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RATIONALE: Diffuse intestinal and mesenteric lipomatosis is a rare condition characterized by the overgrowth of adipose tissue in the intestines and mesentery. This case report aims to highlight the rare occurrence of chronic abdominal distention caused by this disease and its unique invasion into the muscle layer, which has not been previously reported. PATIENT CONCERNS: A 36-year-old woman with a 7-year history of abdominal distension was admitted to our hospital's Department of Gastrointestinal Surgery. DIAGNOSE: Abdominal and pelvic computed tomography revealed diffuse small intestinal lipomatosis. INTERVENTIONS: The patient underwent surgery. We performed an open-field ilectomy involving removal of all lipomatous intestines (250 cm). OUTCOMES: During the surgery, diffuse nodular ileal and mesenteric lipomatosis was confirmed, characterized by the presence of multiple nodular lipomas within the submucosal and muscular layers. The surgical intervention involved the resection of 250 cm of the affected ileum, followed by jejunoileal anastomosis. Postoperative pathology confirmed the diagnosis, with lesions observed in both the submucosa and muscle layers. The patient showed significant improvement in symptoms, with normal intestinal function and weight gain observed over a 10-month follow-up period, and no signs of recurrence. LESSONS: Diffuse intestinal and mesenteric lipomatosis can lead to long-term abdominal distension. Additionally, it may be involved in the muscle layer of the intestinal wall. Surgery is the primary treatment option for symptomatic intestinal lipomatosis.
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Lipomatose , Mesentério , Humanos , Feminino , Adulto , Lipomatose/cirurgia , Lipomatose/patologia , Lipomatose/complicações , Lipomatose/diagnóstico , Mesentério/patologia , Mesentério/cirurgia , Doenças do Íleo/cirurgia , Doenças do Íleo/etiologia , Doenças do Íleo/diagnóstico , Íleo/cirurgia , Íleo/patologia , Tomografia Computadorizada por Raios X , Doença CrônicaRESUMO
AIMS: Limited literature shows the existence of sex differences in the long-term prognosis of heart failure (HF) patients with frailty. In this study, whether sex differences exist in the impact of frailty on death from cardiovascular causes in patients with HF was investigated by conducting a retrospective cohort study. METHODS AND RESULTS: Data from the National Health and Nutrition Examination Survey (NHANES) study (2009-2018) were used to conduct a retrospective cohort study of 958 participants with HF. Patients were grouped based on sex and frailty index (FI). The relationship between death from cardiovascular causes and baseline frailty was assessed by Cox proportional hazard analysis and the Kaplan-Meier (K-M) plot. The study population had an age of 67.3 ± 12.3. Among them, around 54.5% were male. A median follow-up of 3.6 years was performed. After that, females who died from cardiovascular causes exhibited higher baseline FI values, while males did not show this trend (P < 0.05; P = 0.1253). Cox regression analysis demonstrated a significant association between FI and cardiovascular mortality in females (most frail: hazard ratio (HR) = 3.65, 95% confidence interval (CI): 1.07 ~ 12.39, P < 0.05; per 1-unit increase in FI: HR = 1.78, 95% CI: 1.33 ~ 2.39, P < 0.001). A dose-response association between FI and cardiovascular mortality was presented by restricted cubic splines. CONCLUSIONS: Frailty is related to an increased risk of cardiovascular mortality in HF patients, particularly female patients.
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Guiding and dynamically modulating topological defects are critical challenges in defect engineering of liquid crystals. Here, we employ molecular dynamics simulations to investigate the transition dynamics and relative kinetic stability of defect patterns in two-dimensional nematic Gay-Berne liquid crystals confined within rectangular geometries. We observe the formation of various defect patterns including long-axis, diagonal, X-shaped, composite, and bend configurations under different confinement conditions. The competition between boundary effects and the uniformity of nematic orientation induces the continuous realignment of liquid crystal molecules, facilitating the spatially continuous transformation of defect patterns over time. This transition involves changes in both defect types and their locations, typically initiating from defect regions. Furthermore, we demonstrate that the relative stability of these defect patterns can be effectively controlled by adjusting confinement parameters and external field conditions. Our findings provide fundamental insights into the transition kinetics of defect patterns in confined nematic liquid crystals, thereby enhancing our ability to manipulate topological defects for advanced applications.
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BACKGROUND: Tuberculosis (TB) is a major infectious disease with significant public health implications. Its widespread transmission, prolonged treatment duration, notable side effects, and high mortality rate pose severe challenges. This study examines the epidemiological characteristics of TB globally and across major regions, providing a scientific basis for enhancing TB prevention and control measures worldwide. METHODS: The ecological study used data from the Global Burden of Disease (GBD) Study 2021. It assessed new incidence cases, deaths, disability-adjusted life years (DALYs), and trends in age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates for drug-susceptible tuberculosis (DS-TB), multidrug-resistant tuberculosis (MDR-TB), and extensively drug-resistant tuberculosis (XDR-TB) from 1990 to 2021. A Bayesian age-period-cohort model was applied to project ASIR and ASMR. RESULTS: In 2021, the global ASIR for all HIV-negative TB was 103.00 per 100,000 population [95% uncertainty interval (UI): 92.21, 114.91 per 100,000 population], declining by 0.40% (95% UI: - 0.43, - 0.38%) compared to 1990. The global ASMR was 13.96 per 100,000 population (95% UI: 12.61, 15.72 per 100,000 population), with a decline of 0.44% (95% UI: - 0.61, - 0.23%) since 1990. The global age-standardized DALY rate for HIV-negative TB was 580.26 per 100,000 population (95% UI: 522.37, 649.82 per 100,000 population), showing a decrease of 0.65% (95% UI: - 0.69, - 0.57 per 100,000 population) from 1990. The global ASIR of MDR-TB has not decreased since 2015, instead, it has shown a slow upward trend in recent years. The ASIR of XDR-TB has exhibited significant increase in the past 30 years. The projections indicate MDR-TB and XDR-TB are expected to see significant increases in both ASIR and ASMR from 2022 to 2035, highlighting the growing challenge of drug-resistant TB. CONCLUSIONS: This study found that the ASIR of MDR-TB and XDR-TB has shown an upward trend in recent years. To reduce the TB burden, it is essential to enhance health infrastructure and increase funding in low-SDI regions. Developing highly efficient, accurate, and convenient diagnostic reagents, along with more effective therapeutic drugs, and improving public health education and community engagement, are crucial for curbing TB transmission.
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Carga Global da Doença , Saúde Global , Tuberculose , Humanos , Tuberculose/epidemiologia , Saúde Global/estatística & dados numéricos , Incidência , Feminino , Masculino , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Anos de Vida Ajustados por Deficiência , Adulto , Pessoa de Meia-Idade , Teorema de BayesRESUMO
Limited effective targets have challenged the treatment of oral squamous cell carcinoma (OSCC). Casein kinase 2 interacting protein 1 (CKIP-1) is a scaffold protein involved in various diseases. However, the role of CKIP-1 in OSCC remains unclear. The aim of this study was to explore the regulatory role of CKIP-1 in OSCC, as well as the involved mechanism. First, higher expression of CKIP-1 in OSCC tissues and cell lines were found. Series of gain- and loss-of-function experiments demonstrated suppressed malignant behaviours and enhanced apoptosis of OSCC cells when CKIP-1 was silenced. Also, inhibited tumour growth in CKIP-1-silenced group were proved. Further, mitochondrial transcription factor A (TFAM) downregulation, increased ROS production, decreased mitochondrial membrane potential and cGAS-STING activation in CKIP-1-silenced group were observed. The involvement of mitochondrial homeostasis-related TFAM/cGAS-STING axis in CKIP-1-silenced OSCC cells was finally demonstrated by tetramethylpyrazine (TMP) that inhibits TFAM degradation. Taken together, our study demonstrated that CKIP-1 silencing could significantly antagonize OSCC via TFAM/cGAS-STING axis, which may provide a candidate target for OSCC treatment.
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Apoptose , Carcinoma de Células Escamosas , Proteínas de Ligação a DNA , Proteínas de Membrana , Mitocôndrias , Neoplasias Bucais , Transdução de Sinais , Fatores de Transcrição , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Linhagem Celular Tumoral , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Animais , Homeostase , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Camundongos , Inativação Gênica , Espécies Reativas de Oxigênio/metabolismo , Masculino , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
OBJECTIVES: To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022. RESULTS: Among the AAV children, there were 5 males and 20 females, with a median age of onset of 11.0 years. Involvement of the urinary system was seen in 18 cases (72%); respiratory system involvement in 10 cases (40%); skin involvement in 6 cases (24%); eye, ear, and nose involvement in 5 cases (20%); joint involvement in 4 cases (16%); digestive system involvement in 2 cases (8%). Eleven cases underwent kidney biopsy, with 5 cases (46%) showing focal type, 2 cases (18%) showing crescentic type, 2 cases (18%) showing mixed type, and 2 cases (18%) showing sclerotic type. Immune complex deposits were present in 5 cases (45%). Seven cases reached chronic kidney disease (CKD) stage V, with 2 cases resulting in death. Two cases underwent kidney transplantation. At the end of the follow-up period, 2 cases were at CKD stage II, and 1 case was at CKD stage III. Of the 16 cases of microscopic polyangiitis (MPA) group, 13 (81%) involved the urinary system. Of the 9 cases of granulomatosis with polyangiitis (GPA), 6 cases (66%) had sinusitis. Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group (P<0.05), while red blood cell count and glomerular filtration rate were lower in the MPA group (P<0.05). CONCLUSIONS: AAV is more common in school-age female children, with MPA being the most common clinical subtype. The onset of AAV in children is mainly characterized by renal involvement, followed by respiratory system involvement. The renal pathology often presents as focal type with possible immune complex deposits. Children with MPA often have renal involvement, while those with GPA commonly have sinusitis. The prognosis of children with AAV is poor, often accompanied by renal insufficiency.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Feminino , Masculino , Criança , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Estudos Retrospectivos , Adolescente , Pré-Escolar , Insuficiência Renal Crônica/etiologiaRESUMO
The digestion of starch-based foods in the intestinal tract is important for human health. Modeling the details enhances fundamental understanding and glycemic prediction accuracy. It is, however, a challenge to take granular properties into account. A multiscale digestion model has been proposed to characterize mass transfer and hydrolysis reaction at both the intestine and particle scales, seamlessly integrating inter-scale mass exchange. A specific grid scheme was formulated for the shrinkage and transport of the particle computational domain. By incorporating additional glycemic-related processes, e.g., intestinal absorption, a dietary property-based glycemic prediction system has been developed. Its effectiveness was validated based on a human tolerance experiment of cooked rice particles. The model-based investigation comprehensively reveals the impact of initial size on digestion behavior, specifically in terms of enzyme distribution and particle evolution. This work also demonstrates the significance of modeling both particle-scale diffusion and intestine-scale transport, a combination not previously explored. The results indicate that ignoring the former mechanism leads to an overestimation of the glycemic peak by at least 50.8%, while ignoring the latter results in an underestimation of 16.3%.
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Digestão , Modelos Biológicos , Amido , Amido/química , Amido/metabolismo , Humanos , Oryza/química , Índice Glicêmico , Tamanho da Partícula , Hidrólise , Absorção IntestinalRESUMO
BACKGROUND: The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. METHODS: The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. RESULTS: In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37-13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38-0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01-0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92-7.59) and 13.63 (95% CI: 9.44-18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73-2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09-0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00-0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32-8.32) and 10.00 (95% CI: 6.09-14.05), respectively. CONCLUSIONS: The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection.
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Coinfecção , Carga Global da Doença , Infecções por HIV , Tuberculose , Humanos , Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Tuberculose/epidemiologia , Carga Global da Doença/tendências , Incidência , Prevalência , Saúde Global/estatística & dados numéricos , Feminino , Masculino , Adulto , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologiaRESUMO
Purpose: As one of the most important breakthroughs in cancer therapy, immune checkpoint inhibitors have greatly prolonged survival of patients with breast cancer. However, their application and efficacy are limited, especially for advanced HER2-negative breast cancer. It has been reported that epigenetic modulation of the histone deacetylase (HDAC) inhibitor chidamide, as well as immune microenvironment modulation of radiotherapy are potentially synergistic with immunotherapy. Thus, the combination of chidamide, radiotherapy and immunotherapy is expected to improve prognosis of patients with advanced HER2-negative breast cancer. Patients and Methods: This is a single-arm, open, prospective clinical trial investigating the efficacy and safety of the combination of HDAC inhibitor chidamide, anti-PD-1 antibody sintilimab, and the novel immuno-radiotherapy, which aims to enhance efficacy of immunotherapy, in subsequent lines of therapy of HER2-negative breast cancer. Our study will include 35 patients with advanced breast cancer that has failed endocrine therapy and first-line chemotherapy. Participants will receive 30 mg of chidamide twice a week, 200 mg of sintilimab once every 3 weeks, combined with immuno-radiotherapy. Radiotherapy will be centrally 8 Gy for at least one lesion, and at least 1 Gy for the other lesions. We will complete three fractions of radiotherapy in one cycle. The primary endpoint is progression-free survival, and secondary endpoints are objective response rate, disease control rate and safety. Moreover, biomarkers including cytokines and lymphocyte subgroups will be explored. Conclusion: As a single-arm clinical trial, the analysis of the influence of each single treatment is limited. Besides, our study is an open study, which involves neither randomization nor blinding. In spite of the abovementioned limitations, this prospective clinical trial will give an insight into subsequent lines of therapy of HER2-negative advanced breast cancer, prolong the survival or achieve long remission for these participants, and identify potential responders.
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HCC is globally recognized as a major health threat. Despite significant progress in the development of treatment strategies for liver cancer, recurrence, metastasis, and drug resistance remain key factors leading to a poor prognosis for the majority of liver cancer patients. Thus, there is an urgent need to develop effective biomarkers and therapeutic targets for HCC. Collagen, the most abundant and diverse protein in the tumor microenvironment, is highly expressed in various solid tumors and plays a crucial role in the initiation and progression of tumors. Recent studies have shown that abnormal expression of collagen in the tumor microenvironment is closely related to the occurrence, development, invasion, metastasis, drug resistance, and treatment of liver cancer, making it a potential therapeutic target and a possible diagnostic and prognostic biomarker for HCC. This article provides a comprehensive review of the structure, classification, and origin of collagen, as well as its role in the progression and treatment of HCC and its potential clinical value, offering new insights into the diagnosis, treatment, and prognosis assessment of liver cancer.
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Biomarcadores Tumorais , Carcinoma Hepatocelular , Colágeno , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Biomarcadores Tumorais/análise , Colágeno/metabolismo , Prognóstico , Progressão da DoençaRESUMO
Memory inflation is confirmed as the most commonly dysregulation of host immunity with antigen-independent manner in mammals after viral infection. By generating large numbers of effector/memory and terminal differentiated effector memory CD8+ T cells with diminished naïve subsets, memory inflation is believed to play critical roles in connecting the viral infection and the onset of multiple diseases. Here, we reviewed the current understanding of memory inflated CD8+ T cells in their distinct phenotypic features that different from exhausted subsets; the intrinsic and extrinsic roles in regulating the formation of memory inflation; and the key proteins in maintaining the expansion and proliferation of inflationary populations. More importantly, based on the evidences from both clinic and animal models, we summarized the potential mechanisms of memory inflation to trigger autoimmune neuropathies, such as Guillain-Barré syndrome and multiple sclerosis; the correlations of memory inflation between tumorigenesis and resistance of tumour immunotherapies; as well as the effects of memory inflation to facilitate vascular disease progression. To sum up, better understanding of memory inflation could provide us an opportunity to beyond the acute phase of viral infection, and shed a light on the long-term influences of CD8+ T cell heterogeneity in dampen host immune homeostasis.
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Variances in the biological functions of astaxanthin geometric isomers (i.e., all-E, Z) are related to their intestinal absorption, but the mechanism of isomer absorption mediated by transporters remains unclear. Here, models of in vitro cell overexpression, in situ intestinal perfusion, and in vivo mouse inhibition were employed to investigate the impact of cluster of differentiation 36 (CD36) on the absorption of astaxanthin isomers. Cells overexpressing CD36 notably enhanced the uptake of Z-astaxanthin, particularly the 9-Z-isomer (47.76%). The absorption rate and permeability of Z-astaxanthin surpassed that of the all-E-isomer by the in situ model. Furthermore, the addition of the CD36-specific inhibitor sulfo-N-succinimidyl oleate significantly reduced the absorption of Z-astaxanthin in the mouse duodenum and jejunum, especially the 9-Z-isomer (57.66%). Molecular docking and surface plasmon resonance techniques further validated that 9-Z-astaxanthin binds to more amino acids of CD36 with higher affinity and in a fast-binding, fast-dissociating mode, thus favoring transport. Our findings elucidate, for the first time, the mechanism of the CD36-mediated transmembrane transport of astaxanthin geometric isomers.
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Antígenos CD36 , Absorção Intestinal , Simulação de Acoplamento Molecular , Xantofilas , Xantofilas/metabolismo , Xantofilas/química , Animais , Antígenos CD36/metabolismo , Antígenos CD36/genética , Camundongos , Absorção Intestinal/efeitos dos fármacos , Masculino , Humanos , Isomerismo , Camundongos Endogâmicos C57BL , Jejuno/metabolismo , Ligação ProteicaRESUMO
Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we described the changes in various immune cells during bone metastasis and discussed their related mechanisms. Osteoblasts, adipocytes, and other non-immune cells closely related to bone metastasis were also included. This review also summarized the existing treatment methods and potential therapeutic targets, and provided insights for future studies of cancer bone metastasis.
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BACKGROUND: Post-stroke infection is the most common complication of stroke and poses a huge threat to patients. In addition to prolonging the hospitalization time and increasing the medical burden, post-stroke infection also significantly increases the risk of disease and death. Clarifying the risk factors for post-stroke infection in patients with acute ischemic stroke (AIS) is of great significance. It can guide clinical practice to perform corresponding prevention and control work early, minimizing the risk of stroke-related infections and ensuring favorable disease outcomes. AIM: To explore the risk factors for post-stroke infection in patients with AIS and to construct a nomogram predictive model. METHODS: The clinical data of 206 patients with AIS admitted to our hospital between April 2020 and April 2023 were retrospectively collected. Baseline data and post-stroke infection status of all study subjects were assessed, and the risk factors for post-stroke infection in patients with AIS were analyzed. RESULTS: Totally, 48 patients with AIS developed stroke, with an infection rate of 23.3%. Age, diabetes, disturbance of consciousness, high National Institutes of Health Stroke Scale (NIHSS) score at admission, invasive operation, and chronic obstructive pulmonary disease (COPD) were risk factors for post-stroke infection in patients with AIS (P < 0.05). A nomogram prediction model was constructed with a C-index of 0.891, reflecting the good potential clinical efficacy of the nomogram prediction model. The calibration curve also showed good consistency between the actual observations and nomogram predictions. The area under the receiver operating characteristic curve was 0.891 (95% confidence interval: 0.839-0.942), showing predictive value for post-stroke infection. When the optimal cutoff value was selected, the sensitivity and specificity were 87.5% and 79.7%, respectively. CONCLUSION: Age, diabetes, disturbance of consciousness, NIHSS score at admission, invasive surgery, and COPD are risk factors for post-stroke infection following AIS. The nomogram prediction model established based on these factors exhibits high discrimination and accuracy.
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Liver transplantation (LT) rejection remains the most pervasive problem associated with this procedure, while the mechanism involved is still complicated and undefined. One promising solution may involve the use of myeloid-derived suppressor cells (MDSC). However, the immunological mechanisms underlying the effects of MDSC after LT remain unclear. This study is meant to clarify the role MDSCs play after liver transplantation. In this study, we collected liver tissue and peripheral blood mononuclear cells (PBMC) from LT patients showing varying degrees of rejection, as well as liver and spleen tissue samples from mice LT models. These samples were then analyzed using flow cytometry, immunohistochemistry and multiple immunofluorescence. M-MDSCs and CD8 + T-cells extracted from C57/BL6 mice were enriched and cocultured for in vitro experiments. Results, as obtained in both LT patients and LT mice model, revealed that the proportion and frequency of M-MDSC and PD-1 + T-cells increased significantly under conditions associated with a high degree of LT rejection. Within the LT rejection group, our immunofluorescence results showed that a close spatial contiguity was present between PD-1 + T-cells and M-MDSCs in these liver tissue samples and the proportion of CD84/PD-L1 double-positive M-MDSC was greater than that of G-MDSC. There was a positive correlation between the activity of CD84 and immunosuppressive function of M-MDSCs including PD-L1 expression and reactive oxygen species (ROS) production, as demonstrated in our in vitro model. M-MDSCs treated with CD84 protein were able to induce co-cultured CD8 + T-cells to express high levels of exhaustion markers. We found that CD84 regulated M-MDSC function via expression of PD-L1 through activation of the Akt/Stat3 pathway. These results suggest that the capacity for CD84 to regulate M-MDSC induction of CD8 + T-cell exhaustion may play a key role in LT rejection. Such findings provide important, new insights into the mechanisms of tolerance induction in LT.
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Linfócitos T CD8-Positivos , Rejeição de Enxerto , Transplante de Fígado , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Animais , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/imunologia , Rejeição de Enxerto/imunologia , Humanos , Camundongos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Fator de Transcrição STAT3/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Fígado/patologia , Fígado/metabolismoRESUMO
The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.
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Metanol , Methylobacterium , Methylobacterium/metabolismo , Methylobacterium/genética , Methylobacterium/enzimologia , Methylobacterium/crescimento & desenvolvimento , Metanol/metabolismo , Simbiose , Mutação , Aldeído Liases/metabolismo , Aldeído Liases/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Folhas de Planta/microbiologia , Folhas de Planta/crescimento & desenvolvimento , Methylobacterium extorquens/genética , Methylobacterium extorquens/metabolismo , Methylobacterium extorquens/crescimento & desenvolvimento , Methylobacterium extorquens/enzimologia , Desenvolvimento Vegetal , Microbiota/genética , BiomassaRESUMO
Microbial degradation is an important solution for antibiotic pollution in livestock and poultry farming wastes. This study reports the isolation and identification of the novel bacterial strain Serratia entomophila TC-1, which can degrade 87.8 % of 200 mg/L tetracycline (TC) at 35 °C, pH 6.0, and an inoculation amount of 1 % (v/v). Based on the intermediate products, a possible biological transformation pathway was proposed, including dehydration, oxidation ring opening, decarbonylation, and deamination. Using Escherichia coli and Bacillus subtilis as biological indicators, TC degraded metabolites have shown low toxicity. Whole-genome sequencing showed that the TC-1 strain contained tet (d) and tet (34), which resist TC through multiple mechanisms. In addition, upon TC exposure, TC-1 participated in catalytic and energy supply activities by regulating gene expression, thereby playing a role in TC detoxification. We found that TC-1 showed less interference with changes in the bacterial community in swine wastewater. Thus, TC-1 provided new insights into the mechanisms responsible for TC biodegradation and can be used for TC pollution treatment.
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Biodegradação Ambiental , Serratia , Tetraciclina , Serratia/metabolismo , Serratia/genética , Tetraciclina/metabolismo , Antibacterianos/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/análise , Águas Residuárias/microbiologia , Animais , Eliminação de Resíduos Líquidos/métodosRESUMO
PURPOSE: We aimed to develop and evaluate a new diagnostic method, the 'chicken-wing muscle up test', to improve the accuracy of diagnosis of glenolabral articular disruption (GLAD) lesions compared to currently used clinical tests for injuries to the labrum. METHODS: Preoperative evaluations were conducted on 85 patients undergoing arthroscopic surgery at a single center between July 2021 to July 2022. The diagnostic performance of the preoperative clinical examinations (chicken-wing muscle up test, O'Brien test, crank test, and O'Driscoll test) were validated against the findings of arthroscopic examinations. RESULTS: 12 of the 85 patients in this study had arthroscopically confirmed GLAD lesions. The chicken-wing muscle up test demonstrated significantly higher sensitivity (83.33%) for GLAD lesions than the O'Brien test (33.33%), but not the crank test (50.00%) or O'Driscoll test (25.00%), and significantly higher specificity (95.89%) than the O'Brien test (75.34%), crank test (82.19%), and O'Driscoll test (71.23%). The chicken-wing muscle up test had the largest area under the receiver operating characteristic curve (AUC = 0.896, P < 0.001; O'Driscoll test AUC = 0.543, P > 0.05; crank test AUC = 0.661, P > 0.05; O'Brien test AUC = 0.481, P > 0.05), indicating significantly better diagnostic efficacy for GLAD lesions than the other three tests. CONCLUSIONS: The chicken-wing muscle up test is a reliable diagnostic method that improves the accuracy of diagnosis of GLAD lesions.
Assuntos
Artroscopia , Humanos , Feminino , Masculino , Adulto , Artroscopia/métodos , Pessoa de Meia-Idade , Adulto Jovem , Músculo Esquelético , Adolescente , Sensibilidade e Especificidade , Estudos Retrospectivos , Exame Físico/métodosRESUMO
A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications.
RESUMO
Developing a hemostatic material suitable for rapid hemostasis remains a challenge. This study presents a novel aminated gelatin sponge cross-linked with dialdehyde starch, exhibiting excellent biocompatibility and hemostatic ability. This aminated gelatin sponge features hydrophilic surface and rich porous structure with a porosity of up to 80 %. The results show that the aminated gelatin sponges exhibit superior liquid absorption capacity and can absorb up to 30-50 times their own mass of simulated body fluid within 5 min. Compared with the commercial gelatin hemostatic sponge and non-aminated gelatin hemostatic sponge, the aminated gelatin hemostatic sponge can accelerate the hemostatic process through electrostatic interactions, demonstrating superior hemostatic performance in both in vitro and in vivo hemostasis tests. The aminated gelatin sponge can effectively control the hemostatic time within 80 s in the in vivo rat femoral artery injury model, significantly outperforming both commercial and non-aminated gelatin sponges. In addition, the aminated gelatin sponge also exhibits good biocompatibility and certain antibacterial properties. The proposed aminated gelatin sponge has very good application prospects for the management of massive hemorrhage.