Laboratory animal ethics education improves medical students' awareness of laboratory animal ethics.

OBJECTIVE: In this study, we added laboratory animal ethics education into both didactic sessions and practical sessions the general surgery laboratory course, with the didactic sessions focus on teaching the fundamental principles of laboratory animal ethics, while the practical sessions emphasize the application of these principles in laboratory classes and have assessed the changes in medical students' perception of laboratory animal ethics following medical students exposure to such education. METHODS: One hundred and eighty-nine third-year medical students from Wuhan University's Second Clinical College completed a laboratory animal ethics awareness questionnaire and a laboratory animal ethics written examination before and after laboratory animal ethics education. RESULTS: After receiving laboratory animal ethics education, the percentage of students who supported euthanasia for the execution of animals and humane treatment of laboratory animals were 95.2% and 98.8%, respectively, which did not differ from the 94.9% and 96.4% observed before the education. Moreover, there was a notable increase in the proportion of students who knew about regulations related to laboratory animals (from 39.9% to 57.1%), welfare issues (from 31.9% to 50.0%), and the 3R principle (from 30.4% to 58.9%) post-education, all statistically significant at P < 0.05. Test scores also showed improvement, with students scoring (93.02 ± 11.65) after education compared to (67.83 ± 8.08) before, a statistically significant difference. CONCLUSIONS: This research helps to provide information for the good practices of laboratory animal ethics education. After receiving laboratory animal ethics education, students are better able to treat laboratory animals in a correct animal ethical manner. Laboratory animal ethics education helps improve students' knowledge of laboratory animal ethics. Students' perception towards how the laboratory animal ethics course should be delivered may vary. Still, new courses or better organized courses on laboratory animal ethics education are required in order to provide students an in-depth understanding.

Development of Indocyanine Green/Methyl-ß-cyclodextrin Complex-Loaded Liposomes for Enhanced Photothermal Cancer Therapy.

Photothermal therapy (PTT) is a promising cancer therapeutic approach due to its spatial selectivity and high potency. Indocyanine green (ICG) has been considered a biocompatible PTT agent. However, ICG has several challenges to hinder its clinical use including rapid blood clearance and instability to heat, light, and solvent, leading to a loss of photoactivation property and PTT efficacy. Herein, we leveraged stabilizing components, methyl-ß-cyclodextrin and liposomes, in one nanoplatform (ICD lipo) to enhance ICG stability and the photothermal therapeutic effect against cancer. Compared to ICG, ICD lipo displayed a 4.8-fold reduction in degradation in PBS solvent after 30 days and a 3.4-fold reduction in photobleaching after near-infrared laser irradiation. Moreover, in tumor-bearing mice, ICD lipo presented a 2.7-fold increase in tumor targetability and inhibited tumor growth 9.6 times more effectively than did ICG without any serious toxicity. We believe that ICD lipo could be a potential PTT agent for cancer therapeutics.

Transgenic expression of artificial microRNA targeting soybean mosaic virus P1 gene confers virus resistance in plant.

RNA silencing is an innate immune mechanism of plants against invasion by viral pathogens. Artificial microRNA (amiRNA) can be engineered to specifically induce RNA silencing against viruses in transgenic plants and has great potential for disease control. Here, we describe the development and application of amiRNA-based technology to induce resistance to soybean mosaic virus (SMV), a plant virus with a positive-sense single-stranded RNA genome. We have shown that the amiRNA targeting the SMV P1 coding region has the highest antiviral activity than those targeting other SMV genes in a transient amiRNA expression assay. We transformed the gene encoding the P1-targeting amiRNA and obtained stable transgenic Nicotiana benthamiana lines (amiR-P1-3-1-2-1 and amiR-P1-4-1-2-1). Our results have demonstrated the efficient suppression of SMV infection in the P1-targeting amiRNA transgenic plants in an expression level-dependent manner. In particular, the amiR-P1-3-1-2-1 transgenic plant showed high expression of amiR-P1 and low SMV accumulation after being challenged with SMV. Thus, a transgenic approach utilizing the amiRNA technology appears to be effective in generating resistance to SMV.

Age-dependent distribution of IgA and IgG antibody-secreting cells in the pharyngeal tonsil of the Bactrian camel.

The pharyngeal tonsil, located in the nasopharynx, can effectively defend against pathogens invading the body from the upper respiratory tract and play a crucial role in mucosal immunity of the respiratory tract. Immunoglobulin A (IgA) and Immunoglobulin G (IgG) serve as key effector molecules in mucosal immunity, exhibiting multiple immune functions. This study aimed to investigate the distribution patterns and age-related alterations of IgA and IgG antibody-secreting cells (ASCs) in the pharyngeal tonsils of Bactrian camels. Twelve Alashan Bactrian camels were categorized into four age groups: young (1-2 years, n=3), pubertal (3-5 years, n=3), middle-aged (6-16 years, n=3) and old (17-20 years, n=3). The distribution patterns of IgA and IgG ASCs in the pharyngeal tonsils of Bactrian camels of different ages were meticulously observed, analyzed and compared using immunohistochemical and statistical methods. The results revealed that IgA ASCs in the pharyngeal tonsils of all age groups were primarily clustered or diffusely distributed in the reticular epithelium and its subepithelial regions (region A) and around the glands (region C), scattered in the subepithelial regions of non-reticular epithelium (region B), and sporadically distributed in the interfollicular regions (region D). Interestingly, the distribution pattern of IgG ASCs in the pharyngeal tonsils closely mirrored that of IgA ASCs. The distribution densities of IgA and IgG ASCs in these four regions were significantly decreased in turn (P<0.05). However, IgA ASCs exhibited significantly higher densities than IgG ASCs in the same region (P<0.05). Age-related alterations indicated that the distribution densities of IgA and IgG ASCs in each region of the pharyngeal tonsils exhibited a trend of initially increasing and subsequently decreasing from young to old camels, reaching a peak in the pubertal group. As camels age, there was a significant decrease in the densities of IgA and IgG ASCs in all regions of the pharyngeal tonsils (P<0.05). The results demonstrate that the reticular epithelium and its subepithelial regions in the pharyngeal tonsils of Bactrian camels are the primary regions where IgA and IgG ASCs colonize and exert their immune functions. These regions play a pivotal role in inducing immune responses and defending against pathogen invasions in the pharyngeal tonsils. IgA ASCs may be the principal effector cells of the mucosal immune response in the pharyngeal tonsils of Bactrian camels. Aging significantly reduces the densities of IgA and IgG ASCs, while leaving their distribution patterns unaffected. These findings will provide valuable insights for further investigations into the immunomorphology, immunosenescence, and response mechanisms of the pharyngeal tonsils in Bactrian camels.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer.

The immune checkpoint blockade (ICB) response in human cancers is closely linked to the gut microbiota. Here, we report that the abundance of commensal Lactobacillus johnsonii is positively correlated with the responsiveness of ICB. Supplementation with Lactobacillus johnsonii or tryptophan-derived metabolite indole-3-propionic acid (IPA) enhances the efficacy of CD8+ T cell-mediated αPD-1 immunotherapy. Mechanistically, Lactobacillus johnsonii collaborates with Clostridium sporogenes to produce IPA. IPA modulates the stemness program of CD8+ T cells and facilitates the generation of progenitor exhausted CD8+ T cells (Tpex) by increasing H3K27 acetylation at the super-enhancer region of Tcf7. IPA improves ICB responsiveness at the pan-cancer level, including melanoma, breast cancer, and colorectal cancer. Collectively, our findings identify a microbial metabolite-immune regulatory pathway and suggest a potential microbial-based adjuvant approach to improve the responsiveness of immunotherapy.

Short-term outcomes of robot-assisted minimally invasive surgery for brainstem hemorrhage: A case-control study.

Objective: This work focused on investigating if robot-assisted minimally invasive surgery improved middle term vital outcome for primary brainstem hemorrhage (PBSH). Methods: This work obtained clinical data from patients with PBSH admitted from July 2019 to August 2021. All cases were classified as surgical or conservative treatment group. The general information, Glasgow coma scale (GCS) score, Glasgow outcome score (GOS), along with survival time in patients 60 days after robot-assisted surgery were recorded and analyzed. Results: A prospective analysis was performed on 82 cases meeting eligibility criteria, including 36 from surgical group whereas 46 from the conservative group. Sixty days after onset, the death rate was found to be 19.44% and 50.00% of surgical and conservative groups, separately (cases versus controls, P < 0.05). Furthermore, postoperative GOS and GCS scores of surgical group were significantly higher, and hydrocephalus was lower compared with conservative group. Central fever incidence did not exhibit any significant difference between two groups. Conclusion: Robot-assisted PBSH drainage may improve survivorship and reduce the occurrence of hydrocephalus.

ETUNet:Exploring efficient transformer enhanced UNet for 3D brain tumor segmentation.

Medical image segmentation is a crucial topic in medical image processing. Accurately segmenting brain tumor regions from multimodal MRI scans is essential for clinical diagnosis and survival prediction. However, similar intensity distributions, variable tumor shapes, and fuzzy boundaries pose severe challenges for brain tumor segmentation. Traditional segmentation networks based on UNet struggle to establish explicit long-range dependencies from the feature space due to the limitations of the CNN receptive field. This is particularly crucial for dense prediction tasks such as brain tumor segmentation. Recent works have incorporated the powerful global modeling capability of Transformer into UNet to achieve more precise segmentation results. Nevertheless, these methods encounter some issues: (1) the global information is often modeled by simply stacking Transformer layers for a specific module, resulting in high computational complexity and underutilization of the potential of the UNet architecture; (2) the rich boundary information of tumor subregions in multi-scale features is often overlooked. Motivated by these challenges, we propose an advanced fusion of Transformer with UNet by reexamining the core three parts (encoder, bottleneck, and skip connections). Firstly, we introduce a CNN-Transformer module in the encoder to replace the traditional CNN module, enabling the capture of deep spatial dependencies from input images. To address high-level semantic information, we incorporate a computationally efficient spatial-channel attention layer in the bottleneck for global interaction, highlighting important semantic features from the encoder path output. For irregular lesions, we fuse the multi-scale features from the encoder output and the decoder features in the skip connections by calculating cross-attention. This adaptive querying of valuable information from multi-scale features enhances the boundary localization ability of the decoder path and suppresses redundant features with low correlation. Compared to existing methods, our model further enhances the learning capacity of the overall UNet architecture while maintaining low computational complexity. Experimental results on the BraTS2018 and BraTS2020 datasets for brain tumor segmentation tasks demonstrate that our model achieves comparable or superior results compared to recent CNN or Transformer-based models. The average DSC and HD95 on the two datasets are 0.854, 6.688, and 0.862, 5.455 respectively. At the same time, our model achieves optimal segmentation of Enhancing tumors, showcasing the effectiveness of our method. Our code will be made publicly available at https://github.com/wzhangck/ETUnet.

Neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in elderly patients with stage III-IVa nasopharyngeal carcinoma: A real-world study based on medical comorbidities.

PURPOSE: To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III-IVa). METHODS AND MATERIALS: Using an NPC-specific database, 245 elderly patients with stage III-IVa NPC, receiving CCRT +/- NAC, and an Adult Co-morbidity Evaluation 27 (ACE-27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein-Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease-free survival (DFS). RESULTS: Two risk groups were generated by the RPA model. In the high-risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III-IVa), patients treated with NAC plus CCRT achieved improved 5-year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low-risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences. CONCLUSIONS: The addition of NAC to CCRT was associated with better DFS for the high-risk group of elderly LANPC patients with ACE-27 score <2. However, the survival benefit of additional NAC was not observed in low-risk patients.

Nanoreceptors promote mutant p53 protein degradation by mimicking selective autophagy receptors.

In some cancers mutant p53 promotes the occurrence, development, metastasis and drug resistance of tumours, with targeted protein degradation seen as an effective therapeutic strategy. However, a lack of specific autophagy receptors limits this. Here, we propose the synthesis of biomimetic nanoreceptors (NRs) that mimic selective autophagy receptors. The NRs have both a component for targeting the desired protein, mutant-p53-binding peptide, and a component for enhancing degradation, cationic lipid. The peptide can bind to mutant p53 while the cationic lipid simultaneously targets autophagosomes and elevates the levels of autophagosome formation, increasing mutant p53 degradation. The NRs are demonstrated in vitro and in a patient-derived xenograft ovarian cancer model in vivo. The work highlights a possible direction for treating diseases by protein degradation.

A fusion model integrating magnetic resonance imaging radiomics and deep learning features for predicting alpha-thalassemia X-linked intellectual disability mutation status in isocitrate dehydrogenase-mutant high-grade astrocytoma: a multicenter study.

Background: The mutational status of alpha-thalassemia X-linked intellectual disability (ATRX) is an important indicator for the treatment and prognosis of high-grade gliomas, but reliable ATRX testing currently requires invasive procedures. The objective of this study was to develop a clinical trait-imaging fusion model that combines preoperative magnetic resonance imaging (MRI) radiomics and deep learning (DL) features with clinical variables to predict ATRX status in isocitrate dehydrogenase (IDH)-mutant high-grade astrocytoma. Methods: A total of 234 patients with IDH-mutant high-grade astrocytoma (120 ATRX mutant type, 114 ATRX wild type) from 3 centers were retrospectively analyzed. Radiomics and DL features from different regions (edema, tumor, and the overall lesion) were extracted to construct multiple imaging models by combining different features in different regions for predicting ATRX status. An optimal imaging model was then selected, and its features and linear coefficients were used to calculate an imaging score. Finally, a fusion model was developed by combining the imaging score and clinical variables. The performance and application value of the fusion model were evaluated through the comparison of receiver operating characteristic curves, the construction of a nomogram, calibration curves, decision curves, and clinical application curves. Results: The overall hybrid model constructed with radiomics and DL features from the overall lesion was identified as the optimal imaging model. The fusion model showed the best prediction performance with an area under curve of 0.969 in the training set, 0.956 in the validation set, and 0.949 in the test set as compared to the optimal imaging model (0.966, 0.916, and 0.936, respectively) and clinical model (0.677, 0.641, 0.772, respectively). Conclusions: The clinical trait-imaging fusion model based on preoperative MRI could effectively predict the ATRX mutation status of individuals with IDH-mutant high-grade astrocytoma and has the potential to help patients through the development of a more effective treatment strategy before treatment.

The neuroprotection of controlled decompression after traumatic epidural intracranial hypertension through suppression of autophagy via PI3K/Akt signaling pathway.

Acute intracranial hypertension (AIH) is a common and tricky symptom that inflicts upon patients after traumatic brain injury (TBI). A variety of clinical options have been applied for the management of AIH, such as physiotherapy, medication, surgery and combination therapy. Specifically, controlled decompression (CDC) alleviates the extent of brain injury and reduces the incidence of a series of post-TBI complications, thereby enhancing the prognosis of patients suffering from acute intracranial hypertension. The objective of the present project is to illuminate the potential molecular mechanism that underlies the neuroprotective effects of CDC in a rat model of traumatic epidural intracranial hypertension (TEIH). Herein, we observed the functional recovery, the degree of brain edema, the level of apoptosis, the expressions of neuronal cell autophagy-related signaling pathway proteins (including Akt, p-Akt, LC3 and Beclin-1) in rat TEIH model at 24 h post-surgery. The results showed in comparison with rapid decompression (RDC), CDC reduced the degree of brain edema, diminished the level of cellular apoptosis and enhanced neurological function, and whereas the neuroprotective effect of CDC could be reversed by rapamycin (Rap). The expressions of Beclin-1 and LC3 in CDC group were significantly lower than those of RDC group, and the expression levels of these two proteins were significantly elevated after the addition of Rap. The expression of p-Akt in CDC group was considerably enhanced than RDC group. After the addition of LY294002, a PI3K/Akt pathway inhibitor, p-Akt protein expression was reduced, and the neuroprotective effect of the rats was markedly inhibited. Taken together, our data demonstrate the superior neuroprotective effect of CDC with regard to alleviating early brain edema, improving the neurological status, suppressing apoptosis and inhibiting neuronal autophagy via triggering PI3K/Akt signaling pathway.

Ultrasonic-ethanol pretreatment assisted aqueous enzymatic extraction of hemp seed oil with low Δ9-THC.

In this study, ultrasonic-ethanol pretreatment combined with AEE was developed for oil extraction from hemp seeds. The oil yield reached a maximum of 23.32 % at 200 W ultrasonic power and 30 min ultrasonic time, at this point, the degradation rate of Δ9-THC was 83.11 %. By determining the composition of hemp seed before and after pretreatment, it was shown that ultrasonic-ethanol pretreatment reduced the protein content of the raw material. An enzyme mixture consisting of pectinase and hemicellulase (1/1/1, w/w/w) was experimentally determined to be used, and the AEE extraction conditions were optimized using the Plackett-Burman design and the Box-Behnken. The optimal conditions were determined to be pH 5, total enzyme activity of 37,800 U/g, liquid-solid ratio of 10.4 mL/g, enzyme digestion temperature of 32 °C, enzymatic time of 189 min, and oil recovery of 88.38 %. The results of confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) showed that the emulsion formed during ultrasonic ethanol pretreatment was not uniformly distributed, and the droplets appeared to be aggregated; and the irregular pores of hemp seed increased after pretreatment. The contents of Δ9-THC and CBN in the extracted oil samples were 9.58 mg/kg and 52.45 mg/kg, respectively. Compared with the oil extracted by Soxhlet extraction (SE), the oil extracted by this experimental method was of better quality and similar in fatty acid composition.

A randomized controlled trial of standard vs customized graduated elastic compression stockings in patients with chronic venous disease.

OBJECTIVE: This study aimed to compare the efficacy of customized graduated elastic compression stockings (c-GECSs) based on lower leg parameter models with standard GECSs (s-GECSs) in patients with chronic venous disease (CVD). METHODS: In this randomized, single-blind, controlled trial, 79 patients with stage C2 or C3 CVD were assigned to one of two groups: c-GECSs or s-GECSs. The primary outcome was change to Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) scores at months 1, 3, and 6 as compared with baseline. Secondary outcomes included compliance with wearing ECSs, interface pressure at the smallest circumference of the ankle (point B) and the largest circumference of the calf (point C), and calf volume (CV). RESULTS: There were 13 pairs of s-GECS and 2 pairs of c-GECS that showed pressure values higher than the standard at either point B or C. The c-GECSs were significantly superior to s-GECSs in terms of score improvement at all three time points (month 1, 8.47 [95% confidence interval (CI), 7.47-9.45] vs 5.89 [95% CI, 5.00-6.78]; month 3, 9.60 [95% CI, 8.47-10.72] vs 6.72 [95% CI, 5.62-7.83]; month 6, 7.09 [95% CI, 5.93-8.24] vs 3.92 [95% CI, 2.67-5.18]; P < .0001). Besides, at month 1, the mean daily use time of the c-GECS and s-GECS groups was 10.7 and 9.5 hours, respectively (P < .05). Correlation analysis indicated a negative relationship between local high pressure and daily duration in the s-GECS group (rpb = -0.388; n = 38; P < .05). Variances in pressure were greater in the s-GECSs group. The c-GECSs showed advantage in maintaining pressure. Both c-GECSs and s-GECSs effectively reduced CV (mL), with no significant differences between groups (month 1, 90.0 [95% CI, 71.4-108.5] vs 85.0 [95% CI, 65.6-104.2]; month 3, 93.8 [95% CI, 69.7-117.8] vs 85.9 [95% CI, 65.5-106.2]; month 6, 70.8 [95% CI, 46.5-95.2]) vs 60.8 [95% CI, 44.1-77.5]). CONCLUSIONS: The c-GECSs based on individual leg parameter models significantly improved VEINES-QOL scores and provided stable and enduring pressure as compared with s-GECSs for patients with stage C2 or C3 CVD. Although both c-GECSs and s-GECSs effectively reduced CV, the superior fit and comfort of c-GECSs improved patient compliance. Hence, c-GECSs are a viable alternative for patients who have difficulty tolerating s-GECSs.

Prediction of high Ki-67 proliferation index of gastrointestinal stromal tumors based on CT at non-contrast-enhanced and different contrast-enhanced phases.

OBJECTIVES: To evaluate and analyze radiomics models based on non-contrast-enhanced computed tomography (CT) and different phases of contrast-enhanced CT in predicting Ki-67 proliferation index (PI) among patients with pathologically confirmed gastrointestinal stromal tumors (GISTs). METHODS: A total of 383 patients with pathologically proven GIST were divided into a training set (n = 218, vendor 1) and 2 validation sets (n = 96, vendor 2; n = 69, vendors 3-5). Radiomics features extracted from the most recent non-contrast-enhanced and three contrast-enhanced CT scan prior to pathological examination. Random forest models were trained for each phase to predict tumors with high Ki-67 proliferation index (Ki-67>10%) and were evaluated using the area under the receiver operating characteristic curve (AUC) and other metrics on the validation sets. RESULTS: Out of 107 radiomics features extracted from each phase of CT images, four were selected for analysis. The model trained using the non-contrast-enhanced phase achieved an AUC of 0.792 in the training set and 0.822 and 0.711 in the two validation sets, similar to models trained on different contrast-enhanced phases (p > 0.05). Several relevant features, including NGTDM Busyness and tumor size, remained predictive in non-contrast-enhanced and different contrast-enhanced images. CONCLUSION: The results of this study indicate that a radiomics model based on non-contrast-enhanced CT matches that of models based on different phases of contrast-enhanced CT in predicting the Ki-67 PI of GIST. GIST may exhibit similar radiological patterns irrespective of the use of contrast agent, and such radiomics features may help quantify these patterns to predict Ki-67 PI of GISTs. CLINICAL RELEVANCE STATEMENT: GIST may exhibit similar radiomics patterns irrespective of contrast agent; thus, radiomics models based on non-contrast-enhanced CT could be an alternative for risk stratification in GIST patients with contraindication to contrast agent. KEY POINTS: • Performance of radiomics models in predicting Ki-67 proliferation based on different CT phases is evaluated. • Non-contrast-enhanced CT-based radiomics models performed similarly to contrast-enhanced CT in risk stratification in GIST patients. • NGTDM Busyness remains stable to contrast agents in GISTs in radiomics models.

SENP1 knockdown-mediated CTCF SUMOylation enhanced its stability and alleviated lipopolysaccharide-evoked inflammatory injury in human lung fibroblasts via regulation of FOXA2 transcription.

BACKGROUND: Excessive inflammation is the main cause of treatment failure in neonatal pneumonia (NP). CCCTC-binding factor (CTCF) represents an important node in various inflammatory diseases. In the present study, we tried to clarify the function and underlying molecular mechanism of CTCF on an in vitro cellular model of NP, which was generated by simulating the human lung fibroblast cell line WI-38 with lipopolysaccharide (LPS). METHODS: The SUMOylation level and protein interaction were verified by Co-immunoprecipitation assay. Cell viability was measured by Cell Counting Kit-8 assay. Inflammatory factors were examined by Enzyme-linked immunosorbent assay. Cell apoptosis was evaluated by TUNEL assay. The binding activity of CTCF to target promoter was tested by chromatin immunoprecipitation and luciferase reporter assay. RESULTS: LPS treatment restrained cell viability, promoted the production of inflammatory factors, and enhanced cell apoptosis. CTCF overexpression played anti-inflammatory and anti-apoptotic roles. Furthermore, CTCF was modified by SUMOylation with small ubiquitin-like modifier protein 1 (SUMO1). Interfering with sumo-specific protease 1 (SENP1) facilitated CTCF SUMOylation and protein stability, thus suppressing LPS-evoked inflammatory and apoptotic injuries. Moreover, CTCF could bind to the forkhead box protein A2 (FOXA2) promoter region to promote FOXA2 expression. The anti-inflammatory and anti-apoptotic roles of CTCF are associated with FOXA2 activation. In addition, SENP1 knockdown increased FOXA2 expression by enhancing the abundance and binding ability of CTCF. CONCLUSIONS: SUMOylation of CTCF by SENP1 knockdown enhanced its protein stability and binding ability and it further alleviated LPS-evoked inflammatory injury in human lung fibroblasts by positively regulating FOXA2 transcription.

The association between childhood adiposity in northeast China and anthropogenic heat flux: A new insight into the comprehensive impact of human activities.

Anthropogenic heat has been reported to have significant health impacts, but research on its association with childhood adiposity is still lacking. In this study, we matched the 2008-2012 average anthropogenic heat flux, as simulated by a grid estimation model using inventory methods, with questionnaire and measurement data of 49,938 children randomly recruited from seven cities in Northeast China in 2012. After adjusting for social demographic and behavioral factors, we used generalized linear mixed-effect models to assess the association between anthropogenic heat flux and adiposity among children. We also examined the effect modification of various social demographic and behavioral confounders. We found that each 10 W/m2 increase in total anthropogenic heat flux and that from the industry source was associated with an increase of 5.82% (95% CI = 0.84%-11.05%) and 6.62% (95% CI = 0.87%-12.70%) in the odds of childhood adiposity. Similarly, the excess rate of adiposity among children were 5.26% (95% CI = -1.33%-12.29%) and 8.51% (95% CI = 2.24%-15.17%) per 1 W/m2 increase in the anthropogenic heat flux from transportation and buildings, and was 7.94% (95% CI = 2.28%-13.91%) per 0.001 W/m2 increase in the anthropogenic heat flux from human metabolism. We also found generally greater effect estimates among female children and children who were exposed to passive smoking during pregnancy, born by caesarean section, non-breastfed/mixed-fed, or lived within 20 m adjacent to the main road. The potential deleterious effect of anthropogenic heat exposure on adiposity among children may make it a new but major threat to be targeted by future mitigation strategies.

The Role of Small Interfering RNAs in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), a primary liver cancer with high mortality, is the most common malignant tumor in the world. Currently, the effect of routine treatment is poor, especially for this kind of cancer with strong heterogeneity and late detection. In the past decades, the researches of gene therapy for HCC based on small interfering RNA have blossomed everywhere. This is a promising therapeutic strategy, but the application of siRNA is limited by the discovery of effective molecular targets and the delivery system targeting HCC. As the deepening of research, scientists have developed many effective delivery systems and found more new therapeutic targets. CONCLUSIONS: This paper mainly reviews the research on HCC treatment based on siRNA in recent years, and summarizes and classifies the HCC treatment targets and siRNA delivery systems.