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Nerve invasion (NI) is a characteristic feature of pancreatic cancer. Traditional dichotomous statements on the presence of NI are unreasonable because almost all cases exhibit NI when sufficient pathological sections are examined. The critical implications of NI in pancreatic cancer highlight the need for a more effective criterion. This study included 511 patients, who were categorized into a training group and a testing group at a ratio of 7:3. According to the traditional definition, NI was observed in 91.2 % of patients using five pathological slides in our study. The prevalence of NI increased as more pathological slides were used. The criterion of 'two points of intraneural (endoneural) invasion in the case of four pathological slides' has the highest receiver operating characteristic (ROC) score. Based on this new criterion, NI was proved to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) and was also correlated with tumor recurrence (P = 0.004). Interestingly, gemcitabine-based chemotherapy regimen is an independent favorable factor for patients with high NI. In the high NI group, patients who received a gemcitabine-based regimen exhibited a better prognosis than those who did not receive the gemcitabine-based regimen for OS (P = 0.000) and DFS (P = 0.001). In conclusion, this study establishes assessment criteria to evaluate the severity of NI in order to predict patient outcomes.
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Invasividade Neoplásica , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Adulto , Intervalo Livre de Doença , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Gencitabina , Curva ROC , Idoso de 80 Anos ou mais , PrognósticoRESUMO
Background: Intracranial metastasis of gastrointestinal stromal tumors (GISTs) is uncommon and the optimal management for these patients remains undefined. The introduction of selective tyrosine kinase inhibitors (TKI) has drastically improved survival in patients with GISTs. However, its efficacy in patients with intracranial metastasis of GISTs is uncertain due to poor penetration of the blood brain barrier. The role of surgery and radiotherapy in these patients has also not been established. No large-scale studies exist, and the literature is limited to case reports. We report a case treated at our institution, conducted a literature review of existing case reports, and discussed the optimal management of patients with intracranial metastasis of GISTs. Methods: A literature review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All studies with intracranial metastasis of GISTs were included, with data extracted and analyzed in totality. Results: 26 cases were included in the review. The median time to diagnosis of intracranial metastasis in patients with previously known GISTs was 66 months. Solitary metastasis was seen in 16 cases (59.3 %). 18 patients (69.72 %) underwent surgical resection; 14 had additive therapy with 9 receiving TKI. The mean duration of follow up was 11 months. Clinical response was seen in 3 patients in the non-surgical group, all 3 were treated with TKI alone. Conclusion: The effectiveness of TKI in intracranial GISTs metastasis is seen both as first-line therapy for asymptomatic lesions and as an additive treatment post-surgery. Surgery retains a key role in establishing histological and molecular diagnosis and for symptomatic relief of mass effect.
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BACKGROUND AND OBJECTIVE: Asthma is a heterogeneous respiratory disease characterized by airway hyper-responsiveness and reversible airflow blockage. There is ongoing debate about the impact of vitamin D on asthma. This research is focused on investigating the correlation between serum levels of 25-hydroxyvitamin D and asthma. METHODS: This cross-sectional study comprised 22,708 eligible participants. Data on asthma and serum 25-hydroxyvitamin D levels from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were analyzed. Serum 25-hydroxyvitamin D levels were the main factor, with the presence of asthma as the outcome variable. Weighted logistic regression was utilized to investigate the relationship between serum levels of 25-hydroxyvitamin D and asthma, while accounting for factors such as age, gender, race, length of time in US, annual family income, education level, high-density lipoprotein, low-density lipoprotein, triglycerides, and cholesterol. RESULTS: Upon adjusting all variables in model III, epi-25-hydroxyvitamin D3 displayed a negative correlation with current asthma at the lower quartile Q1 (0.784, [0.697 to 0.922]), Q2 (0.841, [0.729 to 0.946]), Q3 (0.396, [0.240 to 0.653]) when compared to the highest quartile Q4 level. However, no significant difference was observed between asthma and 25-hydroxyvitamin D2, as well as 25-hydroxyvitamin D3. CONCLUSIONS: In the U.S. population, elevated levels of epi-25-hydroxyvitamin D3 are correlated with an increased risk of developing existing asthma. However, it is important to interpret this finding carefully given the constraints of cross-sectional studies.
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Lipid droplets (LDs) are spherical organelles that localize in the cytosol of eukaryotic cells. Different proteins are embedded on the surface of LDs, so LDs play a vital role in the physiological activities of cells. The dysregulation of LDs is associated with various human diseases, such as diabetes and obesity. Therefore, it is essential to develop a fluorescent dye that labels LDs to detect and monitor illnesses. In this study, we developed the compound BDAA12C for staining LDs in cells. BDAA12C exhibits excellent LD specificity and low toxicity, enabling us to successfully stain and observe the fusion of LDs in A549 cancer cells. Furthermore, we also successfully distinguished A549 cancer cells and MRC-5 normal cells in a co-culture experiment and in normal and tumour tissues. Interestingly, we found different localizations of BDAA12C in well-fed and starved A549 cancer cells and consequently illustrated the transfer of fatty acids (FAs) from LDs to mitochondria to supply energy for ß-oxidation upon starvation. Therefore, BDAA12C is a promising LD-targeted probe for cancer diagnosis and tracking lipid trafficking within cells.
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Corantes Fluorescentes , Gotículas Lipídicas , Humanos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/química , Corantes Fluorescentes/química , Células A549 , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Ácidos Graxos/química , Técnicas de Cocultura , Mitocôndrias/metabolismo , Acridinas/química , Microscopia de FluorescênciaRESUMO
Substituting mineral fertilizer with manure or a combination of organic amendments plus beneficial soil microorganisms (bio-manure) in agriculture is a standard practice to mitigate N2O and NO emissions while enhancing crop performance and nitrogen use efficiency (NUE). Here, we conducted a greenhouse trial for three consecutive vegetable growth seasons for Spinach, Coriander herb, and Baby bok choy to reveal the response of N2O and NO emissions, NUE, and vegetable quality index (VQI) to fertilization strategies. Strategies included solely chemical nitrogen fertilizer (CN), 20 (M1N4) and 50% (M1N1) substitution with manure, 20 (BM1N4) and 50% (BM1N1) substitution with bio-manure, and no fertilization as a control and were organized in a completely randomized design (n = 3). Manure decreased N2O emissions by 24-45% and bio-manure by 44-53% compared to CN. Manure reduced NO emissions by 28-41% and bio-manure by 55-63%. Bio-manure increased NUE by 0.04-31% and yields by 0.05-61% while improving VQI, attributed to yield growth and reduced vegetable NO3- contents. Improvement of root growth was the main factor that explained the rise of NUE; NUE declined with the increase of N2O emissions, showing the loss of vegetable performance under conditions when denitrification processes prevailed. Under the BM1N1, the highest VQI and the lowest yield-scaled N-oxide emissions were observed, suggesting that substitution with bio-manure can improve vegetable quality and mitigate N-oxide emissions. These findings indicate that substituting 50% of mineral fertilizer with bio-manure can effectively improve NUE and VQI and mitigate N-oxides in intensive vegetable production.
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Fertilizantes , Esterco , Nitrogênio , Solo , Verduras , Verduras/crescimento & desenvolvimento , Nitrogênio/metabolismo , Fertilizantes/análise , Solo/química , Agricultura/métodos , Óxido Nitroso/análise , Óxido Nitroso/metabolismoRESUMO
Atopic dermatitis (AD) is a common skin disease, the pathogenesis of which has not been fully elucidated. The gut microbiota is the largest micro-ecosystem in the human body that affects the immune system and skin barrier function. Recent studies have shown that in addition to the environmental factors, skin barrier, genetic factors and immune response, gut microbiota disturbance may also cause AD. This review described the correlation of AD with gut microbiota and existing research status of AD treatment via targeting gut microbiota.
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Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory skin lesion with an undefined cause. It is more commonly found in the genital area, particularly in adolescents, premenopausal women and postmenopausal women. LSA is difficult to treat and often recurs. The primary treatment for LSA involves the administration of potent topical corticosteroids. Dupilumab is increasingly being used for the treatment of itching in non-atopic dermatitis patients but there are few reports on its use for the treatment of LSA. Here, we present a case of LSA in a 61-year-old woman with extensive vulvar itching. Over four months of dupilumab therapy, significant therapeutic effects were observed, including vulvar skin thinning and pruritus relief without adverse reactions.
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We report the discovery that chemical reactions such as ATP hydrolysis can be catalyzed by condensates formed by intrinsically disordered proteins (IDPs), which themselves lack any intrinsic ability to function as enzymes. This inherent catalytic feature of condensates derives from the electrochemical environments and the electric fields at interfaces that are direct consequences of phase separation. The condensates we studied were capable of catalyzing diverse hydrolysis reactions, including hydrolysis and radical-dependent breakdown of ATP whereby ATP fully decomposes to adenine and multiple carbohydrates. This distinguishes condensates from naturally occurring ATPases, which can only catalyze the dephosphorylation of ATP. Interphase and interfacial properties of condensates can be tuned via sequence design, thus enabling control over catalysis through sequence-dependent electrochemical features of condensates. Incorporation of hydrolase-like synthetic condensates into live cells enables activation of transcriptional circuits that depend on products of hydrolysis reactions. Inherent catalytic functions of condensates, which are emergent consequences of phase separation, are likely to affect metabolic regulation in cells.
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In arid areas, fresh water resources are insufficient, and agricultural water mainly depends on shallow saline groundwater. However, long-term saline irrigation will cause soil salt accumulation and soil environment deterioration, which is not conducive to crop growth. In this study, based on the long-term irrigation of fresh water (0.35 dS·m-1, FW) and saline water (8.04 dS·m-1, SW), biochar (3.7 t·hm-2, BC) and straw (6 t·hm-2, ST) were added to the soil by an equal-carbon design. The aim was to clarify the effects of biochar and straw returning on the physical and chemical properties and microbial community structure of salinized soil. The results showed that saline irrigation significantly increased soil water content, electrical conductivity, available phosphorus, and total carbon content but significantly decreased pH value and available potassium content. The contents of available phosphorus, available potassium, and total carbon in soil were significantly increased by biochar and straw returning, but the conductivity value of soil irrigated with saline water was significantly decreased. The dominant bacteria in each treatment were Proteobacteria, Actinomycetes, Acidobacteria, Chloromycetes, and Blastomonas. Saline water irrigation significantly increased the relative abundance of Blastomonas and Proteobacteria but significantly decreased the relative abundance of Acidobacteria and Actinobacteria. Under the condition of fresh water irrigation, the relative abundance of Chlorocurvula was significantly reduced by the return of biochar. Straw returning significantly increased the relative abundance of Proteobacteria but significantly decreased the relative abundance of Acidobacteria, Actinomyces, Chloromyces, and Blastomonas. Under saline irrigation, the relative abundance of Chlorocurvula and Blastomonas were significantly reduced by biochar return to field. Straw returning significantly increased the relative abundance of Proteobacteria but significantly decreased the relative abundance of Acidobacteria, Actinomyces, Chloromyces, and Blastomonas. LEfSe analysis showed that saline irrigation decreased the potential markers and functional numbers of soil microorganisms.Under saline irrigation, biochar returning increased the number of potential markers and functions of soil microorganisms. Straw returning to field increases the number of potential markers of soil microorganisms. RDA results showed that soil microbial community and functional structure were significantly correlated with EC1:5, SWC, and pH. Saline water irrigation will deteriorate the soil environment, which is not conducive to agricultural production, among which EC1:5, SWC, and pH are important factors driving changes in soil microbial community and functional structure. Using biochar and straw to return to the field can reduce the harm of salt to soil and crops, laying a foundation for improving agricultural productivity.
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Irrigação Agrícola , Carvão Vegetal , Gossypium , Caules de Planta , Microbiologia do Solo , Solo , Irrigação Agrícola/métodos , Solo/química , Gossypium/crescimento & desenvolvimento , Caules de Planta/química , Águas Salinas , Microbiota , Bactérias/classificação , Bactérias/crescimento & desenvolvimentoRESUMO
Water regulates or even governs a wide range of biological processes. Despite its fundamental importance, surprisingly little is known about the structure of intracellular water. Herein we employ a Raman micro-spectroscopy technique to uncover the composition, abundance and vibrational spectra of intracellular water in individual living cells. In three different cell types, we show a small but consistent population (~3%) of non-bulk-like water. It exhibits a weakened hydrogen-bonded network and a more disordered tetrahedral structure. We attribute this population to biointerfacial water located in the vicinity of biomolecules. Moreover, our whole-cell modeling suggests that all soluble (globular) proteins inside cells are surrounded by, on average, one full molecular layer (about 2.6 Angstrom) of biointerfacial water. Furthermore, relative invariance of biointerfacial water is observed among different single cells. Overall, our study not only opens up experimental possibilities of interrogating water structure in vivo but also provides insights into water in life.
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Ligação de Hidrogênio , Análise Espectral Raman , Água , Água/química , Análise Espectral Raman/métodos , Humanos , Animais , Proteínas/química , Proteínas/metabolismo , Análise de Célula Única/métodosRESUMO
Background: Few studies have studied the efficacy of using immersive virtual reality (iVR) to teach surgical skills, especially by using real-world iVR recordings rather than simulations. This study aimed to investigate whether viewing 360° iVR instructional recordings produces greater improvements in basic suturing skills of students without prior medical training, beyond traditional methods like reading written manuals or watching 2D instructional videos. Materials and methods: This was a partially blinded randomized cohort study. 44 pre-university students (aged 17) were randomized equally to either the written instruction manual, 2D instructional video, or iVR recordings. All students first watched a silent 2D demonstration video of the suturing task, before attempting to place three simple interrupted sutures on a piece of meat as a baseline. The time taken for the first attempt was recorded. Students were then given an hour to train using their allocated modality. They attempted the suturing task again, and timings were re-recorded. Four blinded surgically-trained judges independently assessed the quality of the stitches placed both pre and post-intervention. One-way analysis of variance tests (ANOVAs) and independent two-sample t-tests were used to determine the effect of training modality on improvements in suturing scores and time taken to complete suturing from pre to post-training. Results: For suturing scores, the iVR group showed significantly larger score improvements than the Written Manual group (p = 0.031, Cohen's D = 0.92), while this iVR advantage was less pronounced when compared with the 2D Video group (p = 0.16, Cohen's D = 0.65). Similarly for time taken to complete suturing, the iVR group had significantly larger time improvements than the Written Manual group (p = 0.045), although this difference was less robust compared to the 2D Instructional Video group (p = 0.34). Conclusion: This study demonstrates that iVR training using real-world 360° instructional recordings produced significantly greater training gains in suturing scores and efficiency compared to reading written text. iVR training also led to larger training gains in both outcome measures than viewing 2D instructional videos, although the differences between them did not reach statistical significance.
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Unmanned Aerial Vehicle (UAV) aerial sensors are an important means of collecting ground image data. Through the road segmentation and vehicle detection of drivable areas in UAV aerial images, they can be applied to monitoring roads, traffic flow detection, traffic management, etc. As well, they can be integrated with intelligent transportation systems to support the related work of transportation departments. Existing algorithms only realize a single task, while intelligent transportation requires the simultaneous processing of multiple tasks, which cannot meet complex practical needs. However, UAV aerial images have the characteristics of variable road scenes, a large number of small targets, and dense vehicles, which make it difficult to complete the tasks. In response to these issues, we propose to implement road segmentation and on-road vehicle detection tasks in the same framework for UAV aerial images, and we conduct experiments on a self-constructed dataset based on the DroneVehicle dataset. For road segmentation, we propose a new algorithm C-DeepLabV3+. The new algorithm introduces the coordinate attention (CA) module, which can obtain more accurate segmentation target location information and make the segmentation target edges more continuous. Also, the improved algorithm introduces the cascade feature fusion module to prevent the loss of detail information in road segmentation and to obtain better segmentation performance. For vehicle detection, we propose an improved algorithm S-YOLOv5 by adding a parameter-free lightweight attention module SimAM. Finally, the proposed road segmentation-vehicle detection framework is utilized to unite the C-DeepLabV3+ and S-YOLOv5 algorithms for the implementation of the serial tasks. The experimental results show that on the constructed ViDroneVehicle dataset, the C-DeepLabV3+ algorithm has an mPA value of 98.75% and an mIoU value of 97.53%, which can better segment the road area and solve the problem of occlusion. The mAP value of the S-YOLOv5 algorithm has an mAP value of 97.40%, which is more than YOLOv5's 96.95%, which effectively reduces the vehicle omission and false detection rates. By comparison, the results of both algorithms are superior to multiple state-of-the-art methods. The overall framework proposed in this paper has superior performance and is capable of realizing high-quality and high-precision road segmentation and vehicle detection from UAV aerial images.
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ConspectusFirst predicted more than 100 years ago, Raman scattering is a cornerstone of photonics, spectroscopy, and imaging. The conventional framework of understanding Raman scattering was built on Raman cross section σRaman. Carrying a dimension of area, σRaman characterizes the interaction strength between light and molecules during inelastic scattering. The numerical values of σRaman turn out to be many orders of magnitude smaller in comparison to the linear absorption cross sections σAbsorption of similar molecular systems. Such an enormous gap has been the reason for researchers to believe the extremely feeble Raman scattering ever since its discovery. However, this prevailing picture is conceptually problematic or at least incomplete due to the fact that Raman scattering and linear absorption belong to different orders of light-matter interaction.In this Account, we will summarize an alternate way to think about Raman scattering, which we term stimulated response formulation. To capture the third-order interaction nature of Raman scattering, we introduced stimulated Raman cross section, σSRS, defined as the intrinsic molecular property in response to the external photon fluxes. Foremost, experimental measurement of σSRS turns out to be not weak at all or even larger when fairly compared with electronic counterparts of the same order. The analytical expression for σSRS derived from quantum electrodynamics also supports the measurement and proves that σSRS is intrinsically strong. Hence, σRaman and σSRS can be extremely small and large, respectively, for the same molecule at the same time. Our subsequent theoretical studies show that stimulated response formulation can unify spontaneous emission, stimulated emission, spontaneous Raman, and stimulated Raman via eq 10, in a coherent and symmetric way. In particular, an Einstein-coefficient-like equation, eq 12a, was derived, showing that σRaman can be explicitly expressed as σSRS multiplied by an effective photon flux arising from zero-point fluctuation of the vacuum. The feeble vacuum fluctuation hence explains how σSRS can be intrinsically strong while, at the same time, σRaman ends up being many orders of magnitude smaller when both compared to the electronic counterparts. These two sides of the same coin prompted us to propose "the duality of Raman scattering" (Table 1). Finally, this formulation naturally leads to a quantitative treatment of stimulated Raman scattering (SRS) microscopy, providing an intuitive, molecule-centric explanation as to how SRS microscopy can outperform regular Raman microscopy. Hence, as unveiled by the new formulation, a duality of Raman scattering has emerged, with implications for both fundamental science and practical technology.
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Advancements in surgical techniques and the optimization of immunosuppression have boosted organ transplant survival rates; however, liver transplant recipients still risk complications such as hepatic vein occlusive disease (HVOD), also called sinusoidal obstruction syndrome. Rare but potentially fatal HVOD damages endothelial cells due to factors like chemotherapy, stem cell transplantation, and certain medications such as azathioprine and tacrolimus. Typically, HVOD presents with distinct clinical symptoms, including ascites, jaundice, and significant weight gain. Herein, we present the case of a 66-year-old male with decompensated liver cirrhosis due to hepatitis C virus infection. The patient underwent a deceased donor liver transplantation at our center. Unfortunately, 4 months after the transplant, he experienced progressive dyspnea and developed right pleural effusion. Abdominal computed tomography and a liver biopsy confirmed the diagnosis of HVOD, likely induced by tacrolimus. After stopping tacrolimus, we observed a significant decrease in ascites and remission of the patient's clinical symptoms of abdominal distention and dyspnea; subsequently, we introduced cyclosporine. In this report, we describe this specific patient's case and discuss HVOD, including its diagnosis and management.
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Imunossupressores , Transplante de Fígado , Tacrolimo , Humanos , Tacrolimo/efeitos adversos , Masculino , Transplante de Fígado/efeitos adversos , Idoso , Imunossupressores/efeitos adversos , Hepatopatia Veno-OclusivaRESUMO
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15%-30% of children and 10% of adults globally, with its incidence being influenced by genetic, environmental, and various other factors. While the immune plays a crucial role in the development, the composition of gut microbiota and serum metabolites also contribute to its pathogenesis. SUBJECT: Study the characteristics of gut microbiota and serum metabolites in patients with atopic dermatitis METHOD: In this study, we collected stool and serum samples from 28 AD patients and 23 healthy individuals (NC) for metagenomic sequencing of gut microbiota and non-targeted metabolomic sequencing of serum. RESULT: Our results revealed a lower diversity of gut microbiota in the AD group compared to the NC group. The predominant Phylum in AD patients were Bacteroidetes, Pseudomonas, and Verrucomicrobia, with the most dominant bacterial genus being Faecalibacterium. At the species level, Prevotella copri and Faecalibacterium prausnitzii were found to be the most abundant bacteria. Significant differences in serum metabolite profiles were observed between NC and AD patients, with noticeable variations in metabolite expression levels. The majority of metabolites in the serum of AD patients exhibited low expression, while a few showed high expression levels. Notably, metabolites such as Cholesterol glucuronide, Styrene, Lutein, Betaine, Phosphorylcholine, Taurine, and Creatinine displayed the most pronounced alterations. CONCLUSION: These findings contribute to a further understanding of the complexities underlying this disease.
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Dermatite Atópica , Fezes , Microbioma Gastrointestinal , Humanos , Dermatite Atópica/microbiologia , Dermatite Atópica/sangue , Microbioma Gastrointestinal/fisiologia , Masculino , Feminino , Adulto , Fezes/microbiologia , Criança , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Metaboloma/fisiologia , BacteroidetesRESUMO
Biodegradable film mulching has attracted considerable attention as an alternative to conventional plastic film mulching. However, biodegradable films generate transitory microplastics during the film degradation. How much of this transitory microplastics is being formed and their impact on soil health during long-term use of biodegradable plastic film are not known. Here, we quantified the amounts of microplastics (0.1-5 mm in size) in the topsoil (0-20 cm) of two cotton fields with different mulching cultivations: (1) continuous use of conventional (polyethylene, PE) film for 23 years (Plot 1), and (2) 15 years use of conventional film followed by 8 years of biodegradable (polybutylene adipate-co-terephthalate, PBAT) film (Plot 2). We further assessed the impacts of the microplastics on selected soil health parameters, with a focus on soil carbon contents and fluxes. The total amount of microplastics was larger in Plot 2 (8507 particles kg-1) than in Plot 1 (6767 particles kg-1). The microplastics (0.1-1 mm) were identified as derived from PBAT and PE in Plot 2; while in Plot 1, the microplastics were identified as PE. Microplastics > 1 mm were exclusively identified as PE in both plots. Soil organic carbon was higher (27 vs. 30 g C kg-1 soil) but dissolved organic carbon (120 vs. 74 mg C kg-1 soil) and microbial biomass carbon were lower (413 vs. 246 mg C kg-1 soil) in Plot 2 compared to the Plot 1. Based on 13C natural abundance, we found that in Plot 2, carbon flow was dominated from micro- (<0.25 mm) to macroaggregates (0.25-2 and >2 mm), whereas in Plot 1, carbon flow occurred between large and small macroaggregates, and from micro-to macroaggregates. Thus, long-term application of biodegradable film changed the abundance of microplastics, and organic carbon accumulation compared to conventional polyethylene film mulching.
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Carbono , Gossypium , Microplásticos , Poluentes do Solo , Solo , Solo/química , Poluentes do Solo/análise , Carbono/análise , Microplásticos/análise , Biodegradação Ambiental , Agricultura/métodos , Monitoramento Ambiental/métodos , Plásticos Biodegradáveis , PolietilenoRESUMO
BACKGROUND: Schizophrenia is one of the leading causes of disability. Paliperidone palmitate once-monthly injection (PP1M) was developed to provide consistent drug delivery and improve medication adherence for maintenance treatment. It is well known that patients with schizophrenia have higher cardiovascular risks, however little is known about the cardiovascular risks of patients with schizophrenia treated with PP1M in Asia. OBJECTIVE: This study aimed to estimate the incidence of cardiovascular events after initiating PP1M treatment and evaluate the cardiovascular risk associations compared with oral second-generation antipsychotics (SGAs). METHODS: Data from Taiwan's National Health Insurance Research Database were used to identify a cohort of adult patients with schizophrenia who received any SGAs from 1 March 2012 to 31 December 2018. Patients who initiated PP1M treatment were enrolled for descriptive analysis of incidence rates. PP1M patients were propensity matched 1:1 to patients initiating a new oral SGA, for comparative analysis based on demographics, clinical characteristics and treatment history at baseline, in three-step matching procedures, following the prevalent new-user design to enhance comparability. Follow-up ended at the end of the treatment episode of index drug, death, last record available, or end of the study (31 December 2019). Study endpoints included serious cardiovascular events (including severe ventricular arrhythmia and sudden death), expanded serious cardiovascular events (which further included acute myocardial infarction and ischemic stroke), and cardiovascular hospitalizations. Risks of study endpoints between matched cohorts were compared using Cox regression. RESULTS: Overall, 11,023 patients initiating PP1M treatment were identified (49.5% were females; mean age of 43.2 [12.2] years). Overall incidences for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 3.92, 7.88 and 51.96 per 1000 person-years, respectively. In matched cohort analysis (N = 10,115), the hazard ratios (HRs) between initiating PP1M and a new oral SGA for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 0.86 (95% confidence interval [CI] 0.55-1.36), 0.88 (95% CI 0.63-1.21), and 0.78 (95% CI 0.69-0.89), respectively. CONCLUSION: This study reported the population-based incidence of cardiovascular events in schizophrenic patients initiating PP1M treatment. PP1M was not associated with increased risks of serious cardiovascular events but was potentially associated with lower risks of cardiovascular hospitalizations compared with oral SGAs.
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Antipsicóticos , Doenças Cardiovasculares , Palmitato de Paliperidona , Esquizofrenia , Humanos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Feminino , Masculino , Palmitato de Paliperidona/administração & dosagem , Palmitato de Paliperidona/efeitos adversos , Taiwan/epidemiologia , Estudos Retrospectivos , Adulto , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Pessoa de Meia-Idade , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Incidência , InjeçõesRESUMO
Psoriasis and atopic dermatitis (AD) are prevalent inflammatory skin disorders, each stemming from diverse factors, and characterized by recurring episodes. In certain complex cases, the clinical and pathological features exhibit overlapping and atypical characteristics, making accurate clinical diagnosis and targeted treatment a challenge. Psoriasiform dermatitis is the term used to describe such cases. Moreover, when patients have a history of malignancy, the situation becomes even more intricate, resulting in limited treatment options. Biologic therapies have transformed the management of immune-mediated inflammatory diseases, including psoriasis and AD. Meanwhile, the safety of biologics in special populations, especially among patients with a history of malignancy, should be underlined. The selective Janus kinase 1 (JAK1) inhibitor abrocitinib has been approved for the treatment of AD and has showed satisfying efficacy and safety in the treatment of psoriasis in clinical trials. Although unreported, JAK1 inhibitors are thought to have the potential to increase the risk of potential tumors. Apremilast, an oral phosphodiesterase (PDE)-4 inhibitor, is approved for moderate to severe plaque psoriasis. It has been investigated for its efficacy in AD, and is not contraindicated in malignancy. This report presents three cases of psoriasiform dermatitis in patients with a history of malignancy, showcasing significant improvement following treatment with systemic glucocorticoid, abrocitinib, or apremilast.
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The Yellow River water of an urban area located in the middle and lower reaches of the Yellow River was taken as the research objectï¼ in which the seasonal and along-range distribution of total culturable bacteriaï¼ typical antibiotic resistant bacteria ï¼amoxicillin resistant bacteria and sulfamethoxazole-resistant bacteriaï¼ï¼ and their corresponding typical resistance genes ï¼»ß-lactam resistance gene ï¼blaCTX-Mï¼ and sulfamamide resistance genes ï¼sulI and sulâ ¡ï¼ï¼ as well as intâ 1 were investigated. The results showed that the total culturable bacteriaï¼ ß-lactam-resistant bacteria and sulfonamide-resistant bacteria in the Yellow River Basin were significantly affected by temperature and human activities. The composition and quantity of their genera had obvious spatiotemporal distribution characteristicsï¼ in which Bacillus and Pseudomonas were dominant in the composition and number of bacteria. The abundance of resistance genes decreased with the decrease in temperature. The proportion of ß-lactam resistance genes in the total genes was higher than that of sulfanilamide genesï¼ and sulI was the dominant gene in sulfanilamide genes. Correlation analysis showed that class â integron played an important role in accelerating the spread of resistance genes. This study offers insight into the status quo of water resistance pollution in the Yellow River and provides theoretical support for the risk assessment of resistance genes in the middle and lower reaches of the Yellow River Basin.