAP2 at the protein level was verified using immunohistochemistry. KLHL41, MYBPC2, and ERAP2 genes are related to skin photoaging. The prediction model based on the three critical genes can indicate photoaging. These critical genes may have a role in skin photoaging by regulating cell growth, intercellular adhesion, and substance metabolism pathways., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

The increased amount of tertiary lymphoid structures (TLSs) is associated with a favorable prognosis in patients with lung adenocarcinoma (LUAD). However, evaluating TLSs manually is an experience-dependent and time-consuming process, which limits its clinical application. In this multi-center study, we developed an automated computational workflow for quantifying the TLS density in the tumor region of routine hematoxylin and eosin (H&E)-stained whole-slide images (WSIs). The association between the computerized TLS density and disease-free survival (DFS) was further explored in 802 patients with resectable LUAD of three cohorts. Additionally, a Cox proportional hazard regression model, incorporating clinicopathological variables and the TLS density, was established to assess its prognostic ability. The computerized TLS density was an independent prognostic biomarker in patients with resectable LUAD. The integration of the TLS density with clinicopathological variables could support individualized clinical decision-making by improving prognostic stratification., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows screening, follow up, and diagnosis for breast tumor with high sensitivity. Accurate tumor segmentation from DCE-MRI can provide crucial information of tumor location and shape, which significantly influences the downstream clinical decisions. In this paper, we aim to develop an artificial intelligence (AI) assistant to automatically segment breast tumors by capturing dynamic changes in multi-phase DCE-MRI with a spatial-temporal framework. The main advantages of our AI assistant include (1) robustness, i.e., our model can handle MR data with different phase numbers and imaging intervals, as demonstrated on a large-scale dataset from seven medical centers, and (2) efficiency, i.e., our AI assistant significantly reduces the time required for manual annotation by a factor of 20, while maintaining accuracy comparable to that of physicians. More importantly, as the fundamental step to build an AI-assisted breast cancer diagnosis system, our AI assistant will promote the application of AI in more clinical diagnostic practices regarding breast cancer., Competing Interests: D.S. is an employee of Shanghai United Imaging Intelligence Co., Ltd. The company has no role in designing and performing the surveillance and analyzing and interpreting the data., (© 2023 The Authors.)

Purpose: To construct a superior single-sequence radiomics signature to assess lymphatic metastasis in patients with cervical cancer after neoadjuvant chemotherapy (NACT)., Methods: The first half of the study was retrospectively conducted in our hospital between October 2012 and December 2021. Based on the history of NACT before surgery, all pathologies were divided into the NACT and surgery groups. The incidence rate of lymphatic metastasis in the two groups was determined based on the results of pathological examination following lymphadenectomy. Patients from the primary and secondary centers who received NACT were enrolled for radiomics analysis in the second half of the study. The patient cohorts from the primary center were randomly divided into training and test cohorts at a ratio of 7:3. All patients underwent magnetic resonance imaging after NACT. Segmentation was performed on T1-weighted imaging (T1WI), T2-weighted imaging, contrast-enhanced T1WI (CET1WI), and diffusion-weighted imaging., Results: The rate of lymphatic metastasis in the NACT group (33.2%) was significantly lower than that in the surgery group (58.7%, P=0.007). The area under the receiver operating characteristic curve values of Radscore&#95;CET1WI for predicting lymph node metastasis and non-lymphatic metastasis were 0.800 and 0.797 in the training and test cohorts, respectively, exhibiting superior diagnostic performance. After combining the clinical variables, the tumor diameter on magnetic resonance imaging was incorporated into the Rad&#95;clin model constructed using Radscore&#95;CET1WI. The Hosmer-Lemeshow test of the Rad&#95;clin model revealed no significant differences in the goodness of fit in the training (P=0.594) or test cohort (P=0.748)., Conclusions: The Radscore provided by CET1WI may achieve a higher diagnostic performance in predicting lymph node metastasis. Superior performance was observed with the Rad&#95;clin model., 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 © 2023 Ai, Zhang, Ding, Zhong, Li, Li, Zhang, Zhang, Zhang and Hu.)

Background: It is common for elderly patients to be underrepresented in clinical trials for cancer, which can result in a lack of efficacy data and unclear criteria to guide treatment decisions for clinical doctors. Therefore, one of the common challenges in oncology treatment is determining the extent to which patients aged 75 and older have benefited from postoperative chemotherapy., Purpose: The study aimed to explore the effect of adjuvant chemotherapy (AC) on 3-year recurrence-free survival (RFS) after curative resection in patients aged 75 years and older with stage II-III colorectal cancer (CRC)., Methods: The retrospective cohort analysis was performed on patients with stage II-III CRC who received curative resection at three cancer centers in China between 2008 and 2017. Kaplan-Meier curves and Multivariable Cox regression models were used to analyze the impact of AC on RFS in patients. Finally, propensity-score matching was used to reduce selection bias and confounding factors in patients aged 75 years and older with stage II-III CRC., Results: A total of 2885 patients were included (1729 (59.9%) male; 1312 (61.5%) received AC). The pre-matching cohort was comprised of 151 patients aged 75 years and older (median age (IQR)77.00 (76.00, 79.00); 97 (64.2%) male, 51 (72.9%) received AC). Age ( P =0.001), postoperative carcinoembryonic antigen (CEA)( P =0.02) level were associated with prognosis. But AC was not associated with 3-year RFS (HR, 1.27; 95% CI, 0.80-2.0; log-rank P =0.37). After a predisposition 1: 1 match (with or without AC, n = 42), AC remains uncorrelated with 3-year RFS (HR, 1.39; 95% CI, 0.52-3.70; log-rank P =0.66)., Conclusion: Patients over the age of 75 with stage II-III CRC who receive AC or do not face the same risk of postoperative recurrence. As a result, patients with stage II-III postoperative adjuvant chemotherapy can make an informed decision regarding whether they want to undergo chemotherapy based on their age and reduce the unnecessary side effects of chemotherapy., Competing Interests: The authors have declared that there is no conflict of interest., (© 2023 Liu et al.)

Background and Objective: A high degree of lymphocyte infiltration is related to superior outcomes amongst patients with lung adenocarcinoma. Recent evidence indicates that the spatial interactions between tumours and lymphocytes also influence the anti-tumour immune responses, but the spatial analysis at the cellular level remains insufficient., Methods: We proposed an artificial intelligence-quantified Tumour-Lymphocyte Spatial Interaction score (TLSI-score) by calculating the ratio between the number of spatial adjacent tumour-lymphocyte and the number of tumour cells based on topology cell graph constructed using H&E-stained whole-slide images. The association of TLSI-score with disease-free survival (DFS) was explored in 529 patients with lung adenocarcinoma across three independent cohorts (D1, 275; V1, 139; V2, 115)., Results: After adjusting for pTNM stage and other clinicopathologic risk factors, a higher TLSI-score was independently associated with longer DFS than a low TLSI-score in the three cohorts [D1, adjusted hazard ratio (HR), 0.674; 95% confidence interval (CI) 0.463-0.983; p = 0.040; V1, adjusted HR, 0.408; 95% CI 0.223-0.746; p = 0.004; V2, adjusted HR, 0.294; 95% CI 0.130-0.666; p = 0.003]. By integrating the TLSI-score with clinicopathologic risk factors, the integrated model (full model) improves the prediction of DFS in three independent cohorts (C-index, D1, 0.716 vs. 0.701; V1, 0.666 vs. 0.645; V2, 0.708 vs. 0.662) CONCLUSIONS: TLSI-score shows the second highest relative contribution to the prognostic prediction model, next to the pTNM stage. TLSI-score can assist in the characterising of tumour microenvironment and is expected to promote individualized treatment and follow-up decision-making in clinical practice., Competing Interests: Declaration of Competing Interest All the authors have no conflict of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The microplastics (MPs) existed in the environment widely has resulted in novel thinking about in-situ remediation techniques, such as nano-zero-valent iron (nZVI) and sulfided nZVI (S-nZVI), which were often compromised by various environmental factors. In this study, three common MPs such as polyvinyl chloride (PVC), polystyrene (PS), and polypropylene (PP) in soil were found to inhibit the degradation rate of decabromodiphenyl ether (BDE209) by nZVI and S-nZVI to different degrees due to MPs inhibiting of electron transfer which is the main way to degrade BDE209. The inhibition strength was related to its impedance (Z) and electron-accepting (EAC)/-donating capacity (EDC). Based on the explanation of the inhibition mechanism, the reason for different aging degrees of nZVI and S-nZVI in different MPs was illustrated, especially in PVC systems. Furthermore, the aging of reacted MPs, functionalization and fragmentation in particular, indicated that they were involved in the degradation process. Moreover, this work provided new insights into the field application of nZVI-based materials for removing persistent organic pollutants (POPs)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Towards intracellular engineering of living organisms, the development of new biocompatible polymerization system applicable for an intrinsically non-natural macromolecules synthesis for modulating living organism function/behavior is a key step. Herein, we find that the tyrosine residues in the cofactor-free proteins can be employed to mediate controlled radical polymerization under 405 nm light. A proton-coupled electron transfer (PCET) mechanism between the excited-state TyrOH* residue in proteins and the monomer or the chain transfer agent is confirmed. By using Tyr-containing proteins, a wide range of well-defined polymers are successfully generated. Especially, the developed photopolymerization system shows good biocompatibility, which can achieve in-situ extracellular polymerization from the surface of yeast cells for agglutination/anti-agglutination functional manipulation or intracellular polymerization inside yeast cells, respectively. Besides providing a universal aqueous photopolymerization system, this study should contribute a new way to generate various non-natural polymers in vitro or in vivo to engineer living organism functions and behaviours., (© 2023. The Author(s).)

Desmoplastic reaction (DR) is one of many tumor-host interactions and is associated with the overall survival (OS) of patients with colorectal cancer. However, the clinical significance of DR requires further study in large multicenter cohorts and its predictive value in adjuvant chemotherapy (ACT) response remains unclear. Here, a total of 2,225 patients with colorectal cancer from five independent institutions were divided into primary ( N = 1,012 from two centers) and validation ( N = 1,213 from three centers) cohorts. DR was classified as immature, middle, or mature depending on the presence of myxoid stroma and hyalinized collagen bundles at the invasive front of the primary tumor. OS among different subgroups were compared, and the correlations of DR type with tumor-infiltrating lymphocytes (TILs) within stroma, tumor stroma ratio (TSR), and Stroma AReactive Invasion Front Areas (SARIFA) were also analyzed. In the primary cohort, patients with mature DR had the highest 5-year survival rate. These findings were confirmed in validation cohort. In addition, for stage II colorectal cancer, patients classified as non-mature DR would benefit from ACT compared with surgery alone. Furthermore, immature and middle DR were more associated with high TSR, less distribution of TILs within stroma and positive SARIFA compared with mature. Taken together, these data suggest that DR is a robust-independent prognostic factor for patients with colorectal cancer. For patients with stage II colorectal cancer, non-mature DR could be a potential marker for recognizing high-risk patients who may benefit from ACT., Significance: DR has the potential to identify patients with high-risk colorectal cancer and predict the efficacy of adjuvant chemotherapy in patients with stage II colorectal cancer. Our findings support reporting DR types as additional pathologic parameters in clinical practice for more precise risk stratification., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Ultrasonography is an important routine examination for breast cancer diagnosis, due to its non-invasive, radiation-free and low-cost properties. However, the diagnostic accuracy of breast cancer is still limited due to its inherent limitations. Then, a precise diagnose using breast ultrasound (BUS) image would be significant useful. Many learning-based computer-aided diagnostic methods have been proposed to achieve breast cancer diagnosis/lesion classification. However, most of them require a pre-define region of interest (ROI) and then classify the lesion inside the ROI. Conventional classification backbones, such as VGG16 and ResNet50, can achieve promising classification results with no ROI requirement. But these models lack interpretability, thus restricting their use in clinical practice. In this study, we propose a novel ROI-free model for breast cancer diagnosis in ultrasound images with interpretable feature representations. We leverage the anatomical prior knowledge that malignant and benign tumors have different spatial relationships between different tissue layers, and propose a HoVer-Transformer to formulate this prior knowledge. The proposed HoVer-Trans block extracts the inter- and intra-layer spatial information horizontally and vertically. We conduct and release an open dataset GDPH&SYSUCC for breast cancer diagnosis in BUS. The proposed model is evaluated in three datasets by comparing with four CNN-based models and three vision transformer models via five-fold cross validation. It achieves state-of-the-art classification performance (GDPH&SYSUCC AUC: 0.924, ACC: 0.893, Spec: 0.836, Sens: 0.926) with the best model interpretability. In the meanwhile, our proposed model outperforms two senior sonographers on the breast cancer diagnosis when only one BUS image is given (GDPH&SYSUCC-AUC ours: 0.924 vs. reader1: 0.825 vs. reader2: 0.820).

The stress produced from biodegradable plastics on soil ecosystem is a rising global concern. However, effects of such microplastics (MPs) on soil ecology are still debatable. In this study, the biodegradable microplastic PBAT (polyadipate/butylene terephthalate) was used as the target object, compared with the traditional microplastic LDPE (low-density polyethylene). A pot experiment and was high-throughput sequencing analysis used to determine the effect of different additions of MPs on soil bacterial community structure and the correlation between soil bacterial community structure and chemical properties was investigated. Compared with LDPE, the results showed that EC, TN, TP, NH 4 + -N, and NO 3 - -N changed obviously with the increasing of PBAT addition (p < 0.05), but pH changed little and the community richness was significantly higher in soils with low PBAT addition than that with higher PBAT addition. PBAT is beneficial to soil nitrogen fixation, but it will significantly reduce the soil P content and affect the nitrification and denitrification reaction. It suggested that addition of PBAT MPs and its addition amount result in changes in soil fertility, community abundance, and structure and composition of bacterial communities in soil samples, while the presence of PBAT MPs might affect soil carbon-nitrogen cycle., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

CircRNAs are newly identified special endogenous RNA molecules that covalently close a loop by back-splicing with pre-mRNA. In the cytoplasm, circRNAs would act as molecular sponges to bind with specific miRNA to promote the expression of target genes. However, knowledge of circRNA functional alternation in skeletal myogenesis is still in its infancy. In this study, we identified a circRNA-miRNA-mRNA interaction network in which the axis may be implicated in the progression of chicken primary myoblasts' (CPMs) myogenesis by multi-omics (i.e., circRNA-seq and ribo-seq). In total, 314 circRNA-miRNA-mRNA regulatory axes containing 66 circRNAs, 70 miRNAs, and 24 mRNAs that may be relevant to myogenesis were collected. With these, the circPLXNA2 - gga-miR-12207-5P - MDM4 axis aroused our research interest. The circPLXNA2 is highly differentially expressed during differentiation versus proliferation. It was demonstrated that circPLXNA2 inhibited the process of apoptosis while at the same time stimulating cell proliferation. Furthermore, we demonstrated that circPLXNA2 could inhibit the repression of gga-miR-12207-5p to MDM4 by directing binding to gga-miR-12207-5p , thereby restoring MDM4 expression. In conclusion, circPLXNA2 could function as a competing endogenous RNA (ceRNA) to recover the function of MDM4 by directing binding to gga-miR-12207-5p , thereby regulating the myogenesis.

Multiphoton microscopy (MPM) is an enabling technology for visualizing deep-brain structures at high spatial resolution in vivo . Within the low tissue absorption window, shifting to longer excitation wavelengths reduces tissue scattering and boosts penetration depth. Recently, the 2200 nm excitation window has emerged as the last and longest window suitable for deep-brain MPM. However, multiphoton fluorescence imaging at this window has not been demonstrated, due to the lack of characterization of multiphoton properties of fluorescent labels. Here we demonstrate technologies for measuring both the multiphoton excitation and emission properties of fluorescent labels at the 2200 nm window, using (1) 3-photon ( ησ 3 ) and 4-photon action cross sections ( ησ 4 ) and (2) 3-photon and 4-photon emission spectra both ex vivo and in vivo of quantum dots. Our results show that quantum dots have exceptionally large ησ 3 and ησ 4 for efficient generation of multiphoton fluorescence. Besides, the 3-photon and 4-photon emission spectra of quantum dots are essentially identical to those of one-photon emission, which change negligibly subject to the local environment of circulating blood. Based on these characterization results, we further demonstrate deep-brain vasculature imaging in vivo . Due to the superb multiphoton properties of quantum dots, 3-photon and 4-photon fluorescence imaging reaches a maximum brain imaging depth of 1060 and 940 μm below the surface of a mouse brain, respectively, which enables the imaging of subcortical structures. We thus fill the last gap in multiphoton fluorescence imaging in terms of wavelength selection.

Objectives: The stent retriever thrombectomy (SRT) and a direct aspiration first-pass technique (ADAPT) are the two main mechanical thrombectomy (MT) techniques for acute ischemic stroke. Few data are available for comparing the therapeutic effects associated with the two mechanical thrombectomy techniques in acute ischemic stroke with atrial fibrillation. The purpose of this study was to compare the efficacy and safety of both techniques for the treatment of acute large vessel occlusion stroke in the anterior circulation with atrial fibrillation., Methods: Retrospective analysis was performed in stroke patients with atrial fibrillation admitted to Guangzhou Red Cross Hospital from January 2018 to June 2022 who received mechanical thrombectomy by either SRT or ADAPT. Comparisons were made with regards to the initial traits, course of therapy, effectiveness indicators, and complications of these individuals. The primary outcome is recanalization rate., Results: In this study, after screening 431 patients, 92 eligible patients, with 48 patients received SRT and 44 patients received ADAPT, were included. There was no significant difference in the recanalization rate between the two groups (SRT 87.5% vs. ADAPT 84.1%, P = 0.639). Compared with SRT, patients in ADAPT group had a shorter puncture to recanalization time [33.5 min (27.0-59.5) vs. 50.5 min (31.5-91.5), P = 0.009], a higher first pass success recanalization rate (54.5 vs. 33.3%, p = 0.040), and a higher rate of patients with improvement of NIHSS scores ≥4 at discharge (84.1 vs. 56.3%, P = 0.004). However, distal embolization occurred more frequently in the ADAPT group than that in SRT group (50.0 vs. 22.9%, P = 0.007). There was no significant difference between the two groups in the 3-month mRS score, symptomatic cerebral hemorrhage, or mortality., Conclusions: Compared with SRT, ADAPT has similar recanalization rate for the treatment of acute large vessel occlusion stroke in the anterior circulation with atrial fibrillation. However, ADAPT might be more effective in terms of shorter puncture to recanalization time and higher first pass success recanalization rate. Further studies are needed for confirming our results., 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 © 2023 Fan, Li, Li, Tan, Mao, Liu and Zhu.)

Background: Current prognostic prediction models of colorectal cancer (CRC) include only the preoperative measurement of tumor markers, with their available repeated postoperative measurements underutilized. CRC prognostic prediction models were constructed in this study to clarify whether and to what extent the inclusion of perioperative longitudinal measurements of CEA, CA19-9, and CA125 can improve the model performance, and perform a dynamic prediction., Methods: The training and validating cohort included 1453 and 444 CRC patients who underwent curative resection, with preoperative measurement and two or more measurements within 12 months after surgery, respectively. Prediction models to predict CRC overall survival were constructed with demographic and clinicopathological variables, by incorporating preoperative CEA, CA19-9, and CA125, as well as their perioperative longitudinal measurements., Results: In internal validation, the model with preoperative CEA, CA19-9, and CA125 outperformed the model including CEA only, with the better area under the receiver operating characteristic curves (AUCs: 0.774 vs 0.716), brier scores (BSs: 0.057 vs 0.058), and net reclassification improvement (NRI = 33.5%, 95% CI: 12.3 ~ 54.8%) at 36 months after surgery. Furthermore, the prediction models, by incorporating longitudinal measurements of CEA, CA19-9, and CA125 within 12 months after surgery, had improved prediction accuracy, with higher AUC (0.849) and lower BS (0.049). Compared with preoperative models, the model incorporating longitudinal measurements of the three markers had significant NRI (40.8%, 95% CI: 19.6 to 62.1%) at 36 months after surgery. External validation showed similar results to internal validation. The proposed longitudinal prediction model can provide a personalized dynamic prediction for a new patient, with estimated survival probability updated when a new measurement is collected during 12 months after surgery., Conclusions: Prediction models including longitudinal measurements of CEA, CA19-9, and CA125 have improved accuracy in predicting the prognosis of CRC patients. We recommend repeated measurements of CEA, CA19-9, and CA125 in the surveillance of CRC prognosis., (© 2023. The Author(s).)

Background and Purpose: Pain is one of the most common symptoms in patients after stroke. It is a distressing experience that affects patients' quality of life, and it is highly prevalent in clinical practice. The pathogenesis mechanisms of PSP are not so clear, and there is currently a lack of effective medical treatments, hence it is necessary to establish a sufficient understanding of this disease. Limited number of studies have applied bibliometric methods to systematically analyze studies on post-stroke pain. This study aimed to systematically analyze scientific studies conducted worldwide on post-stroke pain from 2012 to 2021 to evaluate global trends in this field using a bibliometric analysis., Methods: Publications related to post-stroke pain from 2012 to 2021 were obtained from the Web of Science Core Collection database. Bibliometrics Biblioshiny R-package software was used to analyze the relationship of publication year with country, institution, journals, authors, and keywords and to generate variant visual maps to show annual publications, most relevant countries, authors, sources, keywords, and top-cited articles., Results: In this study, 5484 papers met the inclusion criteria. The annual growth rate of publications was 5.13%. The USA had the highest number of publications (1381, 25.2%) and citations (36,395), and the University of Toronto had the highest number of papers (156, 2.8%). "Stroke", "management", "pain", "risk", "prevalence", "ischemic stroke", "risk factors", "disease", "diagnosis" and "therapy" are the top 10 keywords., Conclusion: The global research interest regarding PSP has maintained growing over the past ten years. Both central post stroke pain and hemiplegic shoulder pain are the hottest research subjects. Further investigations are needed in order to reveal the mystery of the pathophysiologic mechanisms of CPSP, and high-quality well-designed trials of potential treatments of CPSP and HSP are also needed., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (© 2023 Xiong et al.)