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BACKGROUND: Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled. AIM: To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps. METHODS: Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators. RESULTS: The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones. CONCLUSION: These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.
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Low accuracy of diagnosing prostate cancer (PCa) was easily caused by only assaying single prostate specific antigen (PSA) biomarker. Although conventional reported methods for simultaneous detection of two specific PCa biomarkers could improve the diagnostic efficiency and accuracy, low detection sensitivity restrained their use in extreme early-stage PCa clinical assay applications. In order to overcome above drawbacks, this paper herein proposed a multiplexed dual optical microfibers separately functionalized with gold nanorods (GNRs) and Au nanobipyramids (Au NBPs) nanointerfaces with strong localized surface plasmon resonance (LSPR) effects. The sensors could simultaneously detect PSA protein biomarker and long noncoding RNA prostate cancer antigen 3 (lncRNA PCA3) with ultrahigh sensitivity and remarkable specificity. Consequently, the proposed dual optical microfibers multiplexed biosensors could detect the PSA protein and lncRNA PCA3 with ultra-low limit-of-detections (LODs) of 3.97 × 10-15 mol/L and 1.56 × 10-14 mol/L in pure phosphorus buffer solution (PBS), respectively, in which the obtained LODs were three orders of magnitude lower than existed state-of-the-art PCa assay technologies. Additionally, the sensors could discriminate target components from complicated physiological environment, that showing noticeable biosensing specificity of the sensors. With good performances of the sensors, they could successfully assay PSA and lncRNA PCA3 in undiluted human serum and urine simultaneously, respectively. Consequently, our proposed multiplexed sensors could real-time high-sensitivity simultaneously detect complicated human samples, that providing a novel valuable approach for the high-accurate diagnosis of early-stage PCa individuals.
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Antígenos de Neoplasias , Técnicas Biossensoriais , Ouro , Limite de Detecção , Nanotubos , Antígeno Prostático Específico , Neoplasias da Próstata , RNA Longo não Codificante , Ressonância de Plasmônio de Superfície , Humanos , Antígeno Prostático Específico/sangue , Masculino , Ouro/química , RNA Longo não Codificante/genética , RNA Longo não Codificante/sangue , RNA Longo não Codificante/urina , Antígenos de Neoplasias/urina , Antígenos de Neoplasias/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/urina , Nanotubos/química , Nanopartículas Metálicas/química , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urinaRESUMO
Background: Multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) with high mortality remains a public health crisis and health security threat. This study aimed to explore the predictive value of nutritional indices for all-cause mortality (ACM) in MDR/RR-TB patients. Methods: We retrospectively recruited MDR/RR-TB patients between January 2015 and December 2021, randomly assigning them to training and validation cohorts. Patients were divided into high nutritional risk groups (HNRGs) and low nutritional risk groups (LNRGs) based on the optimal cut-off value obtained from receiver operating characteristic (ROC) analyses of the hemoglobin-albumin-lymphocyte-platelet (HALP) score, prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score. In the training cohort, Kaplan-Meier survival curves and Log rank tests were used to compare overall survival (OS) between the groups. Cox risk proportion regression analyses were used to explore the risk factors of ACM in patients with MDR/RR-TB. The predictive performance of ACM was assessed using area under the curve (AUC), sensitivity and specificity of ROC analyses. Results: A total of 524 MDR/RR-TB patients, with 255 in the training cohort and 269 in the validation cohort, were included. Survival analyses in the training cohort revealed significantly lower OS in the HNRGs compared to the LNRGs. After adjusting for covariates, multivariate analysis identified low HALP score, low PNI and high CONUT score were independent risk factors for ACM in MDR/RR-TB patients. ROC analyses demonstrated good predictive performance for ACM with AUCs of 0.765, 0.783, 0.807, and 0.811 for HALP score, PNI, CONUT score, and their combination, respectively. Similar results were observed in the validation set. Conclusion: HALP score, PNI, and CONUT scores could effectively predict ACM in patients with MDR/RR-TB. Hence, routine screening for malnutrition should be given more attention in clinical practice to identify MDR/RR-TB patients at higher risk of mortality and provide them with nutritional support to reduce mortality.
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OBJECTIVE: To compare the clinical efficacy of ligament advanced reinforcement system (LARS) and autogenous hamstring tendon plus high-strength suture in arthroscopic reconstruction of posterior cruciate ligament(PCL). METHODS: A total of 96 patients with simple PCL injury treated with arthroscopic posterior cruciate ligament reconstructive surgery admitted to our hospital between August 2019 and December 2021 were selected for complete follow-up. There were 78 males and 18 females, 40 cases of left leg and 56 cases of right leg, the aged from 20 to 56 years old with an average of (32.50±8.68 ) years old. The transplants were divided into two groups:LARS group (52 cases) and autogenous hamstring tendon plus high-strength suture group (44 cases). In the LARS group, there were 42 males and 10 females;with an average age of (31.84±8.62) years old;body mass index (BMI) was (24.73±2.29) kgï¹m-2;7 mm LARS was used to reconstruct PCL. In the autologous tendon group, there were 36 males and 8 females, with an average age of (33.06±8.99) years old, BMI was (23.52±2.16) kg·m-2, and the PCL was reconstructed with four strands of hamstring tendons and three pieces of Ethibond suture. All patients underwent functional rehabilitation guided exercise and were followed up regularly after surgery to objectively evaluate the stability of the knee joint by KT-1000 measurement of knee relaxation, and subjective evaluation of knee function by Lysholm score, Tegner score, and International Knee Documentation Council (IKDC) score. Data from preoperative, 3, 6, and 12 month follow-up were collected and analyzed by SPSS software to compare postoperative recovery and ligament relaxation between the two groups of patients. RESULTS: Ninety-six patients were followed up for 12 months. KT-1000 measurement of knee joint in autogenous tendon group and LARS group before operation [(10.73±1.46) points vs (10.55±1.53) points], 6 months after operation[(3.02±0.75) points vs (2.35±0.60) points], 12 months after operation[(3.77±1.76) points vs (2.44±0.60) points]. There was significant difference between the two groups at 6 and 12 months after operation (P<0.05), but there was no significant difference between the two groups at 3 months after operation (P>0.05). In the autogenous tendon group and LARS group, before operation and 12 months after operation, total Lysholm score [(40.6±16.8), (91.25±6.35) points vs (51.92±18.52), (92.35±5.30) points], Tegner score[(1.8±0.7), (5.8±0.6) points vs(1.7±0.8)ã(5.7±0.7) points] and total IKDC score[(54.50±6.33), (83.90±3.93) points vs (54.40±4.24), (83.62±3.64) points], the differences were statistically significant (P<0.05), indicating that the knee function of the two groups was improved after surgery. At 3 and 6 months after operation in the autogenous tendon group and LARS group, the total Lysholm score[(65.86±11.54), (74.60±6.46) points vs (73.46±6.42), (86.73±4.62) points], Tegner score[(2.5±0.6), (3.5±0.5) points vs (4.3±0.7), (5.0±1.4) points], the total scores of IKDC [(55.78±2.68), (70.62±4.74) points vs (65.31±4.60), (79.71±2.93) points]. The difference between two groups was statistically significant (P<0.05). The results showed that the function of the knee joint in the LARS group was better than that the autologous tendon group. However, at 12 months after the operation, there was no significant difference in the score of knee joint function between the two groups (P>0.05). The results showed that the stability of LARS group was better than that of autologous tendon group. CONCLUSION: Both the autogenous hamstring tendon plus high-strength suture and LARS reconstruction can significantly improve the knee function and stability, with satisfactory postoperative results. Howervr the LARS provides superior postoperative stability.
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Tendões dos Músculos Isquiotibiais , Reconstrução do Ligamento Cruzado Posterior , Ligamento Cruzado Posterior , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Tendões dos Músculos Isquiotibiais/transplante , Reconstrução do Ligamento Cruzado Posterior/métodos , Adulto Jovem , Ligamento Cruzado Posterior/cirurgia , Ligamento Cruzado Posterior/lesões , Suturas , Transplante Autólogo , Resultado do TratamentoRESUMO
This paper investigated the effect of total saponins from Rhizoma Panacis Majoris on the proliferation, apoptosis, and autophagy of human cervical carcinoma HeLa cells. The saponin content was detected by ultraviolet-visible spectrophotometry. Cell coun-ting kit-8(CCK-8) assay, 4,6-diamidino-2-phenylindole(DAPI) staining, and flow cytometry were used to detect the effects of total saponins of Panacis Majoris Rhizoma on cell viability, morphology, cell cycle and apoptosis of HeLa cells. Western blot was used to detect the expression of apoptosis-related proteins B cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved caspase-9, and cleaved caspase-3, autophagy-related proteins Beclin-1 and SQSTM1(p62), and the proteins related to the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) and mitogen-activated protein kinase(MAPK) signaling pathways. It was found that the yield and saponin content of total saponins from Rhizoma Panacis Majoris were 6.3% and 78.3%, respectively. Total saponins from Rhizoma Panacis Majoris could significantly inhibit the proliferation(P<0.001), effect the nuclear morphology, block the G_0/G_1 cycle, and induce cell apoptosis in HeLa cells with a concentration-dependent manner. In addition, total saponins from Rhizoma Panacis Majoris up-regulated the expression of pro-apoptotic proteins Bax, cleaved caspase-9, and cleaved caspase-3, and autophagy-related protein p62(P<0.05), while down-regulated the expression of anti-apoptotic protein Bcl-2 and autophagy-related protein Beclin-1(P<0.01). Total saponins from Rhizoma Panacis Majoris could promote the expression of p-p38/p38, p-Jun N-terminal kinase(JNK)/JNK, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR proteins in PI3K/Akt/mTOR and MAPK signaling pathways(P<0.05). In contrast, the effect on p-ERK/ERK expression was not obvious. Therefore, total saponins from Rhizoma Panacis Majoris may inhibit autophagy and promote apoptosis of HeLa cells through the activation of the PI3K/Akt/mTOR, c-JNK, and p38 MAPK signaling pathways, which indicates that total saponins from Rhizoma Panacis Majoris may have a potential role in cervical cancer treatment.
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Apoptose , Autofagia , Proliferação de Células , Rizoma , Saponinas , Neoplasias do Colo do Útero , Humanos , Saponinas/farmacologia , Saponinas/química , Células HeLa , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Rizoma/química , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Feminino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Sobrevivência Celular/efeitos dos fármacosRESUMO
BACKGROUND: Acupuncture (AT) is widely used in treatment of ovulatory disorder infertility (ODI), but the safety and efficacy of AT for ODI still lack an evidence-based basis. AIM: To evaluate the feasibility and effectiveness of AT as an adjunct intervention for ODI. METHODS: The Cochrane Library, Embase, PubMed, VIP, China National Knowledge Infrastructure, WanFang Data, and Chinese biomedical literature databases were searched from inception to January 20, 2024. Two reviewers independently selected studies, collected data, and evaluated methodological quality through the Cochrane Risk of Bias tool. Revman 5.4 was used for meta-analysis, and the Grade system was performed to evaluate the level of evidence for the outcomes of the meta-analysis. RESULTS: A total of 20 randomized controlled trials with 1677 ODI patients were included. Compared with the clomiphene citrate (CC) group, the AT plus CC group exhibited significant improvement of the pregnancy rate [relative risk (RR) = 1.68, 95% confidence interval (CI): 1.45-1.95, P < 0.00001, I 2 = 23%], ovulation rate (RR = 1.34, 95%CI: 1.22-1.47, P < 0.00001, I 2 = 32%), serum E2 level [mean difference (MD) = 31.36, 95%CI: 21.83-40.88, P < 0.00001, I 2 = 97%], thickness of endometrium (MD = 1.76, 95%CI: 0.71-2.81, P = 0.001, I 2 = 98%) and decreasing miscarriage rate (RR = 0.25, 95%CI: 0.09-0.65, P = 0.005, I 2 = 0%), serum follicle-stimulating hormone level (MD = -2.10, 95%CI: -3.27 to -0.94, P = 0.0004, I 2 = 99%), serum luteinizing hormone level (MD = -6.94, 95%CI: -9.89 to -4.00, P < 0.00001, I 2 = 100%), and serum progesterone level (MD = -1.66, 95%CI: -2.98 to -0.34, P = 0.01, I 2 = 96%). The AT group had a more favorable effect than CC group for improving pregnancy rate (RR = 1.52, 95%CI: 1.33-1.73, P < 0.00001, I 2 = 0%), thickness of endometrium (MD = 2.48, 95%CI: 2.15-2.81, P < 0.00001, I 2 = 0%) and reducing miscarriage rate (RR = 0.23, 95%CI: 0.13-0.44, P < 0.00001, I 2 = 0%), serum follicle-stimulating hormone level (MD = -0.55, 95%CI: -0.86 to -0.24, P = 0.0005, I 2 = 0%), and serum progesterone level (MD = -0.24, 95%CI: -0.28 to -0.20, P < 0.00001). However, the level of evidence was predominantly assessed as very low to moderate. CONCLUSION: AT can improve the pregnancy outcomes and sex hormone levels for patients with ODI. However, further studies are needed to confirm these findings.
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Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.
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Transtorno Depressivo Maior , Transcriptoma , Humanos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/fisiopatologia , Feminino , Masculino , Adulto , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Perfilação da Expressão GênicaRESUMO
Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.
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Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Gefitinibe , Indóis , Neoplasias Pulmonares , Mutação , Inibidores de Proteínas Quinases , Quinolinas , Humanos , Gefitinibe/administração & dosagem , Gefitinibe/efeitos adversos , Gefitinibe/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Indóis/administração & dosagem , Indóis/uso terapêutico , Indóis/efeitos adversos , Masculino , Feminino , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Idoso de 80 Anos ou maisRESUMO
Acyl-Coenzyme As (acyl-CoAs) are essential intermediates to incorporate carboxylic acids into the bioactive metabolic network across all species, which play important roles in lipid remodeling, fatty acids, and xenobiotic carboxylic metabolism. However, due to the poor liquid chromatographic behavior, the relatively low mass spectrometry (MS) sensitivity, and lack of authentic standards for annotation, the in-depth untargeted profiling of acyl-CoAs is challenging. We developed a chemical derivatization strategy of acyl-CoAs by employing 8-(diazomethyl) quinoline (8-DMQ) as the labeling reagent, which increased the detection sensitivity by 625-fold with good peak shapes. By applying the MS/MS fragmentation rules learned from the MS/MS spectra of 8-DMQ-acyl-CoA authentic standards, an 8-DMQ-acyl-CoA in silico mass spectral library containing 33,344 high-resolution tandem mass spectra of 8,336 acyl-CoA species was created. The in silico library facilitated the high-throughput and automatic annotation of acyl-CoA using multiple metabolomic data processing tools, such as NIST MS Search and MSDIAL. The feasibility of the in silico library in a complex sample was demonstrated by profiling endogenous acyl-CoAs in multiple organs of an aging mouse. 53 acyl-CoA species were annotated, including 12 oxidized fatty acyl-CoAs and 3 novel nonfatty acyl-CoAs. False positive annotations were further screened by developing an eXtreme Gradient Boosting (XGBoost) based retention time prediction model. The organ distribution and the aging dynamics of acyl-CoAs in a mouse model were discussed for the first time, which helped to elucidate the organ-specific function of acyl-CoAs and the role of different acyl-CoA species during aging.
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The design of novel energetic compounds constitutes a pivotal research direction within the field of energetic materials. However, exploring the intricate relationship between their molecular structure and properties, in order to uncover their potential applications, remains a challenging endeavor. Therefore, employing multi-molecule assembly techniques to modulate the structure and performance of energetic materials holds immense significance. This approach enables the creation of a new generation of energetic materials, fueling research and development efforts in this field. In this study, a series of coordination compounds are synthesized by utilizing tetranitroethide (TNE) as an anion, which possesses a high nitrogen and oxygen content. The synthesis involves the synergistic modification between metal ions and small molecule ligands. Characterization of the obtained compounds is carried out using various techniques, including single crystal X-ray diffraction, IR spectroscopy, elemental analysis, and simultaneous TG-DSC analysis. Additionally, the energy of formation for these compounds is calculated using bomb calorimetry, based on the heat of combustion. The detonation performances of the compounds are determined through calculations using the EXPLO 5 software, and their sensitivities to external stimuli are evaluated.
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OBJECTIVE: This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. METHODS: A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. RESULTS: In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. CONCLUSION: Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.
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Resistência a Medicamentos , Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Lactente , China , Receptores de Interleucina-2/sangue , Criança , Valor Preditivo dos Testes , População do Leste AsiáticoRESUMO
Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.
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Anti-Inflamatórios , Líquens , NF-kappa B , Fenazinas , Streptomyces , Peixe-Zebra , Animais , Streptomyces/química , Líquens/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Fenazinas/farmacologia , Fenazinas/química , Estrutura Molecular , NF-kappa B/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Microglia/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We examined the lipid profiles in the aqueous humor (AH) of myopic patients to identify differences and investigate the relationships among dissertating lipids. Additionally, we assessed spherical equivalents and axial lengths to explore the pathogenesis of myopia. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to qualitatively and quantitatively analyze the lipid composition of samples from myopic patients with axial lengths <26 mm (Group A) and >28 mm (Group B). Differences in lipid profiles between the two groups were determined using univariate and multivariate analyses. Receiver operator characteristic (ROC) curves were used to identify discriminating lipids. Spearman correlation analysis explored the associations between lipid concentrations and biometric parameters. Three hundred and nine lipids across 21 lipid classes have been identified in this study. Five lipids showed significant differences between Group B and Group A (VIP >1, P < 0.05): BMP (20:3/22:3), PG (22:1/24:0), PS (14:1/22:4), TG (44:2)_FA18:2, and TG (55:3)_FA18:1. The area under the curve (AUC) for these lipids was >0.75. Notably, the concentrations of BMP (20:3/22:3), PS (14:1/22:4), and TG (55:3)_FA18:1 were correlated with spherical equivalents, while BMP (20:3/22:3) and PS (14:1/22:4) correlated with axial lengths. Our study identified five differential lipids in myopic patients, with three showing significant correlations with the degree of myopia. These findings enhance our understanding of myopia pathogenesis through lipidomic alterations, emphasizing changes in cell membrane composition and function, energy metabolism and storage, and pathways involving inflammation, peroxisome proliferator-activated receptors (PPAR), and metabolic processes related to phosphatidylserine, phosphatidylglycerol, triglycerides, polyunsaturated fatty acids, and cholesterol.
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In Alzheimer's disease (AD) assessment, traditional deep learning approaches have often employed separate methodologies to handle the diverse modalities of input data. Recognizing the critical need for a cohesive and interconnected analytical framework, we propose the AD-Transformer, a novel transformer-based unified deep learning model. This innovative framework seamlessly integrates structural magnetic resonance imaging (sMRI), clinical, and genetic data from the extensive Alzheimer's Disease Neuroimaging Initiative (ADNI) database, encompassing 1651 subjects. By employing a Patch-CNN block, the AD-Transformer efficiently transforms image data into image tokens, while a linear projection layer adeptly converts non-image data into corresponding tokens. As the core, a transformer block learns comprehensive representations of the input data, capturing the intricate interplay between modalities. The AD-Transformer sets a new benchmark in AD diagnosis and Mild Cognitive Impairment (MCI) conversion prediction, achieving remarkable average area under curve (AUC) values of 0.993 and 0.845, respectively, surpassing those of traditional image-only models and non-unified multimodal models. Our experimental results confirmed the potential of the AD-Transformer as a potent tool in AD diagnosis and MCI conversion prediction. By providing a unified framework that jointly learns holistic representations of both image and non-image data, the AD-Transformer paves the way for more effective and precise clinical assessments, offering a clinically adaptable strategy for leveraging diverse data modalities in the battle against AD.
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Doença de Alzheimer , Imageamento por Ressonância Magnética , Doença de Alzheimer/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Idoso , Feminino , Neuroimagem/métodos , Masculino , Aprendizado Profundo , Disfunção Cognitiva/diagnóstico por imagem , Bases de Dados Factuais , Idoso de 80 Anos ou maisRESUMO
The involvement of the right hemisphere, mainly the activation of the right cerebral regions, in recovery from post-stroke aphasia has been widely recognized. In contrast, the role of the right white matter pathways in the recovery from post-stroke aphasia is rarely understood. In this study, we aimed to provide a primary overview of the correlation between the structural integrity of the right hemispheric neural tracts based on the dual-stream model of language organization and recovery from post-stroke aphasia by systematically reviewing prior longitudinal interventional studies. By searching electronic databases for relevant studies according to a standard protocol, a total of 10 records (seven group studies and three case studies) including 79 participants were finally included. After comprehensively analyzing these studies and reviewing the literature, although no definite correlation was found between the right hemispheric neural tracts and recovery from post-stroke aphasia, our review provideds a new perspective for investigating the linguistic role of the right hemispheric neural tracts. This suggests that the involvement of the right hemispheric neural tracts in recovery from post-stroke aphasia may be mediated by multiple factors; thus, this topic should be comprehensively investigated in the future.
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Afasia , Idioma , Recuperação de Função Fisiológica , Acidente Vascular Cerebral , Humanos , Afasia/etiologia , Afasia/fisiopatologia , Afasia/reabilitação , Acidente Vascular Cerebral/complicações , Recuperação de Função Fisiológica/fisiologia , Vias Neurais/fisiopatologia , Lateralidade Funcional/fisiologia , Substância Branca/patologia , Substância Branca/diagnóstico por imagemRESUMO
Conjugated microporous polymers (CMPs) have unique characteristics and have been used in a range of fascinating applications in separation sciences. In this study, a CMP, designated as CMP-1, was synthesized via the Sonogashira-Hagihara coupling reaction using 1,3,5-triphenylbenzene and 1,4-dibromobenzene as building blocks. CMP-1 features a large surface area, abundant micropore structures, and excellent stability, making it a promising solid-phase extraction adsorbent for the efficient enrichment of neonicotinoid insecticides (NEOs). Under the optimized conditions, CMP-1 was combined with high-performance liquid chromatography and diode array detection to enable the detection of NEOs with a wide linear range (0.5-200 µg·L-1), a low detection limit (0.26-0.58 µg·L-1), and acceptable precision. The developed method was applied to determine spiked NEOs in three types of environmental water samples, with recoveries of 73.7%-112.0% and relative standard deviations of 0.6%-9.4%.
Assuntos
Inseticidas , Limite de Detecção , Neonicotinoides , Polímeros , Extração em Fase Sólida , Poluentes Químicos da Água , Extração em Fase Sólida/métodos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/química , Inseticidas/análise , Inseticidas/isolamento & purificação , Inseticidas/química , Cromatografia Líquida de Alta Pressão/métodos , Neonicotinoides/análise , Neonicotinoides/isolamento & purificação , Neonicotinoides/química , Polímeros/química , Porosidade , AdsorçãoRESUMO
BACKGROUND: The expression patterns and prognostic value of Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family genes in breast cancer remain to be elucidated. METHODS: The expression levels, prognostic value, and biological function of PLODs were determined using Oncomine, cBioPortal, GEPIA, Timer, UALCAN, PrognoScan, GeneMANIA, Metascape, and breast cancer tissue microarrays. RESULTS: The expressions of PLOD1 and PLOD3 were upregulated in breast cancer tissues, indicating worse clinical stages. High expression levels of PLOD family genes were associated with worse disease-free survival and distant metastasis-free survival, while high expression levels of PLOD1 and PLOD3 were related to worse overall survival in all breast cancer patients. The levels of PLOD family genes were all significantly higher in the age ≤51 y group, HR-negative patients, and triple negative breast cancer (TNBC) patients. They are associated with tumor-infiltrating immune cells (TIICs), including CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and dendritic cells. According to co-expression gene analysis and functional enrichment, they are associated with protein hydroxylation, collagen biosynthesis and modifying enzymes, collagen metabolism, RNA splicing, extracellular matrix organization, VEGFA-VEGFR2 signaling pathway, and skeletal system development. Immunohistochemistry showed that the expressions of all PLOD family genes were significantly elevated in breast cancer tissues. PLOD1 expression was positively correlated with ER, TNBC status, and tumor grade. PLOD2 expression was positively connected with Ki-67 status. PLOD3 expression was positively related with age and tumor grade. CONCLUSIONS: PLOD family genes are novel potential prognostic biomarkers for breast cancer, and targeting PLOD inhibitors might be an effective strategy for breast cancer therapy.
Assuntos
Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase , Humanos , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Prognóstico , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismoRESUMO
With emerging Asian-derived diet quality indices and data-driven dietary patterns available, we aimed to synthesize the various dietary patterns and quantify its association with cardiovascular diseases (CVDs) among Asian populations. We systematically searched PubMed, Embase, Scopus, and Web of Science for observational studies in South, Southeast, and East Asia. Dietary patterns were grouped "high-quality," which included high intakes of three or more of the following food groups: 1) fruits and vegetables, 2) whole grains, 3) healthy protein sources (legumes and nuts, fish and seafood, low-fat dairy, and lean meat and poultry), and 4) liquid plant oils. High-quality patterns were further subcategorized based on their derivation methods: non-Asian indices, Asian indices, data-driven patterns, and plant-based indices. Dietary patterns were grouped "low-quality," which included high intakes of two or more of the following: 5) ultraprocessed food, 6) beverages and foods with added sugars, 7) foods high in salt, and 8) alcoholic beverages. Data-driven dietary patterns characterized by animal food sources were labeled "animal-based," and studies using dietary diversity scores were labeled "diet diversity indices." Dietary patterns that could not be meaningfully categorized were summarized narratively. Study-specific effect estimates were pooled using a random-effects model. Forty-one studies were included in this review. Higher adherence to high-quality dietary patterns in the top compared with bottom tertile defined by non-Asian indices (RR: 0.78; 95% CI: 0.69, 0.88; GRADE: moderate), Asian indices (RR: 0.84; 95% CI: 0.79, 0.90; GRADE: low), and data-driven patterns (RR: 0.81; 95% CI: 0.74, 0.89; GRADE: moderate) were associated with lower CVD risk. Plant-based, low-quality, animal-based, and diet diversity indices dietary patterns were not associated with CVD. Associations of Asian diet quality indices and CVD risk were weaker than those with non-Asian indices, highlighting the need for current Asian diet quality criteria to be updated to better capture the impact of diet on CVD. The systematic review and meta-analysis was registered at PROSPERO as CRD42021244318.