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Interferon-alpha (IFN-α) is widely used in the clinical treatment of patients with chronic hepatitis B and hepatocellular carcinoma (HCC). However, high levels of CXCL8 are associated with resistance to IFN-α therapy and poorer prognosis in advanced cancers. In this study, we investigated whether IFN-α could directly induce the production of CXCL8 in HCC cells and whether CXCL8 could antagonize the antitumor activity of IFN-α. We found that IFN-α not only upregulated the expression of the inducible genes CXCL9, CXCL10, CXCL11 and PD-L1, but also significantly stimulated CXCL8 secretion in HCC cells. Mechanically, IFN-α induces CXCL8 expression by activating the AKT and JNK pathways. In addition, our results demonstrate that IFN-α exposure significantly increases the differentiation of HCC stem cells, but this effect is reversed by the addition of the CXCL8 receptor CXCR1/2 inhibitor Reparixin and STAT3 inhibitor Stattic. Besides, our study reveals that the cytokine CXCL8 secreted by IFN-α-induced HCC cells inhibits T-cell function. Conversely, inhibition of CXCL8 promotes TNF-α and IFN-γ secretion by T cells. Finally, liver cancer patients who received anti-PD-1/PD-L1 immunotherapy with high CXCL8 expression had a lower immunotherapy efficacy. Overall, our findings clarify that IFN-α triggers immunosuppression and cancer stem cell differentiation in hepatocellular carcinoma by upregulating CXCL8 secretion. This discovery provides a novel approach to enhance the effectiveness of HCC treatment in the future.
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Carcinoma Hepatocelular , Interferon-alfa , Interleucina-8 , Neoplasias Hepáticas , Humanos , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Diferenciação Celular , Terapia de Imunossupressão , Interferon-alfa/farmacologia , Interferon gama/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Interleucina-8/metabolismoRESUMO
Despite recent advances have been made in clinical treatments of breast cancer, the general prognosis of patients remains poor. Therefore, it is imperative to develop a more effective therapeutic strategy. Lysine demethylase 4B (KDM4B) has been reported to participate in breast cancer development recently, but its exact biological role in breast cancer remains unclear. Here, we observed that KDM4B was down-regulated in human primary BRCA tissues and the low levels of KDM4B expression were correlated with poor survival. Gain- and loss-of-function experiments showed that KDM4B inhibited the proliferation and metastasis of breast cancer cells. Besides, knockdown of KDM4B promoted the epithelial-mesenchymal transition (EMT) and cell stemness in breast cancer cells. Mechanistically, KDM4B down-regulates PHGDH by decreasing the enrichment of H3K36me3 on the promoter region of PHGDH. Knockdown of PHGDH could significantly reversed proliferation, migration, EMT, and cell stemness induced by KDM4B silencing in breast cancer cells. Collectively, we propose a model for a KDM4B/PHGDH axis that provides novel insight into breast cancer development, which may serve as a potential factor for predicting prognosis and a therapeutic target for breast cancer.
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Neoplasias da Mama , Humanos , Feminino , Regulação para Cima , Regulação para Baixo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismoRESUMO
Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.
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Aspergillus , Inibidores de Glicosídeo Hidrolases , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores , Policetídeos , alfa-Glucosidases , Aspergillus/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Policetídeos/farmacologia , Policetídeos/química , Policetídeos/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Células PC12 , Animais , Ratos , alfa-Glucosidases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Estrutura MolecularRESUMO
A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1) is associated with the risk of coronary artery disease, as determined by a genome-wide association study. SVEP1 induces vascular smooth muscle cell proliferation and an inflammatory phenotype to promote atherosclerosis. In the present study, qRTâPCR demonstrated that the mRNA expression of SVEP1 was significantly increased in atherosclerotic plaques compared to normal tissues. Bioinformatics revealed that EGR1 was a transcription factor for SVEP1. The results of the luciferase reporter assay, siRNA interference or overexpression assay, mutational analysis and ChIP confirmed that EGR1 positively regulated the transcriptional activity of SVEP1 by directly binding to its promoter. EGR1 promoted human coronary artery smooth muscle cell (HCASMC) proliferation and migration via SVEP1 in response to oxidized low-density lipoprotein (ox-LDL) treatment. Moreover, the expression level of EGR1 was increased in atherosclerotic plaques and showed a strong linear correlation with the expression of SVEP1. Our findings indicated that EGR1 binding to the promoter region drive SVEP1 transcription to promote HCASMC proliferation and migration.
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MicroRNAs , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/metabolismo , Vasos Coronários/metabolismo , Estudo de Associação Genômica Ampla , Movimento Celular , Lipoproteínas LDL/farmacologia , Células Cultivadas , Proliferação de Células/genética , Miócitos de Músculo Liso/metabolismo , MicroRNAs/genética , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Moléculas de Adesão Celular/genéticaRESUMO
Co-cultivation of isopod-associated fungi Herpotrichia sp. SF09 and Trametes versicolor SF09A led to the reciprocal induction of thirteen new compounds (1-7 and 9-13) with diverse architectures. Importantly, compounds 1 and 2 are rare fungal sesquiterpene-saccharide hybrids incorporating a xylopyranose moiety, compound (±)-3 represents the first example of a natural linear sesquiterpene racemate, and compound 7 is a rare α-pyrone derivative with a xylopyranose motif. Their structures were elucidated by analysis of NMR and mass spectrometry data, and their absolute configurations were determined by Mosher's method, microscale derivatization, and single-crystal X-ray diffraction, as well as ECD calculations. All the isolated compounds ameliorated MPP+-induced oxidative damage in PC12 cells in a dose-dependent fashion. Among them, compounds 5 and 15 showed significant protective action against neuronal injury by MPP+ at 5 µM. Meanwhile, transcriptome sequencing was performed to evaluate the molecular mechanism of the neuroprotective activity for compound 5. Results indicated that compound 5 might mitigate MPP+-induced neuronal injury through the regulation of multiple signaling pathways, including the PI3K-Akt and MAPK pathways. Our findings suggested that compound 5 could be a promising neuroprotective agent for the treatment of Parkinson's disease.
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BACKGROUND: To explore the application effect of 3D printing surgical training models in the preoperative assessment of robot-assisted partial nephrectomy. METHODS: Eighty patients who underwent robot-assisted partial nephrectomy surgery between January 2022 and December 2023 were selected and divided into two groups according to the chronological order. The control group (n = 40) received preoperative assessment with verbal and video education from January 2022 to December 2022, while the observation group (n = 40) received preoperative assessment with 3D printing surgical training models combined with verbal and video education from January 2023 to December 2023. The preoperative anxiety, information demand score, and surgical awareness were compared between the two groups. The physiological stress indicators, including interleukin-6 (IL-6), angiotensin II (AT II), adrenocorticotropic hormone (ACTH), cortisol (Cor), mean arterial pressure (MAP), and heart rate (HR), were also measured at different time points before and after surgery.They were 6:00 am on the day before surgery (T0), 6:00 am on the day of the operation (T1), 6:00 am on the first day after the operation (T2), and 6:00 am on the third day after the operation (T3).The preparation rate before surgery was compared between the two groups. RESULTS: The anxiety and surgical information demand scores were lower in the observation group than in the control group before anesthesia induction, and the difference was statistically significant (P < 0.001). Both groups had lower scores before anesthesia induction than before preoperative assessment, and the difference was statistically significant (P < 0.05). The physiological stress indicators at T1 time points were lower in the observation group than in the control group, and the difference was statistically significant (P < 0.05). The overall means of the physiological stress indicators differed significantly between the two groups (P < 0.001). Compared with the T0 time point, the T1, T2, and T3 time points in both groups were significantly lower, and the difference was statistically significant (P < 0.05). The surgical awareness and preparation rate before surgery were higher in the observation group than in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: The preoperative assessment mode using 3D printing surgical training models combined with verbal and video education can effectively reduce the psychological and physiological stress responses of surgical patients, improve their surgical awareness, and enhance the preparation rate before surgery.
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Nefrectomia , Impressão Tridimensional , Procedimentos Cirúrgicos Robóticos , Humanos , Nefrectomia/métodos , Nefrectomia/educação , Procedimentos Cirúrgicos Robóticos/educação , Feminino , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Modelos AnatômicosRESUMO
This study aims to investigate the effect and mechanism of the EtO Ac extract of Draconis Sanguis(DSE) on improving athero sclerosis in ApoE gene knockout(ApoE~(-/-)) mice. The ApoE~(-/-) mice were randomly divided into five groups: control group, mo delgroup, positive group treated with ezetimibe of 5 mg·kg~(-1)(EG), and low(100 mg·kg~(-1)) and high dose(200 mg·kg~(-1)) groups ofDSE. xcept for the control group, all other groups were fed a high-fat diet and administered drugs for 16 successive weeks. After 16 weeks of Eadministration, the body weight, liver, and epididymal fat mass of the mice were measured; the level of blood lipid and the plaquearea of the aortic outflow tract were detected to evaluate the efficacy of DSE in vivo. In addition, in vitro cultures of human umbilical v ein endothelial cell(HUVEC) were conducted. Oxidative stress of endothelial cells was induced by oxidized low-density lipoprot ein(ox-LDL), and the effects of DSE on oxidative stress-related proteins in endothelial cells were examined. The results sho wedthat both doses of DSE significantly improved the epididymal fat mass and index of ApoE~(-/-) mice with atherosclerosis, lowered thelevels of plasma cholesterol, triglyceride, and non-high density lipoprotein cholesterol, and reduced the plaque area of the aortic ou tflow tract. totIn alvitro experiments confirmed that ox-LDL significantly increased the level of lipid peroxidation marker 4-HNE in HUVECcells, confirming that DSE improved the degree of atherosclerotic lesions in ApoE~(-/-) mice by inhibiting ox-LDL-induced oxidative stress in vascular endothelial cells.
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Apolipoproteínas E , Aterosclerose , Camundongos Knockout , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Aterosclerose/metabolismo , Camundongos , Apolipoproteínas E/genética , Masculino , Humanos , Estresse Oxidativo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Camundongos Endogâmicos C57BLRESUMO
Homogeneous electrocatalysts can indirect oxidate the high overpotential substrates through single-electron transfer on the electrode surface, enabling efficient operation of organic electrosynthesis catalytic cycles. However, the problems of this chemistry still exist such as high dosage, difficult recovery, and low catalytic efficiency. Single-atom catalysts (SACs) exhibit high atom utilization and excellent catalytic activity, hold great promise in addressing the limitations of homogeneous catalysts. In view of this, we have employed Fe-SA@NC as an advanced redox mediator to try to change this situation. Fe-SA@NC was synthesized using an encapsulation-pyrolysis method, and it demonstrated remarkable performance as a redox mediator in a range of reported organic electrosynthesis reactions, and enabling the construction of various C-C/C-X bonds. Moreover, Fe-SA@NC demonstrated a great potential in exploring new synthetic method for organic electrosynthesis. We employed it to develop a new electro-oxidative ring-opening transformation of cyclopropyl amides. In this new reaction system, Fe-SA@NC showed good tolerance to drug molecules with complex structures, as well as enabling flow electrochemical syntheses and gram-scale transformations. This work highlights the great potential of SACs in organic electrosynthesis, thereby opening a new avenue in synthetic chemistry.
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Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the intimal hyperplasia in type 2 diabetes mellitus (T2DM) patients after percutaneous coronary intervention. We aimed to investigate the role of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in VSMC proliferation and migration, as well as the underlying mechanism. T2DM model mice with carotid balloon injury were used in vivo and mouse aortic vascular smooth muscle cells (MOVAS) stimulated by insulin were used in vitro to assess the role of CDKN2B-AS1 in VSMC proliferation and migration following vascular injury in T2DM state. To investigate cell viability and migration, MTT assay and Transwell assay were conducted. To elucidate the underlying molecular mechanisms, the methylation-specific polymerase chain reaction, RNA immunoprecipitation, RNA-pull down, co-immunoprecipitation, and chromatin immunoprecipitation were performed. In vivo, CDKN2B-AS1 was up-regulated in common carotid artery tissues. In vitro, insulin treatment increased CDKN2B-AS1 level, enhanced MOVAS cell proliferation and migration, while the promoting effect was reversed by CDKN2B-AS1 knockdown. CDKN2B-AS1 forms a complex with enhancer of zeste homolog 2 (EZH2) and DNA methyltransferase (cytosine-5) 1 (DNMT1) to regulate smooth muscle 22 alpha (SM22α) methylation levels. In insulin-stimulated cells, SM22α knockdown abrogated the inhibitory effect of CDKN2B-AS1 knockdown on cell viability and migration. Injection of lentivirus-sh-CDKN2B-AS1 relieved intimal hyperplasia in T2DM mice with carotid balloon injury. Up-regulation of CDKN2B-AS1 induced by insulin promotes cell proliferation and migration by targeting SM22α through forming a complex with EZH2 and DNMT1, thereby aggravating the intimal hyperplasia after vascular injury in T2DM.
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Diabetes Mellitus Tipo 2 , RNA Longo não Codificante , Lesões do Sistema Vascular , Animais , Camundongos , Movimento Celular , Proliferação de Células , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Hiperplasia , Insulina/farmacologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologiaRESUMO
BACKGROUND: We analyzed the demographic and clinical characteristics of children with immunoglobulin A (IgA) nephropathy using data in the first pages of electronic health records of 22 hospitals from 2016 to 2018. METHODS: Information collected included gender, age, infection site, etiological infection, acute kidney injury (AKI), and chronic kidney disease (CKD) stages 2-5. We analyzed the gender and age distribution of children with IgA nephropathy, the characteristics of children complicated with AKI and CKD, and the influence of geographical distribution and economic status on the incidence of IgA nephropathy. RESULTS: We included a total of 4006 patients with IgA nephropathy. Incidence in males gradually increased with age. Seventy-nine cases (1.97%) had AKI. We found no significant difference in gender (P = 0.19) or age (P = 0.07) between the AKI and non-AKI groups. Twenty-nine patients had CKD (0.72%), who were significantly older than those in the non-CKD group (P < 0.0001). The incidence of IgA nephropathy in less-developed areas was significantly lower than that in developed areas (P = 0.0002). CONCLUSIONS: The incidence of IgA nephropathy was high mainly in males. Age was an important factor affecting CKD. The disease was related to environment and economic status. IMPACT: We analyze the demographic and clinical characteristics of children with immunoglobulin A (IgA) nephropathy using data in the first pages of electronic health records. This is a large sample, multi-center study. The incidence of IgA nephropathy in males increased gradually with age. Age was an important factor affecting CKD. The disease was related to environment and economic status.
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Injúria Renal Aguda , Glomerulonefrite por IGA , Insuficiência Renal Crônica , Masculino , Humanos , Criança , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/complicações , Imunoglobulina A , Incidência , Estudos RetrospectivosRESUMO
Nanozyme, with enzyme-mimicking activity and excellent stability, has attracted extensive attention. However, some inherent disadvantages, including poor dispersion, low selectivity, and insufficient peroxidase-like activity, still limit its further development. Therefore, an innovative bioconjugation of a nanozyme and natural enzyme was conducted. In the presence of graphene oxide (GO), histidine magnetic nanoparticles (H-Fe3O4) were first synthesized by a solvothermal method. The GO-supported H-Fe3O4 (GO@H-Fe3O4) exhibited superior dispersity and biocompatibility because GO was the carrier and possessed outstanding peroxidase-like activity because of the introduction of histidine. Furthermore, the mechanism of the peroxidase-like activity of GO@H-Fe3O4 was the generation of â¢OH. Uric acid oxidase (UAO) was selected as the model natural enzyme and covalently linked to GO@H-Fe3O4 with hydrophilic poly(ethylene glycol) as a linker. UAO could specifically catalyze the oxidation of uric acid (UA) to generate H2O2, and subsequently, the newly produced H2O2 oxidized the colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue ox-TMB under the catalysis of GO@H-Fe3O4. Based on the above cascade reaction, the GO@H-Fe3O4-linked UAO (GHFU) and GO@H-Fe3O4-linked ChOx (GHFC) were used for the detection of UA in serum samples and cholesterol (CS) in milk, respectively. The method based on GHFU exhibited a wide detection range (5-800 µM) and a low detection limit (1.5 µM) for UA, and the method based on GHFC exhibited a wide detection range (4-400 µM) and a low detection limit (1.13 µM) for CS. These results demonstrated that the proposed strategy had great potential in the field of clinical detection and food safety.
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Peróxido de Hidrogênio , Ácido Úrico , Histidina , Peroxidase/metabolismo , ColorimetriaRESUMO
Researching ultrafast dynamics and creating coherent light sources will both benefit significantly from the establishment of polarization control in high-order harmonic generation (HHG). By employing the time-dependent density functional theory method, we investigate HHG of carbonyl sulfide molecules using a combination of a linear polarized infrared (IR) laser and a weaker orthogonal Terahertz (THz) field. Our findings show that by adjusting the amplitude of the THz field, the movement scale of electrons in the THz direction can be tuned, thereby one can control the harmonic intensity in the IR laser direction. This method allows for the creation of near-circularly polarized attosecond pulses. Furthermore, the ellipticity of the attosecond pulse may be changed by modifying the carrier-envelope phase of the IR laser pulse.
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Light provides energy for photosynthesis and is also an important environmental signal that regulates plant growth and development. Ribose-5-phosphate isomerase plays a crucial role in photosynthesis. However, ribose-5-phosphate isomerase has yet to be studied in soybean photosynthesis. To understand the biological function of GmRPI2, in this study, GmRPI2 was cloned, plant overexpression vectors and gene editing vectors were successfully constructed, and transformed into recipient soybean JN74 using the Agrobacterium-mediated method. Using qRT-PCR, we analyzed that GmRPI2 gene expression was highest in leaves, second highest in roots, and lowest in stems. Promoter analysis revealed the presence of multiple cis-acting elements related to light response in the promoter region of GmRPI2. Compared with the control soybean plants, the net photosynthetic rate and transpiration rate of the overexpression lines were higher than those of the control and gene editing lines, while the intercellular CO2 concentration was significantly lower than that of the control and gene editing lines; the total chlorophyll, chlorophyll a, chlorophyll b contents and soluble sugar contents of the overexpression plants were significantly higher than those of the recipient and editing plants, indicating that the GmRPI2 gene can increase The GmRPI2 gene can increase the photosynthetic capacity of soybean plants, providing a theoretical basis and genetic resources for improving soybean yield by regulating photosynthetic efficiency.
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BACKGROUND: The side effects of pregabalin likely occur after the first dose. We aimed to evaluate the effect of 75 milligrams (mg) of pregabalin prescribed as an initial dose with a slow dose escalation for primary total joint arthroplasty within the enhanced recovery after surgery pathway. METHODS: Participants were randomly assigned to two groups. Fifty-eight patients were enrolled, and twenty-nine were assigned to each group. Group 1 (G1) received pregabalin (37.5 mg) twice on the day before surgery, as well as pregabalin 75 mg two hours pre-operatively; Group 2 (G2) received none on the day before surgery and the same dose of pregabalin at two hours pre-operatively. The primary outcome was dizziness assessed by severity; secondary outcomes included nausea, vomiting, sedation, opioid consumption, independent transfer at six hours post-operatively, time to readiness for independent transfers, time to readiness for discharge, and pain. RESULTS: At two, four, and six hours post-operatively, the proportion of patients experiencing dizziness and nausea was significantly greater in G2 than in G1, and opioid consumption was significantly greater in G2 than in G1 (P = .012). The proportion of independent transfers at six hours post-operatively was significantly greater in G1 than in G2 (P = .010). The time to readiness for independent transfers was significantly shorter in G1 than in G2 (P = .016). CONCLUSION: Prescription of pregabalin 37.5 mg twice on the day before surgery was effective in reducing early postoperative dizziness and nausea after receiving pregabalin 75 mg two hours pre-operatively. It also promoted early independent transfers and reduced opioid consumption.
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Analgésicos , Recuperação Pós-Cirúrgica Melhorada , Humanos , Pregabalina/efeitos adversos , Analgésicos/efeitos adversos , Analgésicos Opioides/efeitos adversos , Tontura/induzido quimicamente , Tontura/tratamento farmacológico , Artroplastia , Náusea , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controleRESUMO
The efficiency of sludge dewatering is limited by extracellular polymeric substances (EPS) during biodrying. This study investigated the effect of photocatalysis-mediated EPS degradation on sludge dewatering performance during the sludge biodrying process. The photocatalysis of municipal sludge was first carried out to choose a cost-efficient catalyst. Then sludge biodrying tests were performed using TiO2-coated amendment (TCA) and uncoated amendment (TUCA) as the control. Municipal sludge photocatalysis results showed that using TiO2 could efficiently degrade carbohydrates and proteins in the EPS within 60 min. After 20-day biodrying, photocatalysis significantly promoted a reduction in the moisture content and EPS by 17.64% and 6.88%, respectively. The surface-enhanced Raman scattering (SERS) intensities of the C-C-O symmetric stretching vibration peak of D-lactose and the C-S stretching vibration peak of cysteine were significantly decreased by approximately 33.19% and 44.76%, respectively, indicating that photocatalysis indeed promoted the reduction of polysaccharides and cysteine in the EPS, especially after the thermophilic phase. The hydrophilic amino acid content decreased by 23.02%, verifying that photocatalysis could improve EPS hydrophobicity. Consequently, municipal sludge biodrying coupled with photocatalysis promotes sludge EPS degradation and enhances sludge dewaterability, improving the efficiency of sludge biodrying.
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Matriz Extracelular de Substâncias Poliméricas , Esgotos , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Cisteína , Água/químicaRESUMO
In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.
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Hipertensão Pulmonar , Panax notoginseng , Hipertensão Arterial Pulmonar , Saponinas , Animais , Masculino , Ratos , Caspase 3/metabolismo , Colágeno , Modelos Animais de Doenças , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Monocrotalina/efeitos adversos , Panax notoginseng/química , Antígeno Nuclear de Célula em Proliferação/metabolismo , Antígeno Nuclear de Célula em Proliferação/farmacologia , Artéria Pulmonar/metabolismo , Ratos Sprague-Dawley , Receptor Notch3/genética , RNA Mensageiro , Solução Salina , Transdução de Sinais , Saponinas/farmacologiaRESUMO
Blunt bowel injury (BBI) is relatively rare but life-threatening when delayed in surgical repair or anastomosis. Providing enteral nutrition (EN) in BBI patients with open abdomen after damage control surgery is challenging, especially for those with discontinuity of the bowel. Here, we report a 47-year-old male driver who was involved in a motor vehicle collision and developed ascites on post-trauma day 3. Emergency exploratory laparotomy at a local hospital revealed a complete rupture of the jejunum and then primary anastomosis was performed. Postoperatively, the patient was transferred to our trauma center for septic shock and hyperbilirubinemia. Following salvage resuscitation, damage control laparotomy with open abdomen was performed for abdominal sepsis, and a temporary double enterostomy (TDE) was created where the anastomosis was ruptured. Given the TDE and high risk of malnutrition, multiple portions EN were performed, including a proximal portion EN support through a nasogastric tube and a distal portion EN via a jejunal feeding tube. Besides, chyme delivered from the proximal portion of TDE was injected into the distal portion of TDE via a jejunal feeding tube. Hyperbilirubinemia was alleviated with the increase in chyme reinfusion. After 6 months of home EN and chyme reinfusion, the patient finally underwent TDE reversal and abdominal wall reconstruction and was discharged with a regular diet. For BBI patients with postoperative hyperbilirubinemia who underwent open abdomen, the combination of multiple portions EN and chyme reinfusion may be a feasible and safe option.
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Traumatismos Abdominais , Enteropatias , Masculino , Humanos , Pessoa de Meia-Idade , Nutrição Enteral , Intestinos/cirurgia , Abdome/cirurgia , Anastomose Cirúrgica , Traumatismos Abdominais/complicações , Traumatismos Abdominais/cirurgiaRESUMO
BACKGROUND: Dynamic-exponential intravoxel incoherent motion (IVIM) imaging is a potential technique for prediction, monitoring, and differential diagnosis of hepatic diseases, especially liver tumors. However, the use of such technique at voxel level is still limited. PURPOSE: To develop an unsupervised deep learning approach for voxel-wise dynamic-exponential IVIM modeling and parameter estimation in the liver. STUDY TYPE: Prospective. POPULATION: Ten healthy subjects (4 males; age 28 ± 6 years). FIELD STRENGTH/SEQUENCE: Single-shot spin-echo echo planar imaging (SE-EPI) sequence with monopolar diffusion-encoding gradients (12 b-values, 0-800 seconds/mm2 ) at 3.0 T. ASSESSMENT: The proposed deep neural network (DNN) was separately trained on simulated and in vivo hepatic IVIM datasets. The trained networks were compared to the approach combining least squares with Akaike information criterion (LSQ-AIC) in terms of dynamic-exponential modeling accuracy, inter-subject coefficients of variation (CVs), and fitting residuals on the simulated subsets and regions of interest (ROIs) in the left and right liver lobes. The ROIs were delineated by a radiologist (H.-X.Z.) with 7 years of experience in MRI reading. STATISTICAL TESTS: Comparisons between approaches were performed with a paired t-test (normality) or a Wilcoxon rank-sum test (nonnormality). P < 0.05 was considered statistically significant. RESULTS: In simulations, DNN gave significantly higher accuracy (91.6%-95.5%) for identification of bi-exponential decays with respect to LSQ-AIC (79.7%-86.8%). For tri-exponential identification, DNN was also superior to LSQ-AIC despite not reaching a significant level (P = 0.08). Additionally, DNN always yielded comparatively low root-mean-square error for estimated parameters. For the in vivo IVIM measurements, inter-subject CVs (0.011-0.150) of DNN were significantly smaller than those (0.049-0.573) of LSQ-AIC. Concerning fitting residuals, there was no significant difference between the two approaches (P = 0.56 and 0.76) in both the simulated and in vivo studies. DATA CONCLUSION: The proposed DNN is recommended for accurate and robust dynamic-exponential modeling and parameter estimation in hepatic IVIM imaging. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.
Assuntos
Aprendizado Profundo , Imagem de Difusão por Ressonância Magnética , Adulto , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Fígado/diagnóstico por imagem , Masculino , Movimento (Física) , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: Intravoxel incoherent motion (IVIM) tensor imaging is a promising technique for diagnosis and monitoring of cardiovascular diseases. Knowledge about measurement repeatability, however, remains limited. PURPOSE: To evaluate short-term repeatability of IVIM tensor imaging in normal in vivo human hearts. STUDY TYPE: Prospective. POPULATION: Ten healthy subjects without history of heart diseases. FIELD STRENGTH/SEQUENCE: Balanced steady-state free-precession cine sequence and single-shot spin-echo echo planar IVIM tensor imaging sequence (9 b-values, 0-400 seconds/mm2 and six diffusion-encoding directions) at 3.0 T. ASSESSMENT: Subjects were scanned twice with an interval of 15 minutes, leaving the scanner between studies. The signal-to-noise ratio (SNR) was evaluated in anterior, lateral, septal, and inferior segments of the left ventricle wall. Fractional anisotropy (FA), mean diffusivity (MD), mean fraction (MF), and helix angle (HA) in the four segments were independently measured by five radiologists. STATISTICAL TESTS: IVIM tensor indexes were compared between observers using a one-way analysis of variance or between scans using a paired t-test (normal data) or a Wilcoxon rank-sum test (non-normal data). Interobserver agreement and test-retest repeatability were assessed using the intraclass correlation coefficient (ICC), within-subject coefficient of variation (WCV), and Bland-Altman limits of agreements. RESULTS: SNR of inferior segment was significantly lower than the other three segments, and inferior segment was therefore excluded from repeatability analysis. Interobserver repeatability was excellent for all IVIM tensor indexes (ICC: 0.886-0.972; WCV: 0.62%-4.22%). Test-retest repeatability was excellent for MD of the self-diffusion tensor (D) and MF of the perfusion fraction tensor (fp ) (ICC: 0.803-0.888; WCV: 1.42%-9.51%) and moderate for FA and MD of the pseudo-diffusion tensor (D* ) (ICC: 0.487-0.532; WCV: 6.98%-10.89%). FA of D and fp and HA of D presented good test-retest repeatability (ICC: 0.732-0.788; WCV: 3.28%-8.71%). DATA CONCLUSION: The D and fp indexes exhibited satisfactory repeatability, but further efforts were needed to improve repeatability of D* indexes. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.
Assuntos
Imagem de Difusão por Ressonância Magnética , Imagem Ecoplanar , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Voluntários Saudáveis , Humanos , Movimento (Física) , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: We sought to identify the absolute risk of specific HPV genotype for cervical intraepithelial neoplasia grade 2/3 or worse (CIN2+/3+) and to develop a risk-based management strategy in an HPV-positive population. METHODS: HPV genotyping was performed based on a 3-year cervical cancer screening cohort. The study endpoints were histologic CIN2+/3+. The prevalence of specific HPV genotype was calculated by minimum, any type, and hierarchical attribution estimate. The absolute CIN2+/3+ risks of specific HPV genotype were estimated and risk-based management strategy was established according to the American Society for Colposcopy and Cervical Pathology guideline. The efficacy of conventional and risk-based management strategies for non-16/18 HPVs were further evaluated. RESULTS: Eligible data were available for 8,370 women with a median age of 48 years (interquartile range, 42-53 years). At baseline, there were 1,062 women with HPV-positive disease, including 424 with multiple and 639 with single infections. CIN2+/3+ cases represented 113/74, 23/8, 20/7, and 52/31 patients at baseline and first-, second-, and third-year visits, respectively. Women with multiple HPV infections at baseline were more prone to persistent infection than those with single infection (P<.0001). HPV16 and HPV52 were the top 2 ranking among baseline and 3-year cumulative CIN2+/3+ cases. Based on the absolute risk of specific HPV genotype combined with cytology for CIN2+/3+, all non-16/18 HPVs were divided into 4 risk-stratified groups. Compared with conventional strategy, the risk-based strategy had higher specificity (P=.0000) and positive predictive value (P=.0322) to detect CIN3+ and needed fewer colposcopies for each CIN3+ case. CONCLUSIONS: Based on our study findings, we propose a new extended HPV genotyping protocol, which would provide a better strategy for achieving precise risk-based management of HPV-positive populations.