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1.
Arq. bras. cardiol ; 116(5): 959-967, nov. 2021. tab
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1248915

RESUMO

Resumo Fundamento: Para pacientes com infarto do miocárdio com elevação do segmento ST (IAMCST) que sofrem de obstrução coronariana microvascular funcional e estrutural (OCM) subsequente, nenhuma abordagem terapêutica específica e definitiva de atenuação foi comprovada como válida em testes de larga escala atuais, o que destaca a necessidade de abordar seu reconhecimento precoce. Objetivos: Este estudo teve como objetivo comparar o desempenho de dois escores de risco clínico com uma medida objetiva de OCM durante intervenção coronária percutânea (ICP) em casos de IAMCST Métodos: A medição do índice de resistência microcirculatória (IRM) foi realizada e os parâmetros clínicos e angiográficos basais também foram registrados. Os pacientes foram divididos em entre os grupos OM (obstrução microvascular) e NOM (não-obstrução microvascular), de acordo com o valor de IRM pós-procedimento. O risco de OCM foi avaliado para todos os participantes pelos escores preditivos SAK e ATI, respectivamente. Cada sistema foi calculado somando-se as pontuações de todas as variáveis. As curvas de características do operador receptor (ROC) e a área sob a curva (AUC) de dois modelos de risco foram utilizadas para avaliar o desempenho discriminatório. Um ecocardiograma foi realizado sete dias após o procedimento para avaliar a fração de ejeção do ventrículo esquerdo (FEVE). Um valor P bicaudal de <0,05 foi considerado estatisticamente significativo. Resultados: Entre os 65 pacientes elegíveis com IAMCST, 48 foram alocados no grupo NOM e 17 no grupo OM, com uma incidência de OCM de 26,15%. Não houve diferença significativa na AUC entre os dois escores. A FEVE avaliada para o grupo NOM foi maior do que para o grupo OM. Conclusão: Os escores SAK e ATI tiveram bom desempenho para estimar o risco de OCM após ICP primário para pacientes com IAMCST.


Abstract Background: For patients with ST-segment elevation myocardial infarction (STEMI) that are suffering from subsequent coronary microvascular functional and structural obstruction (CMVO), no specific and definitive therapeutic approaches of attenuation have been proven valid in up-to-date large-scale tests, which highlights the urge to address its early recognition. Objectives: This study aimed to compare the performance of two clinical risk scores with an objective measurement of CMVO during percutaneous coronary intervention (PCI) with STEMI. Methods: The Index of Microcirculatory Resistance (IMR) measurement was conducted and the baseline clinical and angiographic parameters were also recorded. The patients were divided into MO (Microvascular obstruction) or NMO (Non-microvascular obstruction) groups according to the post-procedure IMR value. The CMVO risk was evaluated for all participants by SAK and ATI predictive scores, respectively. Each system was calculated by summing the scores of all variables. The receiver operator characteristic (ROC) curves and the area under the curve (AUC) of two risk models were used to evaluate the discriminatory performance. An echocardiography was performed seven days after the procedure to evaluate left ventricular ejection fraction (LVEF). A two-sided P-value of <0.05 was considered statistically significant. Results: Among the 65 eligible STEMI patients, 48 patients were allocated in the NMO group and 17 in the MO group, with a CMVO incidence of 26.15%. There was no significant difference in the AUC between both scores. The LVEF evaluated for the NMO group was higher than that of MO group. Conclusion: Both SAK and ATI scores performed well in estimating CMVO risk after primary PCI for STEMI patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34595847

RESUMO

OBJECTIVE: Native American (NA) populations have higher rates of rheumatic disease and present with overlapping disease symptoms and nontraditional serological features, thus presenting an urgent need for better biomarkers in NA diagnostics. This study utilized a machine-learning approach to identify immune signatures that more effectively stratify NA rheumatic disease patients. METHODS: Adult NA patients with autoantibody-positive (AAB+) rheumatoid arthritis (RA) (n=28), autoantibody negative (AAB-) RA (n=18), systemic autoimmune rheumatic disease (n=28), arthralgia/osteoarthritis (n=28), polyarthritis/undifferentiated connective tissue disease (n=28), and controls (n=28) provided serum samples for cytokine, chemokine, and autoantibody assessment. Random Forest clustering and soluble mediator groups were used to identify patients and controls with similar biologic signatures. ACR criteria specific for systemic disease and RA identified differences in disease manifestations across clusters. RESULTS: Serum soluble mediators were not homogenous between different NA rheumatic disease diagnostic groups reflecting the heterogeneity of autoimmune diseases. Clustering by serum biomarkers created five analogous immune phenotypes. Soluble mediators and pathways associated with chronic inflammation and involvement of the innate, B cell, Tfh cell, and IFN-associated pathways, along with regulatory signatures, distinguished the five immune signatures among patients. Select clinical features were associated with individual immune profiles. Subjects with low inflammatory and higher regulatory signatures were more likely to have few clinical manifestations, whereas those with T cell pathway involvement had more arthritis. CONCLUSION: Serum protein signatures distinguished NA rheumatic disease patients into distinct immune subsets. Following these immune profiles over time may assist with earlier diagnoses and help guide more personalized treatment approaches.

3.
J Orthop Trauma ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34629391

RESUMO

OBJECTIVES: To characterize the location and frequency of the fracture lines and comminution zones of both-column fractures using fracture mapping. METHODS: Both-column fractures were retrospectively reviewed in four Level-I trauma centers. Mimics software was used to reconstruct the both-column fractures and simulate the fracture reduction. Then, the fracture lines and the intra- and extra-articular comminution zones were drawn on a 3-D innominate bone template. The distribution of fracture lines and fracture fragments were also be mapped on the 2-D template of the acetabulum. All the included patients were divided into low- and high-variety group according to the anterior column fracture line above or below the anterior superior spine. The anatomical characteristics of the posterior wall fragment were also analyzed in these two groups. RESULTS: Seventy-eight both-column fracture patients were included. The "T" type or inverted "Y" type main fracture lines divided the innominate bone into low-variety (n=11) and high-variety (n=67) both-column fractures. The extra-articular comminution zones are usually distributed between the posterior iliac fragment and anterior column fragment. High-variety-type both-column fractures are usually combined with "high" and "sharp" posterior wall fragments, while low-variety-type both-column fractures are usually accompanied by "low" and "flat" posterior wall fragments. The comminution zones in the acetabulum are mostly concentrated in the anterior and inferior parts of the acetabulum. CONCLUSIONS: The innominate bone is divided into three major parts in the both-column fracture, and the fracture center is located at the proximal of the acetabular dome. The both-column fractures are divided into low- and high-variety patterns. The location of the anterior column fracture determined the characteristics of the posterior wall fragment.

4.
Front Immunol ; 12: 747076, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603334

RESUMO

Objectives: To elucidate heterogeneity of IgG4-related disease (IgG4-RD) based on B cell immunophenotyping. Methods: Immunophenotyping of 4 B-cell subsets in peripheral blood from patients with active IgG4-RD (aIgG4-RD, n=105) was performed using flow cytometry to get preliminary B-cell heterogeneity spectrum. Then 10 B-cell subsets were characterized in aIgG4-RD (n = 49), remissive IgG4-RD (rIgG4-RD, n = 49), and healthy controls (HCs, n = 47), followed by principal components analysis (PCA) and cluster analysis to distinguish B-cell immunophenotypes and classify IgG4-RD patients into subgroups. Results: Cluster analysis identified two endotypes in 105 aIgG4-RD patients based on 4 B-cell subsets: Group1 with higher Breg and naive B cells (n = 48), and Group2 with higher plasmablasts and memory B cells (MBCs) (n = 57). PCA indicated that aIgG4-RD consisted of plasmablast-naive B cell and MBCs-Breg axes abnormalities. There was a negative relationship between naive B cells and disease activity. Both plasmablasts and MBCs were positively associated with serological biomarkers. Cluster analysis stratified aIgG4-RD patients into 3 subgroups based on 10 B-cell subsets: subgroup1 with low MBCs and normal Breg, subgroup2 with high MBCs and low Breg, and subgroup3 with high plasmablasts and low naive B cells. Patients in subroup2 and subgroup3 were more likely to be resistant to treatment. Conclusion: Patients with aIgG4-RD can be divided into 3 subgroups based on B cell heterogeneity. The B cell immunophenotyping could help elucidate the pathogenesis of IgG4-RD, identify patients with potential refractory IgG4-RD, and provide important information for the development of new therapies.

5.
Int J Radiat Biol ; : 1-24, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597214

RESUMO

PURPOSE: This research compared differences of dosimetric and biological parameters between PET/CT-guided isotoxic SIB-IMRT plans and conventional radiotherapy plans for patients with LA-NSCLC, and it also evaluated the factors that affect dose escalation. MATERIALS AND METHODS: This study consisted of a retrospective cohort of thirty patients with IIIA-IIIB NSCLC. SIB-IMRT (Plan_iso) and conventional radiotherapy (Plan_primary) plans were generated using auto-planning. Dosimetric parameters such as mean lung dose (MLD) and other indicators were compared. Tumor control probability (TCP) of PTV and normal tissue complication probability (NTCP) of total lung, heart, esophagus and spinal cord were calculated. The relationships between dose escalation and 3D length of PTV and other factors were analyzed. Paired-samples t-test, Mann-Whitney U test, and Chi-Square test were performed for comparisons between datasets. A P < 0.05 was considered statistically significant. RESULTS: The dosimetric parameters of PTV in Plan_iso were higher than those of PTV in Plan_primary, and there were significant differences (p < 0.05). Compared with Plan_primary, Plan_iso slightly increased dosimetric parameters of total lung, heart, spinal cord, esophagus and MUs. The absolute differences were small. TCPs of PTV in Plan_iso were significantly higher than those in Plan_primary. NTCPs of total lung, esophagus and spinal cord in Plan_iso were higher than those in Plan_primary. There were significant differences, but the absolute differences were small. NTCP of heart in Plan_iso was slightly higher than that in Plan_primary, but there was no statistical difference. CONCLUSIONS: For LA-NSCLC, the SIB based on isotoxic radiotherapy can significantly increase TCP under the premise that the toxicity of OARs is comparable.

6.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(5): 524-530, 2021 Oct 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34636199

RESUMO

OBJECTIVES: To compare the effects of different irradiators on the establishment of osteoradionecrosis of jaw model (ORNJ) to explore an ideal modeling method. METHODS: A total of 33 adult SD rats were included and randomly divided into three groups according to the radiation equipment, namely, the blank control (CN, 3 rats), group A (linear accelerator irradiation, 15 rats), and group B (small-animal irradiator irradiation, 15 rats). Groups A and B were irradiated with daily fractions of 7, 8, and 9 Gy for 5 days and further divided into three subgroups as follows: group A35/B35, 35 Gy; group A40/B40, 40 Gy; and group A45/B45, 45 Gy. The left mandibular molars of the rats were extracted 1 week after irradiation. The rats were sacrificed 3 weeks after tooth extraction, and the mandible specimens were obtained for gross observation, micro-CT scanning, and histological detection to evaluate the success rate of modeling. RESULTS: At 3 weeks after dental extractions, complete gingival healing was found in the regions of dental extractions in groups A35 and A40. However, failed gingival healing and bone exposure were found in groups A45 and B. Hematoxylin and eosin staining showed necrotic bone of the irradiated mandible in groups A40, A45,and B, with success modeling rates of 40% in group A and 93.3% in group B. CONCLUSIONS: Small-animal irradiator irradiation is an ideal device for establishing ORNJ model.


Assuntos
Osteorradionecrose , Animais , Mandíbula , Dente Molar , Osteorradionecrose/etiologia , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-X
7.
Invest Ophthalmol Vis Sci ; 62(13): 11, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34643663

RESUMO

Purpose: This exploratory study aimed to investigate the morphological and pathological alterations of the meibomian gland (MG) with the Staphylococcus aureus crude extracts (SACEs) treatment. Methods: Mouse MG explants were cultured and differentiated with or without SACEs for 48 hours. Explant's viability and cell death were determined by thiazolyl blue tetrazolium bromide (MTT) assay and TUNEL assay. MG morphology was observed by Hematoxylin and Eosin staining. Lipid droplet production was detected by Nile Red staining and LipidTox immunostaining. The pro-inflammatory cytokines were detected by ELISA. The relative gene and protein expression in MG explants was determined via quantitative RT-PCR, immunostaining, and immunoblotting. The components of the SACEs were analyzed by immunoblotting and silver staining. Results: Our findings demonstrated that the SACEs treatment induced overexpression of keratin 1 (Krt1) in the ducts and acini of MG explants, accompanied by a decrease in viability and an increase in cell death in explants. Furthermore, the SACEs treatment dose-dependently increased the levels of TNF-α, IL-1ß, and IL-6 in MG explants. The SACEs treatment induced activation of the nuclear factor kappa B (NF-κB) and AIM2 (absent in melanoma 2)/ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) inflammasome signaling pathway in explants. Further investigation showed expression of the key adipogenesis-related molecule peroxisome proliferator-activated receptor γ was decreased after SACEs treatment. However, no change was found in the lipid synthesis of MG explants after treatment with the SACEs. Staphylococcal enterotoxins B (SEB) was detected in the SACEs. SEB induced the overexpression of Krt1 and IL-1ß in ducts and acini of MG explants. Conclusions: Our findings confirm that Staphylococcus aureus induced hyperkeratinization and pro-inflammatory cytokines expression in MG explants ducts and acini. These effects might be mediated by SEB. Activation of the NF-κB and AIM2/ASC signaling pathway is involved in this process.

8.
Clin Lung Cancer ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34645582

RESUMO

BACKGROUND: Pleural effusion (PE) has been one of the promising sources of liquid biopsy in advanced lung cancer patients. However, its clinical utility is not widely accepted due to the lack of full estimation of its potential versus routine clinical samples. METHOD: A total of 164 advanced lung cancer patients were enrolled with 164 matched tumor tissue and PE-cfDNA, 153 accompanied plasma and 63 1PE-sDNA. RESULT: PE-cfDNA displayed significantly higher median mutant allele frequency and an overall mutation concordance rate of 65% to tissue, which was higher than PE-sDNA (43%) and plasma-cfDNA (43%). The discrepancies between PE-cfDNA and tumor tissue were high in several genes, including SMARCA4, PIK3CA, ERBB2, KM T2A, ALK and NF1. For clinically actionable mutations, the concordance rate between PE-cfDNA and tumor tissue is 87%. Eleven patients were identified with actionable mutations in PE-cfDNA and four patients benefited from PE-cfDNA-guided targeted. Meanwhile, PE-cfDNA recapitulated mutations of diverse tissue origins and provided more mutational information under the circumstance that tumor tissue or tumor tissue of different origins were unavailable. The combination of tumor tissue and PE-cfDNA profiling increased positive detection rates of patients compared to tumor tissue alone. Our finding highlighted the importance of PE-cfDNA in the optimal selection of patients for targeted therapy. CONCLUSION: The PE-cfDNA-based liquid biopsy displays better performance in the characterization of gene alterations than PE-sDNA and plasma-cfDNA. PE-cfDNA together with tumor tissue profiling optimizes comprehensively genomic profiling of lung cancer patients, which might be important for selecting patients for better treatment management.

9.
Front Public Health ; 9: 764364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650957

RESUMO

This paper employs data from the 2016 and 2018 China Family Panel Studies (CFPS) to study the impact of participation in Urban and Rural Resident Basic Medical Insurance (URRBMI) on children's educational outcomes by using the logit model, double selection Lasso model, and propensity score matching. It is found that participating in URRBMI has no significant effect on children's Chinese performance, but has a significant negative effect on children's mathematics performance. The negative effect is more obvious for children who participating in the New Cooperative Medical Scheme (NCMS). The paper also studies the channel effects of participation in URRBMI on children's educational outcomes trough two different ways. It is noticed that both channel effects are not significant, that is, participation in URRBMI neither improves children's health nor changes household education expenditures.

10.
Am J Gastroenterol ; 116(9): 1924-1928, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465694

RESUMO

INTRODUCTION: We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis. METHODS: Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs). RESULTS: Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment. DISCUSSION: Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C/tratamento farmacológico , Falência Renal Crônica/terapia , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Esquema de Medicação , Feminino , Fluorenos/administração & dosagem , Hepatite C/complicações , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Sofosbuvir/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento
11.
Org Biomol Chem ; 19(36): 7867-7874, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34492676

RESUMO

A visible light mediated stereospecific C(sp2)-H difluoroalkylation of (Z)-aldoximes to (E)-difluoroalkylated ketoximes has been described. In this reaction, (hetero)-aromatic and aliphatic difluoroalkylated ketoximes could be obtained with the retention of the configuration of the starting aldoximes. A preliminary mechanism study showed that a difluoromethyl radical via an SET pathway was involved.

12.
Eur J Prev Cardiol ; 28(11): 1229-1234, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34551078

RESUMO

BACKGROUND: Death of the spouse in middle and old age is associated with an increased risk of cardiovascular and total mortality, particularly during the months after the loss. Knowledge regarding the effect of bereavement on prognosis in acute myocardial infarction (AMI) is limited. We analysed whether bereavement the year before the AMI is associated with prognosis. METHODS: We studied first AMI patients who participated in the Stockholm Heart Epidemiology Program (N = 1732). During or shortly after the hospitalization, patients or their family members completed a questionnaire regarding bereavement, sociodemographic, clinical and lifestyle factors; five months after their first infarction, surviving patients attended a clinical examination. Participants were followed for cardiovascular events and mortality for a median of 14 years. RESULTS: Overall bereavement, that is, death of a close friend or family member (including spouse/partner), the year before the first AMI was not associated with the combined outcome of non-fatal recurrent AMI and death due to ischaemic heart diseases. However, exposure to the loss of the spouse/partner was associated with an increased risk of the outcome (adjusted hazard ratio and (95% confidence interval): 1.55 (1.06-2.27)). We found no evidence that psychiatric disorders or blood lipids, glucose, coagulation and inflammatory markers mediated this association. CONCLUSIONS: Loss of spouse/partner the year before the first AMI was associated with an increased risk of the combination of non-fatal recurrent AMI and death due to ischaemic heart disease. If confirmed by others, the findings may be informative for tertiary prevention of AMI.

13.
Med Dosim ; 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34551878

RESUMO

To evaluate the dosimetric effect of intensity-modulated radiation therapy (IMRT) for postoperative non-small cell lung cancer (NSCLC), with and without the air cavity in the planning target volume (PTV). Two kinds of IMRT plans were made for 21 postoperative NSCLC patients. In Plan-0: PTV included the tracheal air cavity, and in Plan-1: the air cavity was subtracted from the PTV. For PTV, the dosimetric parameters, including Dmean, D98, D95, D2, D0.2, conformity index (CI), and homogeneity index (HI) were evaluated. For organs at risk (OARs), the evaluation indexes, included the V5, V20 and the mean lung dose (MLD) of total lung, the V30, V40, and the mean heart dose (MHD) of heart, the spinal cord Dmax, and the V35 and the mean esophageal dose (MED) of esophagus. The number of segments and MUs were also recorded. Additionally, the correlation between the Plan-1 dosimetric change value relative to Plan-0, the size of air cavity, and the volume proportion of the cavity in the PTV was also analyzed. The Dmean of PTV, D2, D0.2, HI and CI in Plan-1 decreased compared with those in Plan-0. For OARs, the V30, MHD, and MED also decreased. The CI change value of Plan-1 relative to Plan-0 had a significantly negative correlation with the size and the volume proportion of air cavity, and the MED change value also had a significantly negative correlation with the air cavity size. The IMRT plans for patients with postoperative NSCLC can achieve a better target dose distribution and offer an improved sparing of the heart and esophagus by removing the PTV air cavity, while reducing the target conformity. The change value of CI and MED had a significantly negative correlation with the air cavity size.

14.
BMC Musculoskelet Disord ; 22(1): 777, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34511102

RESUMO

BACKGROUND: Biomechanical studies have demonstrated that uncovertebral joint contributes to segment mobility and stability to a certain extent. Simultaneously, osteophytes arising from the uncinate process are a common cause of cervical spondylotic radiculopathy (CSR). For such patients, partial uncinatectomy (UT) may be required. However, the clinical efficacy and sagittal alignment of partial UT during anterior cervical discectomy and fusion (ACDF) have not been fully elucidated. METHODS: A total of 87 patients who had undergone single level ACDF using a zero-profile device from July 2014 to December 2018 were included. Based on whether the foraminal part of the uncovertebral joint was resected or preserved, the patients were divided into the ACDF with UT group (n = 37) and the ACDF without UT group (n = 50). Perioperative data, radiographic parameters, clinical outcomes, and complications were compared between the two groups. RESULTS: The mean follow-up was 16.86 ± 5.63 and 18.36 ± 7.51 months in the ACDF with UT group and ACDF without UT group, respectively (p > 0.05). The average preoperative VAS arm score was 5.89 ± 1.00 in the ACDF with UT group and 5.18 ± 1.21 in the ACDF without UT group (p = 0.038). However, the average VAS arm score was 4.22 ± 0.64, 4.06 ± 1.13 and 1.68 ± 0.71, 1.60 ± 0.70 at 1 week post operation and at final follow up, respectively, (p > 0.05). We also found that the C2-7 SVA and St-SVA at the last follow-up and their change (last follow-up value - preoperative value) in the ACDF with UT group were significantly higher than ACDF without UT group (p < 0.05). No marked differences in the other cervical sagittal parameters, fusion rate or complications, including dysphagia, ASD, and subsidence, were observed. CONCLUSIONS: Our result indicates that ACDF using a zero-p implant with or without partial UT both provide satisfactory clinical efficacy and acceptable safety. However, additional partial UT may has a negative effect on cervical sagittal alignment.


Assuntos
Radiculopatia , Fusão Vertebral , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Seguimentos , Humanos , Radiculopatia/diagnóstico por imagem , Radiculopatia/cirurgia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
15.
J Formos Med Assoc ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34538552

RESUMO

BACKGROUND/PURPOSE: Direct-acting antiviral agents (DAAs) have revolutionized the paradigm for HCV treatment. However, patients with HBV and HCV co-infection receiving DAAs are at significant risk of HBV reactivation, with limited literature addressing the roles of serum chemokines/chemokines. We aimed to explore the profiles and predictive value of serum cytokines/chemokines regarding HBV reactivation in this clinical setting. METHODS: From 2017 to 2019, 25 patients with HBV and HCV co-infection scheduled for DAA therapy were prospectively enrolled. At enrolment and after DAA treatment, serial serum cytokine/chemokine levels were examined. The baseline and dynamic levels were compared between those with versus without HBV virologic (defined by an increase of serum HBV DNA to >10 times) and clinical reactivation (defined by > 1.5-fold elevated ALT level than nadir and >100 U/L; or > 2-fold increase from nadir and greater than the upper normal limit, in addition to virologic reactivation). RESULTS: There were 20 patients (80%) experiencing HBV virologic reactivation and 6 patients (24%) experiencing clinical reactivation. Patients with clinical reactivation had higher pre-treatment TNF-alpha (27.93 versus 18.85 pg/mL, P = 0.015), lower week-4 IFN-gamma (1.07 versus 8.74 pg/mL, P = 0.020) levels and significant declines of CCL2 and TNF-alpha (P < 0.05). Single or combination of these cytokines helped predict clinical reactivation (all P < 0.05). CONCLUSION: Higher serum TNF-alpha at baseline and lower IFN-gamma at week 4 were associated with mild clinical reactivation of HBV in patients with HBV/HCV co-infection receiving DAAs. Combination of these cytokines reliably predicted HBV reactivation early.

16.
Front Immunol ; 12: 720354, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539656

RESUMO

Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosa-associated invariant T (MAIT) cells are a group of innate-like T cells enriched in the intestine that can be activated by riboflavin metabolites from various microorganisms. However, little is known about the function or mechanism of action of MAIT cells in the occurrence of gut aGVHD in humans. In our study, multiparameter flow cytometry (FCM) was used to evaluate the number of MAIT cells and functional cytokines. 16S V34 region amplicon sequencing analysis was used to analyze the intestinal flora of transplant patients. In vitro stimulation and coculture assays were used to study the activation and function of MAIT cells. The number and distribution of MAIT cells in intestinal tissues were analyzed by immunofluorescence technology. Our study showed that the number and frequency of MAIT cells in infused grafts in gut aGVHD patients were lower than those in no-gut aGVHD patients. Recipients with a high number of MAITs in infused grafts had a higher abundance of intestinal flora in the early posttransplantation period (+14 days). At the onset of gut aGVHD, the number of MAIT cells decreased in peripheral blood, and the activation marker CD69, chemokine receptors CXCR3 and CXCR4, and transcription factors Rorγt and T-bet tended to increase. Furthermore, when gut aGVHD occurred, the proportion of MAIT17 was higher than that of MAIT1. The abundance of intestinal flora with non-riboflavin metabolic pathways tended to increase in gut aGVHD patients. MAIT cells secreted more granzyme B, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ under the interleukin (IL)-12/IL-18 stimulation [non-T-cell receptor (TCR) signal] and secreted most of the IL-17 under the cluster of differentiation (CD)3/CD28 stimulation (TCR signal). MAIT cells inhibited the proliferation of CD4+ T cells in vitro. In conclusion, the lower number of MAIT cells in infused grafts was related to the higher incidence of gut aGVHD, and the number of MAIT cells in grafts may affect the composition of the intestinal flora of recipients early after transplantation. The flora of the riboflavin metabolism pathway activated MAIT cells and promoted the expression of intestinal protective factors to affect the occurrence of gut aGVHD in humans.

17.
Microb Ecol ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545413

RESUMO

Nitrogen (N) and phosphorus (P) have significant effects on soil microbial community diversity, composition, and function. Also, trees of different life stages have different fertilization requirements. In this study, we designed three N additions and three P levels (5 years of experimental treatment) at two Metasequoia glyptostroboides plantations of different ages (young, 6 years old; middle mature, 24 years old) to understand how different addition levels of N and P affect the soil microbiome. Here, the N fertilization of M. glyptostroboides plantation land (5 years of experimental treatment) significantly enriched microbes (e.g., Lysobacter, Luteimonas, and Rhodanobacter) involved in nitrification, denitrification, and P-starvation response regulation, which might further lead to the decreasing in alpha diversity (especially in 6YMP soil). The P addition could impact the genes involved in inorganic P-solubilization and organic P-mineralization by increasing soil AP and TP. Moreover, the functional differences in the soil microbiomes were identified between the 6YMP and 24YMP soil. This study provides valuable information that improves our understanding on the effects of N and P input on the belowground soil microbial community and functional characteristics in plantations of different stand ages.

18.
Acad Radiol ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481706

RESUMO

RATIONALE AND OBJECTIVES: To investigate the microperfusion and water molecule diffusion alterations in sensorimotor-related areas in amyotrophic lateral sclerosis (ALS) using intravoxel incoherent motion (IVIM) magnetic resonance imaging. MATERIALS AND METHODS: IVIM data were obtained from 43 ALS patients and 31 controls. This study employed the revised ALS Functional Rating Scale (ALSFRS-R) in evaluating disease severity. IVIM-derived metrics were calculated, including diffusion coefficient (D), pseudo-diffusion coefficient, and perfusion fraction. Conventional apparent diffusion coefficient was also computed. Atlas-based analysis was conducted to detect between-group difference in these metrics in sensorimotor-related gray/white matter areas. Spearman correlation analysis was employed to establish correlation between various metrics and ALSFRS-R. RESULTS: ALS patients had perfusion fraction (× 10-3) reduction in the left presupplementary motor area (60.72 ± 16.15 vs. 71.15 ± 12.98, p = 0.016), right presupplementary motor area (61.35 ± 17.02 vs. 72.18 ± 14.22, p = 0.016), left supplementary motor area (55.73 ± 12.29 vs. 64.12 ± 9.17, p = 0.015), and right supplementary motor area (56.53 ± 11.93 vs. 63.67 ± 10.03, p = 0.020). Patients showed D (× 10-6 mm2/s) increase in a white matter tract projecting to the right ventral premotor cortex (714.20 ± 39.75 vs. 691.01 ± 24.53, p = 0.034). A negative correlation between D of right ventral premotor cortex tract and ALSFRS-R score was observed (r = -0.316, p = 0.039). CONCLUSION: These findings suggest aberrant microperfusion and water molecule diffusion in the sensorimotor-related areas in ALS patients, which are associated with motor impairment in ALS.

19.
J Clin Nurs ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570940

RESUMO

AIMS AND OBJECTIVE: To explore the experiences of frontline nurses through analyzing nurse online diaries during the pandemic. BACKGROUND: Over 42,600 healthcare professionals took care of patients with COVID-19 in Wuhan in the initial months between 23 January 2020 and 8 April 2020. Many used to write online diaries on Sina Microblog and still wrote about their experiences in the front line on this site. However, there has been little research on frontline nurses' experiences in the initial months of the pandemic through analyzing their narratives. DESIGN: A qualitative descriptive design. METHODS: A qualitative content analysis was used to analyze online diaries written by frontline nurses in Wuhan. A total of 205 entries in online diaries were collected from 12 frontline nurses, as accessible to those who subscribed to Sina Microblog social media site, between 23 January 2020 and 8 April 2020. NVivo12 was used to help analyze the data, and COREQ reporting guidelines were also used in this study. RESULTS: Two themes were identified: constructing a better self and constructing a strong support network. A better self was constructed in describing positive emotions, commitment to care, pride and achievements, and whole-person growth. A strong support network was constructed through social support via different sources and gaining self-support via narrating their personal experiences in diaries. CONCLUSIONS: Frontline nurses demonstrated personal growth, psychological well-being, and professionalism in the process of constructing a better self and a strong support network. RELEVANCE TO CLINICAL PRACTICE: The findings indicate that frontline nurses can use narratives as debriefing opportunities and a way of gaining self-support. We suggest that online communities of professional support be used as an essential platform for sharing narratives and gaining a more comprehensive understanding of frontline nurses in the COVID-19 pandemic and other global public health events.

20.
Nat Biomed Eng ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580438

RESUMO

The preferential activation of regulatory T (Treg) cells by interleukin-2 (IL-2), which selectively binds to the trimeric IL-2 receptor (IL-2R) on Treg cells, makes this cytokine a promising therapeutic for the treatment of autoimmune diseases. However, IL-2 has a narrow therapeutic window and a short half-life. Here, we show that the pharmacokinetics and half-life of IL-2 can be substantially improved by orthogonally conjugating the cytokine to poly(ethylene glycol) (PEG) moieties via a copper-free click reaction through the incorporation of azide-bearing amino acids at defined sites. Subcutaneous injection of a PEGylated IL-2 that optimally induced sustained Treg-cell activation and expansion over a wide range of doses through highly selective binding to trimeric IL-2R led to enhanced therapeutic efficacy in mouse models of lupus, collagen-induced arthritis and graft-versus-host disease without compromising the immune defences of the host against viral infection. Site-specific PEGylation could be used more generally to engineer cytokines with improved therapeutic performance for the treatment of autoimmune diseases.

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