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1.
World J Gastroenterol ; 30(10): 1377-1392, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38596500

RESUMO

BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.


Assuntos
Doença de Crohn , Enterite , Tuberculose Gastrointestinal , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Espectroscopia de Infravermelho com Transformada de Fourier , Diagnóstico Diferencial , Parafina , Tuberculose Gastrointestinal/diagnóstico , Tuberculose Gastrointestinal/patologia , Enterite/diagnóstico , Aprendizado de Máquina , Proteínas Mutadas de Ataxia Telangiectasia
2.
Artigo em Inglês | MEDLINE | ID: mdl-38598397

RESUMO

Spiking neural networks (SNNs) are attracting widespread interest due to their biological plausibility, energy efficiency, and powerful spatiotemporal information representation ability. Given the critical role of attention mechanisms in enhancing neural network performance, the integration of SNNs and attention mechanisms exhibits tremendous potential to deliver energy-efficient and high-performance computing paradigms. In this article, we present a novel temporal-channel joint attention mechanism for SNNs, referred to as TCJA-SNN. The proposed TCJA-SNN framework can effectively assess the significance of spike sequence from both spatial and temporal dimensions. More specifically, our essential technical contribution lies on: 1) we employ the squeeze operation to compress the spike stream into an average matrix. Then, we leverage two local attention mechanisms based on efficient 1-D convolutions to facilitate comprehensive feature extraction at the temporal and channel levels independently and 2) we introduce the cross-convolutional fusion (CCF) layer as a novel approach to model the interdependencies between the temporal and channel scopes. This layer effectively breaks the independence of these two dimensions and enables the interaction between features. Experimental results demonstrate that the proposed TCJA-SNN outperforms the state-of-the-art (SOTA) on all standard static and neuromorphic datasets, including Fashion-MNIST, CIFAR10, CIFAR100, CIFAR10-DVS, N-Caltech 101, and DVS128 Gesture. Furthermore, we effectively apply the TCJA-SNN framework to image generation tasks by leveraging a variation autoencoder. To the best of our knowledge, this study is the first instance where the SNN-attention mechanism has been employed for high-level classification and low-level generation tasks. Our implementation codes are available at https://github.com/ridgerchu/TCJA.

3.
Chin J Integr Med ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38570473

RESUMO

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

4.
BMC Urol ; 24(1): 91, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643096

RESUMO

BACKGROUND: Sleep quality may be related to benign prostatic hyperplasia (BPH), however causal associations have not been established. This study aimed to evaluate causal relationships between six sleep traits ([i] day time napping, [ii] daytime sleepiness, [iii] insomnia, [iv] long sleep duration, [v] short sleep duration, and [vi] sleep duration per hour) and BPH through a bidirectional Mendelian randomization (MR) study. METHODS: Genome-wide association summary statistics of sleep traits and BPH were downloaded from public databases. Inverse variance weighting (IVW) was used as the main approach for causal inference. For causal estimates identified by IVW, various sensitivity analyses were performed to assess the reliability of the results: (i) four additional MR methods to complement IVW; (ii) Cochran's Q test to assess heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test to assess horizontal pleiotropy; and (iv) leave-one-out method to assess stability. RESULTS: Forward MR analyses indicated that genetically predicted insomnia symptom significantly increased BPH risk (OR = 1.267, 95% CI: 1.003-1.601, P = 0.048), while reverse MR analyses identified that genetically predicted liability to BPH significantly increased the incidence of insomnia (OR = 1.026, 95% CI: 1.000-1.052, P = 0.048). In a replicate MR analysis based on summary statistics including exclusively male participants, the finding of increased risk of BPH due to genetically predicted insomnia symptom was further validated (OR = 1.488, 95% CI: 1.096-2.022, P = 0.011). No further causal links were identified. In addition, sensitivity tests demonstrated the reliability of the MR results. CONCLUSION: This study identified that a higher prevalence of genetically predicted insomnia symptoms may significantly increase the risk of BPH, while genetically predicted liability to BPH may in turn increase the incidence of insomnia symptom. Therefore, improving sleep quality and reducing the risk of insomnia could be a crucial approach for the prevention of BPH.


Assuntos
Hiperplasia Prostática , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Distúrbios do Início e da Manutenção do Sono/genética , Hiperplasia Prostática/complicações , Hiperplasia Prostática/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes
5.
Reprod Toxicol ; 126: 108597, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38643889

RESUMO

Previous studies indicated conflicting findings regarding the association between vitamin D and abnormal spermatozoa. Herein, we assessed the causal association between circulating 25-Hydroxyvitamin D (25OHD) levels and the risk of abnormal spermatozoa by utilizing bidirectional Mendelian randomization (MR) analysis. Genome-wide association study summary statistics for 25OHD and abnormal spermatozoa were obtained from publicly accessible databases. Single nucleotide polymorphisms (SNPs) associated with 25OHD and SNPs associated with abnormal spermatozoa were used as instrumental variables (IVs) for forward MR analysis and reverse MR analysis, respectively. Inverse variance weighted (IVW) was the main MR approach, while weighted median, MR-Egger, and maximum likelihood methods were employed to supplement IVW. In addition, several sensitivity tests assessed the reliability of MR analysis. Forward MR analysis showed that elevated 25OHD levels significantly reduced abnormal spermatozoa risk (odds ratio [OR] = 0.75, 95 % confidence interval [CI]: 0.56-1.00, P = 4.98E-02), and the effect remained statistically significant after excluding SNPs associated with confounders (OR = 0.73, 95 % CI: 0.54-0.98, P = 3.83E-02) or only utilizing SNPs located near 25OHD-associated genes only as IVs (OR = 0.58, 95 % CI: 0.41-0.81, P = 1.67E-03). Reverse MR analysis indicated abnormal spermatozoa not affecting 25OHD level (P > 0.05). Sensitivity tests showed that MR analyses were not affected by heterogeneity and horizontal polytropy. Overall, the present MR study supports that elevated 25OHD levels reduce the risk of abnormal spermatozoa. Therefore, ensuring adequate vitamin D intake and maintaining stable levels of 25OHD may be effective strategies to optimize reproductive outcomes.

6.
Int J Gen Med ; 17: 925-934, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495921

RESUMO

Objective: To explore the application of serum cardiac troponin T (cTnT), brain natriuretic peptide (BNP) levels, and electrocardiogram changes in the treatment and prognosis evaluation of severe pneumonia in children. Methods: 120 children with severe pneumonia (severe group) admitted to our hospital from June 2020 to December 2022 were selected as the study subjects with prospective study. They were divided into survival group (n=78) and death group (n=42) based on their survival status; 120 children with mild pneumonia were selected as the control group. Compare the levels of serum cTnT and BNP, as well as the changes in electrocardiogram, to analyze their predictive value for the prognosis of pediatric patients and the influencing factors of prognosis. Results: The proportion of children with cTnT, BNP, and abnormal electrocardiogram after treatment was lower than before treatment (P<0.05). The proportion of children with cTnT, BNP, and abnormal electrocardiogram in the severe group was higher than that in the mild group (P<0.05). The proportion of children with serum cTnT, BNP levels, and abnormal electrocardiogram in the death group after treatment was higher than that in the survival group (P<0.05). Bundle branch block, low or inverted T waves, cTnT, and BNP are prognostic factors for children with severe pneumonia (P<0.05). The combined prediction of serum cTnT and BNP for the prognosis of severe pneumonia in children is better than that of single prediction (Z combined detection - cTnT=2.474, Z combined detection - BNP=2.494, P=0.013, 0.013). Conclusion: The proportion of abnormal cTnT, BNP, and electrocardiogram is increased in patients with severe pneumonia, and those with high expression and abnormalities have poor prognosis. cTnT and BNP have high predictive value for the prognosis of children with severe pneumonia.

7.
Dig Dis Sci ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507126

RESUMO

BACKGROUND: We previously treated small gastric submucosal tumors originating from the muscularis propria layer by precutting endoscopic band ligation but lacked precise pathological results. Then, precutting endoscopic band ligation was modified by additional snare resection after ligation to obtain tumor specimens, termed precutting endoscopic band ligation-assisted resection. AIMS: In this study, we aimed to explore the safety, feasibility, and efficacy of precutting endoscopic band ligation-assisted resection. METHODS: From 2021 to 2022, a total of 16 consecutive patients underwent precutting endoscopic band ligation-assisted resection to treat small gastric submucosal tumors originating from the muscularis propria. The clinical demography, perioperative data, and follow-up outcomes were retrospectively collected. RESULTS: With a mean operative time of 21.3 min, all lesions were successfully and completely resected, and no severe adverse events or local recurrences occurred postoperatively. More importantly, en bloc and R0 resection were achieved in all 16 patients. CONCLUSION: Precutting endoscopic band ligation-assisted resection is a safe, effective, and time-saving endoscopic technique for managing gastric small gastric submucosal tumors originating from the muscularis propria for both diagnosis and eradication.

8.
Sci Rep ; 14(1): 7348, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-38538978

RESUMO

To evaluate the current incidence of pulmonary hemorrhage and the potential factors contributing to its increased risk after percutaneous CT-guided pulmonary nodule biopsy and to summarize the technical recommendations for its treatment. In this observational study, patient data were collected from ten medical centers from April 2021 to April 2022. The incidence of pulmonary hemorrhage was as follows: grade 0, 36.1% (214/593); grade 1, 36.8% (218/593); grade 2, 18.9% (112/593); grade 3, 3.5% (21/593); and grade 4, 4.7% (28/593). High-grade hemorrhage (HGH) occurred in 27.2% (161/593) of the patients. The use of preoperative breathing exercises (PBE, p =0.000), semiautomatic cutting needles (SCN, p = 0.004), immediate contrast enhancement (ICE, p =0.021), and the coaxial technique (CoT, p = 0.000) were found to be protective factors for HGH. A greater length of puncture (p =0.021), the presence of hilar nodules (p = 0.001), the presence of intermediate nodules (p = 0.026), a main pulmonary artery diameter (mPAD) larger than 29 mm (p = 0.015), and a small nodule size (p = 0.014) were risk factors for high-grade hemorrhage. The area under the curve (AUC) was 0.783. These findings contribute to a deeper understanding of the risks associated with percutaneous CT-guided pulmonary nodule biopsy and provide valuable insights for developing strategies to minimize pulmonary hemorrhage.


Assuntos
Anormalidades Cardiovasculares , Pneumopatias , Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Humanos , Incidência , Pneumopatias/diagnóstico por imagem , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Hemorragia/epidemiologia , Hemorragia/etiologia , Biópsia Guiada por Imagem/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Fatores de Risco , Estudos Retrospectivos , Anormalidades Cardiovasculares/etiologia , Neoplasias Pulmonares/patologia , Nódulo Pulmonar Solitário/diagnóstico por imagem
9.
Trials ; 25(1): 49, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218850

RESUMO

BACKGROUND: The management of small gastric submucosal tumors (SMTs) originating from the muscularis propria layer (SMT-MPs) remains a subject of debate. Endoscopic submucosal dissection (ESD) is currently considered the optimal treatment for resection. However, high expenses, complex procedures, and the risk of complications have limited its application. Our previously proposed novel operation, precutting endoscopic band ligation (precutting EBL), has been demonstrated in a long-term, single-arm study to be an effective and safe technique for removing small gastric SMTs. However, the absence of a pathological examination and the potential for delayed perforation have raised concerns. Thus, we modified the precutting EBL by adding endoscopic resection to the snare after ligation and closure, yielding the precutting endoscopic band ligation-assisted resection (precutting EBLR). Moreover, the initial pilot study confirmed the safety and efficacy of the proposed approach and we planned a randomized controlled trial (RCT) to further validate its clinical feasibility. METHODS: This was a prospective, single-center, open-label, parallel group, and randomized controlled trial. Approximately 40 patients with SMT-MPs will be included in this trial. The patients included were allocated to two groups: ESD and precutting EBLR. The basic clinical data of the patients were collected in detail. To better quantify the difference between ESD and precutting EBLR, the primary outcome was set as the operation duration. The secondary outcomes included total operation cost and hospitalization, intraoperative adverse events, and postoperative recurrence. The primary outcome was tested for superiority, while the secondary outcomes were tested for noninferiority. SPSS is commonly used for statistical analysis. DISCUSSION: This study was designed to validate the feasibility of a novel operation for removing gastric SMT-MPs. To intuitively assess this phenomenon, the operation durations of precutting EBLR and ESD were compared, and other outcomes were also recorded comprehensively. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200065473 . Registered on November 5, 2022.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Ligadura , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Resultado do Tratamento
10.
Quant Imaging Med Surg ; 14(1): 208-218, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38223129

RESUMO

Background: Pneumothorax is a common complication induced by computed tomography (CT)-guided percutaneous needle biopsy, with a frequency of 17-40.4%. It remains debatable how to predict and prevent the occurrence of post-biopsy pneumothorax. In a real-world setting, we investigated the characteristics associated with pneumothorax in primary lung nodule biopsy. Methods: This clinical registry cohort study recorded patients with newly diagnosed pulmonary nodules from 10 medical centers from April 2021 to April 2022, and the data were input into the electronic data capture (EDC) system. The eligibility criteria for participants included being within the age range of 18 to 80 years and expressing a willingness to undergo percutaneous puncture biopsy, among other requirements. Conversely, the exclusion criteria included an inability to cooperate throughout the biopsy process and the emergence of new health issues during the study duration resulting in attendance delays, among other factors. This study collected data from 924 patients, out of which 593 were included after exclusion. The essential characteristics, imaging features of pulmonary nodules, and technical factors associated with percutaneous biopsy were recorded. T-tests or one-way analysis of variance (ANOVA) were performed for continuous variables and Pearson's χ2 test, likelihood ratio, or Fisher's exact test were applied for categorical variables for comparison as appropriate, followed by multivariate logistic regression. Results: The overall incidence of pneumothorax was 13.0% (77/593), among which timely pneumothorax was 10.3% (61/593), delayed pneumothorax was 2.7% (16/593), and the rate of chest tube placement was 3.4% (20/593). There was no significant difference in the incidence of pneumothorax in a needle size range of 16-19 G (P=0.129), but the incidence of pneumothorax was lower with 17 G needles than with 18 G. An increased morbidity of pneumothorax was correlated with age (P=0.003), emphysema (P=0.006), and operation time (P=0.002). There was no significant increase in the incidence of pneumothorax between 1 or 2 passes through the pleura (P=0.062). However, multiple pleural passes (3 times) increased the chances of pneumothorax significantly (P=0.022). These risk factors have a certain clinical value in predicting the incidence of post-biopsy pneumothorax, and the area under the curve (AUC) was 0.749. Conclusions: The most common post-biopsy complication, pneumothorax, was managed conservatively in most cases. A maximum of two pleural passes does not increase the incidence of pneumothorax, and the 17 G needle is more suitable for percutaneous biopsy of pulmonary nodules in the real world.

11.
Adv Mater ; : e2311432, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191132

RESUMO

Sodium layered-oxides (Nax TMO2 ) sustain severe interfacial stability issues when subjected to battery applications. Particularly at high potential, the oxidation limits including transition metal dissolution and SEI reformation are intertwined upon the cathode, resulting in poor cycle ability. Herein, by rearranging the complex and structure of Helmholtz absorption plane adjacent to Nax TMO2 cathodes, the mechanism of constructing stable cathode/electrolyte interphase to push up oxidation limits is clarified. The strong absorbent fluorinated anions replace the solvents into the inner Helmholtz plane, thereby reorganizing the Helmholtz absorption structure and spontaneously inducing an anion-dominated interphase to envelop more active sites for layered oxides. More importantly, such multi-component cathode/electrolyte interphase proves effective for long-term durability of a series of manganese-based oxide cathodes, which achieves 1500-cycles lifetime against high oxidation voltage limit beyond 4.3 V. This work unravels the key role of breaking high-oxidation limits in attaining higher energy density of layered-oxide systems. This article is protected by copyright. All rights reserved.

12.
Drug Resist Updat ; 73: 101051, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219531

RESUMO

Trastuzumab resistance in HER2+ breast cancer (BC) is the major reason leading to poor prognosis of BC patients. Oncogenic gene overexpression or aberrant activation of tyrosine kinase SRC is identified to be the key modulator of trastuzumab response. However, the detailed regulatory mechanisms underlying SRC activation-associated trastuzumab resistance remain poorly understood. In the present study, we discover that SRC-mediated YAP1 tyrosine phosphorylation facilitates its interaction with transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha, TFAP2A), which in turn promotes YAP1/TEAD-TFAP2A (YTT) complex-associated transcriptional outputs, thereby conferring trastuzumab resistance in HER2+ BC. Inhibition of SRC kinase activity or disruption of YTT complex sensitizes cells to trastuzumab treatment in vitro and in vivo. Additionally, we also identify YTT complex co-occupies the regulatory regions of a series of genes related to trastuzumab resistance and directly regulates their transcriptions, including EGFR, HER2, H19 and CTGF. Moreover, YTT-mediated transcriptional regulation is coordinated by SRC kinase activity. Taken together, our study reveals that SRC-mediated YTT complex formation and transcriptions are responsible for multiple mechanisms associated with trastuzumab resistance. Therefore, targeting HER2 signaling in combination with the inhibition of YTT-associated transcriptional outputs could serve as the treatment strategy to overcome trastuzumab resistance caused by SRC activation.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Trastuzumab/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Fosforilação , Fator de Transcrição AP-2/metabolismo , Receptor ErbB-2/genética , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Quinases da Família src/metabolismo , Quinases da Família src/uso terapêutico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tirosina/metabolismo , Tirosina/uso terapêutico
13.
Artigo em Inglês | MEDLINE | ID: mdl-38096640

RESUMO

The low susceptibility to mastitis of female donkey (jenny) mammary glands and the strong immune properties of donkey milk are acknowledged, but little is known about the genes involved in mammary gland immunity in jennies. Herein, we used RNA-sequencing and bioinformatics analyses to explore jenny mammary gland transcriptomes and detect potential functional differentially expressed (DE) mRNAs related to immunity during four specific developmental stages: foetal (F), pubertal (P), adult parous nonlactation (N) and lactation (L). A total of 2497, 583 and 1820 DE mRNAs were identified in jenny mammary glands at F vs. P, P vs. N, and N vs. L, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) analyses revealed numerous GO terms related to immune function, especially between F and P. Seven significantly enriched profiles were identified, among which 497 and 1261 DE mRNAs were upregulated in profiles 19 and 17. Eleven mRNAs were enriched in over 10 KEGG pathways. ß-2-microglobulin (B2M), immunoglobulin heavy constant mu (IGHM), toll like receptor 2 (TLR2), toll like receptor 4 (TLR4) and myeloid differentiation factor 88 (MYD88) were mainly involved in phosphoinositide 3-kinase (PI3K)-Akt signalling, phagosome and nuclear factor kappa-B (NF-kappa B) signalling pathways. The findings provide insight into the molecular features underpinning the low prevalence of intramammary infections (i.e., mastitis) in donkeys.


Assuntos
Equidae , Mastite , Feminino , Animais , Humanos , Equidae/genética , Equidae/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Perfilação da Expressão Gênica , Transcriptoma , RNA Mensageiro/genética , Imunidade
14.
bioRxiv ; 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38076896

RESUMO

Malignant peripheral nerve sheath tumor (MPNST) is a rare, aggressive soft-tissue sarcoma with a poor prognosis and is insensitive to immune checkpoint blockade (ICB) therapy. Loss-of-function of the histone modifying polycomb repressive complex 2 (PRC2) components, EED or SUZ12, is one of the main mechanisms of malignant transformation. In a murine model of MPNST, PRC2-loss tumors have an "immune desert" phenotype and intratumoral (IT) delivery immunogenic modified vaccinia virus Ankara (MVA) sensitized the PRC2-loss tumors to ICB. Here we show that IT MQ833, a second-generation recombinant modified vaccinia virus Ankara virus, results in neutrophil recruitment and activation and neutrophil-dependent tumor killing in the MPNST model. MQ833 was engineered by deleting three viral immune evasion genes, E5R, E3L, and WR199, and expressing three transgenes, including the two membrane-bound Flt3L and OX40L, and IL-12 with an extracellular matrix anchoring signal. Furthermore, we explored strategies to enhance anti-tumor effects of MQ833 by co-administration of granulocyte colony-stimulating factor (G-CSF).

15.
Int J Surg ; 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38079604

RESUMO

BACKGROUND: There are challenges for beginners to identify standard biliopancreatic system (BPS) anatomical sites on endoscopic ultrasonography (EUS) images. Therefore, we aimed to develop a convolutional neural network (CNN)-based model to identify standard BPS anatomical sites on EUS images. METHODS: The standard anatomical structures of the gastric and duodenal regions observed by EUS was divided into 14 sites. We used 6230 EUS images with standard anatomical sites selected from 1812 patients to train the CNN model, and then tested its diagnostic performance both in internal and external validations. Internal validation set tests were performed on 1569 EUS images of 47 patients from 2 centers. Externally validated datasets were retrospectively collected from 16 centers, and finally 131 patients with 85,322 EUS images were included. In the external validation, all EUS images were read by CNN model, beginners, and experts, respectively. The final decision made by the experts was considered as the gold standard, and the diagnostic performance between CNN model and beginners were compared. RESULTS: In the internal test cohort, the accuracy of CNN model was 92.1%-100.0% for 14 standard anatomical sites. In the external test cohort, the sensitivity and specificity of CNN model were 89.45%-99.92% and 93.35%-99.79%, respectively. Compared with beginners, CNN model had higher sensitivity and specificity for 11 sites, and was in good agreement with the experts (Kappa values 0.84-0.97). CONCLUSIONS: We developed a CNN-based model to automatically identify standard anatomical sites on EUS images with excellent diagnostic performance, which may serve as a potentially powerful auxiliary tool in future clinical practice.

16.
Entropy (Basel) ; 25(12)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38136523

RESUMO

Networks are omnipresent in the realm of science, serving as a central focus in our modern world [...].

18.
J Am Chem Soc ; 145(47): 25766-25775, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37971755

RESUMO

Tuning the spin state of metal carbynes, which have broad applications in organic synthesis and material science, presents a formidable challenge for modern chemists as the strong field nature of carbyne ligands dictates low-spin ground spin states (S = 0 or 1/2) for known metal carbynes. Through the oxidative addition reaction of a low-coordinate iron(0) N-heterocyclic carbene complex with the C-S bond of a thioazole-2-ylidene, we synthesized the first triplet (S = 1) metal terminal carbyne, an iron cyclic carbyne complex. Different from the classical metal carbynes, the triplet complex features an LXZ-type carbyne ligand and a weak Fe≡C triple bond, which endow it with the unique reactivity pattern of facile carbyne coupling, weak affinity toward nucleophiles, and facial addition reactions with electrophiles.

19.
Neurosurg Rev ; 46(1): 305, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37982900

RESUMO

Treatment of blood blister-like aneurysms (BBAs) of the supraclinoid internal carotid artery (ICA) with flow diverters (FDs) has become widespread in recent years. However, ruptured blood blister-like aneurysm (BBA) of ICA treatment with flow diverter-assisted coil embolization (FDAC) remains controversial. Moreover, limited direct comparative studies have been conducted between the two treatment modalities, FDs and FDAC, for BBAs. The purpose of this study was to document our experience and evaluate the effectiveness and safety of FDAC. We conducted a retrospective analysis of clinical and radiological information from ten patients who experienced ruptured BBAs of the supraclinoid ICA at our center from January 2021 to February 2023. The technical details of FDAC for ruptured BBAs were described, and the technical steps were named "pipeline embolization device (PED)-Individualized shaping(microcatheter)-Semi deploying-Rivet(coils)-Massage(microwire)" as the PEISSERM technique. Clinical outcomes were assessed using the modified Rankin Scale (mRS), whereas radiological results were determined through angiography. A pooled analysis was implemented, incorporating data from literature sources that reported perioperative and long-term clinical and angiographic outcomes of ruptured BBAs treated with FD and FDAC strategies, along with our data. Data in our analysis pool were categorized into FD and FDAC strategy groups to explore the preferred treatment modalities for BBAs. The PEISSERM technique was utilized to treat ten patients, seven males, and three females, with an average age of 41.7 years. A single PED was deployed in conjunction with coils in all ten patients. All PEDs were documented to have good wall apposition. The immediate postoperative angiograms demonstrated Raymond grade I in ten aneurysms. Angiographic follow-up of nine patients at 4-25 months showed total occlusion of the aneurysms. At the most recent follow-up, the mRS scores of nine patients hinted at a good prognosis. Pooled analysis of 233 ICA-BBA cases of FD revealed a technical success rate of 91% [95% confidence interval (CI), 0.88 to 0.95], a rate of complete occlusion of 79% (95% CI, 0.73 to 0.84), a recurrence rate of 2% (95% CI, 0.00 to 0.04), a rebleed rate of 2% (95% CI, 0.00 to 0.04), and the perioperative stroke rate was 8% (95% CI, 0.04 to 0.11). The perioperative mortality was 4% (95% CI, 0.01 to 0.07). The long-term good clinical outcome rate was 85% (95% CI, 0.80 to 0.90). The mortality rate was 6% (95% CI, 0.03 to 0.09). Results from the subgroup analysis illustrated that the FDAC strategy for BBAs had a significantly higher immediate postoperative complete occlusion rate (P < 0.001), total occlusion rate (P = 0.016), and a good outcome rate (P = 0.041) compared with the FD strategy. The FDAC strategy can yield a higher rate of good outcomes than the FD strategy. The PEISSERM technique employed by the FDAC is a reliable and effective treatment approach as it can minimize the hemodynamic burden of BBA's fragile dome, thereby achieving an excellent occlusion rate. The PEISSERM technique in the FDAC strategy contributes to understanding the BBA's treatment and offers a potentially optimal treatment for BBA.


Assuntos
Aneurisma Roto , Artéria Carótida Interna , Feminino , Masculino , Humanos , Adulto , Artéria Carótida Interna/cirurgia , Estudos Retrospectivos , Aneurisma Roto/cirurgia , Angiografia , Prótese Vascular
20.
Sci Rep ; 13(1): 16967, 2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37807016

RESUMO

The stability of the surrounding rock for the construction excavation and the reinforcement of the lining structure during operation in the water-rich area is a difficult problem for the design of high-head underground turnout pipes. Firstly, according to the mechanism of excavation load release and surrounding rock damage evolution, the seepage effect of excavation in the construction of the forked caves is coupled to the surrounding rock stress damage, and an iterative method of numerical simulation of the coupled mutual feedback effect of excavation surrounding rock stress and seepage is proposed. Then, based on the cracking characteristics of the high internal water pressure reinforced concrete turnpike lining, a numerical analysis method of the coupling interaction between lining cracking and internal water seepage is proposed by coupling internal water seepage to stress damage in the lining by cracking the forked pipe structure. Applying the aforementioned method to a forked pipe project, the results show that: during the construction period, there is a significant increase in the damage zone, stress, and displacement of the rock around the cavern after considering the coupled iterations; during the operation period, with the increase in internal water pressure, the lining structure accelerates cracking due to the external infiltration of internal water; after the internal water is applied, the surrounding rock bears the main internal water pressure and the reinforcement bears only part of the circumferential force. The method provides theoretical support for the analysis and calculation of the reinforcement of similar underground high-pressure tunnels for rock support and lining structures and has certain theoretical and engineering significance.

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