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PURPOSE: Upper cervical fracture combined with non-contiguous lower cervical fracture are not uncommon but complicated. In order to outline a management principle for the upper cervical fracture combined with non-contiguous lower cervical fracture and assess its clinical characteristics, we retrospectively analyzed 59 cases of patients who underwent surgical treatment for upper cervical fracture combined with non-contiguous lower cervical fracture. METHODS: 59 patients of upper cervical fracture combined with non-contiguous lower cervical fracture were treated by surgery in our hospital. According to the AO Spine classification for cervical fractures, there were 21 cases of type B atlas fractures, nine cases of type C atlas fractures; 15 cases of type B axis fractures, 14 cases of type C axis fractures; 19 cases of type B lower cervical fractures, 40 cases of type C lower cervical fractures. The operation time, intraoperative blood loss, complications, VAS scores, JOA scores, ASIA grades, and radiological evaluation of cervical lordosis and stability were collected and recorded. RESULTS: Our results showed the segments of upper cervical fracture combined with non-contiguous lower cervical fracture are mainly concentrated in the atlas-axis and C6, C7 levels. There were 43 cases (72.88%) of associated injuries, mainly involving head trauma and thoracic injuries. Four patients underwent anterior approach surgery only, 43 patients underwent posterior approach surgery only, and 12 patients underwent combined anterior and posterior approach surgery in one stage. All patients had regular follow up with an average duration of 67.83 ± 11.25 months (range, 39 to 103 months). The VAS scores and JOA scores at 12 months postoperatively and at final follow-up showed significant improvement compared to preoperative scores (P < 0.05). At the final follow-up, ASIA grades had improved by 0 to 2 levels. The cervical lordosis at the final follow-up (24.71°±7.39°) showed no statistically significant difference compared to preoperative measurements (26.89°±13.32°). Surgical complications occurred in 17 patients. No cases of vertebral artery injury, screw loosening, or other internal fixation failures were found at final follow-up. CONCLUSIONS: Upper cervical fracture combined with non-contiguous lower cervical fracture can result in varying extents of cervical spinal cord injury and combined trauma in other parts. Surgical treatment of these injuries can achieve favourable clinical and radiological outcomes in the medium to long term follow-up. More research is still needed to optimize clinical decision-making regarding surgical approach.
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Background: Enterostomy is important for radical resection of colorectal cancer (CRC). Nevertheless, the notable occurrence of complications linked to enterostomy results in a reduction in patients' quality of life and impedes adjuvant therapy. This study sought to forecast early stoma-related complications (ESRCs) by leveraging easily accessible nutrition-inflammation markers in CRC patients. Methods: This study involved 470 individuals with colorectal cancer who underwent intestinal ostomy at Changhai Hospital Affiliated with Naval Medical University as the internal cohort. Between January 2016 and December 2018, the patients were enrolled and randomly allocated into a primary training group and a secondary validation group, with a ratio of 2:1 being upheld. The research encompassed collecting data on each patient's clinical and pathological status, along with preoperative laboratory results. Independent risk factors were identified through Lasso regression and multivariate analysis, leading to the development of clinical models represented by a nomogram. The model's utility was assessed using decision curve analysis, calibration curve, and ROC curve. The final model was validated using an external validation set of 179 individuals from January 2015 to December 2021. Results: Among the internal cohort, stoma complications were observed in 93 cases. Multivariate regression analysis confirmed that age, stoma site, and elevated markers (Mon, NAR, and GLR) in conjunction with diminished markers (GLB and LMR) independently contributed to an increased risk of ESRCs. The clinical model was established based on these seven factors. The training, internal, and external validation groups exhibited ROC curve areas of 0.839, 0.812, and 0.793, respectively. The calibration curve showed good concordance among the forecasted model with real incidence of ostomy complications. The model displayed outstanding predictive capability and is deemed applicable in clinical settings, as evidenced by Decision Curve Analysis. Conclusion: This study identified nutrition-inflammation markers (GLB, NAR, and GLR) in combination with demographic data as crucial predictors for forecasting ESRCs in colorectal cancer patients. A novel prognostic model was formulated and validated utilizing these markers.
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Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study provides a comprehensive map of m1A in dinoflagellate mRNA and shows that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetric distribution along mature transcripts. In Amphidinium carterae, we identify 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many of which are involved in regulating carbon and nitrogen metabolism. Enriched within 3'UTRs, dinoflagellate mRNA m1A levels negatively correlate with translation efficiency. Nitrogen depletion further decreases mRNA m1A levels. Our data suggest that distinctive patterns of m1A modification might influence the expression of metabolism-related genes through translational control.
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High-intensity interval training (HIIT) has been found to be more effective in relieving heart failure (HF) symptoms, than moderate-intensity continuous aerobic training (MICT). Additionally, higher meteorin-like protein (Metrnl) levels are seen after HIIT versus MICT. We investigated whether Metrnl contributed to post-HF cardiac functional improvements, and the signaling pathways involved. 50 HF patients underwent MICT, and another 50, HIIT, which was followed by cardiac function and serum Metrnl measurements. Metrnl was also measured in both blood and skeletal muscle samples of mice with transverse aortic constriction-induced HF after undergoing HIIT. Afterward, shRNA-containing adenovectors were injected into mice, yielding five groups: control, HF, HF + HIIT + scrambled shRNA, HF + HIIT + shMetrnl, and HF + Metrnl (HF + exogenous Metrnl). Mass spectrometry identified specific signaling pathways associated with increased Metrnl, which was confirmed with biochemical analyses. Glucose metabolism and mitochondrial functioning were evaluated in cardiomyocytes from the five groups. Both HF patients and mice had higher circulating Metrnl levels post-HIIT. Metrnl activated AMPK in cardiomyocytes, subsequently increasing histone deacetylase 4 (HDAC4) phosphorylation, leading to its cytosolic sequestration and inactivation via binding with chaperone protein 14-3-3. HDAC4 inactivation removed its repression on glucose transporter type 4, which, along with increased mitochondrial complex I-V expression, yielded improved aerobic glucose respiration and alleviation of mitochondrial dysfunction. All these changes ultimately result in improved post-HF cardiac functioning. HIIT increased skeletal muscle Metrnl production, which then operated on HF hearts to alleviate their functional defects, via increasing aerobic glucose metabolism through AMPK-HDAC4 signaling.
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Chronic pain, as a social public health problem, has a serious impact on the quality of patients' life. Currently, the main drugs used to treat chronic pain are opioids, antipyretic, and nonsteroidal anti-inflammatory drugs (NSAIDs). But the obvious side effects limit their use, so it is urgent to find new therapeutic targets. Postsynaptic density (PSD)-95 protein plays an important role in the occurrence and development of chronic pain. The over-expression of the PSD-95 protein and its interaction with other proteins are closely related to the chronic pain. Besides, the PSD-95-related drugs that inhibit the expression of PSD-95 as well as the interaction with other protein have been proved to treat chronic pain significantly. In conclusion, although more deep studies are needed in the future, these studies indicate that PSD-95 and the related proteins, such as NMDA receptor (NMDAR) subunit 2B (GluN2B), AMPA receptor (AMPAR), calmodulin-dependent protein kinase II (CaMKII), 5-hydroxytryptamine 2A receptor (5-HT2AR), and neuronal nitric oxide synthase (nNOS), are the promising therapeutic targets for chronic pain.
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Medical Speed-of-sound (SoS) imaging, which can characterize medical tissue properties better by quantifying their different SoS, is an effective imaging method compared with conventional B-mode ultrasound imaging. As a commonly used diagnostic instrument, a hand-held array probe features convenient and quick inspection. However, artifacts will occur in the single-angle SoS imaging, resulting in indistinguishable tissue boundaries. In order to build a high-quality SoS image, a number of raw data are needed, which will bring difficulties to data storage and processing. Compressed sensing (CS) theory offers theoretical support to the feasibility that a sparse signal can be rebuilt with random but less sampling data. In this study, we proposed an SoS reconstruction method based on CS theory to process signals obtained from a hand-held linear array probe with a passive reflector positioned on the opposite side. The SoS reconstruction method consists of three parts. Firstly, a sparse transform basis is selected appropriately for a sparse representation of the original signal. Then, considering the mathematical principles of SoS imaging, the ray-length matrix is used as a sparse measurement matrix to observe the original signal, which represents the length of the acoustic propagation path. Finally, the orthogonal matching pursuit algorithm is introduced for image reconstruction. The experimental result of the phantom proves that SoS imaging can clearly distinguish tissues that show similar echogenicity in B-mode ultrasound imaging. The simulation and experimental results show that our proposed method holds promising potential for reconstructing precision SoS images with fewer signal samplings, transmission, and storage.
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Algoritmos , Fantasmas de Imagen , Ultrasonografía , Ultrasonografía/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Procesamiento de Señales Asistido por Computador , HumanosRESUMEN
The temperature response of pavement is not only crucial for assessing the internal stresses within pavement structures but is also an essential parameter in pavement design. Investigating the temperature response of rubberized concrete pavements (RCP) can support the construction of large-scale rubber concrete pavements. This study constructed a pavement monitoring system based on fiber Bragg grating technology to investigate the temperature distribution, temperature strain, temperature effects, and temperature stress of RCP. The results show that the daily temperature-time history curves of concrete pavement exhibit a significant asymmetry, with the heating phase accounting for only one-third of the curve. The temperature at the middle of RCP is 1.8 °C higher than that of ordinary concrete pavement (OCP). The temperature distribution along the thickness of the pavement follows a "spindle-shaped" pattern, with higher temperatures in the center and lower temperatures at the ends. Additionally, the addition of rubber aggregates increases the temperature strain in the pavements, makes the temperature-strain hysteresis effect more pronounced, and increases the curvature of the pavement slab. However, the daily stress range at the bottom of RCP is approximately 0.7 times that of OCP.
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In autonomous driving, environmental perception technology often encounters challenges such as false positives, missed detections, and low accuracy, particularly in detecting small objects and complex scenarios. Existing algorithms frequently suffer from issues like feature redundancy, insufficient contextual interaction, and inadequate information fusion, making it difficult to perform multi-task detection and segmentation efficiently. To address these challenges, this paper proposes an end-to-end multi-task environmental perception model named YOLO-Mg, designed to simultaneously perform traffic object detection, lane line detection, and drivable area segmentation. First, a multi-stage gated aggregation network (MogaNet) is employed during the feature extraction process to enhance contextual interaction by improving diversity in the channel dimension, thereby compensating for the limitations of feed-forward neural networks in contextual understanding. Second, to further improve the model's accuracy in detecting objects of various scales, a restructured weighted bidirectional feature pyramid network (BiFPN) is introduced, optimizing cross-level information fusion and enabling the model to handle object detection at different scales more accurately. Finally, the model is equipped with one detection head and two segmentation heads to achieve efficient multi-task environmental perception, ensuring the simultaneous execution of multiple tasks. The experimental results on the BDD100K dataset demonstrate that the model achieves a mean average precision (mAP50) of 81.4% in object detection, an Intersection over Union (IoU) of 28.9% in lane detection, and a mean Intersection over Union (mIoU) of 92.6% in drivable area segmentation. The tests conducted in real-world scenarios show that the model performs effectively, significantly enhancing environmental perception in autonomous driving and laying a solid foundation for safer and more reliable autonomous driving systems.
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Several chemotherapeutics against breast cancer are constrained by their adverse effects and chemoresistance. The development of novel chemotherapeutics to target metastatic breast cancer can bring effective clinical outcomes. Many breast cancer patients present with tumors that are positive for estrogen receptors (ERs), highlighting the importance of targeting the ER pathway in this particular subtype. Although selective estrogen receptor modulators (SERMs) are commonly used, their side effects and resistance issues necessitate the development of new ER-targeting agents. In this study, we report that a newly synthesized compound, TTP-5, a hybrid of pyrimidine, triazole, and tert-butyl-piperazine-carboxylate, effectively binds to estrogen receptor alpha (ERα) and suppresses breast cancer cell growth. We assessed the impact of TTP-5 on cell proliferation using MTT and colony formation assays and evaluated its effect on cell motility through wound healing and invasion assays. We further explored the mechanism of action of this novel compound by detecting protein expression changes using Western blotting. Molecular docking was used to confirm the interaction of TTP-5 with ERα. The results indicated that TTP-5 significantly reduced the proliferation of MCF-7 cells by blocking the ERα signaling pathway. Conversely, although it did not influence the growth of MDA-MB-231 cells, TTP-5 hindered their motility by modulating the expression of proteins associated with epithelial-mesenchymal transition (EMT), possibly via the Wnt/ß-catenin pathway.
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Organic afterglow with long-persistent luminescence (LPL) after photoexcitation is highly attractive, but the realization of narrowband afterglow with small full-width at half-maximum (FWHM) is a huge challenge since it is intrinsically contradictory to the triplet- and solid-state emission nature of organic afterglow. Here, narrow-band, long-lived, and full-color organic LPL is realized by isolating multi-resonant thermally activated delayed fluorescent (MR-TADF) fluorophores in a glassy steroid-type host through a facile melt-cooling treatment. Such prepared host becomes capable of exciton dissociation and recombination (EDR) upon photoirradiation for both long-lived fluorescence and phosphorescence; and, the efficient Förster resonance energy transfer (FRET) from the host to various MR-TADF emitters leads to high-performance LPL, exhibiting small FWHM of 33 nm, long persistent time over 10 s, and facile color-tuning in a wide range from deep-blue to orange (414-600 nm). Moreover, with the extraordinary narrowband LPL and easy processability of the material, centimeter-scale flexible optical waveguide fibers and integrated FWHM/color/lifetime-resolved multilevel encryption/decryption devices have been designed and fabricated. This novel EDR and singlet/triplet-to-singlet FRET strategy to achieve excellent LPL performances illustrates a promising way for constructing flexible organic afterglow with easy preparation methods, shedding valuable scientific insights into the design of narrow-band emission in organic afterglow.
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BACKGROUND: Evidence on the link between iron status markers and insulin resistance (IR) is limited. We aimed to explore the relationship between iron status and IR among U.S. adults. METHODS: This study involved 2993 participants from the National Health and Nutrition Examination Survey (NHANES) 2003-2006, 2017-2020. IR is characterized by a HOMA-IR value of ≥2.5. Weighted linear and multivariable logistic regression analyses were used to examine the linear relationships between iron status and IR. Furthermore, restricted cubic splines (RCS) were used to identify the non-linear dose-response associations. Stratified analyses by age, sex, BMI and PA were also performed. Last, ROC curve was used to evaluate the predictive value of iron status in IR. RESULTS: In weighted linear analyses, serum iron (SI) exhibited a negative correlation with HOMA-IR (ß (95% CI) = -0.03(-0.05, -0.01), P = 0.01). In weighted multivariate logistic analyses, iron intake and serum transferrin receptor (sTfR) were positively correlated with IR (OR =1.02; 95% CI=1.00-1.04, P = 0.04; OR =1.07; 95% CI=1.02-1.13, P = 0.01). Also, SI and transferrin saturation (TSAT) were negatively correlated with IR (OR =0.96; 95% CI=0.94-0.98, P <0.0001; OR =0.98; 95% CI=0.97-0.99, P <0.001) after adjusting for confounding factors. RCS depicted a nonlinear dose-response relationship between sTfR and TSAT and IR. This correlation remained consistent across various population subgroups. ROC curve showed that TSAT performed better than iron intake, SI, sTfR and TSAT in ROC analyses for IR prediction. CONCLUSION: All biomarkers demonstrated significantly lower risk of IR with increasing iron levels, which will contribute to a more comprehensive and in-depth understanding of the relationship between the two and provide a solid foundation for future exploration of the mechanisms underlying their relationship.
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Understanding the genetic basis of salt resistance in crops is crucial for agricultural productivity. This study investigates the phenotypic and genetic basis of salt stress response in rice (Oryza sativa L.), focusing on germination and seedling traits. Under salt stress conditions, significant differences were observed in seed germination and seedling traits between parental LH99 (Indica rice LuHui 99) and SN265 (japonica rice ShenNong 265). Transgressive segregation was evident within the RIL population, indicating complex genetic interactions. Nine QTLs were detected at germination and seedling stages under salt stress, namely qSGE5 and qSGE7 for seed germination energy (SGE); qSGP7 for seed germination percentage (SGP); qSSH7, qSSH9-1, and qSSH9-2 for seeding height (SSH); qSRN6 for root number (SRN); and qSDW6 and qSDW9 for dry weight (SDW). Among them, qSSH9-1 and qSDW9 were localized in the same interval, derived from the salt-resistant parent SN265. PCA revealed distinct trait patterns under salt stress, captured by six PCs explaining 81.12% of the total variance. PC composite scores were used to localize a QTL associated with early salt resistance in rice qESC9, which was located in the same interval as qSSH9-1 and qSDW9, and was subsequently unified under the name qESC9, an important QTL for early-growth salt tolerance in rice. Correlation analysis also confirmed a relationship between alleles of qESC9 and the resistance to salt, underscoring the critical role this locus plays in the determination of overall salt tolerance in rice. Physiological analyses of extreme phenotype lines highlighted the importance of ion exclusion mechanisms in salt-resistant lines, while salt-susceptible lines exhibited elevated oxidative stress and impaired antioxidant defense, contributing to cellular damage. This comprehensive analysis sheds light on the genetic and physiological mechanisms underlying salt stress response in rice, providing valuable insights for breeding programs aimed at enhancing salt resistance in rice.
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Excessive residue of metronidazole (MNZ) in food is harmful to the human body. There is an urgent demand to develop a portable tool for MNZ detection on-site. In this study, fifteen aptamers were prepared through targeted base mutation. Apt1-3 with the highest enrichment was chosen for further study. Its affinity was characterized by molecular docking simulation, AuNPs colorimetric assay, graphene oxide (GO) fluorescence assay, and exonuclease assay. Kd was determined by GO fluorescence assay (Kd: 92.60 ± 25.59 nM). Its specificity was also characterized by an exonuclease assay. A novel aptasensor was constructed by using the newly identified aptamer combined with the smartphone dark box. The principle of color change is caused by the aggregation state of AuNPs. Smartphones act as reading instruments. The detection can be completed in just a few seconds without the aid of instruments, achieving a detection limit of 0.15 nmol/mL and a range of 6.7-44.4 nmol/mL (R 2 = 0.9810). Therefore, the constructed smartphone colorimetric sensor based on mutant aptamers has important applications in food detection.
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BACKGROUND & AIMS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after TIPS remains inconclusive. This study aimed to identify the ideal moment of hemodynamic measurements and the optimal target of PPG in patients undergoing covered TIPS for variceal bleeding. METHODS: Between May 2018 and December 2021, 466 consecutive patients with recurrent variceal bleeding treated with covered TIPS were prospectively included. Post-TIPS PPG were measured immediately (immediate PPG), 24-72 hours (early PPG), and again 1 month (late PPG) after TIPS placement. The agreement among PPGs measured at different time points was assessed by intra-class correlation coefficient (ICC) and Bland-Altman method. The unadjusted and confounder-adjusted effects of PPGs on the clinical outcomes (portal hypertension complications [PHC], overt hepatic encephalopathy [OHE], further decompensation, and death) were assessed using Fine and Gray competing risk regression models. RESULTS: The agreement between early PPG and late PPG (ICC: 0.34) was better than that between immediate PPG and late PPG (ICC: 0.23, p<0.001). Early PPG revealed an excellent predictive value for PHC risk (early PPG ≥ vs <12 mmHg: adjusted HR [95%CI]: 2.17 [1.33-3.55], p=0.002) as well as OHE (0.40 [0.17-0.91], p=0.030) while immediate PPG did not. Late PPG showed a predictive value for PHC risk but not OHE. By targeting the lowest risk of further decompensation, we identified an optimal hemodynamic target with early PPG ranging 11 to 14 mmHg that was associated with a decreased risk of OHE while effectively preventing PHC. CONCLUSIONS: PPG measured 24 to 72 hours after TIPS correlates with long term PPG and clinical outcomes, and hemodynamic target with a PPG 11-14 mmHg reduced encephalopathy but not compromised clinical efficacy. IMPACT AND IMPLICATIONS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) remains inconclusive. Here we show that post-TIPS PPG measured at least 24 hours but not immediately after the procedure correlated with long-term PPG and clinical events, therefore should be used for decision making in order to improve clinical outcomes. Targeting post-TIPS PPG at 11-14 mmHg or 20%-50% relative reduction from pre-TIPS baseline that measured 24-72 hours after procedure reduced encephalopathy but not compromised clinical efficacy, therefore could be used to guide TIPS creation and revision in patients with cirrhosis and variceal bleeding undergoing covered TIPS. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, ID: NCT03590288.
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AIMS: The parabrachial nucleus (PBN) promotes wakefulness states under general anesthesia. Recent studies have shown that glutamatergic neurons within the PBN play a crucial role in facilitating emergence from anesthesia. Our previous study indicates that vesicular glutamate transporter 2 (vglut2) expression neurons of the PBN extend into the extended amygdala (EA). However, the modulation of PBNvglut2-EA in general anesthesia remains poorly understood. This study aims to investigate the role of PBNvglut2-EA in alterations of consciousness during sevoflurane anesthesia. METHODS: We first validated vglut2-expressing neuron projections from the PBN to the EA using anterograde tracing. Then, we conducted immunofluorescence staining of c-Fos to investigate the role of the EA involved in the regulation of consciousness during sevoflurane anesthesia. After, we performed calcium fiber photometry recordings to determine the changes in PBNvglut2-EA activity. Lastly, we modulated PBNvglut2-EA activity under sevoflurane anesthesia using optogenetics, and electroencephalogram (EEG) was recorded during specific optogenetic modulation. RESULTS: The expression of vglut2 in PBN neurons projected to the EA, and c-Fos expression in the EA was significantly reduced during sevoflurane anesthesia. Fiber photometry revealed that activity in the PBNvglut2-EA pathway was suppressed during anesthesia induction but restored upon awakening. Optogenetic activation of the PBNvglut2-EA delayed the induction of anesthesia. Meanwhile, EEG recordings showed significantly decreased δ oscillations and increased ß and γ oscillations compared to the EYFP group. Furthermore, optogenetic activation of the PBNvglut2-EA resulted in an acceleration of awakening from anesthesia, accompanied by decreased δ oscillations on EEG recordings. Optogenetic inhibition of PBNvglut2-EA accelerated anesthesia induction. Surprisingly, we found a sex-specific regulation of PBNvglut2-EA in this study. The activity of PBNvglut2-EA was lower in males during the induction of anesthesia and decreased more rapidly during sevoflurane anesthesia compared to females. Photoactivation of the PBNvglut2-EA reduced the sensitivity of males to sevoflurane, showing more pronounced wakefulness behavior and EEG changes than females. CONCLUSIONS: PBNvglut2-EA is involved in the promotion of wakefulness under sevoflurane anesthesia. Furthermore, PBNvglut2-EA shows sex differences in the changes of consciousness induced by sevoflurane anesthesia.
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Amígdala del Cerebelo , Anestésicos por Inhalación , Ratones Endogámicos C57BL , Neuronas , Núcleos Parabraquiales , Sevoflurano , Proteína 2 de Transporte Vesicular de Glutamato , Vigilia , Sevoflurano/farmacología , Animales , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Proteína 2 de Transporte Vesicular de Glutamato/genética , Proteína 2 de Transporte Vesicular de Glutamato/biosíntesis , Vigilia/efectos de los fármacos , Vigilia/fisiología , Ratones , Anestésicos por Inhalación/farmacología , Núcleos Parabraquiales/efectos de los fármacos , Núcleos Parabraquiales/metabolismo , Núcleos Parabraquiales/fisiología , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Ratones Transgénicos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/metabolismo , Optogenética/métodos , ElectroencefalografíaRESUMEN
Objective: To explore the diagnostic value of micropure imaging (MI) combined with strain elastography (SE) in correcting artificial intelligence (AI) S-Detect technology for benign and malignant breast complex cystic and solid masses. Methods: The S-Detect diagnosis results were corrected based on the manifestations of MI and SE of the 145 breast complex cystic and solid masses. Postoperative pathological results were used as the gold standard to calculate the diagnostic sensitivity, specificity, and accuracy before and after correction. Additionally, receiver operating characteristic (ROC) curves were drawn for both groups, and the areas under the curves were compared. Results: There were 80 benign and 65 malignant pathological results. After the correction of S-Detect, the diagnostic sensitivity, specificity, and accuracy, as well as the areas under the ROC curves, were all improved compared to before the correction. Conclusion: Combining MI and SE to correct the diagnostic results of S-Detect can help improve the diagnostic efficacy of breast complex cystic and solid masses.
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Inteligencia Artificial , Neoplasias de la Mama , Diagnóstico por Imagen de Elasticidad , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Sensibilidad y Especificidad , Curva ROC , Mama/diagnóstico por imagenRESUMEN
BACKGROUND: Multiple endocrine neoplasias (MENs) are a group of hereditary diseases involving multiple endocrine glands, and their prevalence is low. MEN type 1 (MEN1) has diverse clinical manifestations, mainly involving the parathyroid glands, gastrointestinal tract, pancreas and pituitary gland, making it easy to miss the clinical diagnosis. CASE SUMMARY: We present the case of a patient in whom MEN1 was detected early. A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hospital. Blood tests at admission revealed hypercalcemia and hypophosphatemia, and emission computed tomography of the parathyroid glands revealed a hyperfunctioning parathyroid lesion. Gastroscopy findings suggested a duodenal bulge and ulceration. Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb. Further blood tests revealed elevated levels of serum gastrin. Surgery was performed, and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy. The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year. CONCLUSION: For patients who present with gastrointestinal symptoms accompanied by hypercalcemia and hypophosphatemia, clinicians need to be alert to the possibility of MEN1.
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Hipercalcemia , Neoplasia Endocrina Múltiple Tipo 1 , Neoplasias de las Paratiroides , Paratiroidectomía , Humanos , Neoplasia Endocrina Múltiple Tipo 1/cirugía , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Neoplasia Endocrina Múltiple Tipo 1/patología , Masculino , Neoplasias de las Paratiroides/cirugía , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/patología , Neoplasias de las Paratiroides/complicaciones , Persona de Mediana Edad , Hipercalcemia/diagnóstico , Hipercalcemia/etiología , Hipercalcemia/sangre , Adenoma/cirugía , Adenoma/diagnóstico , Adenoma/patología , Adenoma/sangre , Neoplasias Duodenales/cirugía , Neoplasias Duodenales/diagnóstico , Neoplasias Duodenales/patología , Hipofosfatemia/etiología , Hipofosfatemia/diagnóstico , Dolor Abdominal/etiología , Dolor Abdominal/diagnóstico , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/sangre , Tumores Neuroendocrinos/patología , Diarrea/etiología , Diarrea/diagnóstico , Detección Precoz del Cáncer/métodos , Gastroscopía , Resultado del TratamientoRESUMEN
Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for novel therapeutic targets. This study aimed to elucidate the role of endoplasmic reticulum membrane protein complex subunit 1 (EMC1) in HCC progression and its therapeutic potential. Methods: Publicly available sequencing data and biopsy specimens were analyzed to assess EMC's clinical value and functions in HCC. In vitro experiments validated EMC functions, and multiplex immunofluorescence analysis examined EMC-associated sorafenib resistance mechanisms. EMC1 expression was knocked down in HCC cell lines, followed by cell viability, wound healing, and transwell migration assays. Tumor growth and response to sorafenib treatment were evaluated in mouse models. Metabolomic analysis assessed changes in the TCA cycle. Results: EMC genes were aberrantly expressed in HCC, and high EMC1 expression correlated with poorer survival rates. EMC1 disruption enhanced HCC cells' sensitivity to sorafenib, reducing cell viability, increasing apoptosis, and decreasing tumor size and weight. EMC1 maintained cancer cell stemness and promoted M2 macrophage infiltration. Metabolomic analysis revealed significant changes in the TCA cycle, indicating EMC1's role in HCC metabolic reprogramming. Importantly, EMC1 is highly associated with sorafenib resistance, potentially linked to CTNNB1 mutation or activation. Conclusion: EMC1 plays a critical role in regulating the sorafenib resistance in HCC. Targeting EMC1 may improve HCC treatment efficacy.
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Introduction: Nuclear factor kappa (NF-κB) plays a key role in cancer cell proliferation; thus, small molecule inhibitors of NF-κB activity can effectively inhibit breast cancer (BC) progression. We have previously reported oxazine and piperazine-linked pyrimidines as novel anti-cancer agents that can suppress NF-κB activation in BC cells. Moreover, the TRX-01 compound, an oxazine-linked pyrimidine, inhibited MCF-7 cells at a concentration of 9.17 µM in the Alamar Blue assay. Methods: This work involved the analysis of frontier molecular orbitals, HOMO-LUMO interactions, and molecular electrostatic potential for the TRX-01 structure. Additionally, the TRX-01 compound was studied for cytotoxicity, and migration as well as invasion assays were performed on BC cells. Results: Finally, TRX-01 blocked the translocation of NF-κB from the cytoplasm to the nucleus in MCF-7 cells and reduced NF-κB and IκBα levels in a dose-dependent manner. It also suppressed migratory and invasive properties of BC cells. Conclusion: Overall, the data indicates that TRX-01 can function as a novel blocker of BC growth and metastasis by targeting NF-κB activation.
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accurately synthesizing coordination-driven metal-organic cages with customized shape and cavity remain a great challenge for chemists. In this work, a bottom-up step-wise coordination-driven self-assembly approach was put forward. Employing this strategy, three terpyridyl heterometallic-organic truncated tetrahedral cages with different sizes and cavity were precisely synthesized. Firstly, the coordination of tripodal organic ligands with Ru2+ afforded dendritic metal-organic ligands L1-L3. Then the Ru building blocks complexed with Fe2+ and shrunk to form the desired heterometallic-organic cages (C1-C3). These discrete heterometallic-organic supramolecular cages were fully characterized and displayed the large and open cavities varied from 7205 Å3 to 9384 Å3. Notably, these cages could not be directly constructed by single-step assembly process using initial organic ligands or dimeric metal-organic ligands, indicative of the irreplaceability of a bottom-up step-wise assembly strategy for size-customized architectures. This work paves a new way for precisely constructing metal-organic cages with well-defined cavities.