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RATIONALE: The interstitial pneumonia (IP) linked to vedolizumab (VDZ) in patients with ulcerative colitis (UC) is rare. Prompt diagnosis and treatment can improve patient outcomes. PATIENT CONCERNS: A 39-year-old man with UC who received VDZ as sole therapy developed symptoms such as chest tightness, cough, and suffocation. DIAGNOSES: IP was confirmed through pulmonary function tests, chest computed tomography, and bronchoscopic biopsy. INTERVENTIONS: The patient was given methylprednisolone and VDZ cessation. OUTCOMES: The patient's symptoms improved and remained symptom-free after nearly 2 years. LESSONS: VDZ-induced IP should be considered when evaluating pulmonary infections in UC patients treated with VDZ.
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Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Fármacos Gastrointestinais , Doenças Pulmonares Intersticiais , Humanos , Colite Ulcerativa/tratamento farmacológico , Masculino , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Metilprednisolona/uso terapêuticoRESUMO
Vedolizumab (VDZ), a monoclonal antibody to α4ß7 integrin, is available for patients with moderate-to-severe ulcerative colitis (UC). This study planned to assess the real-world effectiveness and safety of VDZ for UC patients in Northern China. We enrolled patients with moderate-to-severe UC who underwent VDZ induction therapy from March 2021 to November 2022 at the Affiliated Hospital of Qingdao University. The primary outcome was clinical remission at weeks 14 and 52 after the initial VDZ therapy. Overall adverse events and risk factors associated with loss of response (LOR) were also evaluated. Seventy-three UC patients receiving VDZ therapy were included in this study. The rates of clinical response, clinical remission, and steroid-free clinical remission were 69.9%, 39.7%, and 34.2% at week 14 and 90.5%, 66.7%, and 64.4% at week 52, respectively. The mucosal remission rates were 37.5% (18/48) at week 14â ±â 8 and 27.3% (9/33) at week 52â ±â 16, while only 2 and 3 patients achieved mucosal healing at weeks 14â ±â 8 and 52â ±â 16, respectively. Of the UC patients, 23.3% experienced adverse events associated with VDZ, most of which were mild and self-limiting. Until the last follow-up, 37 of 73 UC patients experienced LOR during the maintenance period. Patients with a higher ulcerative colitis endoscopic severity index (UCEIS), partial Mayo scores (PMS), or hemoglobin below 120 g/L at baseline were more likely to experience LOR after VDZ induction therapy. VDZ is an effective and safe agent for patients with moderate-to-severe UC in Northern China. A high baseline UCEIS, PMS, or hemoglobinâ <â 120 g/L may be an independent risk factor for LOR during the maintenance period.
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Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Fármacos Gastrointestinais , Índice de Gravidade de Doença , Humanos , Colite Ulcerativa/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Masculino , Feminino , Adulto , China , Pessoa de Meia-Idade , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Resultado do Tratamento , Indução de Remissão/métodos , Adulto JovemRESUMO
High exhaust temperature is an intrinsic nature of natural gas engines which underlies power de-rating and thermal aging of after-treatment system; therefore, this study integrates an organic Rankine cycle (ORC) system between engine and it's three-way catalyst (TWC) to address these challenges. ORC facilitates power output enhancement through exhaust energy recovery and alleviates thermal aging by reducing exhaust temperature. To estimate the effectiveness of this hypothesized system, a simulation-based investigation is performed. First, simulation models, including engine, TWC, and vehicle dynamic models, are built and validated by experimental data. According to the temperature characteristics of different TWCs, three scenarios, representing old, current, and prospective TWC technology, are formulated to estimate the ORC performance under Worldwide Harmonized Light Vehicles Test Cycle. Results show that ORC system can substantially alleviate the thermal damage caused by high exhaust temperature and extend TWC lifespan. It is estimated that over 98.5 % of thermal damage can be decreased by proper ORC setting, and the average TWC lifespan extension can be at least 55.4, making a reduced noble metal usage and cost of TWC. Meanwhile, with the decrease of the working temperature of TWC, ORC can recover exhaust energy under more road conditions, further improving the net power and shortening the payback period of extra ORC hardware costs. A reduction in the working temperature of TWC from 770.5 K to 618 K yields a 109 % enhancement in maximum power, coupled with a 62.30 % reduction in the payback period. These findings fully reflect the advantage of ORC-TWC coupling and indicate that ORC is supposed to be used more for the TWC with a low working temperature to maximize economic effectiveness. This study provides a novel pathway for thermal aging alleviation of TWC and a valuable reference for prospective studies on matching ORC with TWC under road conditions.
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Background: The incidence of complications in gastric cancer (GC) patients after surgery was increasing, and it was not clear whether postoperative complications would have an impact on prognosis. The current study attempted to investigate the role of postoperative complication for prognosis on GC patients undergoing radical resection. Materials and Methods: Eligible studies were searched in three databases, including PubMed, Embase, and the Cochrane Library, in accordance with the searching strategy on September 4th, 2022. The survival values were most concerned; then, hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled up. All prognostic values, including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and recurrence-free survival (RFS), were allowed. Subgroup analysis based on complication types was used for further in-depth research. Results: A total of 29 studies involving 33,858 patients were included in this study. Intra-abdominal abscess (19.4%) was the most common complications in the included studies, followed by anastomotic leakage (17.0%) and pneumonia (16.4%). There were 23, 4, 6, and 10 studies that reported OS, DFS, DSS, and RFS, respectively. After analysis, postoperative complication was found to be an independent prognostic factor for OS (HR = 1.52, I2 = 1.14%, 95% CI = 1.42-1.61, P = .00), DFS (HR = 1.71, I2 = 0.00%,95% CI = 1.44-1.98, P < .05), DSS (HR = 1.60, I2 = 54.58%, 95% CI = 1.26-1.93, P < .1), and RFS (HR = 1.26, I2 = 0.00%, 95% CI = 1.11-1.41, P < .05). Subgroup analysis found that noninfectious complication was not significantly associated with OS (HR = 1.39, I2 = 0.00%, 95% CI = 0.96-1.82, P > .05). Conclusion: Surgeons needed to pay more attention to GC patients who developed postoperative complications, especially infectious complications, and take proactive management to improve the prognosis.
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Complicações Pós-Operatórias , Neoplasias Gástricas , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/mortalidade , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Gastrectomia/efeitos adversosRESUMO
Polyglycylation is a post-translational modification that generates glycine side chains in the C-terminal domains of both α- and ß-tubulins. To date, the patterns and significance of polyglycylation across insect species remain largely unknown. The TTLL3B was thought to be a polyglycylase and be essential for polyglycylation in dipteran insects. In this study, the TTLL3B of Bactrocera dorsalis (BdTTLL3B) was identified and characterized. The BdTTLL3B expressed remarkably higher in adult males, especially in testes. The spatio-temporal patterns of polyglycylation were consistent with that of BdTTLL3B. Along with spermatogenesis, the intensity of polyglycylation was enhanced steadily and concentrated in elongated flagella. The expression of recombinant BdTTLL3B in Hela cells, which are genetically deficient in polyglycylation, catalyzed intracellular polyglycylation, validating the identity of BdTTLL3B as a polyglycylase. Knockout of BdTTLL3B significantly suppressed polyglycylation in testes and impaired male fertility, probably due to abnormal morphology of mitochondrial derivatives and over-accumulation of paracrystalline. Taken together, these findings indicated that the BdTTLL3B-mediated polyglycylation is involved in the spermatogenesis and play an important role in fertility of adult B. dorsalis. Therefore, the BdTTLL3B can be considered as a candidate target gene for the management of B. dorsalis, such as developing gene silencing/knockout-based sterile insect technology (SIT).
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Espermatogênese , Tephritidae , Animais , Tephritidae/genética , Tephritidae/metabolismo , Masculino , Humanos , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Testículo/metabolismo , Processamento de Proteína Pós-Traducional , Células HeLa , Sequência de Aminoácidos , Fertilidade/genéticaRESUMO
We have previously identified a latent interaction mechanism between non-small cell lung cancer cells (NSCLCC) and their associated macrophages (TAM) mediated by mutual paracrine activation of the HMGB1/RAGE/NF-κB signaling. Activation of this mechanism results in TAM stimulation and PD-L1 upregulation in the NSCLCC. In the present work, we found that free DOX at a low concentration that does not cause DNA damage could activate the HMGB1/RAGE/NF-κB/PD-L1 pathway byinducing oxidative stress. It was thus proposed that a combination of low-dose DOX and a PD-L1 blocker delivered in the NSCLC tumor would achieve synergistic TAM stimulation and thereby synergetic anti-tumor potency. To prove this idea, DOX and BMS-202 (a PD-L1 blocker) were loaded to black phosphorus (BP) nanoparticles after dosage titration to yield the BMS-202/DOX@BP composites that rapidly disintegrated and released drug cargo upon mild photothermal heating at 40 °C. In vitro experiments then demonstrated that low-dose DOX and BMS-202 delivered via BMS-202/DOX@BP under mild photothermia displayed enhanced tumor cell toxicity with a potent synergism only in the presence of TAM. This enhanced synergism was due to an anti-tumor M1-like TAM phenotype that was synergistically induced by low dose DOX plus BMS-202 only in the presence of the tumor cells, indicating the damaged tumor cells to be the cardinal contributor to the M1-like TAM stimulation. In vivo, BMS-202/DOX@BP under mild photothermia exhibited targeted delivery to NSCLC graft tumors in mice and synergistic anti-tumor efficacy of delivered DOX and BMS-202. In conclusion, low-dose DOX in combination with a PD-L1 blocker is an effective strategy to turn TAM against their host tumor cells exploiting the HMGB1/RAGE/NF-κB/PD-L1 pathway. The synergetic actions involved highlight the value of TAM and the significance of modulating tumor cell-TAM cross-talk in tumor therapy. Photothermia-responsive BP provides an efficient platform to translate this strategy into targeted, efficacious tumor therapy.
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The destructive agricultural pest oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), has been causing huge damage to the fruits and vegetable industry. Although many pertinent studies have been conducted on B. dorsalis, the functions of fat body still remain largely unknown. To this end, the comparative transcriptome analysis between fat body and carcass was performed in an attempt to provide insights into functions of fat body of B. dorsalis in the present study. A total of 1431 upregulated and 2511 downregulated unigenes were discovered in the fat body vs carcass comparison, respectively. The enrichment analysis of differentially expressed genes (DEG) revealed that most of the enriched pathways were related to metabolism. The reliability of DEG analysis was validated by qRT-PCR measurements of 12 genes in starch and sucrose metabolism pathway, including the trehalose-6-phosphate synthase (BdTPS) which was highly expressed in eggs, 5 d-old adults, and fat body. The RNAi of BdTPS significantly affected trehalose and chitin metabolism, larval growth, and larva-pupa metamorphosis. Collectively, the findings in this study enriched our understanding of fat body functions in metabolism and demonstrated the indispensable roles of BdTPS in trehalose-related physiological pathways.
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Corpo Adiposo , Glucosiltransferases , Tephritidae , Animais , Reprodutibilidade dos Testes , Trealose/metabolismo , Perfilação da Expressão Gênica , Tephritidae/genética , Tephritidae/metabolismo , TranscriptomaRESUMO
The present work was an endeavor to shed light on how mild photothermia possibly synergizes with immune checkpoint inhibition for tumor therapy. We established mild photothermal heating protocols to generate temperatures of 43 °C and 45 °C in both in vitro and in vivo mouse 4T1 triple-negative breast cancer (TNBC) models using polyglycerol-coated carbon nanohorns (CNH-PG) and 808 nm laser irradiation. Next, we found that 1) CNH-PG-mediated mild photothermia (CNH-PG-mPT) significantly increased expression of the immune checkpoint PD-L1 and type-1 macrophage (M1) markers in the TNBC tumors; 2) CNH-PG-mPT had a lower level of anti-tumor efficacy which was markedly potentiated by BMS-1, a PD-L1 blocker. These observations prompted us to explore the synergetic mechanisms of CNH-PG-mPT and BMS-1 in the context of tumor cell-macrophage interactions mediated by PD-L1 since tumor-associated macrophages (TAMs) are a major source of PD-L1 expression in tumors. In vitro, the study then identified two dimensions where BMS-1 potentiated CNH-PG-mPT. First, CNH-PG-mPT induced PD-L1 upregulation in the tumor cells and showed a low level of cytotoxicity which was potentiated by BMS-1. Second, CNH-PG-mPT skewed TAMs towards an M1-like anti-tumor phenotype with upregulated PD-L1, and BMS-1 bolstered the M1-like phenotype. The synergistic effects of BMS-1 and CNH-PG-mPT both on the tumor cells and TAMs were more pronounced when the two cell populations were in co-culture. Further in vivo study confirmed PD-L1 upregulation both in tumor cells and TAMs in the TNBC tumors following treatment of CNH-PG-mPT. Significantly, TAMs depletion largely abolished the anti-TNBC efficacy of CNH-PG-mPT alone and in synergy with BMS-1. Collectively, our findings reveal PD-L1 upregulation to be a key response of TNBC to mild photothermal stress, which plays a pro-survival role in the tumor cells while also acting as a brake on the M1-like activation of the TAMs. Blockade of mPTinduced PDL1 achieves synergistic anti-TNBC efficacy by taking the intrinsic survival edge off the tumor cells on one hand and taking the brakes off the M1-like TAMs on the other. Our findings reveal a novel way (i.e. mild thermia plus PD-L1 blockade) to modulate the TAMs-tumor cell interaction to instigate a mutiny of the TAMs against their host tumor cells.
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Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antígeno B7-H1/metabolismo , Terapia Fototérmica , Macrófagos/metabolismo , Fenótipo , Linhagem Celular TumoralRESUMO
This study explored the possible hemodynamic changes of the retina and choroid after horizontal strabismus surgery using swept-source optical coherence tomography angiography (SS-OCTA). 32 eyes of 32 patients who underwent unilateral horizontal rectus muscle recession-resection surgery were included. SS-OCTA examinations were performed preoperatively and one week postoperatively. Several OCTA measurements were used, including vessel density (VD) of the superficial vascular complex (SVC), VD of the deep vascular complex (DVC), VD of the choriocapillaris (CC), choroidal vascular index (CVI) and choroidal thickness (CT). No significant change in VD of SVC, DVC, and CC was observed whereas CT increased significantly with CVI unchanged. Recession-resection surgery for horizontal strabismus seemed not to significantly influence the microcirculation of the retina and CC in the early postoperative period. However, choroidal thickening happened with a constant CVI probably due to the postoperative inflammation. Further studies are needed to investigate the long-term effects of unilateral recession-resection surgery for horizontal strabismus on the microcirculation of the retina and choroid.
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Vasos Retinianos , Estrabismo , Humanos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/fisiologia , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos , Microcirculação/fisiologia , Retina , Corioide/diagnóstico por imagem , Corioide/irrigação sanguínea , Estrabismo/diagnóstico por imagem , Estrabismo/cirurgiaRESUMO
The scoring systems commonly used to assess endoscopic disease severity of ulcerative colitis (UC) in clinical research and practice include the Mayo endoscopic score (MES), ulcerative colitis endoscopic severity index (UCEIS), and degree of ulcerative colitis burden of luminal inflammation (DUBLIN). We aimed to assess and compare the predictive efficacy of the MES, DUBLIN score and UCEIS score for prognosis in UC patients treated with vedolizumab (VDZ). Seventy-four UC patients who treated with VDZ from September 2021 to February 2023 were retrospectively enrolled. We used the MES, DUBLIN and UCEIS score to evaluate endoscopic findings. The predictive capability of these 3 scores for surgery or therapeutic escalation was assessed using the receiver operating characteristic curve. The mean MES, DUBLIN and UCEIS score significantly improved from 2.83â ±â 0.38, 7.80â ±â 1.82 and 6.24â ±â 1.51 to 2.07â ±â 0.88, 5.57â ±â 2.68, and 3.72â ±â 2.12, respectively (Pâ <â .001). Lower pre-therapeutic UCEIS scores were associated with favorable short-term outcomes. Importantly, the post-therapeutic UCEIS score showed the best predictive capability with an area under curve of 0.871 (95% confidence interval: 0.767-0.976), specificity of 0.654, sensitivity of 0.900, and cutoff value of 3.5. A UCEIS score ofâ ≥â 4 after treatment was correlated with surgical operation or treatment escalation. The UCEIS score is superior to the MES and DUBLIN score in reflecting short-term outcomes and long-term prognosis in UC patients treated with VDZ, and clinical remission could be defined as a UCEIS scoreâ ≤â 3.
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Colite Ulcerativa , Humanos , Colite Ulcerativa/tratamento farmacológico , Colonoscopia , Estudos Retrospectivos , Índice de Gravidade de Doença , PrognósticoRESUMO
Ubiquitin-conjugating enzyme E2 C (UBE2C) plays a carcinogenic role in gastric cancer (GC); yet, its role in cisplatin (DDP) resistance in GC is enigmatic. This study sought to probe into the impact of UBE2C on DDP resistance in GC and its concrete molecular mechanism in GC progression. Bioinformatics analysis was used to analyze differentially expressed mRNAs and predict upstream regulatory molecules in GC. Real-time quantitative reverse transcriptase polymerase chain reaction and western blot were used to detect the expression of UBE2C and MYB proto-oncogene like 2 (MYBL2). Dual luciferase and chromatin immunoprecipitation (ChIP) assays were used to verify the binding relationship. Cell counting kit-8 was used to detect cell viability and calculate IC50 values. Flow cytometry was used to detect the cell cycle. Comet assay was used to detect DNA damage. Western blot was used to detect the expression of DNA loss-related proteins (γ-H2AX, ATM/p-ATM). The knockdown of highly expressed UBE2C in GC cell lines could reduce cell viability, induce G2/M arrest, induce apoptosis, and promote DNA damage and DDP sensitivity. Bioinformatics analysis predicted that the substantially upregulated MYBL2 was an upstream transcription factor in UBE2C. The binding relationship between the UBE2C promoter region and MYBL2 was verified by dual luciferase and ChIP. Overexpression of UBE2C in the rescue experiment was found to reverse the inhibited GC progression and promoted DDP sensitivity brought by the knockdown of MYBL2. In conclusion, the MYBL2/UBE2C regulatory axis may be a potential way to overcome DDP resistance in GC.
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PURPOSE: To evaluate the retinal and choroidal microvasculature after one or two horizontal rectus muscle surgeries in strabismus patients using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: 30 eyes of 26 patients who underwent horizontal rectus muscle surgery were included in this study. Group A, A' and Group B , B' respectively consisted preoperative and postoperative measurements of patients who underwent one or two horizontal rectus muscle surgeries. We analyzed the vessel density (VD) of the superficial vascular complex (SVC), the deep vascular complex (DVC), the choriocapillary layer (CC), choroidal vascular index (CVI), choroidal thickness (T-Ch) and retinal nerve fiber layer thickness (T-RNFL) preoperatively, and one week postoperatively. RESULTS: Only in the nasal sector of the perifoveal zone, the VD in SVC demonstrated a significant increase in Group A' (p = 0.027). There was a statistically significant difference in the VD changes of SVC between Group A and Group B (p = 0.043). The VD in DVC did not change significantly in the whole macular compared with the preoperative. Moreover, in both Group A' and Group B', the VD in CC showed a reduction in a single sector of the parafoveal area (p < 0.05). Group A' have increased CVI in the nasal sector of the perifoveal region (p = 0.008). In addition, the T-Ch increase in the perifoveal region was more significant in Group B' than in Group A' (p < 0.05). Group A' showed statistically significant decreases in T-RNFL in the foveal and parafoveal regions (p < 0.05). CONCLUSION: This study revealed that the increase in choroidal thickness was more significant after two rectus muscle surgery. In addition, there were microvascular changes in sectional macular regions after strabismus surgery. OCTA is an excellent way to study the impact of strabismus surgery on the macular structure and blood flow.
We used SS-OCTA, which provided more objective and accurate measurements, to assess macular vessel density and thickness of retinal and choroid after one or two horizontal rectus muscle surgeries.
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Vasos Retinianos , Estrabismo , Humanos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/fisiologia , Tomografia de Coerência Óptica/métodos , Angiografia , MúsculosRESUMO
The oriental fruit fly, Bactrocera dorsalis (Hendel), is a notorious invasive pest that has raised concerns worldwide. Validamycin has been demonstrated to be a very strong inhibitor against trehalase in a variety of organisms. However, whether validamycin can inhibit trehalase activity to suppress trehalose hydrolysis and affect any other relevant physiological pathways in B. dorsalis remains unknown. In this study, the effects of validamycin injection on the synthesis and metabolism of trehalose and chitin were evaluated. The results show that validamycin injection significantly affected trehalase activity and caused trehalose accumulation. In addition, the downstream pathways of trehalose hydrolysis, including the synthesis and metabolism of chitin, were also remarkably affected as the expressions of the key genes in these pathways were significantly regulated and the chitin contents were changed accordingly. Intriguingly, the upstream trehalose synthesis was also affected by validamycin injection due to the variations in the expression levels of key genes, especially BdTPPC1. Moreover, BdTPPC1 was predicted to have a binding affinity to validamycin, and the subsequent in vitro recombinant enzyme activity assay verified the inhibitory effect of validamycin on BdTPPC1 activity for the first time. These findings collectively indicate that validamycin can be considered as a promising potential insecticide for the management of B. dorsalis.
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The recurrent neural network architecture improves the processing ability of time-series data. However, issues such as exploding gradients and poor feature extraction limit its application in the automatic diagnosis of mild cognitive impairment (MCI). This paper proposed a research approach for building an MCI diagnostic model using a Bayesian-optimized bidirectional long short-term memory network (BO-BiLSTM) to address this problem. The diagnostic model was based on a Bayesian algorithm and combined prior distribution and posterior probability results to optimize the BO-BiLSTM network hyperparameters. It also used multiple feature quantities that fully reflected the cognitive state of the MCI brain, such as power spectral density, fuzzy entropy, and multifractal spectrum, as the input of the diagnostic model to achieve automatic MCI diagnosis. The results showed that the feature-fused Bayesian-optimized BiLSTM network model achieved an MCI diagnostic accuracy of 98.64% and effectively completed the diagnostic assessment of MCI. In conclusion, based on this optimization, the long short-term neural network model has achieved automatic diagnostic assessment of MCI, providing a new diagnostic model for intelligent diagnosis of MCI.
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Disfunção Cognitiva , Redes Neurais de Computação , Humanos , Teorema de Bayes , Algoritmos , Encéfalo , Disfunção Cognitiva/diagnósticoRESUMO
The electroencephalogram (EEG) signal is a general reflection of the neurophysiological activity of the brain, which has the advantages of being safe, efficient, real-time and dynamic. With the development and advancement of machine learning research, automatic diagnosis of Alzheimer's diseases based on deep learning is becoming a research hotspot. Started from feedforward neural networks, this paper compared and analysed the structural properties of neural network models such as recurrent neural networks, convolutional neural networks and deep belief networks and their performance in the diagnosis of Alzheimer's disease. It also discussed the possible challenges and research trends of this research in the future, expecting to provide a valuable reference for the clinical application of neural networks in the EEG diagnosis of Alzheimer's disease.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Redes Neurais de Computação , Aprendizado de Máquina , Encéfalo , EletroencefalografiaRESUMO
State of charge (SOC) of ultracapacitor plays an important role in the energy management optimization of hybrid energy storage system for electric vehicles. In addition to the perfection of the model and the SOC estimation algorithm, the parameter identification method and temperature factor should also be considered. In this paper, an ultracapacitor test platform is established, the characteristic parameters of ultracapacitor at full temperature range are obtained. This paper uses the forgetting factor recursive least squares algorithm (FFRLS) to identify the parameters of the second-order equivalent circuit model of ultracapacitor online. The extended Kalman filter (EKF) algorithm is used to estimate the SOC of ultracapacitor cell. The results show that: (1) FFRLS algorithm can identify R 0 , R 1 , R 2 , C 1 , and C 2 values of ultracapacitor at full temperature range. Under the hybrid pulse power characterization working condition, the average mean absolute error between the estimated voltage and the actual voltage is about 0.0132 V. (2) EKF algorithm has a good adaptability to estimate SOC of ultracapacitor under different temperatures and working conditions. The SOC estimation error under different working conditions is low. From the perspective of mean square error, the estimation error at -20 °C is the lowest. (3) FFRLS and EKF joint estimation algorithm with good robustness and reliability can be used to estimate the SOC of ultracapacitor under different temperatures and working conditions. This study can provide a useful guidance for the parameter identification and SOC estimation of ultracapacitor for electric vehicle at different temperatures.
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RATIONALE: Intestinal stricture and obstruction are rare complications of ulcerative colitis (UC). Currently, there are only a few studies on the treatment of UC with intestinal stenosis, however there are no reports on the treatment of UC with benign intestinal stenosis with ustekinumab (UST). PATIENT CONCERNS: A 22-year-old woman was admitted to our hospital due to a 3-year history of recurrent bloody mucous in stool with intermittent abdominal pain and distension developed in the past month. She was steroid-dependent and had developed a secondary loss of response to infliximab. DIAGNOSES: She was diagnosed with UC combined with incomplete intestinal obstruction due to stenosis. The stricture had a mixed pattern with both inflammatory and fibrotic components, with the former covering a larger section of the intestine. INTERVENTIONS: The patient was given UST for 56 weeks. OUTCOMES: The patient's symptoms subsided after treatment with UST. The ulcers healed, and the stenosis was reduced. LESSONS: UST is effective against UC with benign intestinal stenosis. It is thought that UST inhibits the production of transforming growth factor-ß and interleukin-17, leading to the suppression of myofibroblast proliferation, ultimately alleviating intestinal stenosis.
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Colite Ulcerativa , Obstrução Intestinal , Feminino , Humanos , Adulto Jovem , Adulto , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/diagnóstico , Infliximab , Ustekinumab/uso terapêutico , Interleucina-17 , Constrição Patológica/etiologia , Constrição Patológica/complicações , Obstrução Intestinal/complicações , Fatores de Crescimento TransformadoresRESUMO
Photodynamic therapy (PDT) has recently emerged as a promising, targeted treatment modality for glioblastoma (GBM) which is the most vicious type of brain tumor. Successful GBM-PDT hinges upon light activation of a photosensitizer accumulated in the tumor. However, inadequate tumor accumulation of photosensitizer severely limits the success of PDT of GBM. To tackle this difficulty, we herein propose a drug delivery strategy of "platelets with photo-controlled release property". This strategy exploits platelets as carriers to deliver a photosensitizer which, in the current study, is a nano-composite (BNPD-Ce6) comprised of chlorine e6 (Ce6) loaded to boron nitride nanoparticles with a surface coating of polyglycerol and doxorubicin. To demonstrate the working mechanism and therapeutic advantage of this strategy, we loaded mouse platelets with BNPD-Ce6 to yield the nano-device BNPD-Ce6@Plt. In vitro experiments showed BNPD-Ce6@Plt to have a high loading capacity and efficiency. Laser irradiation (LI) at a wavelength of 808 nm induced ROS generation in BNPD-Ce6@Plt which displayed rapid activation, aggregation, and speedy discharge of BNPD-Ce6 into co-cultured GL261 mouse GBM cells which in turn, after LI, exhibited marked ROS generation, DNA damage, reduced viability, and cell death. In vivo animal experiments, mice that were intravenously injected with BNPD-Ce6@Plt exhibited rapid and extensive BNPD-Ce6 accumulation in both subcutaneous and intra-brain GL261 tumors shortly after LI of the tumors and the tumors displayed massive tissue necrosis after LI for a second time. Finally, a PDT regimen of two intravenous BNPD-Ce6@Plt injections each followed by multiple times of extracranial LI at the tumor site significantly inhibited the growth of intra-brain GL261 tumors and markedly increased the survival of the host animals. No apparent tissue damage was found in vital organs. Our findings make a compelling case for the notion that platelets are efficient carriers that can photo-controllably deliver nano-photosensitizers to achieve highly targeted and efficacious PDT of GBM. This work presents a novel approach to GBM-PDT with great translational potential.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Fotoquimioterapia , Porfirinas , Camundongos , Animais , Glioblastoma/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Preparações de Ação Retardada , Linhagem Celular Tumoral , Porfirinas/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológicoRESUMO
BACKGROUND: The compound Biejia-Ruangan tablet (CBRT), as an adjunctive therapy to entecavir, is a potential treatment for hepatic fibrosis (HF) in patients with chronic hepatitis B (HBV). However, the present study yielded inconsistent results. In this systematic review and meta-analysis, we comprehensively investigated the efficacy and safety of CBRT as an adjunctive modality to entecavir for the treatment of HBV infection complicated with HF. METHODS: We searched the Cochrane Library, PubMed, Embase, CNKI, VIP, CBM, and Wangfang databases through April 1, 2022, for randomized controlled trials (RCTs) assessing the effect and safety of CBRT as an adjunctive modality to entecavir for HBV complicated with HF. The primary outcomes were biochemical parameters of serum hyaluronic acid, laminin (LN), pretype-III collagen (PC-III), and type IV collagen (IV-C). The secondary outcomes were liver function indices of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBiL) levels, total effect rate, and occurrence rate of adverse events. Two researchers independently conducted study selection, data extraction, and quality assessment. Statistical analysis was performed using the RevMan 5.3 software. RESULTS: Eight RCTs involving 747 patients were included. Compared with entecavir monotherapy, CBRT as an adjunctive therapy to entecavir exerted more encouraging effect in serum levels of hyaluronic acid (mean difference [MD] = -28.15; 95% confidence interval [CI]: -43.82 to -12.47; P < .001), LN (MD = -29.46; 95% CI: -50.69 to -8.23; P < .001), PC-III (MD = -11.83; 95% CI: -19.43 to -4.23; P < .001), and IV-C (MD = -19.62; 95% CI: -29.76 to -9.49; P < .001); levels of serum ALT (MD = -16.83; 95% CI: -26.30 to -7.36; P < .001), AST (MD = -20.52; 95% CI: -33.11 to -7.93; P < .001), and TBiL (MD = -7.54; 95% CI: -11.58 to -3.49; P < .001); and total effect rate (odds ratio = 3.53; 95% CI: 1.71-7.29; P < .001). Meta-analysis results also showed that CBRT as an adjunctive therapy to entecavir had a lower occurrence rate of adverse events (odds ratio = 0.54; 95% CI: 0.22-1.34; P < .001) than entecavir alone. CONCLUSION: The results of this study showed that CBRT as an adjunctive modality to entecavir may benefit HBV patients complicated with HF. High-quality RCTs are needed to confirm the current findings in the future.
Assuntos
Hepatite B Crônica , Guanina/análogos & derivados , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Ácido Hialurônico/uso terapêutico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , ComprimidosRESUMO
BACKGROUND: This systematic review and meta-analysis aimed to assess the efficacy of trastuzumab combined with chemotherapy for the treatment in HER2-positive advanced gastric cancer (HER2-PAGC). METHODS: This systematic review and meta-analysis was designed using randomized controlled trials that compared trastuzumab in combination with chemotherapy and chemotherapy alone. A comprehensive search was conducted in the following databases from their inception onwards: PubMed, EMBASE, Cochrane Library, WANGFANG, and CNKI. We also searched other literature sources to avoid missing relevant studies. Two reviewers independently performed all record selection, data collection, and methodological assessments. Any confusion was resolved by discussion or referral to a third reviewer. If there were ample data from eligible studies, we performed a fixed-effects meta-analysis. Whenever this was not possible, we conducted a narrative synthesis. RESULTS: Meta-analysis results showed that trastuzumab in combination with chemotherapy achieved better outcomes on response rate (trastuzumab plus CFC vs CFC: odds ratio [OR] = 1.56, 95% confidence interval [CI] [1.17-2.09], I2 = 0%, P < .003; trastuzumab plus OT vs OT: OR = 2.97, 95% CI [1.74-5.09], I2 = 0%, P < .0001; and trastuzumab plus CC vs CC: OR = 2.62, 95% CI [1.84-3.73], I2 = 0%, P < .0001), and disease control rate (trastuzumab plus CFC vs CFC: OR = 1.61, 95% CI [1.17-2.21], I2 = 0%, P = .004; trastuzumab plus OT vs OT: OR = 4.29, 95% CI [2.33-7.90], I2 = 0%, P < .0001; and trastuzumab plus CC vs CC: OR = 2.99, 95% CI [1.99-4.48], I2 = 0%, P < .0001). However, there were no significant differences in the adverse events. CONCLUSIONS: The results of this study revealed that the efficacy of trastuzumab combined with chemotherapy was superior to that of chemotherapy alone for the treatment of HER2-PAGC. The 2 modalities showed similar safety profiles.