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1.
Front Nutr ; 11: 1389417, 2024.
Article En | MEDLINE | ID: mdl-38746938

Objective: This study aims to evaluate the origin of the neonatal gut microbiota on the 14th day and probiotic intervention in the third trimester. Methods: Samples were obtained from a total of 30 pregnant individuals and their offspring, divided into a control group with no intervention and a probiotic group with live combined Bifidobacterium and Lactobacillus tablets, analyzing by 16S rRNA amplicon sequencing of the V4 region to evaluate the composition of them. Non-metric multidimensional scaling and SourceTracker were used to evaluate the origin of neonatal gut microbiota. Results: We found that the microbiota in the neonatal gut at different times correlated with that in the maternal microbiota. The placenta had more influence on meconium microbiota. Maternal gut had more influence on neonatal gut microbiota on the 3rd day and 14th day. We also found that the maternal gut, vaginal, and placenta microbiota at full term in the probiotic group did not have a significantly different abundance of Bifidobacterium, Lactobacillus, or Streptococcus. However, some other bacteria changed in the maternal gut and their neonatal gut in the probiotic group.

2.
Eur J Med Chem ; 271: 116437, 2024 May 05.
Article En | MEDLINE | ID: mdl-38701712

As a cytosolic enzyme involved in the purine salvage pathway metabolism, purine nucleoside phosphorylase (PNP) plays an important role in a variety of cellular functions but also in immune system, including cell growth, apoptosis and cancer development and progression. Based on its T-cell targeting profile, PNP is a potential target for the treatment of some malignant T-cell proliferative cancers including lymphoma and leukemia, and some specific immunological diseases. Numerous small-molecule PNP inhibitors have been developed so far. However, only Peldesine, Forodesine and Ulodesine have entered clinical trials and exhibited some potential for the treatment of T-cell leukemia and gout. The most recent direction in PNP inhibitor development has been focused on PNP small-molecule inhibitors with better potency, selectivity, and pharmacokinetic property. In this perspective, considering the structure, biological functions, and disease relevance of PNP, we highlight the recent research progress in PNP small-molecule inhibitor development and discuss prospective strategies for designing additional PNP therapeutic agents.


Enzyme Inhibitors , Purine-Nucleoside Phosphorylase , Small Molecule Libraries , Purine-Nucleoside Phosphorylase/antagonists & inhibitors , Purine-Nucleoside Phosphorylase/metabolism , Humans , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Molecular Structure , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Structure-Activity Relationship , Drug Development
3.
Sensors (Basel) ; 24(9)2024 May 01.
Article En | MEDLINE | ID: mdl-38733010

Underwater visual detection technology is crucial for marine exploration and monitoring. Given the growing demand for accurate underwater target recognition, this study introduces an innovative architecture, YOLOv8-MU, which significantly enhances the detection accuracy. This model incorporates the large kernel block (LarK block) from UniRepLKNet to optimize the backbone network, achieving a broader receptive field without increasing the model's depth. Additionally, the integration of C2fSTR, which combines the Swin transformer with the C2f module, and the SPPFCSPC_EMA module, which blends Cross-Stage Partial Fast Spatial Pyramid Pooling (SPPFCSPC) with attention mechanisms, notably improves the detection accuracy and robustness for various biological targets. A fusion block from DAMO-YOLO further enhances the multi-scale feature extraction capabilities in the model's neck. Moreover, the adoption of the MPDIoU loss function, designed around the vertex distance, effectively addresses the challenges of localization accuracy and boundary clarity in underwater organism detection. The experimental results on the URPC2019 dataset indicate that YOLOv8-MU achieves an mAP@0.5 of 78.4%, showing an improvement of 4.0% over the original YOLOv8 model. Additionally, on the URPC2020 dataset, it achieves 80.9%, and, on the Aquarium dataset, it reaches 75.5%, surpassing other models, including YOLOv5 and YOLOv8n, thus confirming the wide applicability and generalization capabilities of our proposed improved model architecture. Furthermore, an evaluation on the improved URPC2019 dataset demonstrates leading performance (SOTA), with an mAP@0.5 of 88.1%, further verifying its superiority on this dataset. These results highlight the model's broad applicability and generalization capabilities across various underwater datasets.

4.
Int J Mol Sci ; 25(8)2024 Apr 22.
Article En | MEDLINE | ID: mdl-38674155

Different levels of EspP2 expression are seen in strains of Glaesserella parasuis with high and low pathogenicity. As a potential virulence factor for G. parasuis, the pathogenic mechanism of EspP2 in infection of host cells is not clear. To begin to elucidate the effect of EspP2 on virulence, we used G. parasuis SC1401 in its wild-type form and SC1401, which was made EspP2-deficient. We demonstrated that EspP2 causes up-regulation of claudin-1 and occludin expression, thereby promoting the adhesion of G. parasuis to host cells; EspP2-deficiency resulted in significantly reduced adhesion of G. parasuis to cells. Transcriptome sequencing analysis of EspP2-treated PK15 cells revealed that the Rap1 signaling pathway is stimulated by EspP2. Blocking this pathway diminished occludin expression and adhesion. These results indicated that EspP2 regulates the adhesion of Glaesserella parasuis via Rap1 signaling pathway.


Haemophilus parasuis , Signal Transduction , rap1 GTP-Binding Proteins , Animals , Haemophilus parasuis/pathogenicity , Haemophilus parasuis/genetics , rap1 GTP-Binding Proteins/metabolism , rap1 GTP-Binding Proteins/genetics , Bacterial Adhesion , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Occludin/metabolism , Occludin/genetics , Claudin-1/metabolism , Claudin-1/genetics , Cell Line , Swine
5.
Chemosphere ; 357: 141938, 2024 Jun.
Article En | MEDLINE | ID: mdl-38631498

The peroxynitrite photocatalytic degradation system was considered a green, convenient, and efficient water treatment process, but not satisfying against some antibiotics, e.g. sulfonamides (SAs). To improve the photocatalytic degradation efficiency of SAs, sulfur was introduced to a magnetic Fe-MOF (Fe-metal organic framework) Prussian blue analog to achieve a heteroatomic material CuFeO@S, which was applied in heterogeneous visible light photo-assisted catalytic process with persulfate (PS) as an oxidant. The characterization results of CuFeO@S by XRD and XPS confirmed the presence of Fe3O4 (for magnetic separation), Cu+ (for activation of PS) and S2- (for narrowing the energy band and prolonging the lifetime of photo-generated electronics). Through systematic optimization of reaction conditions in CuFeO@S + PS + hv system, efficient degradation of four tested SAs was achieved in 30 min (removal rate of 97-100% for the tested 4 SAs). Moreover, the material could be magnetically recycled and reused for over 7 cycles with a removal rate of >90% for sulfamerazine. Furthermore, the removal rate of sulfamerazine in pond water reached 99% at a mineralization rate of about 34% (decrease in total organic matter), demonstrating its potential in the treatment of antibiotic-containing wastewater.


Ferrocyanides , Oxidation-Reduction , Sulfonamides , Water Pollutants, Chemical , Ferrocyanides/chemistry , Water Pollutants, Chemical/chemistry , Sulfonamides/chemistry , Catalysis , Sulfur/chemistry , Water Purification/methods , Sulfates/chemistry , Light , Metal-Organic Frameworks/chemistry
6.
Eur J Med Chem ; 271: 116399, 2024 May 05.
Article En | MEDLINE | ID: mdl-38640868

The structural optimization of B14, an antibacterial agent we previously obtained, has led to the discovery of a new class of CH2-linked quinolone-aminopyrimidine hybrids with potent anti-MRSA activities. Surprisingly, the hybrids lacking a C-6 fluoro atom at the quinolone nucleus showed equal or even stronger anti-MRSA activities than their corresponding 6-fluoro counterparts, despite the well-established structure-activity relationships (SARs) indicating that the 6-fluoro substituent enhances the antibacterial activity in conventional fluoroquinolone antibiotics. Moreover, these new hybrids, albeit structurally related to conventional fluoroquinolones, showed no cross-resistance with fluoroquinolone drugs. The most active compound, 15m, exhibited excellent activities with a MIC value of 0.39 µg/mL against both fluoroquinolone-sensitive strain USA500 and -resistant MRSA isolate Mu50. Further resistance development studies indicated MRSA is unlikely to acquire resistance against 15m. Moreover, 15m displayed favorable in vivo half-life and safety profiles. These findings suggest a rationale for further evolution of quinolone antibiotics with a high barrier to resistance.


Anti-Bacterial Agents , Fluoroquinolones , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Pyrimidines , Quinolones , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Methicillin-Resistant Staphylococcus aureus/drug effects , Structure-Activity Relationship , Pyrimidines/pharmacology , Pyrimidines/chemistry , Pyrimidines/chemical synthesis , Fluoroquinolones/pharmacology , Fluoroquinolones/chemistry , Fluoroquinolones/chemical synthesis , Quinolones/pharmacology , Quinolones/chemistry , Quinolones/chemical synthesis , Molecular Structure , Drug Resistance, Bacterial/drug effects , Dose-Response Relationship, Drug , Animals , Humans
7.
Clin. transl. oncol. (Print) ; 26(4): 797-807, Abr. 2024. ilus
Article En | IBECS | ID: ibc-VR-44

Tumor cells must resist the host's immune system while maintaining growth under harsh conditions of acidity and hypoxia, which indicates that tumors are more robust than normal tissue. Immunotherapeutic agents have little effect on solid tumors, mostly because of the tumor density and the difficulty of penetrating deeply into the tissue to achieve the theoretical therapeutic effect. Various therapeutic strategies targeting the tumor microenvironment (TME) have been developed. Immunometabolic disorders play a dominant role in treatment resistance at both the TME and host levels. Understanding immunometabolic factors and their treatment potential may be a way forward for tumor immunotherapy. Here, we summarize the metabolism of substances that affect tumor progression, the crosstalk between the TME and immunosuppression, and some potential tumor-site targets. We also summarize the progress and challenges of tumor immunotherapy.(AU)


Humans , Male , Female , Immunotherapy , Metabolism , Hypoxia , Tumor Microenvironment , Neoplasms/drug therapy
8.
J Med Chem ; 67(8): 6425-6455, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38613499

The RAS-RAF-MEK-ERK signaling cascade is abnormally activated in various tumors, playing a crucial role in mediating tumor progression. As the key component at the terminal stage of this cascade, ERK1/2 emerges as a potential antitumor target and offers a promising therapeutic strategy for tumors harboring BRAF or RAS mutations. Here, we identified 36c with a (thiophen-3-yl)aminopyrimidine scaffold as a potent ERK1/2 inhibitor through structure-guided optimization for hit 18. In preclinical studies, 36c showed powerful ERK1/2 inhibitory activities (ERK1/2 IC50 = 0.11/0.08 nM) and potent antitumor efficacy both in vitro and in vivo against triple-negative breast cancer and colorectal cancer models harboring BRAF and RAS mutations. 36c could directly inhibit ERK1/2, significantly block the phosphorylation expression of their downstream substrates p90RSK and c-Myc, and induce cell apoptosis and incomplete autophagy-related cell death. Taken together, this work provides a promising ERK1/2 lead compound for multiple tumor-treatment drug discovery.


Antineoplastic Agents , Protein Kinase Inhibitors , Pyrimidines , Humans , Pyrimidines/pharmacology , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Structure-Activity Relationship , Mice , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Thiophenes/pharmacology , Thiophenes/chemical synthesis , Thiophenes/chemistry , Mitogen-Activated Protein Kinase 3/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Cell Line, Tumor , Drug Discovery , Apoptosis/drug effects , Female , Mice, Nude , Drug Screening Assays, Antitumor , Molecular Structure , Cell Proliferation/drug effects , Xenograft Model Antitumor Assays , Mice, Inbred BALB C
9.
World J Gastroenterol ; 30(13): 1859-1870, 2024 Apr 07.
Article En | MEDLINE | ID: mdl-38659484

BACKGROUND: Portal hypertension (PHT), primarily induced by cirrhosis, manifests severe symptoms impacting patient survival. Although transjugular intrahepatic portosystemic shunt (TIPS) is a critical intervention for managing PHT, it carries risks like hepatic encephalopathy, thus affecting patient survival prognosis. To our knowledge, existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes. Consequently, the development of an innovative modeling approach is essential to address this limitation. AIM: To develop and validate a Bayesian network (BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS. METHODS: The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed. Variables were selected using Cox and least absolute shrinkage and selection operator regression methods, and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT. RESULTS: Variable selection revealed the following as key factors impacting survival: age, ascites, hypertension, indications for TIPS, postoperative portal vein pressure (post-PVP), aspartate aminotransferase, alkaline phosphatase, total bilirubin, prealbumin, the Child-Pugh grade, and the model for end-stage liver disease (MELD) score. Based on the above-mentioned variables, a BN-based 2-year survival prognostic prediction model was constructed, which identified the following factors to be directly linked to the survival time: age, ascites, indications for TIPS, concurrent hypertension, post-PVP, the Child-Pugh grade, and the MELD score. The Bayesian information criterion was 3589.04, and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16. The model's accuracy, precision, recall, and F1 score were 0.90, 0.92, 0.97, and 0.95 respectively, with the area under the receiver operating characteristic curve being 0.72. CONCLUSION: This study successfully developed a BN-based survival prediction model with good predictive capabilities. It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.


Bayes Theorem , Hypertension, Portal , Liver Cirrhosis , Portasystemic Shunt, Transjugular Intrahepatic , Humans , Hypertension, Portal/surgery , Hypertension, Portal/mortality , Hypertension, Portal/etiology , Hypertension, Portal/diagnosis , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/mortality , Middle Aged , Female , Male , Retrospective Studies , Prognosis , Liver Cirrhosis/surgery , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Treatment Outcome , Aged , Adult , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/surgery , Hepatic Encephalopathy/mortality , Risk Factors , Portal Pressure
10.
Front Med (Lausanne) ; 11: 1363405, 2024.
Article En | MEDLINE | ID: mdl-38633304

Psoriasis and atopic dermatitis (AD) are prevalent inflammatory skin disorders, each stemming from diverse factors, and characterized by recurring episodes. In certain complex cases, the clinical and pathological features exhibit overlapping and atypical characteristics, making accurate clinical diagnosis and targeted treatment a challenge. Psoriasiform dermatitis is the term used to describe such cases. Moreover, when patients have a history of malignancy, the situation becomes even more intricate, resulting in limited treatment options. Biologic therapies have transformed the management of immune-mediated inflammatory diseases, including psoriasis and AD. Meanwhile, the safety of biologics in special populations, especially among patients with a history of malignancy, should be underlined. The selective Janus kinase 1 (JAK1) inhibitor abrocitinib has been approved for the treatment of AD and has showed satisfying efficacy and safety in the treatment of psoriasis in clinical trials. Although unreported, JAK1 inhibitors are thought to have the potential to increase the risk of potential tumors. Apremilast, an oral phosphodiesterase (PDE)-4 inhibitor, is approved for moderate to severe plaque psoriasis. It has been investigated for its efficacy in AD, and is not contraindicated in malignancy. This report presents three cases of psoriasiform dermatitis in patients with a history of malignancy, showcasing significant improvement following treatment with systemic glucocorticoid, abrocitinib, or apremilast.

11.
J Dairy Sci ; 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38642661

Spermatogenesis is a continuous process in which functional sperm are produced through a series of mitotic and meiotic divisions and morphological changes in germ cells. The aberrant development and fate transitions of spermatogenic cells cause hybrid sterility in mammals. Cattle-yak, a hybrid animal between taurine cattle (Bos taurus) and yak (Bos grunniens), exhibits male-specific sterility due to spermatogenic failure. In the present study, we performed single-cell RNA sequencing analysis to identify differences in testicular cell composition and the developmental trajectory of spermatogenic cells between yak and cattle-yak. The composition and molecular signatures of spermatogonial subtypes were dramatically different between these 2 animals, and the expression of genes associated with stem cell maintenance, cell differentiation and meiotic entry was altered in cattle-yak, indicating the impairment of undifferentiated spermatogonial fate decisions. Cell communication analysis revealed that signaling within different spermatogenic cell subpopulations was weakened, and progenitor spermatogonia were unable or delayed receiving and sending signals for transformation to the next stage in cattle-yak. Simultaneously, the communication between niche cells and germ cells was also abnormal. Collectively, we obtained the expression profiles of transcriptome signatures of different germ cells and testicular somatic cell populations at the single-cell level and identified critical regulators of spermatogonial differentiation and meiosis in yak and sterile cattle-yak. The findings of this study shed light on the genetic mechanisms that lead to hybrid sterility and speciation in bovid species.

12.
Adv Mater ; : e2312219, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38608672

Targeting the competitive-cooperative relationships among tumor cells and various immune cells can efficiently reverse the immune-dysfunction microenvironment to boost the immunotherapies for the triple-negative breast cancer treatment. Hence, a bacterial outer membrane vesicle-based nanocomplex is designed for specifically targeting malignant cells and immune cells to reconcile the relationships based on metabolic-immune crosstalk. By uniquely utilizing the property of charge-reversal polymers to realize function separation, the nanocomplexes could synergistically regulate tumor cells and immune cells. This approach could reshape the immunosuppressive competition-cooperation pattern into one that is immune-responsive, showcasing significant potential for inducing tumor remission in TNBC models.

13.
Adv Sci (Weinh) ; : e2306671, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38639383

Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy-saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide-induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC.

14.
BMC Cancer ; 24(1): 402, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38561760

BACKGROUND: Among the most common forms of cancer worldwide, breast cancer posed a serious threat to women. Recent research revealed a lack of oxygen, known as hypoxia, was crucial in forming breast cancer. This research aimed to create a robust signature with hypoxia-related genes to predict the prognosis of breast cancer patients. The function of hypoxia genes was further studied through cell line experiments. MATERIALS AND METHODS: In the bioinformatic part, transcriptome and clinical information of breast cancer were obtained from The Cancer Genome Atlas(TCGA). Hypoxia-related genes were downloaded from the Genecards Platform. Differentially expressed hypoxia-related genes (DEHRGs) were identified. The TCGA filtered data was evenly split, ensuring a 1:1 distribution between the training and testing sets. Prognostic-related DEHRGs were identified through Cox regression. The signature was established through the training set. Then, it was validated using the test set and external validation set GSE131769 from Gene Expression Omnibus (GEO). The nomogram was created by incorporating the signature and clinicopathological characteristics. The predictive value of the nomogram was evaluated by C-index and receiver operating characteristiccurve. Immune microenvironment and mutation burden were also examined. In the experiment part, the function of the two most significant hypoxia-related genes were further explored by cell-line experiments. RESULTS: In the bioinformatic part, 141 up-regulated and 157 down-regulated DEHRGs were screened out. A prognostic signature was constructed containing nine hypoxia genes (ALOX15B, CA9, CD24, CHEK1, FOXM1, HOTAIR, KCNJ11, NEDD9, PSME2) in the training set. Low-risk patients exhibited a much more favorable prognosis than higher-risk ones (P < 0.001). The signature was double-validated in the test set and GSE131769 (P = 0.006 and P = 0.001). The nomogram showed excellent predictive value with 1-year OS AUC: 0.788, 3-year OS AUC: 0.783, and 5-year OS AUC: 0.817. Patients in the high-risk group had a higher tumor mutation burden when compared to the low-risk group. In the experiment part, the down-regulation of PSME2 inhibited cell growth ability and clone formation capability of breast cancer cells, while the down-regulation of KCNJ11 did not have any functions. CONCLUSION: Based on 9 DEHRGs, a reliable signature was established through the bioinformatic method. It could accurately predict the prognosis of breast cancer patients. Cell line experiment indicated that PSME2 played a protective role. Summarily, we provided a new insight to predict the prognosis of breast cancer by hypoxia-related genes.


Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Prognosis , Nomograms , Hypoxia/genetics , Oxygen , Tumor Microenvironment/genetics , Adaptor Proteins, Signal Transducing , Proteasome Endopeptidase Complex
15.
Zhen Ci Yan Jiu ; 49(4): 415-423, 2024 Apr 25.
Article En, Zh | MEDLINE | ID: mdl-38649211

OBJECTIVES: To explore the mechanism of core points in acupuncture and moxibustion treatment for epilepsy by using data mining technique, so as to provide a reference for clinical practice and experimental research. METHODS: The data comes from relevant documents collected from CNKI, Wanfang, SinoMed, VIP, PubMed, Embase, Cochrane Library, EBSCO, Web of Science databases. The selected acupoints were analyzed in descriptive statistics, high-frequency acupoints group and core acupoint prescription. Further, potential target mining, "core acupoint prescription-target-epilepsy" network construction, protein-protein interactions (PPI) network establishment and core target extraction, gene ontology (GO) and KEGG gene enrichment analysis of the core acupoint prescription were carried out to predict its anti-epileptic potential mechanism. RESULTS: A total of 122 acupoint prescriptions were included. The core acupoint prescriptions were Baihui (GV20), Hegu (LI4), Neiguan (PC6), Shuigou (GV26) and Taichong (LR3). 277 potential targets were identified, among which 134 were shared with epilepsy. The core targets were extracted by PPI network topology analysis, including signal transducer and activator of transcription 3, tumor necrosis factor (TNF), interleukin (IL)-6, protein kinase B1, c-Jun N-terminal kinase, brain-derived neurotrophic factor, tumor protein 53, vascular endothelial growth factor A, Caspase-3, epidermal growth factor receptor, etc. The main anti-epileptic pathways of the core acupoints were predicted by KEGG enrichment, including lipid and atherosclerosis, neurodegeneration, phosphatidylinositol-3-kinase/protein B kinase signaling pathway, mitogen-activated protein kinase signaling pathway, cyclic adenosine monophosphate signaling pathway, TNF signaling pathway, IL-17 signaling pathway, hypoxia-inducible factor-1 signaling pathway, apoptosis, etc., involving neuronal death, synaptic plasticity, oxidative stress, inflammation and other related biological process. CONCLUSIONS: The core acupoint prescription of acupuncture and moxibustion intervention for epilepsy can act on multiple targets and multiple pathways to exert anti-epileptic effects, which can provide a theoretical basis for further clinical application and mechanism research.


Acupuncture Points , Acupuncture Therapy , Data Mining , Epilepsy , Moxibustion , Humans , Epilepsy/therapy , Epilepsy/genetics , Epilepsy/metabolism , Protein Interaction Maps , Signal Transduction
16.
IEEE Trans Med Imaging ; PP2024 Apr 02.
Article En | MEDLINE | ID: mdl-38564344

Treatment planning, which is a critical component of the radiotherapy workflow, is typically carried out by a medical physicist in a time-consuming trial-and-error manner. Previous studies have proposed knowledge-based or deep-learning-based methods for predicting dose distribution maps to assist medical physicists in improving the efficiency of treatment planning. However, these dose prediction methods usually fail to effectively utilize distance information between surrounding tissues and targets or organs-at-risk (OARs). Moreover, they are poor at maintaining the distribution characteristics of ray paths in the predicted dose distribution maps, resulting in a loss of valuable information. In this paper, we propose a distance-aware diffusion model (DoseDiff) for precise prediction of dose distribution. We define dose prediction as a sequence of denoising steps, wherein the predicted dose distribution map is generated with the conditions of the computed tomography (CT) image and signed distance maps (SDMs). The SDMs are obtained by distance transformation from the masks of targets or OARs, which provide the distance from each pixel in the image to the outline of the targets or OARs. We further propose a multi-encoder and multi-scale fusion network (MMFNet) that incorporates multi-scale and transformer-based fusion modules to enhance information fusion between the CT image and SDMs at the feature level. We evaluate our model on two in-house datasets and a public dataset, respectively. The results demonstrate that our DoseDiff method outperforms state-of-the-art dose prediction methods in terms of both quantitative performance and visual quality.

17.
Article En | MEDLINE | ID: mdl-38652500

BACKGROUND: Appendectomy is a common surgical procedure to treat appendicitis. Limited studies examined its association on prostate cancer, with one large cohort study suggesting significant increased risk of overall and advanced prostate cancer, especially among younger men. METHODS: A total of 49,104 men in the Health Professionals Follow-up Study were followed from 1986 to 2016. Cox proportional hazards models were applied to evaluate the association between self-reported history of appendectomy and risk of overall and subtype specific prostate cancer, adjusted for multiple risk factors. RESULTS: During 30 years of follow-up, we documented 7,253 overall prostate cancer including 579 advanced and 1,092 lethal events. Compared to men without appendectomy, those who reported at baseline having had appendectomy were not at higher risk of overall (hazard ratio (HR)=1.01, 95% CI = 0.95 to 1.07), advanced (HR=0.99, 95% CI = 0.81 to 1.23) or lethal (HR=1.04, 95% CI = 0.89 to 1.20) prostate cancer. The association remained null when stratified by age. CONCLUSIONS: We found no evidence of an association between appendectomy and risk of overall and clinically important prostate cancer. IMPACT: We showed that appendectomy was not associated with overall or advanced prostate cancer adjusted for multiple risk factors among a large population of men with 30 years of follow-up.

18.
Br J Cancer ; 130(10): 1709-1715, 2024 Jun.
Article En | MEDLINE | ID: mdl-38491175

BACKGROUND: Multivitamin use is common among cancer patients. Whether post-diagnostic multivitamin supplementation is beneficial for prostate cancer survival is largely unknown, and some evidence even suggests potential harm. METHODS: We prospectively assessed post-diagnostic multivitamin use in relation to prostate cancer survival among 4756 men with nonmetastatic prostate cancer at diagnosis in the Health Professionals Follow-up Study (1986-2016). Cox regression models were used to evaluate the association between post-diagnostic multivitamin use and frequency and risk of lethal prostate cancer (distant metastases or prostate cancer-specific death) and all-cause mortality. RESULTS: We observed 438 lethal prostate cancer and 2609 deaths during a median follow-up of 11 years. Compared to non-users, post-diagnostic multivitamin use was not associated with risk of lethal prostate cancer (HR [95% CI], 0.98 [0.74-1.30]) or all-cause mortality (1.00 [0.88-1.12]), after adjustment for potential confounders. Similarly, null associations were observed across various categories of use frequency. Compared to non-users, men who used multivitamins regularly (6-9 tablets/week) after cancer diagnosis had similar risk of lethal prostate cancer (0.96 [0.72-1.28]) and all-cause mortality (0.99 [0.88-1.12]). CONCLUSIONS: We found no evidence that post-diagnostic multivitamin use among men with nonmetastatic prostate cancer was associated with better or worse survival in a well-nourished population.


Prostatic Neoplasms , Vitamins , Humans , Male , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/diagnosis , Vitamins/administration & dosage , Vitamins/therapeutic use , Aged , Middle Aged , Prospective Studies , Follow-Up Studies , Dietary Supplements , Adult , Proportional Hazards Models
19.
Oncol Lett ; 27(4): 187, 2024 Apr.
Article En | MEDLINE | ID: mdl-38486945

Ganglioneuroblastoma (GNB), predominantly observed in children, is an uncommon malignant tumor in adults, with established treatment protocols notably lacking. The present study details the case of a 20-year-old woman who presented with a left adrenal gland mass, identified during a physical examination. Additionally, an unidentified mass was noted near the renal hilum in the preoperative evaluation. Following thorough preoperative preparation, both the primary adrenal gland mass and the renal hilar mass were surgically removed. The procedure concluded successfully. Pathological analysis confirmed that the left adrenal mass was a GNB and identified the renal hilar mass as a metastatic extension. Postoperative examination revealed a new formation at the original surgical site, later verified as a postoperative scar. Through the publication of a case report and extensive literature review, the present study aims to enhance our understanding of this condition, providing valuable diagnostic, therapeutic and post-recovery references for this rare adult disease.

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