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Community detection and structural hole spanner (the node bridging different communities) identification, revealing the mesoscopic and microscopic structural properties of complex networks, have drawn much attention in recent years. As the determinant of mesoscopic structure, communities and structural hole spanners discover the clustering and hierarchy of networks, which has a key impact on transmission phenomena such as epidemic transmission, information diffusion, etc. However, most existing studies address the two tasks independently, which ignores the structural correlation between mesoscale and microscale and suffers from high computational costs. In this article, we propose an algorithm for simultaneously detecting communities and structural hole spanners via hyperbolic embedding (SDHE). Specifically, we first embed networks into a hyperbolic plane, in which, the angular distribution of the nodes reveals community structures of the embedded network. Then, we analyze the critical gap to detect communities and the angular region where structural hole spanners may exist. Finally, we identify structural hole spanners via two-step connectivity. Experimental results on synthetic networks and real networks demonstrate the effectiveness of our proposed algorithm compared with several state-of-the-art methods.
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Our objective was to summarize the side effect of chimeric antigen receptor (CAR)-T cell therapy in patients with acute lymphocytic leukemia (ALL) and lymphoma. Two independent reviewers extracted relevant data. A total of 35 hematologic malignancy studies with CD19 CAR-T cell were included (1412 participants). Severe cytokine release syndrome (sCRS) proportion was experienced by 18.5% (95% confidence interval [CI], 0.128-0.259; P = 0.000) of 982 patients with the National Cancer Institute/Lee/common terminology criteria for adverse events grading system. The pooled neurotoxicity proportion was 21.7% (95% CI, 0.167-0.287; P = 0.000) of 747 patients with the same grading system. For all of the 25 clinical trials with the same grading system, subgroup analysis was performed. Based on the different disease type, a pooled prevalence of 35.7% was observed with event rate (ER) of 0.358 (95% CI, 0.289-0.434; P = 0.000) for ALL in 12 clinical trials. For lymphoma, a pooled prevalence of 13% was observed with ER of 0.073 (95% CI, 0.028-0.179; P = 0.000) in eight clinical trials. It was demonstrated that the patients who were older than 18 years of age have the lower sCRS incidence of 16.1% (95% CI, 0.110-0.250; P = 0.000) compared with 28.6% of the remaining population who were younger than 18 years of age (95% CI, 0.117-0.462: P = 0.023) in our analysis. Based on the different co-stimulatory domain, the sCRS of 16.5% was observed with ER of 0.175 (95% CI, 0.090-0.312; P = 0.000) for 4-1BB. The sCRS of 22.2% was observed with ER of 0.193 (95% CI, 0.107-0.322; P = 0.000) for CD28. For both the CD28 and 4-1BB, the sCRS of 17.3% was observed with ER of 0.170 (95% CI, 0.067-0.369; P = 0.003). Sub-analysis sCRS of the impact with cell dose and specific disease indication were also demonstrated. Limitations include heterogeneity of study populations, as well as high risk of bias of included studies. These results are helpful for physicians, patients and the other stakeholders to understand the adverse events and to further promote the improvement of CAR-T cell therapy in the future.
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Antígenos CD19/inmunología , Tratamiento Basado en Trasplante de Células y Tejidos/efectos adversos , Síndrome de Liberación de Citoquinas/epidemiología , Neoplasias Hematológicas/terapia , Inmunoterapia Adoptiva/efectos adversos , Linfoma/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores Quiméricos de Antígenos/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD28/inmunología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Niño , Femenino , Humanos , Inmunoterapia Adoptiva/métodos , Incidencia , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Immunotherapy with chimeric antigen receptor T (CAR-T) cells has proved remarkably effective in recently published clinical trials. In this meta-analysis, we performed a systematic review in terms of the clinical response treated with CAR-T cells in acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and lymphomas patients. Thirty-eight published clinical studies including 665 patients were eligible for response rate (RR) evaluation. The overall pooled RR of CD19-CAR-T cells was 72% (95% confidence interval: 62-77%). The various clinical parameters were analyzed. RR was 81% in ALL, 68% in lymphoma and 70% in CLL. RR in patients who received interleukin (IL)-2 was 70%, whereas in those who did not receive IL-2, it was 74%. RR was 75% with lymphodepletion and 56% without lymphodepletion. RR with autologous cells was 76% and 57% with allogeneic cells. In conclusion, this meta-analysis showed a high clinical RR of CD19-CAR-T cell-based immunotherapy in patients with refractory B-cell malignancies.
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Antígenos CD19/inmunología , Inmunoterapia Adoptiva/métodos , Leucemia de Células B/inmunología , Leucemia de Células T/inmunología , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/inmunología , Linfocitos B/inmunología , Linfocitos B/patología , Ensayos Clínicos como Asunto , Femenino , Humanos , Inmunoterapia Adoptiva/efectos adversos , Leucemia de Células B/terapia , Leucemia de Células T/terapia , Linfoma/inmunología , Linfoma/terapia , Linfoma de Células B/inmunología , Linfoma de Células B/terapia , Linfoma de Células T/inmunología , Linfoma de Células T/terapia , Masculino , Receptores Quiméricos de Antígenos/genética , Linfocitos T/metabolismo , Linfocitos T/trasplanteRESUMEN
OBJECTIVE: To assess the association between chronic obstructive pulmonary disease (COPD) comorbidities and clinical characteristics, and to explore the inflammation mechanism. METHODS: 220 stable COPD patients were included. Clinical characteristics and comorbidities were recorded, and blood samples were collected. The relationship among the number and type of comorbidities, Charlson comorbidity index (CCI), clinical characteristics and the levels of plasma inflammatory markers [interleukin (IL)-6, high sensitivity C-reaction protein (hs-CRP), tumor necrosis factor-α (TNF-α), IL-8] were studied. RESULTS: The top five comorbidities were hypertension, metabolic syndrome and diabetes osteoporosis, bronchiectasis and peripheral vascular diseases. The level of plasma IL-6 was greater in higher CCI score (≥4) group compared with lower CCI score (<4) group ( P=0.011). Levels of IL-6 and IL-8 and the number of hospitalization in prior year were positively correlated with CCI and age adjusted CCI (r<0.03, P<0.05). There was a correlation between the COPD comorbidities and systemic inflammatory response (r<0.3, P<0.05). CONCLUSION: Patients with a higher CCI score had more severe symptoms, functional impairment and higher level of inflammatory factors and high frequency of hospital admission due to acute exacerbation. The mechanism by which COPD may play a role in systemic inflammatory response deserves further study.
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Enfermedad Pulmonar Obstructiva Crónica , Biomarcadores , Comorbilidad , Humanos , Inflamación , Interleucina-6 , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Factor de Necrosis Tumoral alfaRESUMEN
Tumor-infiltrating lymphocytes (TILs) that test positive for forkhead box P3 (FOXP3) and elevated preoperative serum albumin levels have been positively associated with survival in colorectal cancer (CRC). This study aimed to investigate correlations among FOXP3+ TILs, preoperative serum albumin, overall survival, and other clinicopathological features of CRC patients. Surgical specimens from 340 stage II-III CRC patients were stained immunohistochemically for the presence of FOXP3+ TILs. Serum albumin levels were determined using an automatic biochemistry analyzer. Associations between various clinicopathological features and patient survival were analyzed via a Cox proportional hazards regression model. The correlation between FOXP3+ TILs and preoperative serum albumin was assessed using Pearson's correlation analysis. Survival curves were constructed by the Kaplan-Meier method. A high FOXP3+ TIL density (>15/five high-power fields), elevated preoperative serum albumin (≥35 g/L), and proximal colon carcinoma were significantly associated with better survival, and high FOXP3+ TIL number and elevated preoperative serum albumin were independent predictors of better survival. The correlation between the number of FOXP3+ TILs and preoperative serum albumin level was significant but neither of these correlated with gender, age, tumor size, tumor differentiation, mucinous tumor, T4 stage, postoperative chemotherapy, or tumor location. Our findings suggest that increased FOXP3+ TILs and high preoperative serum albumin levels are independent prognostic markers for improved survival in CRC patients. Furthermore, the number of FOXP3+ TILs correlates with preoperative serum albumin levels in these patients.
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Neoplasias Colorrectales/genética , Factores de Transcripción Forkhead/biosíntesis , Linfocitos Infiltrantes de Tumor/patología , Pronóstico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Factores de Transcripción Forkhead/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Periodo Preoperatorio , Albúmina SéricaRESUMEN
PURPOSE: Obstructive sleep apnea (OSA) is suggested as a potential risk factor of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism is still far from clear. The aim of this observational study was to investigate the influence of OSA-related hypoxia on severity of liver injury in patients with NAFLD. METHODS: Consecutive patients with ultrasound-diagnosed NAFLD who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for biological profile measurements, and demographic data were collected. Subjects were divided into control, moderate, and severe groups. RESULTS: A total of 85 subjects with 73 males and 12 females were included (mean age, 44.67 ± 1.28 years; mean body mass index, 27.28 ± 0.33 kg/m(2)). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, gamma glutamyltransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose, and high-sensitivity C-reactive protein significantly increased with the aggravation of OSA. In multivariate analysis, oxygen desaturation index was the major contributing factor for elevated ALT (ß = 0.435, p = 0.000), average O2 saturation was the major independent predictor of elevated AST (ß = -0.269, p = 0.020). CONCLUSIONS: OSA-related hypoxia was independently associated with the biochemical evidence of liver injury in the presence of NAFLD.
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Hipoxia/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Apnea Obstructiva del Sueño/diagnóstico , Adulto , Anciano , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/etiología , Polisomnografía , Apnea Obstructiva del Sueño/complicaciones , Estadística como Asunto , Ultrasonografía , Adulto JovenRESUMEN
Ionizing radiation (IR) leads to oxidizing events such as excessive reactive oxygen species (ROS) in the exposed cells, resulting in further oxidative damage to lipids, proteins and DNA. To screen the potential radio-protective drug, the intracellular ROS was measured in irradiated U937 cells pretreated with 80 candidate traditional herbal medicine, respectively. Isofraxidin (IF) was one possible radio-protector in these 80 drugs. This study investigated the radio-protective role of IF, a Coumarin compound, in human leukemia cell lines, for the first time. Results indicate that IF protects against IR-induced apoptosis in U937 cells in the time- and concentration- dependent manner. IF decreases IR-induced intracellular ROS generation, especially hydroxyl radicals formation, inhibits IR-induced mitochondrial membrane potential loss and reduces IR-induced high intracellular Ca(2+) levels regardless of ER stress. IF down-regulates the expression of caspase-3, phospho-JNK, phospho-p38 and activates Bax in mitochondria. IF inhibits cytochrome c release from mitochondria to cytosol. IF also moderates IR-induced Fas externalization and caspase-8 activation. IF also exhibits significant protection against IR-induced cell death in other leukemia cell lines such as Molt-4 cells and HL60 cells regardless of p53. Taken together, the data demonstrate that IF protects leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in a p53-independent manner.
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Apoptosis/efectos de los fármacos , Cumarinas/farmacología , Depuradores de Radicales Libres/farmacología , Mitocondrias/metabolismo , Protectores contra Radiación/farmacología , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Cumarinas/química , Ensayos de Selección de Medicamentos Antitumorales , Depuradores de Radicales Libres/química , Humanos , Leucemia , Linfoma , Potencial de la Membrana Mitocondrial , Protectores contra Radiación/química , Transducción de Señal , Rayos XRESUMEN
Ionizing radiation (IR) can generate reactive oxygen species (ROS). Excessive ROS have the potential to damage cellular macromolecules including DNA, proteins, and lipids and eventually lead to cell death. In this study, we evaluated the potential of arbutin, a drug chosen from a series of traditional herbal medicine by measuring intracellular hydroxyl radical scavenging ability in X-irradiated U937 cells. Arbutin (hydroquinone-ß-D-glucopyranoside), a naturally occurring glucoside of hydroquinone, has been traditionally used to treat pigmentary disorders. However, there are no reports describing the effect of arbutin on IR-induced apoptosis. We confirmed that arbutin can protect cells from apoptosis induced by X-irradiation. The combination of arbutin and X-irradiation could reduce intracellular hydroxyl radical production and prevent mitochondrial membrane potential loss. It also could down-regulate the expression of phospho-JNK, phospho-p38 in whole cell lysate and activate Bax in mitochondria. Arbutin also inhibits cytochrome C release from mitochondria to cytosol. To verify the role of JNK in X-irradiation-induced apoptosis, the cells were pretreated with a JNK inhibitor, and found that JNK inhibitor could reduce apoptosis induced by X-irradiation. Taken together, our data indicate that arbutin plays an anti-apoptotic role via decreasing intracellular hydroxyl radical production, inhibition of Bax-mitochondria pathway and activation of the JNK/p38 MAPK pathway.
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Apoptosis/efectos de los fármacos , Arbutina/farmacología , Depuradores de Radicales Libres/farmacología , Protectores contra Radiación/farmacología , Apoptosis/efectos de la radiación , Arbutina/química , Arbutina/metabolismo , Caspasa 8/metabolismo , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fosforilación , Especies Reactivas de Oxígeno/metabolismo , Células U937 , Receptor fas/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVE: This study aimed to explore the effect of narrative nursing on improving the negative emotions, sleep quality, and quality of life of patients with moderate to severe cancer pain. METHODS: A total of 80 patients with moderate to severe cancer pain who had been hospitalized in the lymphoma oncology department in our hospital from March 2019 to September 2021 were selected as the study subjects and randomly divided into the conventional nursing and narrative nursing groups, with 40 cases in each group. A conventional nursing intervention was conducted for one group, and narrative nursing was provided for the second group in addition to the conventional nursing. The anxiety and depression, sleep quality, quality of life, and satisfaction with pain management of the patients in the two groups were compared before and after the intervention. RESULTS: In the narrative nursing group, the self-rating anxiety scale and self-rating depression scale scores were significantly lower than those in the conventional nursing group after the intervention (P < 0.05). The scores for sleep quality, sleep duration, sleep efficiency, and daytime dysfunction and the total Pittsburgh Sleep Quality Index scores were significantly lower in the narrative nursing group compared with the conventional care group (P < 0.05). The scores for the physical function, living ability, social adaptation, and psychological status items in the Quality of Life Questionnaire Core 30 were significantly higher in the narrative nursing group than in the conventional care group (P < 0.05). The patients' satisfaction with pain management was higher in the narrative nursing group than in the conventional care group (P < 0.05). CONCLUSION: Narrative nursing can alleviate the negative emotions of anxiety and depression in patients with moderate to severe cancer pain and improve their sleep quality, quality of life, and pain management satisfaction.
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The 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) pathological classification system of lupus nephritis specified the importance of vascular damage and indicated this should be included in the diagnostic summary. Few pathological studies of lupus nephritis, however, focus on the patterns of renal vascular involvement. Here we assessed renal vascular lesions in lupus nephritis based on the 2003 ISN/RPS classification system and evaluated their association with clinical and pathological data in a large cohort from a single center in China. Among 341 patients with lupus nephritis, 279 were diagnosed with single or multiple renal vascular lesions that included 253 with vascular immune complex deposits, 82 with atherosclerosis, 60 with thrombotic microangiopathy, 13 with noninflammatory necrotizing vasculopathy, and 2 with true renal vasculitis. Patients with thrombotic microangiopathy had the poorest renal outcome. In multivariate Cox hazard analysis after inclusion of renal vascular lesions, the new chronicity index score became a significantly better independent risk factor for renal outcome (hazard ratio 2.32). Thus, renal vascular lesions are common in lupus nephritis and closely correlate with clinical disease activity and renal outcome. Inclusion of a detailed description of renal vascular lesions in the ISN/RPS classification of lupus nephritis may strengthen its predictive value for renal outcome.
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Aterosclerosis/diagnóstico , Riñón/irrigación sanguínea , Nefritis Lúpica/diagnóstico , Microangiopatías Trombóticas/diagnóstico , Vasculitis/diagnóstico , Adulto , Complejo Antígeno-Anticuerpo/análisis , Aterosclerosis/clasificación , Aterosclerosis/patología , Aterosclerosis/terapia , Biomarcadores/análisis , Biopsia , Vasos Sanguíneos/inmunología , Vasos Sanguíneos/patología , China , Enfermedad Crónica , Femenino , Humanos , Estimación de Kaplan-Meier , Nefritis Lúpica/clasificación , Nefritis Lúpica/inmunología , Nefritis Lúpica/patología , Nefritis Lúpica/terapia , Masculino , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Microangiopatías Trombóticas/clasificación , Microangiopatías Trombóticas/patología , Microangiopatías Trombóticas/terapia , Vasculitis/clasificación , Vasculitis/patología , Vasculitis/terapia , Adulto JovenRESUMEN
OBJECTIVES: Although sirolimus tablets and oral solutions have been used in clinical practice, no study has been reported on the pharmacokinetics and bioavailability of a single-dose of sirolimus tablets in healthy Chinese volunteers. The purpose of this study was to compare the bioavailability and pharmacokinetic (PK) properties of two different 1-mg sirolimus tablets in healthy Chinese male volunteers and evaluate whether a generic tablet of sirolimus meets the criteria for bioequivalence from the State Food and Drug Administration (SFDA) of China when compared with a reference product. MATERIALS AND METHODS: A total of 24 healthy Chinese volunteers was eligible for this 6 mg single dose, randomized-sequence, open-label, 2-period crossover study. Blood samples were collected before dosing and at 0.25, 0.50, 0.75, 1.0, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 120, 168, 216, and 264 hours after dosing. Whole blood sirolimus concentration was analyzed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic properties of sirolimus were assessed using noncompartmental analysis. RESULTS: The mean (range) Cmax values of the test and the reference were 15.25 (8.48 - 24.40) and 13.43 (7.90 - 22.90) ng/ml; AUC0-t values were 475.65 (293.33 - 1049.86) and 451.96 (221.52 - 809.11) ng/h/ml. The medians (range) tmax values were 2.0 (1.0 - 8.0) and 2.0 (1.0 - 8.0) hours, respectively. The 90% confidence intervals (CIs) for the ratios of Cmax, AUC0-264, and AUC0-∞ were 103.7% to 124.4%, 97.5% to 113.6%, and 98.0% to 114.8%, respectively. CONCLUSION: In this single-dose crossover study the test sirolimus tablets met the criteria for bioequivalence in terms of both rate and extent. Each sirolimus formulation was well tolerated during the study.
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Sirolimus/farmacocinética , Adulto , Área Bajo la Curva , Pueblo Asiatico , Disponibilidad Biológica , Química Farmacéutica , Estudios Cruzados , Medicamentos Genéricos/farmacocinética , Voluntarios Sanos , Humanos , Masculino , Sirolimus/administración & dosificación , Sirolimus/sangre , Comprimidos/farmacocinética , Equivalencia Terapéutica , Estados Unidos , United States Food and Drug Administration , Adulto JovenRESUMEN
BACKGROUND: Lupus nephritis is considered to be a principal cause of morbidity and mortality in SLE. Few studies focus on the association between anti-C1q antibodies in circulation and renal C1q deposition in human lupus nephritis. In this study, we detected the serum levels of C1q, presence of anti-C1q antibodies in circulation, renal C1q deposition and further analyzed their associations with clinical and pathological activity in a large cohort of Chinese lupus nephritis patients. METHODS: Sera and renal biopsies from 218 consecutive patients with lupus nephritis with long-term follow up data were studied. Sera were tested for levels of C1q and anti-C1q autoantibodies. Associations of levels of C1q, anti-C1q autoantibodies with renal deposition of C1q, clinical and histopathological data and renal outcome were further investigated. RESULTS: The levels of serum C1q were significantly lower in lupus nephritis than that in normal controls [33.81 ± 20.36 v.s. 61.97 ± 10.50 µg/ml (P < 0.001)]. The prevalence of anti-C1q antibodies, ratios of glomerular and vascular deposition of C1q in patients with lupus nephritis were 42.7% (93/218), 71.6% (156/218) and 86.2% (188/218), respectively. The serum C1q levels and anti-C1q antibodies were associated with SLEDAI scores (P < 0.001, P = 0.012, respectively), renal total activity indices scores (P < 0.001, P < 0.001, respectively). Granular positive staining of C1q and IgG by immunofluorescence was co-localized almost completely along the glomerular capillary wall and mesangial areas. Patients with anti-C1q antibodies presented with significantly lower serum C1q levels than those without it (23.82 [0.60, 69.62] µg/ml v.s. 37.36 [0.64, 82.83] µg/ml, P < 0.001). The presence of anti-C1q antibodies was associated with the presence of glomerular C1q deposition (P < 0.001), but not with the presence of renal vascular C1q deposition (P = 0.203). CONCLUSION: Anti-C1q autoantibodies were closely associated with serum levels of C1q and glomerular deposition of C1q. Kidney is at least one of the target organs of anti-C1q autoantibodies.
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Autoanticuerpos/sangre , Biomarcadores/sangre , Complemento C1q/metabolismo , Progresión de la Enfermedad , Glomérulos Renales/metabolismo , Nefritis Lúpica/sangre , Adulto , Femenino , Estudios de Seguimiento , Humanos , Nefritis Lúpica/diagnóstico , Masculino , Adulto JovenRESUMEN
PURPOSE: Patients with heart failure (HF) are often limited in their ability to perform exercise. Cardiac rehabilitation (CR) improves aerobic capacity and quality of life (QOL) and is recommended for patients with clinically stable HF; however, it is underutilized. The aim of this study was to investigate the factors associated with participation and completion rates and predictive of improvement after phase II CR in patients with HF. METHODS: Participation and completion rates were calculated for all patients with HF enrolled in a multidisciplinary management program from October 2008 to December 2018. Functional capacity and QOL were estimated. In patients undergoing CR, changes in peak oxygen uptake (VË o2peak ) were measured. RESULTS: Of 662 patients enrolled, 448 (68%) completed the cardiopulmonary exercise test (CPX). Phase II CR was recommended in 411 patients, of whom 291 (71%) participated in CR. Participation was significantly related to sex and the time interval in days between hospital discharge and the CPX. Overall, 171 patients completed 36 sessions of CR (with a completion rate of 59%). During CR, there were 18 (6%) adverse events. Cardiac rehabilitation was associated with improvement in VË o2peak from 1153 ± 393 to 1342 ± 470 mL/min (a 16% improvement; P < .001) and in QOL. The independent predictors of increase in VË o2peak included sex, age, diabetes mellitus, and entry VË o2peak . CONCLUSIONS: In patients with HF, factors associated with CR participation rate included sex and days between hospital discharge and the CPX. Participation in CR improved VË o2peak and QOL. The improvement was related to male sex, younger age, no diabetes mellitus, and higher entry VË o2peak .
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Rehabilitación Cardiaca , Insuficiencia Cardíaca , Humanos , Masculino , Calidad de Vida , Insuficiencia Cardíaca/rehabilitación , Ejercicio Físico , Terapia por EjercicioRESUMEN
Spider silk is repeatedly stretched while performing biological functions. There is a close relationship between the shape change of the fibre materials and their mechanical properties. However, the effect of the deformation and interval time on the structure and tensile behaviour properties of spider silk after repeatedly stretching by given strain value has been rarely reported. Here we found that major ampullate silk (MAS) can revert its tensile behaviour independent of its previous loading history via intervals of approximately 8 s to 5 min with constant and increased elongation, respectively, after being subjected to yield and hardening regions. The true stress-true strain curve beyond a given value of true strain is independent from the previous loading history of the sample. Even after longer intervals (≥1 h), MAS can reproduce the last tensile behaviour via one stretched. Despite recognizing the development of irreversible deformations in the material when tested in air, the reversible change in tensile behaviour outside the spider silk's elastic region has rarely been observed before. MAS has at least one proper ground state that allows it to present good shape and mechanical behaviour memory in terms of longitudinal stretching, functioning as a new strategy to achieve certain tensile properties. The analysis of the true stress-true strain curves was performed from a series of loadingâunloading tests to evaluate the evolution of those mechanical parameters with the cycle number. The elastic modulus measured in the loading steps increases monotonously with increasing values of true strain reached in the cycles. In contrast, a marginal variation is found in the values of the yield stress measured in the different cycles. The memory and variation in the mechanical behaviour and performance of MAS can be accounted for through the irreversible and reversible deformation micromechanisms and its combination in which the viscoelasticity of the material plays a leading role. These findings may be helpful to guide the biomimetic design of novel fibre materials such as spider silk gut via artificially stretching spider silk glands.
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Biomimética , Seda , Módulo de ElasticidadRESUMEN
BACKGROUND: The renal pathological manifestations of malignancy-associated membranous nephropathy (M-MN) and idiopathic membranous nephropathy (I-MN) are similar. It has been suggested that glomerular IgG4 deposition may play an important role in the pathogenesis of I-MN. In the present study, we compared the IgG subclass of immune complex deposition, clinical data and pathological data of patients with M-MN and I-MN. METHODS: Eight patients with M-MN and 42 patients with I-MN diagnosed between 1997 and 2009 in our hospital were enrolled. The clinical and pathological data were retrospectively collected, and glomerular IgG subclass deposition was detected by immunohistochemistry. RESULTS: Patients with M-MN were older (P = 0.003), with lower serum albumin (P = 0.034) and higher serum C-reactive protein (CRP) level (P = 0.003) than patients with I-MN. The majority of patients with M-MN had earlier pathological stages (P = 0.003) and less IgG deposition in glomeruli (P = 0.029). Absence of IgG4 deposition in glomeruli was notably observed in patients with M-MN (7/8 in M-MN versus 6/42 in I-MN, P < 0.001) and it was an independent predictor for occurrence of malignancy (hazard ratio 0.065, 95% confidence intervals 0.007-0.571, P = 0.014). CONCLUSION: Absence of glomerular IgG4 deposition, together with older age, severe hypoalbuminemia and high serum CRP level could be useful clues to differentiate M-MN from I-MN.
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Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/inmunología , Inmunoglobulina G/metabolismo , Glomérulos Renales/inmunología , Neoplasias Renales/diagnóstico , Neoplasias Renales/inmunología , Adulto , Factores de Edad , Anciano , Biopsia , Proteína C-Reactiva/metabolismo , Diagnóstico Diferencial , Femenino , Glomerulonefritis Membranosa/patología , Humanos , Riñón , Glomérulos Renales/patología , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Albúmina Sérica/metabolismoRESUMEN
BACKGROUND: The recently published histopathologic classification of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis might greatly aid in the prognostication of patients at the time of diagnosis. This study aims to re-evaluate the new classification for its prognostic capacity in an independent Chinese series. METHODS: One hundred and twenty-one consecutive patients with ANCA-associated glomerulonephritis, diagnosed in our center from 1997 to 2010, were included in this retrospective study. The renal specimens were reviewed according to the proposed histopathologic classification. The predictive value of the classification for renal outcome and renal response to treatment was analyzed. RESULTS: Thirty-three (27.3%), 24 (19.8%), 53 (43.8%) and 11 (9.1%) patients were classified as focal, mixed, crescentic and sclerotic ANCA-associated glomerulonephritis, respectively. The renal biopsy categories correlated with initial serum creatinine and the renal response to treatment (P < 0.001, P < 0.01, respectively). The probability of progressing to end-stage renal disease (ESRD) increased with ascending categories of focal, mixed, crescentic and sclerotic glomerulonephritis (P < 0.01). The patients with focal, mixed and crescentic ANCA-associated glomerulonephritis were all at decreased risk for developing ESRD compared with the patients with in the sclerotic category (P < 0.05). CONCLUSIONS: The proposed classification system was re-evaluated for the first time in a relatively large and independent series of patients. This system reflects the severity of the initial renal impairment and can predict, at least to some extent, the renal response to treatment. More importantly, it can independently predict renal outcome, in particular development of ESRD.
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Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/clasificación , Glomerulonefritis/clasificación , Glomerulonefritis/patología , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Femenino , Estudios de Seguimiento , Glomerulonefritis/complicaciones , Humanos , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
OBJECTIVE: To validate a novel method of expanding late endothelial progenitor cells (EPC) in vitro. METHODS: We cultured mononuclear cells (MNC) from human peripheral blood on the plate with the feeder layer cells, i.e. irradiated late EPC or human umbilical vein endothelial cells. After 21 days, the numbers of late EPC colonies were counted separately. And the surface antigen of late EPC was detected by fluorescence-activated cell sorter (FACS) and their in vitro ability of forming vascular structure examined by matrigel. RESULTS: Both colony numbers of late EPC with feeder layer cell culturing were over 20 times than those without (40.0 ± 3.9, 39.3 ± 3.1 vs 2.0 ± 1.3, both P < 0.05). And the former's late EPC colony appeared earlier. The late EPC expressed CD31, CD34, eNOS, Flt-1, P1H12, Sendo, VE cadherin and CD117. And vascular structures were discerned. CONCLUSIONS: The method of feeder layer cells may vastly expand the quantity of late EPC. And microenvironment plays an important role in its expansion.
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Técnicas de Cultivo de Célula , Células Endoteliales/citología , Células Madre/citología , Adulto , Diferenciación Celular , Células Cultivadas , Endotelio Vascular/citología , Humanos , Masculino , Trofoblastos/citología , Adulto JovenRESUMEN
OBJECTIVE: To study the role of the feeder layer cells as niche in the process of expansion of late endothelial progenitor cell in vitro. METHODS: We cultured mononuclear cells (MNC)from human peripheral blood (PB)on the plate with the feeder layer cells which were irradiated late endothelial progenitor cells(EPC)or human umbilical vein endothelial cells (HUVEC) by EGM-2. After 21 days, the numbers of obtained late EPC colonies were counted separately, and their surface antigen of the late EPC was verified by fluorescence-activated cell sorter (FACS) analysis, and their ability of forming vessel structure with Matrigel in vitro. The differentiation of single stem cell on the feeder layer cell was traced by video-microscopy. RESULTS: After 21 days of culture,(40.0±3.9)and(39.3±3.1)late EPC colonies that MNC of a hundred milliliter PB were cultured, respectively, on the feeder layer cells of EPC and HUVEC were much more than (2.0±1.3) colonies cultured on without the feeder layer cells (all P <0.05). These cells also expressed CD31,CD34,eNOS,FLt-1,P1H12,Sendo,VE cadherin,and CD117, as shown by FACS analysis. Furthermore, they formed vessel structure with Matrigel in vitro. The video-microscopy showed the asymmetric cell division was participated by the feeder layer cell during the expansion of single stem cell. CONCLUSION: The massive expansion of late EPC can be achieved by the provision of the feeder layer cells, which may be involved in the stem cell asymmetric cell division.
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Microambiente Celular , Células Endoteliales/citología , Células Nutrientes , Células Madre/citología , Comunicación Celular , Técnicas de Cultivo de Célula , Diferenciación Celular , Proliferación Celular , Sangre Fetal/citología , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Trofoblastos/citologíaRESUMEN
BACKGROUND: Currently, ongoing trials of mesenchymal stem cells (MSC) therapies for coronavirus disease 2019 (COVID-19) have been reported. AIM: In this study, we investigated whether MSCs have therapeutic efficacy in novel COVID-19 patients. METHODS: Search terms included stem cell, MSC, umbilical cord blood, novel coronavirus, severe acute respiratory syndrome coronavirus-2 and COVID-19, applied to PubMed, the Cochrane Controlled Trials Register, EMBASE and Web of Science. RESULTS: A total of 13 eligible clinical trials met our inclusion criteria with a total of 548 patients. The analysis showed no significant decrease in C-reactive protein (CRP) levels after stem cell therapy (P = 0.11). A reduction of D-dimer levels was also not observed in patients after stem cell administration (P = 0.82). Furthermore, interleukin 6 (IL-6) demonstrated no decrease after stem cell therapy (P = 0.45). Finally, we investigated the overall survival (OS) rate after stem cell therapy in COVID-19 patients. There was a significant improvement in OS after stem cell therapy; the OS of enrolled patients who received stem cell therapy was 90.3%, whereas that of the control group was 79.8% (P = 0.02). CONCLUSION: Overall, our analysis suggests that while MSC therapy for COVID-19 patients does not significantly decrease inflammatory markers such as CRP, D-dimer and IL-6, OS is improved.
RESUMEN
BACKGROUND: Cardiac troponins are highly sensitive and specific biomarkers for cardiac injury. Previous studies evaluating the effect of positive airway pressure (PAP) on cardiac troponins in patients with sleep-disordered breathing (SDB) have yielded conflicting results. The meta-analysis was performed to examine the effect of PAP on cardiac troponins in SDB patients. METHODS: PubMed, Web of Science, and EMBASE before September 2021 on original English language studies were searched. The data on cardiac troponins in both baseline and post-PAP treatment were extracted from all studies. The data on the change of cardiac troponins in both PAP and control group were extracted from randomized controlled trials. Standardized mean difference (SMD) was used to synthesize quantitative results. RESULTS: A total of 11 studies were included. PAP treatment was not associated with a significant change in cardiac troponin T between the baseline and post-PAP treatment (SMD = -0.163, 95% confidence interval [CI] = -0.652 to 0.326, z = 0.65, p = .514). The pooled estimate of SMD of cardiac troponin I between the pre- and post-PAP treatment was 0.287, and the 95% CI was -0.586 to 1.160 (z = 0.64, p = .519). The pooled SMD of change of cardiac troponin T between the PAP group and control group was -0.473 (95% CI = -1.198 to 0.252, z = 1.28, p = .201). CONCLUSIONS: This meta-analysis revealed that PAP treatment was not associated with any change of cardiac troponin in SDB patients.