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Background: Mitochondria have always been considered too be closely related to the occurrence and development of malignant tumors. However, the bioinformatic analysis of mitochondria in lung adenocarcinoma (LUAD) has not been reported yet. Methods: In the present study, we constructed a novel and reliable algorithm, comprising a consensus cluster analysis and risk assessment model, to predict the survival outcomes and tumor immunity for patients with terminal LUAD. Results: Patients with LUAD were classified into three clusters, and patients in cluster 1 exhibited the best survival outcomes. The patients in cluster 3 had the highest expression of PDL1 (encoding programmed cell death 1 ligand 11) and HAVCR2 (encoding Hepatitis A virus cellular receptor 2), and the highest tumor mutation burden (TMB). In the risk assessment model, patients in the low-risk group tended to have a significantly better survival outcome. Furthermore, the risk score combined with stage could act as a reliable independent prognostic indicator for patients with LUAD. The prognostic signature is a novel and effective biomarker to select anti-tumor drugs. Low-risk patients tended to have a higher expression of CTLA4 (encoding cytotoxic T-lymphocyte associated protein 4) and HAVCR2. Moreover, patients in the high-risk group were more sensitive to Cisplatin, Docetaxel, Erlotinib, Gemcitabine, and Paclitaxel, while low-risk patients would probably benefit more from Gefitinib. Conclusion: We constructed a novel and reliable algorithm comprising a consensus cluster analysis and risk assessment model to predict survival outcomes, which functions as a reliable guideline for anti-tumor drug treatment for patients with terminal LUAD.
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Vegetation redistribution may bring unexpected climate-soil carbon cycling in terrestrial biomes. However, whether and how vegetation redistribution alters the soil carbon pool under climate change is still poorly understood on the Tibetan Plateau. Here, we applied the G-Range model to simulate the cover of herbs, shrubs and trees, net primary productivity (NPP) and soil organic carbon density (SOCD) at the depth of 60 cm on Tibetan Plateau for the individual years 2020 and 2060, using climate projection for Representative Concentration Pathways (RCP) 4.5 and RCP8.5 scenarios with the RegCM4.6 model system. Vegetation redistribution was defined as the transitions in bare ground, herbs, shrubs and trees between 2020 and 2060, with approximately 57.9 % (RCP4.5) and 59 % (RCP8.5) of the area will redistribute vegetation over the whole Tibetan Plateau. The vegetation cover will increase by about 2.4 % (RCP4.5) and 1.9 % (RCP8.5), while the NPP and SOCD will decrease by about -14.3 g C m-2 yr-1 and -907 g C m-2 (RCP4.5), and -1.8 g C m-2 yr-1and -920 g C m-2 (RCP8.5). Shrubs and trees will expand in the east, and herbs will expand in the northwest part of the Plateau. These areas are projected to be hotspots with greater SOCD reduction in response to future climate change, and will include lower net plant carbon input due to the negative NPP. Our study indicates that the SOC pool will become a carbon source under increased air temperature and rainfall on the Tibetan Plateau by 2060, especially for the area with vegetation redistribution. These results revealed the potential risk of vegetation redistribution under climate change in alpine ecosystems, indicating the policymakers need to pay attention on the vegetation redistribution to mitigate the soil carbon emission and achieve the goal of carbon neutrality on the Tibetan Plateau.
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Water commonly occurs in coal reservoirs, and it can block the gas flow channels. This has a significant influence on methane transportation within coal. To reveal the gas emission law of water-containing coal across the rank range, three typical coal samples with different coal ranks covering lignite to anthracite were selected in this work. The initial velocity of gas emission (ΔP) under the effect of moisture was measured, and the combination of scanning electron microscopy and mercury injection method was adopted to study the pores and fracture characteristics within coal. Distribution features of oxygen-containing groups in coal were explored by X-ray photoelectron spectroscopy. The microscopic influence mechanism of the water content on ΔP in coal was also comprehensively elucidated. The experimental results show that the moisture content has an obvious inhibitory effect on the ΔP of coal, but the degree of influence on different coal rank samples was different. As the pore space of anthracite (sample XJ) is developed with numerous gas transportation channels, the ΔP has less changes at the lower moisture content (<4.36%). When the moisture content is >4.36%, a large number of water molecules will band together to form water clusters, hindering the gas release, thus greatly reducing the ΔP. However, the change of lignite (sample SL) shows an inverse trend to that of anthracite. Its ΔP is sensitive to the moisture content due to the small number of pores and low porosity. In addition, a great number of oxygen-containing groups in lignite can also provide good surface hydrophilicity for water molecules, and even a small amount of the moisture content (<3.21%) can block most of the pore and facture channels within coal, leading to the remarkable decrease in ΔP. For bituminous coal (sample ML), the distribution of pores and oxygen-containing groups is the most uniform, and the ΔP decreases linearly with the increase in the moisture content.
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BACKGROUND: Postoperative anastomotic leakage (PAL) is a serious complication of gastric cancer surgery. Although perioperative management has made considerable progress, anastomotic leakage (AL) cannot always be avoided. The purpose of this study is to evaluate whether intraoperative leak testing (IOLT) can reduce the incidence of PAL and other postoperative outcomes in gastric cancer surgery. MATERIALS AND METHODS: In this meta-analysis, we searched the PubMed, Embase, and Cochrane Library databases for clinical trials to assess the application of IOLT in gastric cancer surgery. All patients underwent laparoscopic radical gastrectomy for gastric cancer surgery. Studies comparing the postoperative outcomes of IOLT and no intraoperative leak testing (NIOLT) were included. Quality assessment, heterogeneity, risk of bias, and the level of evidence of the included studies were evaluated. PAL, anastomotic-related complications, 30-day mortality, and reoperation rates were compared between the IOLT and NIOLT group. RESULTS: Our literature search returned 721 results, from which six trials (a total of 1,666 patients) were included in our meta-analysis. Statistical heterogeneity was low. The primary outcome was PAL. IOLT reduced the incidence of PAL [2.09% vs 6.68%; (RR = 0.31, 95% Cl 0.19-0.53, P < 0.0001]. Anastomotic-related complications, which included bleeding, leakage, and stricture, were significantly higher in the NIOLT group than in the IOLT group [3.24% VS 10.85%; RR = 0.30, 95% Cl 0.18-0.53, P < 0.0001]. Moreover, IOLT was associated with lower reoperation rates [0.94% vs 6.83%; RR = 0.18, 95% CI 0.07-0.43, P = 0.0002]. CONCLUSION: Considering the observed lower incidence of postoperative anastomotic leakage (PAL), anastomotic-related complications, and reoperation rates, IOLT appears to be a promising option for gastric cancer surgery. It warrants further study before potential inclusion in future clinical guidelines.
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Fístula Anastomótica , Gastrectomia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/prevenção & controle , Fístula Anastomótica/etiologia , Gastrectomia/métodos , Gastrectomia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Reoperação/estatística & dados numéricos , Resultado do Tratamento , IncidênciaRESUMO
Shear failure often occurs in engineering rock mass (such as inclined pillar) in gently inclined strata. Prediction and characterization the orientation of shear failure plane is the foundation of rock mass engineering reinforcement. In this paper, sandstone samples are used to perform uniaxial and shear tests to obtain the basic mechanical parameters. Then, by employing the numerical method, the combined compression-shear loading tests were carried out for inclined specimens varied from 0° to 25° at an interval of 5°, to obtain the dip effect on the orientation of rock failure plane. The results show that the failure plane of rock changes with the change of dip angle of rock sample. Based on the Mohr-Coulomb criterion, the ultimate stress state of rock was characterized under combined compression-shear loading. The ultimate strength of rock is equal to the ratio of the stress circle radius of rock under combined compression-shear condition to the stress circle radius of rock under uniaxial compression condition, multiplied by the uniaxial compressive strength. The fracture angle of rock was defined under combined compression-shear loading. A theoretical model was developed for predicting the fracture angle. The developed model could be characterized by internal friction angle, dip angle of rock sample and Poisson's ratio. Finally, the numerical results of the fracture angle were analyzed, which are consistent with the predicted results of the model. The investigation shows that the rock fracture angle has a dip effect, which decreases with the increase of the inclination angle of the sample. The research results provide a new means to identify the potential failure plane of engineering rock mass, and lay a theoretical foundation for calculating the orientation of rock fracture plane.
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ETHNOPHARMACOLOGICAL RELEVANCE: Guanxinning(GXN) tablet is a patented traditional Chinese medicine widely used to prevent and treat cardiovascular diseases. However, its potential mechanism and target in anti-diabetic atherosclerosis have not been clarified. AIM: The aim of this study was to investigate the underlying targets and mechanisms of action GXN in the treatment of diabetic atherosclerosis, employing a combination of network pharmacology, molecular docking, and in vitro experimental verification. METHODS: We predicted the core components and targets of GXN in the treatment of diabetic atherosclerosis through various databases, and made analysis and molecular docking. In vitro, we induced injury in human umbilical vein endothelial cells using glucose/palmitate and observed the effects of GXN on cellular damage high-glucose and high-fat conditions, subsequently elucidating its molecular mechanisms. RESULTS: A total of 14 active components and 157 targets of GXN were identified. Using the PPI network, we selected 9 core active components and 20 targets of GXN. GO functional analysis revealed that these targets were primarily associated with apoptosis signaling pathways in response to endoplasmic reticulum stress and reactive oxygen species responses. Molecular docking confirmed the strong binding affinities of the primary active components of GXN with ERN1, MAPK1 and BECN1. In vitro experiments demonstrated the ability of GXN to restore endothelial cell activity, enhance cell migration and inhibit sICAM secretion, and upregulate the expression of endoplasmic reticulum stress-related proteins (IRE1, XBP1) and autophagy-related proteins (Beclin1, LC3A, and LC3B), while simultaneously inhibiting endothelial cell apoptosis under high-glucose and high-fat conditions. CONCLUSIONS: Our findings suggest that GXN can potentially safeguard endothelial cells from the adverse effects of high-glucose and high-fat by modulating the interactions between endoplasmic reticulum stress and autophagy. Therefore, GXN is a promising candidate for the prevention and treatment of diabetic atherosclerosis.
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Aterosclerose , Diabetes Mellitus , Medicamentos de Ervas Chinesas , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Aterosclerose/tratamento farmacológico , Glucose , Células Endoteliais da Veia Umbilical Humana , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Diabetes Mellitus/tratamento farmacológicoRESUMO
Warming can decrease feeding activity of soil organisms and affect biogeochemical cycles. The ant Formica manchu is active on the nest surface and prefers a hot, dry environment; therefore, warming may provide a favourable environment for its activities. We hypothesized that F. manchu benefit from warming and mitigate the negative effects of warming on litter decomposition. We examined the effects of ant nests (nest absence versus nest presence) and warming (+1.3 and +2.3°C) on litter decomposition, soil properties and the plant community in alpine grassland. Decomposition stations with two mesh sizes were used to differentiate effects of microorganisms (0.05 mm) and macroinvertebrates (1 cm) on decomposition. Ant nests increased litter decomposition with and without macroinvertebrates accessing the decomposition station when compared to plots without ant nests. Only litter decomposition in ant nests with macroinvertebrates having access to the decomposition station was not affected negatively by warming. Plots with ant nests had greater soil carbon, nutrient contents and plant growth than plots without ant nests, regardless of warming. Our results suggest that ant nests maintain ecosystem processes and functions under warming. Consequently, a management strategy in alpine grasslands should include the protection of these ants and ant nests.
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Formigas , Ecossistema , Animais , Pradaria , Plantas , Solo/químicaRESUMO
The soil carbon (C) and nitrogen (N) availability are important in the regulation of soil C cycling under climate change. Fertilizers alter soil C and N availability, which can affect C balance. However, the impact of fertilizers on C balance in grassland restoration has been equivocal and warrants more research. We determined the direct and indirect effects of the addition of three levels of C (sucrose) (0, 60, and 120 kg C ha-1 yr-1), three levels of N (urea) (0, 50, and 100 kg N ha-1 yr-1), and a combination of C plus N at each of the levels on soil respiration (Rs) dynamics and C balance in an alpine meadow in northern Tibet (4700 m above sea level). This study was undertaken during the middle of the growing season in 2011-2012. The addition of C and/or N stimulated CO2 emission, which was 2-fold greater in 2011 (102-144 g C m-2) than in 2012 (43-54 g C m-2). The rate of Rs increased with the addition of N, but was not affected with the addition of C plus N. Microbial biomass C, dissolved organic C and inorganic N were the main drivers of Rs. We concluded that N addition stimulated Rs to a greater extent than C addition in the short term. The application of fertilizer in the restoration of degraded grassland should be re-considered.
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Pradaria , Nitrogênio , Nitrogênio/análise , Carbono , Solo , Fertilizantes , EcossistemaRESUMO
In underground mining, the dip angle is one of the widely recognized factors that cause the asymmetric deformation of the goaf/stope roof, but characterizing the degree of asymmetric roof deformation is still a challenge. The goal of this research is to try to solve this problem with a theoretical model and numerical method. In an inclined ore seam, the mining load produces both normal and tangential effects on the inclined roof. A theoretical model was developed employing thin plate theory for enabling describe the asymmetric deformation of the roof caused by inclination. The proposed model describes not only the bending deformation state of the roof but also the deformation characteristics. Subsequently, the law of asymmetric deformation of roofs with varying inclinations was presented by numerical method. Under the same conditions, the numerical results of the asymmetric deformation of the roof are consistent with the theoretical results. Finally, the degree of asymmetrical deformation was characterized and quantified by the distance between the maximum subsidence point and the center of the roof. There exist three modes of asymmetric deformation, which are controlled by both dip angle and in-situ stress ratio. The results show that the shear load caused by dip angle is the root cause of asymmetric deformation of the roof. This study provides a theoretical basis for the asymmetric deformation control of the inclined roof.
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For centuries, the search for nutritional interventions to underpin cardiovascular treatment and prevention guidelines has contributed to the rapid development of the field of dietary patterns and cardiometabolic disease (CMD). Numerous studies have demonstrated that healthy dietary patterns with emphasis on food-based recommendations are the gold standard for extending lifespan and reducing the risks of CMD and mortality. Healthy dietary patterns include various permutations of energy restriction, macronutrients, and food intake patterns such as calorie restriction, intermittent fasting, Mediterranean diet, plant-based diets, etc. Early implementation of healthy dietary patterns in patients with CMD is encouraged, but an understanding of the mechanisms by which these patterns trigger cardiometabolic benefits remains incomplete. Hence, this review examined several dietary patterns that may improve cardiometabolic health, including restrictive dietary patterns, regional dietary patterns, and diets based on controlled macronutrients and food groups, summarizing cutting-edge evidence and potential mechanisms for CMD prevention and treatment. Particularly, considering individual differences in responses to dietary composition and nutritional changes in organ tissue diversity, we highlighted the critical role of individual gut microbiota in the crosstalk between diet and CMD and recommend a more precise and dynamic nutritional strategy for CMD by developing dietary patterns based on individual gut microbiota profiles.
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There is mounting evidence demonstrating that oral dysbiosis causes periodontal disease and promotes the development of cardiovascular disease. The advancement of omics techniques has driven the optimization of oral microbiota species analysis and has provided a deeper understanding of oral pathogenic bacteria. A bi-directional relationship exists between the oral microbiota and the host, and oral-gut microbiota transfer is known to alter the composition of the gut microbiota and may cause local metabolic disorders. Furthermore, cardiovascular health can also be highly affected by oral microbiota functions and metabolites, including short-chain fatty acids (SCFAs), nitric oxide (NO), hydrogen sulfide (H2S), and some lipid metabolites. Studies have found that trimethylamine oxide (TMAO) may have adverse effects on cardiovascular health, whereas SCFAs, NO, and H2S have cardioprotective effects. SCFAs and H2S exert varying oral and cardiovascular effects, however reports on this specific topic remain controversial. Previous evidences are accustomed to summarizing the functions of oral microbiota in the context of periodontitis. The direct relationship between oral microbiota and cardiovascular diseases is insufficient. By systematically summarizing the methods associated with oral microbiota transplantation (OMT), this review facilitates an investigation into the causal links between oral microbiota and cardiovascular disease. The concomitant development of omics, bioinformatics, bacterial culture techniques, and microbiota transplantation techniques is required to gain a deeper understanding of the relationship between oral microbiota and cardiovascular disease occurrence.
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Doenças Cardiovasculares , Microbioma Gastrointestinal , Microbiota , Doenças Periodontais , Humanos , Doenças Cardiovasculares/etiologia , DisbioseRESUMO
There are high- and low-frequency noise signals in a microseismic signal that can lead to the distortion and submersion of an effective waveform. At present, effectively removing high- and low-frequency noise without losing the effective signal of local waveform spikes remains a challenge. This work addresses this issue with an improved wavelet adaptive thresholding method. Because a denoised signal conceptually approximates the minimum error, a dynamic selection model is established for the optimal threshold. On this basis, an adaptive correction factor aj is proposed to reflect the noise intensity, which uses the 1/2 power of the ratio of the median absolute value to the amplitude of the monitoring data to reflect the noise intensity of the wavelet detail signal and corrects the size of the denoising scale. Finally, the performance of the improved method is quantitatively evaluated in terms of the denoising quality and efficiency using the signal-to-noise ratio, root-mean-square error, sample entropy and running time.
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INTRODUCTION: Incarcerated femoral hernia is a common surgical acute abdominal disease. Laparoscopic surgery is considered a safe and effective method for treating incarcerated femoral hernias, which have different surgical approaches to releasing the contents of the hernia. PRESENTATION OF CASE: We report the case of a 65-year-old female with a right incarcerated femoral hernia with an irreducible mass in the right femoral region for 2 days diagnosed by physical examination and abdominal ultrasonography. We used a catheter to inject normal saline into the hernia sac during surgery. Injury and rupture of the small intestine were avoided, and the polypropylene mesh was successfully repaired. DISCUSSION: Incarcerated femoral hernias is a common surgical emergency that can lead to intestinal obstruction, strangulation, or infarction. Laparoscopy is advantageous for treating incarcerated femoral hernias. In our case, spatial replacement theory was used to release the incarcerated small intestine. The principle is that changing the internal and external pressures of the hernial sac returns the hernia contents. The non-necrotic small intestine did not lead to intraperitoneal infection, and the standard transabdominal preperitoneal repair was simultaneously performed with a polypropylene mesh. CONCLUSION: Laparoscopic incarcerated femoral hernia repair is a common emergency surgery that is safe and feasible for treating incarcerated femoral hernia using the spatial replacement method, the most beneficial to patients.
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Intermittent hypoxia (IH) has a dual nature. On the one hand, chronic IH (CIH) is an important pathologic feature of obstructive sleep apnea (OSA) syndrome (OSAS), and many studies have confirmed that OSA-related CIH (OSA-CIH) has atherogenic effects involving complex and interacting mechanisms. Limited preventive and treatment methods are currently available for this condition. On the other hand, non-OSA-related IH has beneficial or detrimental effects on the body, depending on the degree, duration, and cyclic cycle of hypoxia. It includes two main states: intermittent hypoxia in a simulated plateau environment and intermittent hypoxia in a normobaric environment. In this paper, we compare the two types of IH and summarizes the pathologic mechanisms and research advances in the treatment of OSA-CIH-induced atherosclerosis (AS), to provide evidence for the systematic prevention and treatment of OSAS-related AS.
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Aterosclerose , Apneia Obstrutiva do Sono , Aterosclerose/terapia , Humanos , Hipóxia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapiaRESUMO
Objective: To establish an artificial intelligence-based method to quantitatively evaluate subtle pathological changes in retinal nerve cells and synapses in monosodium glutamate (MSG) mice and provide an effective animal model and technique for quantitative evaluation of retinal neurocytopathies. Methods: ICR mice were subcutaneously injected with MSG to establish a model of metabolic syndrome. We then established a mouse model of type 1 diabetes, type 2 diabetes, and KKAy mouse model as control. The HE sections of the retina were visualized using an optical microscope. AI technology was used for quantitative evaluation of the retinal lesions in each group of rats. The surface area custom parameters of the retinal nerve fiber layer (RNFL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer plexiform layer (OPL) were defined as SR, SIPL, SINL, and SOPL, respectively. Their heights were defined as HR, HIPL, HINL, and HOPL, and the number of ganglion cells was defined as A. Then, the attention-augmented fully convolutional Unet network was used to segment the retinal HE images, and AI technology to identify retinal neurocytopathies quantitatively. Results: The attention-augmented fully convolutional Unet network increased PA and IOU parameters for INL, OPL, RNFL, and ganglion cells and was superior in recognizing fine structures. A quantitative AI identification of the height of each layer of the retina showed that the heights of the IPL and INL of the MSG model were significantly less than those of the control groups; the retinas of the other diabetic models did not exhibit this pathological feature. The RNFLs of type 2 diabetes were thinner, and the characteristics of retinopathy were not obvious in the other animal models. The pathological changes seen on HE images were consistent with the results of the quantitative AI evaluation. Immunohistochemistry results showed that NMDAR2A, GluR2, and NRG1 were significantly downregulated in the retina of MSG mice. Conclusions: The MSG retinopathy model is closely associated with neurotransmitter abnormalities and exhibits important characteristics of retinal neurodegeneration, making it suitable for studying retinal neurocytopathies. The AI recognition technology for retinal images established in the present study can be used for the quantitative and objective evaluation of drug efficacy.
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Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Retinopatia Diabética , Animais , Inteligência Artificial , Diabetes Mellitus Tipo 2/patologia , Retinopatia Diabética/induzido quimicamente , Retinopatia Diabética/patologia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos ICR , Ratos , Retina/patologia , Células Ganglionares da Retina/patologia , Glutamato de Sódio/toxicidadeRESUMO
Depression is a common comorbidity of type 2 diabetes mellitus (T2DM). T2DM with comorbid depression increases the risk of cardiovascular events and death. Depression and T2DM and its macrovascular complications exhibited a two-way relationship. Regarding treatment, antidepressants can affect the development of T2DM and cardiovascular events, and hypoglycemic drugs can also affect the development of depression and cardiovascular events. The combination of these two types of medications may increase the risk of the first myocardial infarction. Herein, we review the latest research progress in the exacerbation of cardiovascular disease due to T2DM with comorbid depression and provide a rationale and an outlook for the prevention and treatment of cardiovascular disease in T2DM with comorbid depression.
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BACKGROUND: Nonacog alfa (recombinant factor IX [FIX]) is approved in China for the control and prevention of bleeding events in patients with hemophilia B. This was the first study to assess prophylaxis and on-demand therapy with recombinant FIX replacement in a real-world setting in China. This study aimed to evaluate the safety and efficacy of nonacog alfa in Chinese patients with hemophilia B. METHODS: In this open-label, multicenter study (clinicaltrials.gov identifier NCT02336178), patients received on-demand or prophylactic treatment with intravenous nonacog alfa for approximately 6 months or 50 exposure days, whichever occurred first. The primary safety outcome was medically important events (i.e., development of FIX inhibitors, allergic reactions, and thrombotic events). Key secondary efficacy outcomes included the annualized bleeding rate for on-demand treatment and prophylaxis, response to on-demand treatment, the number of infusions per bleeding event, and the number of breakthrough bleeding events within 48 hours of prophylaxis. RESULTS: Seventy male patients (mean [standard deviation] age 7.8 [7.2] years) were enrolled (on-demand, nâ=â37; prophylaxis, nâ=â57 [24 patients were included in both groups]). Thirty-eight (54%) patients had up to 50 FIX exposure days before the study. The only medically important event was a transient low-titer FIX inhibitor (incidence 1.4%, 95% confidence interval, 0-7.7). The mean annualized bleeding rate was 26.3 for on-demand treatment and 6.5 for prophylaxis. A mean (standard deviation) of 1.5 (1.7) nonacog alfa infusions were given per bleeding episode; 78.8% of episodes resolved with 1 infusion. Response was "excellent" or "good" for 88% of the on-demand infusions. Twenty-three bleeding events (nâ=â11 patients) occurred within 48âhours of 2032 prophylaxis doses (1.13%). CONCLUSION: In the real-world setting, nonacog alfa is safe and effective for on-demand treatment and for prophylaxis for patients with hemophilia B in China.
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Terapia de Reposição de Enzimas/efeitos adversos , Fator IX/efeitos adversos , Hemofilia B/tratamento farmacológico , Hemorragia/epidemiologia , Adolescente , Criança , Pré-Escolar , China , Terapia de Reposição de Enzimas/métodos , Fator IX/administração & dosagem , Hemofilia B/complicações , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Lactente , Infusões Intravenosas , Masculino , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Moroctocog alfa albumin-free cell culture (AF-CC) increases plasma levels of factor VIII (FVIII) activity and, in China, is indicated for the control and prevention of bleeding episodes in patients with hemophilia A. This study aimed to evaluate the efficacy, safety, and recovery data of moroctocog alfa (AF-CC) in patients with hemophilia participating in two open-label studies, both conducted in China. METHODS: The authorization study (clinicaltrials.gov identifier NCT00868530) enrolled patients aged ≥6 years, previously treated with ≥1 exposure day of FVIII replacement therapy. The real-world study (clinicaltrials.gov identifier NCT02492984) enrolled patients of any age who were previously untreated or requiring surgical prophylaxis. In both studies, on-demand treatment was administered over 6 months. Key assessments included response to treatment, FVIII inhibitor development, and recovery. RESULTS: In the authorization study (N = 53; mean age, 23.2 years; severe hemophilia, 23%), response was excellent/good for 90% of infusions at 24 hours. Seven patients developed inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.77 (0.50) and 1.67 (0.45) (IU/dL)/(IU/kg), respectively. In the real-world study (N = 85; mean age, 9.5 years; severe hemophilia, 58%), response was rated as excellent or good for most (87%) on-demand infusions and for all surgical prophylaxis patients (n = 14). Seven patients developed FVIII inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.71 (0.50) and 1.68 (0.31) (IU/dL)/(IU/kg), respectively. No new safety signals were observed in either study. CONCLUSION: On-demand treatment and surgical prophylaxis with moroctocog alfa (AF-CC) is safe and effective for both previously treated and previously untreated Chinese patients with hemophilia A.
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BACKGROUND AND OBJECTIVES: The impact of metabolic syndrome (MetS) on surgical outcome, mostly in patients with HBV-related hepatocellular carcinoma (HCC) who underwent hepatectomy. METHODS: A propensity score matching analysis was conducted. Patients were categorized into two groups MetS-related hepatocellular carcinoma (MetS-HCC) and 1:1 matched non-MetS-related HCC (non-MetS-HCC). Surgical outcomes were compared between the two groups. RESULTS: Seventy-four MetS-HCC patients and 74 propensity score-matched non-MetS-HCC patients were selected for analysis. The incidence of surgical site infection was higher in the MetS-HCC group than in the non-MetS-HCC group (12.16% vs 0%, P < .005). There was no difference in the recurrence-free survival and overall survival between patients in the MetS-HCC group and in non-MetS-HCC group (P > .05). Microvascular invasion and severe postoperative complications were independent risk factors for recurrence-free survival and overall survival. CONCLUSIONS: Hepatectomy for patients with mostly HBV-related HCC in the presence of MetS can result in a higher rate of postoperative surgical site infection compared with those in the absence of MetS, but long-term survival rates are comparable.