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Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy. Methods: A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results: Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG (χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG (χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion: Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.
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Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva , Mieloma Múltiple , Trasplante Autólogo , Humanos , Mieloma Múltiple/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Femenino , Inmunoterapia Adoptiva/métodos , Anciano , Adulto , Resultado del Tratamiento , Receptores Quiméricos de AntígenosRESUMEN
The seamless phase â ¡/â ¢ design integrates independent phase â ¡ and phase â ¢ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase â ¡ and phase â ¢ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase â ¡/â ¢ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase â ¡/â ¢ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.
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Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Proyectos de Investigación , Humanos , Vacunas contra Papillomavirus/administración & dosificación , Desarrollo de Vacunas/métodosRESUMEN
Objective: To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis. Methods: This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results: Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions: The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.
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Glucemia , Quemaduras , Masculino , Anciano , Femenino , Humanos , Estudios Retrospectivos , Creatinina , Mioglobina , Ácido Úrico , Pronóstico , Quemaduras/diagnóstico , Ácido Láctico , Productos de Degradación de Fibrina-Fibrinógeno , Factores de Riesgo , Bilirrubina , Sodio , UreaRESUMEN
1. The objective of this study was to investigate the protective effects of a peptidoglycan produced by Limosilactobacillus reuteri against aflatoxin B1 (AFB1) induced toxicity in vitro and in vivo in broiler chicks.2. Toxin adsorption experiments were carried out firstly in vitro. These experiments indicated that the absorption efficiency of the peptidoglycan for AFB1 was 64.3-75.9%.3. In the in vivo experiments, Hy-Line Brown chicks were fed a diet containing AFB1 at 71.43 µg/kg with and without peptidoglycan supplementation at concentrations of 100, 200, or 300 g/kg feed from 0-42 d of age.4. The peptidoglycan supplementation in AFB1-contaminated diets resulted in significant improvements in terms of average daily gain, feed intake, feed conversion ratio, white blood cell count, haemoglobin content, glutathione peroxidase activity, immunoglobulin (Ig) A, IgG, IgM and Newcastle disease virus antibody titres (p < 0.05) and diminished liver steatosis.5. In conclusion, peptidoglycan supplementation alleviated AFB1-induced toxicity through adsorbing toxins and improving growth performance, antioxidant ability, immunity and liver pathological changes in chicks. The optimal supplemental dose was 200 mg/kg in feed.
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Antioxidantes , Suplementos Dietéticos , Limosilactobacillus reuteri , Peptidoglicano , Peptidoglicano/administración & dosificación , Peptidoglicano/metabolismo , Peptidoglicano/uso terapéutico , Aflatoxina B1/toxicidad , Antioxidantes/administración & dosificación , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Animales , Pollos/crecimiento & desarrollo , Adsorción , Alimentación AnimalRESUMEN
Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.
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Antígeno de Maduración de Linfocitos B , Inmunoterapia Adoptiva , Mieloma Múltiple , Humanos , Antígenos CD19 , Antígeno de Maduración de Linfocitos B/uso terapéutico , Bilirrubina , Hígado , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Linfocitos TRESUMEN
Mucormycosis is a relatively rare but dangerous infectious diseases. Burn patients, especially severe burn patients, are at high risk of mucormycosis. In recent years, the incidence of mucormycosis in burn patients has increased. At present, there are a few domestic literatures on mucormycosis in burns, with most being case reports without systematic summary. Based on the relevant literature at home and abroad in recent years, this article reviewed the epidemiological characteristics, clinical manifestations, diagnostic methods, and treatment methods of mucormycosis in burns, hoping to provide some basis for the diagnosis and treatment of mucormycosis in burns in China.
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Quemaduras , Mucormicosis , Humanos , Mucormicosis/diagnóstico , Mucormicosis/terapia , Mucormicosis/etiología , Quemaduras/complicaciones , Quemaduras/terapia , Quemaduras/diagnóstico , Desbridamiento , Antifúngicos/uso terapéutico , ChinaRESUMEN
The hazard of vehicle emissions mainly come from the four wheel positioning, drum test and vehicle emissions test sections in automobile assembly workshop, which can lead to abnormal hemoglobin and hepatic insufficiency in workers. We researched on preventing toxic gases technologies for the vehicle emissions generated by these three sections, designed the ventilation facilities, and then detected and evaluated the operation effect, thereby improving the working environment, ensuring the occupational health of workers, and providing scientific basis for the control of vehicle emissions hazards.
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Automóviles , Emisiones de Vehículos , Humanos , Emisiones de Vehículos/análisis , Gases , Arquitectura y Construcción de Instituciones de SaludRESUMEN
BACKGROUND AND PURPOSE: Patients with suspected stroke are referred to the nearest hospital and are managed either in a spoke center (SC), a primary stroke center (PSC), or a comprehensive stroke center (CSC) in order to benefit from early intravenous thrombolysis (IVT). In case of large vessel occlusion (LVO), mechanical thrombectomy (MT) is only performed in the CSC, whereas the effectiveness of MT is highly time-dependent. There is a debate about the best management model of patients with suspected LVO. Therefore, we aimed to compare functional and safety outcomes of LVO patients eligible for MT managed through our regional telestroke system. METHOD: We performed a retrospective analysis of our observational prospective clinical registry in all consecutive subjects with LVO within six hours of onset who were admitted to the SC, PSC, or CSC in the east of France between October 2017 and November 2022. The primary endpoint was the functional independence defined as modified Rankin scale (mRS) score 0 to 2 at 90 days. Secondary endpoints were functional outcome, early neurological improvement, symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: Among the 794 included patients with LVO who underwent MT, 122 (15.4%) were managed by a SC, 403 (50.8%) were first admitted to a PSC, and 269 (33.9%) were first admitted to the CSC. The overall median NIHSS and ASPECTS score were 16 and 8, respectively. Multivariate analysis did not find any significant difference for the primary endpoint between patients managed by PSC versus CSC (OR 1.06 [95% CI 0.64;1.76], P=0.82) and between patient managed by SC versus CSC (OR 0.69 [0.34;1.40], P=0.30). No difference between the three groups was found except for the parenchymal hematoma rate between PSC and CSC (15.7 versus 7.4%, OR 2.25 [1.07;4.74], P=0.032). CONCLUSIONS: Compared with a first admission to a CSC, the clinical outcomes of stroke patients with LVO eligible for MT first admitted to a SC or a PSC are similar.
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Objective: To explore the effect of early rehabilitation training on motor function and neural function of patients with brainstem hemorrhage after stereotactic individualized operation. Methods: A total of 84 patients with brainstem hemorrhage after stereotactic individualized surgery admitted to Nanyang Central Hospital from January 2020 to January 2022 were selected as the study subjects.The patients were randomly divided into observation group (n=42) and control group (n=42) according to random number table method. The control group received conventional Western medicine treatment, and the observation group received early rehabilitation training on the basis of drug treatment in the control group. The motor function assessment [Fugl Meyer Assessment (FMA) scores], neural function [National Institutes of Health Stroke Scale (NIHSS) scores], ability of daily living [Barthel index (BI) scores], cerebral blood flow [mean blood flow (MBF), mean flow velocity (MFV), peripheral vascular resistance (PVR)] and nerve factor [serum neuron specific enolase (NSE), brain derived neurotrophic factor (BDNF), central nervous specific protein(S100ß)] levels were compared between the two groups before and after the treatment. In addition, the rehabilitation effect and complications of the two groups were observed. Results: The total effective rate (95.24%) in the observation group was higher than that in the control group (76.19%%) (P<0.05). After the treatment, the FMA scores, BI scores, MBF, MFV and BDNF levels of the two groups were higher than those before the treatment, and the observation group were higher than the control group (P<0.05). NIHSS scores, PVR, NSE and S100ß levels in the two groups after the treatment were lower than those before the treatment, and those in the observation group were lower than those in the control group (P<0.05). The incidence of complications in the observation group [7.14% (3/42)]was lower than that in the control group [23.81% (10/42), P<0.05]. Conclusion: For patients with brain stem hemorrhage after stereotactic individualized surgery, early rehabilitation training can improve the motor, neural function and daily living ability, rehabilitation effect, regulate cerebral hemodynamics and nerve factor levels, and reduce the incidence of complications.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/complicaciones , Factor Neurotrófico Derivado del Encéfalo , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/rehabilitación , Proteínas del Tejido Nervioso , Tronco Encefálico , Resultado del TratamientoRESUMEN
Objective: To explore the reentry rate of reactive blood donors in the bloodborne pathogen infection screening in Hangzhou City, and analyze the donation behavior of those who successfully returned. Methods: A retrospective analysis of the return data of blood donors with reactive bloodborne pathogen screening markers was conducted at Zhejiang Provincial Blood Center from June 2017 to May 2022. The reentry process for blood donors with reactive bloodborne pathogen screening markers in Hangzhou City is as follows: after the initial screening period of 6 months, donors can voluntarily apply for return to the blood center. Samples are collected and subjected to routine enzyme-linked immunosorbent assay (ELISA) screening for HBsAg, anti-HCV, HIV Ab/Ag, and anti-TP, as well as a single nucleic acid (HIV/HCV/HBV) test. For samples that show non-reactivity in both ELISA and nucleic acid tests, serum biomarker testing for the reasons of exclusion is performed using chemiluminescence immunoassay (CLIA), and those with non-reactivity are allowed to return. Results: A total of 4 583 reactive blood donors who met the criteria for re-entry applied for reentry, out of which 475 applications were received from donors in the Hangzhou area. Among these, 279 donors were successfully readmitted, resulting in a success rate of 58.74% (279/475). By the end of December 2021, out of the 174 donors who successfully returned, 114 donors chose to donate again. They collectively donated 39 530 ml of whole blood and 1 147.2 therapeutic doses of platelets. Among these, 21 donors once again showed reactivity for pathogen infection biomarkers, accounting for 18.42% (21/114). Conclusion: The reentry strategy has somewhat mitigated the attrition of blood donors. Nevertheless, there are instances where donors who were successfully readmitted show reactivity once more in the screening for pathogen infection biomarkers.
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Infecciones por VIH , Ácidos Nucleicos , Humanos , Donantes de Sangre , Patógenos Transmitidos por la Sangre , Estudios Retrospectivos , Tamizaje Masivo/métodos , Biomarcadores , Virus de la Hepatitis BRESUMEN
Objective: To conduct a visual analysis of the literature on burn-related coagulation dysfunction and to explore the current research status, evolution process, hot topics, and future research trends in burn-related coagulation dysfunction at home and abroad. Methods: The bibliometrics method was used. The literature on burn-related coagulation dysfunction which were published in Web of Science and China National Knowledge Internet databases from January 1, 1950 to May 1, 2022, and met the inclusion criteria were retrieved for publication volume analysis. The literature on burn-related coagulation dysfunction were retrieved as above in the core collection of Web of Science and China National Knowledge Internet databases, and CiteSpace 5.8.R3 software was used to perform co-occurrence analysis, cluster analysis, and literature co-citation analysis of key words. Results: A total of 501 and 235 literature on burn-related coagulation dysfunction were retrieved from Web of Science database and China National Knowledge Internet database, respectively. The literature on burn-related coagulation dysfunction emerged from 1975 and 1950, respectively, in China and abroad, which were gradually increased later. The frequency and centrality of Chinese key words such as , , were high in 235 literature in China National Knowledge Internet database, and the frequency and centrality of key words such as burn, coagulation, and deep vein thrombosis were high in 340 literature in the core collection of Web of Science database. In China National Knowledge Internet database, the top 6 Chinese key words in terms of burst intensity were , , , , , , and the first 3 among which were burst key words in the early stage; and in the core collection of Web of Science database, the key words with higher burst intensity were disseminated intravascular coagulation and pulmonary embolism, which were the burst key words in the early stage. The representative clustering labels in China National Knowledge Internet database were #0 , #1 , and #2 , etc., and the representative clustering labels in the core collection of Web of Science database were #0 risk, #1 surgical patient, and #2 sepsis. Early researches in China National Knowledge Internet database and the core collection of Web of Science database focused on the presence of burn-related coagulation dysfunction itself, while the late researches focused on the relationship between burn-related coagulation dysfunction and inflammation, immunity, coagulation in general, and wounds. From 2010 onwards, there were a large number of core cited literature in the core collection of Web of Science database, and the prevention and treatment of vein thromboembolism was the most popular research direction in recent years. The researches on optimization and standardization of diagnostic methods and the overall mechanism of burn-related coagulation dysfunction would be the main research directions in the future. Conclusions: The research hotspots and evolution processes of burn-related coagulation dysfunction at home and abroad have both similarities and differences, and the current research hotspot is the relationship between coagulation and inflammation, immunity. With researches increasingly deepening, the researches on optimization and standardization of diagnostic methods and the overall mechanism of burn-related coagulation dysfunction will be the main research directions in the future.
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Trastornos de la Coagulación Sanguínea , Quemaduras , Humanos , Inflamación , Quemaduras/complicaciones , Bibliometría , ChinaRESUMEN
Immune activation is one of the major factors of secondary injury post burn, and is the main organismal response in the anti-infection process. As an important part of the innate immune response, the complement system is able to induce the activation of immune cells after burns, promote inflammation and mediate the breakdown of the immune barrier, and even engage in complex cross-linking with the coagulation cascade. This article reviews the role of complement system activation in post-burn immunity and its possibility of clinical translation from the perspectives of innate immunity, acquired immunity, and cross-linking of the complement system with the coagulation cascade.
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Activación de Complemento , Inflamación , Humanos , Activación de Complemento/fisiología , Coagulación SanguíneaRESUMEN
Objective: To explore the effects and mechanism of annexin A1 (ANXA1)-overexpressing human adipose-derived mesenchymal stem cells (AMSCs) in the treatment of mice with acute respiratory distress syndrome (ARDS). Methods: The experimental study method was adopted. After the adult AMSCs were identified by flow cytometry, the 3rd passage cells were selected for the follow-up experiments. According to the random number table (the same grouping method below), the cells were divided into ANXA1-overexpressing group transfected with plasmid containing RNA sequences of ANXA1 gene and no-load control group transfected with the corresponding no-load plasmid. The other cells were divided into ANXA1-knockdown group transfected with plasmid containing small interfering RNA sequences of ANXA1 gene and no-load control group transfected with the corresponding no-load plasmid. At post transfection hour (PTH) 72, the fluorescence expression was observed under a fluorescence microscope imaging system, and the protein and mRNA expressions of ANXA1 were detected by Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction respectively (with the sample numbers being 3). Fifty male C57BL/6J mice aged 6-8 weeks were divided into sham injury group, ARDS alone group, normal cell group, ANXA1-overexpressing group, and ANXA1-knockdown group, with 10 mice in each group. Mice in the last 4 groups were treated with endotoxin/lipopolysaccharide to make ARDS lung injury model, and mice in sham injury group were simulated to cause false injury. Immediately after injury, mice in sham injury group and ARDS alone group were injected with normal saline through the tail vein, while mice in normal cell group, ANXA1-overexpressing group, and ANXA1-knockdown group were injected with normal AMSCs, ANXA1-overexpressing AMSCs, and ANXA1-knockdown AMSCs, correspondingly. At post injection hour (PIH) 24, 5 mice in each group were selected, the Evans blue staining was performed to observe the gross staining of the right lung tissue, and the absorbance value of bronchoalveolar lavage fluid (BALF) supernatant of left lung was detected by microplate reader to evaluate the pulmonary vascular permeability. Three days after injection, the remaining 5 mice in each group were taken, the right lung tissue was collected for hematoxylin-eosin staining to observe the pathological changes and immunohistochemical staining to observe the CD11b and F4/80 positive macrophages, and the levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-1ß in BALF supernatant of left lung were determined by enzyme-linked immunosorbent assay. Data were statistically analyzed with paired sample t test, one-way analysis of variance, and least significant difference test. Results: At PTH 72, AMSCs in both ANXA1-overexpressing group and ANXA1-knockdown group expressed higher fluorescence intensity than AMSCs in corresponding no-load control group, respectively. At PTH 72, compared with those in corresponding no-load control group, the protein and mRNA expressions of ANXA1 in ANXA1-overexpressing group were significantly increased (wth t values of 249.80 and 6.56, respectively, P<0.05), while the protein and mRNA expressions of ANXA1 in ANXA1-knockdown group were significantly decreased (wth t values of 176.50 and 18.18, respectively, P<0.05). At PIH 24, compared with those in sham injury group (with the absorbance value of BALF supernatant being 0.041±0.009), the lung tissue of mice in ARDS alone group was obviously blue-stained and the absorbance value of BALF supernatant (0.126±0.022) was significantly increased (P<0.05). Compared with those in ARDS alone group, the degree of blue-staining in lung tissue of mice was significantly reduced in normal cell group or ANXA1-overexpressing group, and the absorbance values of BALF supernatant (0.095±0.020 and 0.069±0.015) were significantly decreased (P<0.05), but the degree of blue-staining in lung tissue and the absorbance value of BALF supernatant (0.109±0.016, P>0.05) of mice in ANXA1-knockdown group had no significant change. Compared with that in normal cell group, the absorbance value of BALF supernatant of mice in ANXA1-overexpressing group was significantly decreased (P<0.05). Three days after injection, the lung tissue structure of mice in ARDS alone group was significantly damaged compared with that in sham injury group. Compared with those in ARDS alone group, hemorrhage, infiltration of inflammatory cells, alveolar collapse, and interstitial widening in the lung tissue of mice were significantly alleviated in normal cell group and ANXA1-overexpressing group, while no significant improvement of above-mentioned lung tissue manifestation was observed in ANXA1-knockdown group. Three days after injection, the numbers of CD11b and F4/80 positive macrophages in the lung tissue of mice in ARDS alone group were significantly increased compared with those in sham injury group. Compared with those in ARDS alone group, the numbers of CD11b and F4/80 positive macrophages in lung tissue of mice in normal cell group, ANXA1-overexpressing group, and ANXA1-knockdown group reduced, with the most significant reduction in ANXA1-overexpressing group. Three days after injection, compared with those in sham injury group, the levels of TNF-α, IL-6, and IL-1ß in BALF supernatant of mice in ARDS alone group were significantly increased (P<0.05). Compared with those in ARDS alone group, the levels of TNF-α, IL-6, and IL-1ß in BALF supernatant of mice in normal cell group and ANXA1-overexpressing group, as well as the level of IL-1ß in BALF supernatant of mice in ANXA1-knockdown group were significantly decreased (P<0.05). Compared with that in normal cell group, the level of TNF-α in BALF supernatant of mice was significantly decreased in ANXA1-overexpressing group (P<0.05) but significantly increased in ANXA1-knockdown group (P<0.05). Conclusions: Overexpression of ANXA1 can optimize the efficacy of AMSCs in treating ARDS and enhance the effects of these cells in inhibiting inflammatory response and improving pulmonary vascular permeability, thereby alleviating lung injury of mice with ARDS.
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Anexina A1 , Lesión Pulmonar , Células Madre Mesenquimatosas , Síndrome de Dificultad Respiratoria , Ratas , Ratones , Humanos , Masculino , Animales , Ratas Sprague-Dawley , Anexina A1/genética , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6 , Ratones Endogámicos C57BL , Síndrome de Dificultad Respiratoria/terapia , Células Madre Mesenquimatosas/metabolismo , ARN MensajeroRESUMEN
AIMS: To build machine learning-based radiomics models to discriminate between high- (HGGs) and low-grade gliomas (LGGs) and to compare the effectiveness of three-dimensional arterial spin labelling (3D-ASL) to evaluate which is a better method. MATERIALS AND METHODS: We retrospectively analysed the magnetic resonance imaging T1WI-enhanced images of 105 patients with gliomas that were pathologically confirmed in our hospital. We divided the patients into a training group and a verification group at a ratio of 8:2; 200 patients from the Brain Tumour Segmentation Challenge 2020 were selected as the test group for image segmentation, feature extraction and screening. We constructed models using multilayer perceptron (MLP), support vector machine, random forest and logistic regression and evaluated their predictive performance. We obtained the mean maximum relative cerebral blood flow (rCBFmax) value from 3D-ASL of 105 patients from the hospital to evaluate its efficacy in discriminating between HGGs and LGGs. RESULTS: In machine learning, the MLP classifier model exhibited the best performance in discriminating between HGGs and LGGs; the areas under the curve obtained by MLP and rCBFmax were 0.968 versus 0.815 (verification group) and 0.981 versus 0.815 (test group), respectively. The machine learning-based MLP classifier model performed better in discriminating between HGGs and LGGs than 3D-ASL. CONCLUSION: In our study, we found that machine learning-based radiomics models and 3D-ASL were valuable in discriminating between HGGs and LGGs and between them, the machine learning-based MLP model had better diagnostic performance.
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BACKGROUND: The prognosis of natural killer/T cell lymphoma (NKTCL) with multifocal small intestine involvement complicated by intestinal perforation is extremely poor. There is no evidence-based treatment strategy for this intractable condition. CASE PRESENTATION: A 30-year-old male was admitted to our hospital in April 2017 and presented with recurrent fever for three months and multiple painless subcutaneous nodules in the abdominal wall. An excision biopsy of the subcutaneous nodules in the abdominal wall revealed NKTCL. The patient was diagnosed with stage IVB NKTCL with skin and multifocal small intestinal involvement according to the imaging results. The first intestinal perforation occurred due to tumor infiltration before the initial treatment. The second intestinal perforation occurred after receiving two cycles of chemotherapy with a modified SMILE regimen. The histone deacetylase inhibitor (HDACi) chidamide was administered as a single-agent therapy after recovery from the second intestinal perforation. Complete remission was achieved. Unfortunately, five months later, the patient was confirmed to have relapsed and received the salvage chemotherapy. The patient suffered from disease progression again after the fourth cycle of chemotherapy. At this point, from May 29, 2018, the patient started to receive injections of the anti-programmed death 1 (PD-1) antibody camrelizumab as a salvage treatment. Two months after the initial anti-PD-1 antibody camrelizumab injection, the response was partial remission. Disease progression was confirmed in March 2021, with a progression-free survival time of 34 months. CONCLUSIONS: NKTCL patients with multifocal small intestine involvement have a high risk of intestinal perforation. The possible etiologies of bowel perforation include tumor infiltration, tumor necrosis in response to therapy, and acute inflammation. The anti-PD-1 antibody camrelizumab may be a new candidate agent for treating this type of intractable NKTCL. Further observations are necessary to identify the efficacy and safety of new agents in the future.
Asunto(s)
Perforación Intestinal , Linfoma de Células T , Linfoma , Masculino , Humanos , Adulto , Perforación Intestinal/tratamiento farmacológico , Progresión de la Enfermedad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: There is an increasing number of transradial approach (TRA) for carotid artery stenting (CAS), however, similar techniques and materials as for femoral access are used. We report the results of TRA lower profile technique for CAS using a 7 F Simmons guiding catheter, especially in terms of feasibility and procedural safety in a single center. MATERIALS AND METHODS: We retrospectively analyzed 68 consecutive patients with symptomatic extracranial carotid stenoses who underwent 75 CAS between January 2018 and December 2021. The success and crossover rate, procedural time, fluoroscopy, clinical outcomes, technical considerations, and procedural complications were analyzed. RESULTS: TRA CAS with Simmons guiding catheter was successful in 67/75 (89.3%) cases, with a 7 (9.3%) crossover rate. Fluoroscopy mean time was 15.8â minutes. Two forearm hematomas were described. No ischemic or surgical site complications were reported. CONCLUSIONS: In our experience frontline TRA with a 7 F Simmons guiding catheter is feasible with high procedural success and a low rate of access site complications.
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To explore the relationship between the early or delayed age at natural menopause and metabolic syndrome (MS) in women. A total of 4 734 natural menopausal women who completed the baseline survey from November 2017 to January 2020 in the Guangzhou Middle-aged and Elderly Chronic Disease Prospective Cohort Study were selected in this cross-sectional study. Data on general demographic characteristics, disease history and female physiological health indicators were collected. Logistic regression model and restricted cubic spline curve were used to analyze the relationship between the age at natural menopause and MS. The results showed that the mean age of the subjects was (60±6) years old. The median (Q1,Q3) age at natural menopause was 50 (49, 52) years old, and the prevalence of MS was 14.8%(699/4 734). After adjusting for confounders, the age at natural menopause was closely related to MS in an approximate"U"shape. Compared with the group of normal age at natural menopause, the early age at menopause (OR=1.52, 95%CI: 1.12-2.06) and delayed age at menopause (OR=1.77, 95%CI: 1.36-2.30) had a higher risk of MS. In the group with time since menopause ≤6 years and 7-9 years, the risk of MS in the group with delayed age at menopause was 2.40 times (95%CI: 1.54-3.75) and 2.19 times (95%CI: 1.11-4.31) higher than that in the group with normal menopausal age, respectively. In conclusion, the early and delayed age at natural menopause increased the risk of MS. The increased risk of MS in delayed age at natural menopause mainly occurred within 10 years since menopause.