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1.
Front Oncol ; 14: 1376502, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628672

RESUMO

Purpose: Dysregulated expression of microRNA (miRNAs) in lung cancer has been wildly reported. The clinicopathologic significance of miR-9-5p in non-small-cell lung cancer (NSCLC) patients and its effect on NSCLC progression were explored in this study. Patients and methods: A total of 76 NSCLC patients were included. miR-9-5p expression was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Then, in vitro experiments including cell growth curve assays, colony formation assays, and transwell migration assays were performed. Further clinicopathological and prognostic values were explored using bioinformatics analysis of the TCGA database. Results: miR-9-5p expression was significantly increased in tumor tissues (both P < 0.0001). miR-9-5p expression was relatively higher in larger tumors (P = 0.0327) and in lung squamous carcinoma (LUSC) (P = 0. 0143). In addition, miR-9-5p was significantly upregulated in the normal lung tissues of cigarette smokers (P = 0.0099). In vitro, miR-9-5p was correlated with cell proliferation and migration. After that, bioinformatics analysis of the TCGA database indicated that miR-9-5p was correlated with tumor size (P = 0.0022), lymphatic metastasis (P = 0.0141), LUSC (P < 0.0001), and smoking history (P < 0.0001). Finally, a prognostic study indicated high miR-9-5p expression was correlated with poor prognosis in LUAD (P = 0.0121). Conclusion: Upregulation of miR-9-5p may have an oncogenic effect in NSCLC and may be related to smoking. The conclusion of this study may help find new prognostic and therapeutic targets for NSCLC and the exploration of the relationship between smoking and lung cancer.

2.
World J Clin Cases ; 12(1): 217-223, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38292640

RESUMO

BACKGROUND: Addison's disease (AD) is a rare but potentially fatal disease in Western countries, which can easily be misdiagnosed at an early stage. Severe adrenal tuberculosis (TB) may lead to depression in patients. CASE SUMMARY: We report a case of primary adrenal insufficiency secondary to adrenal TB with TB in the lungs and skin in a 48-year-old woman. The patient was misdiagnosed with depression because of her depressed mood. She had hyperpigmentation of the skin, nails, mouth, and lips. The final diagnosis was adrenal TB that resulted in the insufficient secretion of adrenocortical hormone. Adrenocortical hormone test, skin biopsy, T cell spot test of TB, and adrenal computed tomography scan were used to confirm the diagnosis. The patient's condition improved after hormone replacement therapy and TB treatment. CONCLUSION: Given the current status of TB in high-burden countries, outpatient doctors should be aware of and pay attention to TB and understand the early symptoms of AD.

3.
J Neuroinflammation ; 20(1): 309, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129902

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system that involves B-cell receptor signaling as well as astrocyte-microglia interaction, which both contribute to evolution of NMOSD lesions. MAIN BODY: Through transcriptomic and flow cytometry analyses, we found that Bruton's tyrosine kinase (BTK), a crucial protein of B-cell receptor was upregulated both in the blood and cerebrospinal fluid of NMOSD patients. Blockade of BTK with zanubrutinib, a highly specific BTK inhibitor, mitigated the activation and maturation of B cells and reduced production of causal aquaporin-4 (AQP4) autoantibodies. In a mouse model of NMO, we found that both BTK and pBTK expression were significantly increased in microglia. Transmission electron microscope scan demonstrated that BTK inhibitor ameliorated demyelination, edema, and axonal injury in NMO mice. In the same mice colocalization of GFAP and Iba-1 immunofluorescence indicated a noticeable increase of astrocytes-microglia interaction, which was alleviated by zanubrutinib. The smart-seq analysis demonstrated that treatment with BTK inhibitor instigated microglial transcriptome changes including downregulation of chemokine-related genes and genes involved in the top 5 biological processes related to cell adhesion and migration, which are likely responsible for the reduced crosstalk of microglia and astrocytes. CONCLUSIONS: Our results show that BTK activity is enhanced both in B cells and microglia and BTK inhibition contributes to the amelioration of NMOSD pathology. These data collectively reveal the mechanism of action of BTK inhibition and corroborate BTK as a viable therapeutic target.


Assuntos
Neuromielite Óptica , Animais , Humanos , Camundongos , Tirosina Quinase da Agamaglobulinemia/metabolismo , Aquaporina 4 , Linfócitos B/metabolismo , Microglia/metabolismo , Neuromielite Óptica/patologia , Receptores de Antígenos de Linfócitos B/metabolismo
4.
J Neuroimmunol ; 384: 578218, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37801952

RESUMO

Levels of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) are useful biomarkers of disease activity and disability in neuromyelitis optica spectrum disorder (NMOSD). Here we investigated the association of sNfL and sGFAP levels with brain and spinal cord volumes in patients with NMOSD. Fifteen patients with NMOSD were enrolled in this prospective study. The median baseline level of sNfL was 42.2 (IQR, 16.1-72.6) pg/mL and decreased to 8.5 (IQR, 7.4-16.6) pg/mL at the end of the study. The reduction in sNfL was associated with a 7.5% loss of cervical spinal cord volume (CSCV) (p = 0.001). The levels of sGFAP reduced from 239.2 (IQR, 139.0-3393.3) pg/mL at baseline to 108.5 (IQR, 74.2-154.6) pg/mL. However, there was no strong correlation between sGFAP levels and CSCV changes during the follow-up period. Our data suggested that sNfL level is a useful biomarker for predicting spinal cord atrophy in patients with NMOSD.


Assuntos
Neuromielite Óptica , Humanos , Filamentos Intermediários , Estudos Prospectivos , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Proteínas de Neurofilamentos , Biomarcadores , Atrofia/patologia
5.
J Neuroimmunol ; 382: 578167, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37536049

RESUMO

Autoreactive CD4+ helper T cells are implicated in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). Both PD-1+CXCR5+CD4+ T follicular helper (Tfh) cells and PD-1+CXCR5-CD4+ T peripheral helper (Tph) cells can contribute to B-cell immune responses and the production of antibodies. Here we show the effect of B-cell depletion with rituximab on the homeostasis of Tfh cells, Tph cells and their subsets in patients with NMOSD. After rituximab treatment, total Tph cells, total Tfh cells, Tph17 cells, Tph17.1 cells, Tph1 cells, and Tfh1 cells tended to decrease at month 1, but gradually increased at month 6 and restored at month 12. Besides, Tph17.1 cells and Tfh17.1 cells were correlated with the proportion of CD19- antibody-secreting cells. Our data suggest that rituximab induced a fluctuation of proinflammatory Tph and Tfh subsets within one year after initiation of the treatment.


Assuntos
Neuromielite Óptica , Humanos , Neuromielite Óptica/tratamento farmacológico , Células T Auxiliares Foliculares , Rituximab/farmacologia , Rituximab/uso terapêutico , Receptor de Morte Celular Programada 1 , Linfócitos T Auxiliares-Indutores
6.
J Neurol ; 270(1): 348-356, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36066625

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune disease that can cause permanent neurological disabilities. However, the interleukin-6 (IL-6) signaling pathway is a promising therapeutic target for relapse prevention. Therefore, this study evaluated the long-term effectiveness of tocilizumab, a humanized anti-IL-6 receptor antibody, for NMOSD. We enrolled 65 patients with NMOSD who received regular intravenous administration of tocilizumab (8 mg/kg) between October 2017 and January 2022. Then, we retrospectively collected data on the clinical characteristics and baseline glial fibrillary acidic protein (GFAP) and neurofilament light chain levels. The primary outcome was the annualized relapse rate (ARR). Risk factors were assessed using a multivariable logistic regression model. During the median follow-up of 34.1 (interquartile range: 25.5-39.3) months, 23% (15/65) of patients relapsed during tocilizumab treatment, but the median ARR decreased from 1.9 (range 0.12-6.29) to 0.1 (range 0-1.43, p < 0.0001). A prolonged infusion interval (> 4 weeks, odds ratio [OR]: 10.7, 95% confidence interval [CI]: 1.6-71.4, p = 0.014) and a baseline plasma GFAP level of > 220 pg/mL (OR: 20.6, 95% CI 3.3-129.4, p = 0.001) were risk factors for future relapses. During treatment, the median Expanded Disability Status Scale score significantly decreased in aquaporin-4 antibody-positive and -negative patients, but the pain did not considerably improve. There were no severe safety concerns. Tocilizumab treatment significantly reduced the relapse rate in patients with NMOSD. However, prolonged infusion intervals and high baseline plasma GFAP levels may increase the relapse risk during tocilizumab therapy.


Assuntos
Neuromielite Óptica , Humanos , Estudos Retrospectivos , Autoanticorpos , Receptores de Interleucina-6/uso terapêutico , Recidiva , Aquaporina 4
7.
Heliyon ; 8(9): e10730, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36177239

RESUMO

Familial amyloid polyneuropathy, an autosomal-dominant disease due to mutations in the transthyretin gene, often affects the heart and liver, and is treated best with a combined heart-liver transplantation (CHLT). Although it remains an uncommonly performed procedure, the number of patients undergoing CHLT is increasing. Because of the complexity associated with dual pathophysiology, CHLT poses an extraordinary challenge for anesthesia management. Either both heart and liver transplantation are performed on cardiopulmonary bypass (CPB); or heart transplantation is performed on CPB, followed by liver transplantation with venovenous bypass. Recent reports suggested that liver transplantation can be performed without bypass using the inferior vena cava-sparing technique. However, both bypass and caval sparing technique have their own complications. Here, we present the anesthesia management in a case of sequential heart-liver transplantation using a routine caval cross-clamp technique without venovenous bypass. A 48-year-old man complaining of chest tightness, chest pain, and shortness of breath was diagnosed with amyloid cardiomyopathy. Cardiac ultrasonography revealed thickening of ventricular walls and left ventricular systolic insufficiency (ejection fraction decreased from 46% to ∼20% in 6 months), which was refractory to medical therapy. Symptoms occurred repeatedly. Therefore, CHLT was planned. Heart transplantation was performed smoothly under general anesthesia and standard CPB. His heart functioned well with dobutamine and epinephrine infusion. Subsequently, the patient was weaned from CPB. Liver transplantation was planned using the piggyback procedure with the caval sparing technique. However, upon caval clamping, unexpected blood loss occurred. Clamping of the caval was tested followed by cross-clamping. Norepinephrine, epinephrine, and dobutamine were administered. After the hepatic vein was anastomosed, the clamp was released and nitroglycerin was administered. Hemodynamics was stable, and the patient was discharged after 37 days of hospitalization. The case indicates that CHLT could be performed using caval clamp without venovenous bypass in selected patients.

8.
Front Immunol ; 12: 660230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745082

RESUMO

Background: Interleukin-6 receptor blockade is effective in reducing the risk of relapses in neuromyelitis optica spectrum disorder (NMOSD). However, its efficacy during acute attacks of NMOSD remains elusive. Objective: We investigated the effects of tocilizumab on disability during acute attacks, as well as its maintenance, in patients with moderate-to-severe myelitis. Methods: Nineteen patients with NMOSD received tocilizumab treatment as add-on to high-dose methylprednisolone (HDMP) in acute myelitis and twenty-two patients who only received HDMP were compared. Disease disability was assessed using a multi-level scaling system that included the expanded disability status scale (EDSS), Hauser ambulation index (HAI), modified Rankin scale (mRS), pain numerical rating scale (NRS), functional assessment of chronic illness therapy-fatigue scale (FACIT-F), activity of daily living (ADL), EuroQol five-dimensions-three-level questionnaire (EQ-5D-3L), and sensory function score and bowel and bladder function score in Kurtzke functional systems scores (FSS). Results: Improved EDSS, HAI, and mRS, as well as increased ADL and EQ-5D-3L were significant in patients on tocilizumab compared with those on steroids as monotherapy at 3 months (p < 0.05). Both groups of patients showed improved pain, fatigue, sensory function, and autonomic function at follow-ups, compared with baseline respectively. The changes in NRS, FACIT-F, and sensory and autonomic FSS showed no significant differences between the two groups. Tocilizumab significantly lowered the risk of relapses (HR = 0.21, 95% CI 0.06-0.76, p = 0.017) and reduced the annualized relapse rate compared with those by steroids (0.1 ± 0.2 vs 0.5 ± 0.6, p = 0.013). Conclusion: Early initiation of tocilizumab provided a safe and effective add-on alternative during attacks, and its maintenance contributed to a significant reduction of relapse rate in NMOSD.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Mielite/tratamento farmacológico , Neuromielite Óptica/tratamento farmacológico , Atividades Cotidianas , Adulto , Idoso , Feminino , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Mielite/fisiopatologia , Mielite/psicologia , Neuromielite Óptica/fisiopatologia , Neuromielite Óptica/psicologia , Qualidade de Vida , Recidiva
9.
Ther Adv Neurol Disord ; 14: 17562864211054952, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777577

RESUMO

BACKGROUND: Neurofilament light chain (NfL) and glial fibrilliary acidic protein (GFAP) have been suggested to be biomarkers of the pathophysiological process of neuromyelitis optica spectrum disorders (NMOSD), but the relationship between the plasma levels of these molecules with disease activity and treatment is incompletely understood. OBJECTIVE: To investigate the treatment effects of disease-modifying drugs on plasma neurofilament light chain (pNfL) and plasma glial fibrillary acidic protein (pGFAP) and explore the predictive value of pNfL and pGFAP in the activity of NMOSD. METHODS: pNfL and pGFAP levels were measured using single-molecule arrays in 72 patients with NMOSD and 38 healthy controls (HCs). Patients with NMOSD received tocilizumab (n = 29), rituximab (n = 23), oral prednisone (n = 16), and oral azathioprine or mycophenolate mofetil (n = 4). RESULTS: NMOSD patients had significantly higher pNfL and pGFAP levels than HCs (pNfL, 18.3 (11.2-39.3) versus 11.5 (7.0-23.3) pg/mL; p = 0.001; pGFAP, 149.7 (88.6-406.5) versus 68.7 (59.4-80.8) pg/mL; p < 0.001). Multivariable regression analyses indicated that baseline pNfL concentration was associated with age (p = 0.017), Expanded Disability Status Scale (EDSS) score (p = 0.002), and recent relapses (p < 0.001). Baseline pGFAP concentration was also associated with EDSS (p < 0.001) and recent relapses (p < 0.001). Compared with prednisone, tocilizumab and rituximab significantly reduced pNfL [tocilizumab, exp(ß), 0.65; 95% confidence interval (CI), 0.56-0.75; p < 0.001; rituximab, exp(ß), 0.79; 95% CI = 0.68-0.93; p = 0.005] and pGFAP levels [tocilizumab, exp(ß), 0.64; 95% CI, 0.51-0.80; p < 0.001; rituximab, exp(ß), 0.77; 95% CI, 0.61-0.98; p = 0.041] at the end of the study. The pNfL levels in the tocilizumab and rituximab groups were reduced to those of HCs [tocilizumab, 8.5 (7.06-17.90) pg/mL; p = 0.426; rituximab, 14.0 (9.94-21.80) pg/mL; p = 0.216]. However, the pGFAP levels did not decrease to those of HCs in NMOSD patients at the end of study [tocilizumab, 88.9 (63.4-131.8) pg/mL; p = 0.012; rituximab, 141.7 (90.8-192.7) pg/mL; p < 0.001]. CONCLUSION: pNfL and pGFAP may serve as biomarkers for NMOSD disease activity and treatment effects.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34465614

RESUMO

BACKGROUND AND OBJECTIVES: To assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow in patients with NMOSD. RESULTS: Across the tissue types tested, 4 major subpopulations of B cells with distinct signatures were identified: naive B cells, memory B cells, age-associated B cells, and antibody-secreting cells (ASCs). NMOSD B cells show proinflammatory activity and increased expression of chemokine receptor genes (CXCR3 and CXCR4). Circulating B cells display an increase of antigen presentation markers (CD40 and CD83), as well as activation signatures (FOS, CD69, and JUN). In contrast, the bone marrow B-cell population contains a large ASC fraction with increased oxidative and metabolic activity reflected by COX genes and ATP synthase genes. Typically, NMOSD B cells become hyperresponsive to type I interferon, which facilitates B-cell maturation and anti-aquaporin-4 autoantibody production. The pool of ASCs in blood and CSF were significantly elevated in NMOSD. Both CD19- and CD19+ ASCs could be ablated by tocilizumab, but not rituximab treatment in NMOSD. DISCUSSION: B cells are compartmentally fine tuned toward autoreactivity in NMOSD and become hyperreactive to type I interferon. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD.


Assuntos
Linfócitos B/metabolismo , Neuromielite Óptica/metabolismo , Transcriptoma , Adulto , Aquaporina 4/imunologia , Linfócitos B/efeitos dos fármacos , Medula Óssea/metabolismo , Humanos , Fatores Imunológicos/farmacologia , Células B de Memória/efeitos dos fármacos , Células B de Memória/metabolismo , Neuromielite Óptica/sangue , Neuromielite Óptica/líquido cefalorraquidiano , Neuromielite Óptica/tratamento farmacológico , Análise de Sequência de RNA
11.
Front Immunol ; 12: 703931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394101

RESUMO

Tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, showed its therapeutic efficacy on neuromyelitis optica spectrum disorder (NMOSD). To assess the immunological effects of this drug on B cells, follicular T helper (Tfh) cells, and peripheral T helper (Tph) cells in patients with NMOSD, peripheral B cell and Tfh cell phenotypes were evaluated in 26 patients with NMOSD before and after tocilizumab treatment by nine-color flow cytometry, as well as the expression of costimulatory and co-inhibitory molecules on B cells. Results showed that the frequency of CD27+IgD- switched memory B cells, CD27-IgD- double-negative B cells, and CD27highCD38high antibody-secreting cells was increased in patients with NMOSD. Tocilizumab treatment led to a significant shift of B cells to naïve B cells from memory B cells after 3 months. Three markers on B cells associated with T-cell activation (i.e., CD86 CD69, and HLA-DR) were downregulated after tocilizumab treatment. The frequencies of total Tfh and Tph cells were decreased, whereas that of follicular regulatory T cells tended to increase. Intrinsic increased PD-L1 and PD-L2 expression was characteristic of B cells in patients with NMOSD. Tocilizumab selectively restored PD-L1 on B-cell subsets. These results provided evidence that tocilizumab enhanced B- and T-cell homoeostasis by regulating B-cell differentiation and inhibiting lymphocyte activation in patients with NMOSD.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Ativação Linfocitária/efeitos dos fármacos , Células B de Memória , Neuromielite Óptica , Linfócitos T Auxiliares-Indutores , Adulto , Antígenos de Diferenciação/sangue , Antígenos de Diferenciação/imunologia , Feminino , Humanos , Masculino , Células B de Memória/imunologia , Células B de Memória/metabolismo , Pessoa de Meia-Idade , Neuromielite Óptica/sangue , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo
12.
Lupus ; 30(10): 1553-1564, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34139926

RESUMO

OBJECTIVE: The skin is the second most affected organ after articular involvement in systemic lupus erythematosus (SLE) patients. Cutaneous involvement occurs in approximately 80% of patients during the course of SLE. Interaction between the host and skin microorganism is a complex process. There are few studies on the diversity of skin microbes in SLE patients. Therefore, this study aims to explore the relationship between skin microorganisms and SLE. METHODS: A total of 20 SLE patients, 20 controls with rosacea and 20 healthy controls were selected as study subjects. Both the skin microbiota of rash region and non-rash region for each SLE patient were collected.16S rRNA gene sequencing was used to detected skin microbiota from 80 specimens. α-Diversity and ß-diversity of skin microbiota were analyzed based on operational taxonomic units (OTUs) and minimal entropy decomposition (MED). Using Wilcoxon test and Linear Discriminate Analysis Effect Size (LEfSe), skin microbial diversity and composition were analyzed. Functional capabilities of microbiota were estimated through Kyoto Encyclopedia of Genes and Genomes database. RESULTS: Compared to rash region of SLE, diversity and richness were increased in healthy controls, and decreased in non-rash region of SLE and rash region of controls with rosacea. Additionally, changes of skin microbial composition were found at different taxonomic levels between four groups. For example, genus Halomonas was increased and genera Pelagibacterium, Novosphingobium, and Curvibacter were decreased in rash region compared to non-rash region of SLE based on OTUs and MED. Based on OTUs, metabolic pathways were also found differences in SLE patients, such as Xenobiotics Biodegradation and Metabolism. CONCLUSION: Compositions and diversity of skin microbiota in SLE patients are changed. This pilot study provides some suggestive evidence for further exploration of skin microbiota in SLE patients with cutaneous involvement.


Assuntos
Exantema , Lúpus Eritematoso Sistêmico , Microbiota , Rosácea , Humanos , Projetos Piloto , RNA Ribossômico 16S/genética
13.
Lancet Neurol ; 19(5): 391-401, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32333897

RESUMO

BACKGROUND: Azathioprine is used as a first-line treatment to prevent relapses of neuromyelitis optica spectrum disorder (NMOSD). Tocilizumab has been reported to reduce NMOSD disease activity in retrospective case reports. We aimed to compare the safety and efficacy of tocilizumab and azathioprine in patients with highly relapsing NMOSD. METHODS: We did an open-label, multicentre, randomised, phase 2 trial at six hospitals in China. We recruited adult patients (aged ≥18 years) with highly relapsing NMOSD diagnosed according to 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, who had an Expanded Disability Status Scale (EDSS) score of 7·5 or lower, and had a history of at least two clinical relapses during the previous 12 months or three relapses during the previous 24 months with at least one relapse within the previous 12 months. Patients were randomly assigned (1:1) to intravenous tocilizumab (8 mg/kg every 4 weeks) or oral azathioprine (2-3 mg/kg per day) by an independent statistician using computer-generated randomisation software with permuted blocks of four. The central review committee, EDSS raters, laboratory personnel, and radiologists were masked to the treatment assignment, but investigators and patients were aware of treatment allocation. The minimum planned duration of treatment was 60 weeks following randomisation. The primary outcome was time to first relapse in the full analysis set, which included all randomly assigned patients who received at least one dose of study drug, and the per-protocol population, which included all patients who used azathioprine or tocilizumab as monotherapy. For the analyses of the primary outcome, the patients were prespecified into two subgroups according to concomitant autoimmune disease status. Safety was assessed in the full analysis set. This study is registered with ClinicalTrials.gov, NCT03350633. FINDINGS: Between Nov 1, 2017, and Aug 3, 2018, we enrolled 118 patients, of whom 59 were randomly assigned to tocilizumab and 59 were randomly assigned to azathioprine. All 118 patients received one dose of study drug and were included in the full analysis set. 108 participants were included in the per-protocol analysis (56 in the tocilizumab group and 52 in the azathioprine group). In the full analysis set, median time to the first relapse was longer in the tocilizumab group than the azathioprine group (78·9 weeks [IQR 58·3-90·6] vs 56·7 [32·9-81·7] weeks; p=0·0026). Eight (14%) of 59 patients in the tocilizumab group and 28 (47%) of 59 patients in the azathioprine group had a relapse at the end of the study (hazard ratio [HR] 0·236 [95% CI 0·107-0·518]; p<0·0001). In the per-protocol analysis, 50 (89%) of 56 patients in the tocilizumab group were relapse-free compared with 29 (56%) of 52 patients in the azathioprine group at the end of the study (HR 0·188 [95% CI 0·076-0·463]; p<0·0001); the median time to first relapse was also longer in the tocilizumab group than the azathioprine group (67·2 weeks [IQR 47·9-77·9] vs 38·0 [23·6-64·9]; p<0·0001). In the prespecified subgroup analysis of the full analysis set stratified by concomitant autoimmune diseases, among patients without concomitant autoimmune diseases, three (9%) of 34 patients in the tocilizumab group and 13 (35%) of 37 patients in the azathioprine group had relapsed by the end of the study. Among patients with concomitant autoimmune diseases, a lower proportion of patients in the tocilizumab group had a relapse than in the azathioprine group (five [20%] of 25 patients vs 15 [68%] of 22 patients; HR 0·192 [95% CI 0·070-0·531]; p=0·0004). 57 (97%) of 59 patients in the tocilizumab group and 56 (95%) of 59 patients in the azathioprine group had adverse events. Treatment-associated adverse events occurred in 36 (61%) of 59 tocilizumab-treated patients and 49 (83%) of 59 azathioprine-treated patients. One death (2%) occurred in the tocilizumab group and one (2%) in the azathioprine group, but neither of the deaths were treatment-related. INTERPRETATION: Tocilizumab significantly reduced the risk of a subsequent NMOSD relapse compared with azathioprine. Tocilizumab might therefore be another safe and effective treatment to prevent relapses in patients with NMOSD. FUNDING: Tianjin Medical University, Advanced Innovation Center for Human Brain Protection, National Key Research and Development Program of China, National Science Foundation of China.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Azatioprina/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
Protein Pept Lett ; 25(9): 822-829, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30182829

RESUMO

BACKGROUND: In the post-genome age, it is more urgent to understand the functions of genes and proteins. Since experimental methods are usually costly and time consuming, computational predictions are recognized as an alternative approach. In developing a predictive method for functional genomics and proteomics, one of the most important steps is to represent biological sequences with a fixed length numerical form, which can be further analyzed using machine learning algorithms. Chou's pseudo-amino acid compositions and the pseudo k-nucleotide compositions are algorithms for this purpose. CONCLUSION: Since the appearance of these algorithms, several software tools have been developed as implementations. These software tools facilitate the application of these algorithms. As these software tools are developed with different technologies and for different application scenarios, we will briefly review the technical aspect of these software tools in this short review.


Assuntos
Biologia Computacional/métodos , Proteínas/genética , Proteínas/metabolismo , Sequência de Aminoácidos , Bases de Dados de Proteínas , Aprendizado de Máquina , Modelos Moleculares , Software
15.
Interact Cardiovasc Thorac Surg ; 27(5): 695-702, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29741691

RESUMO

OBJECTIVES: In this meta-analysis, we conducted a pooled analysis of clinical studies comparing the efficacy of a volume threshold of 300 ml/day before removing a chest tube (CT) versus 100 ml/day after a lobectomy. METHODS: According to the recommendations of the Cochrane Collaboration, we established a rigorous study protocol. We performed a systematic electronic search of PubMed, Embase, Cochrane Library, Web of Science databases, CNKI, the Wanfang database, CBMdisc and Google Scholar to identify articles to include in our meta-analysis. A literature search was performed using relevant keywords. A meta-analysis was performed using RevMan© software. RESULTS: Five studies, published between 2014 and 2015, including 615 patients (314 patients who had the CT removed when daily drainage was <300 ml and 301 patients who had the CT removed when daily drainage was <100 ml) met the selection criteria. From the available data, the patients using the volume threshold of 300 ml/day had a significantly decreased duration of drainage [MD = -44.07; 95% confidence interval (CI) -64.45 to -23.68; P < 0.0001] and hospital stay after operation (MD = -2.25; 95% CI -3.52 to -0.97; P = 0.0006) compared with patients using a volume threshold of 100 ml/day after a pulmonary lobectomy. However, no significant differences were observed in postoperative complications, such as pleural fluid reaccumulation [Odds ratio (OR) = 1.73; 95% CI = 0.74-4.07; P = 0.21] and atelectasis (OR = 0.97; 95% CI = 0.52-1.81; P = 0.93). Thoracentesis rates after removing the CT also showed no significant difference (OR = 1.53; 95% CI 0.55-4.22; P = 0.41). CONCLUSIONS: Our results showed that a higher volume threshold, up to 300 ml/day, is effective in reducing hospitalization times and duration of drainage in patients who undergo a lobectomy. Moreover, the volume threshold of 300 ml/day does not increase the occurrence of postoperative atelectasis, pleural fluid reaccumulation and thoracentesis rates. However, this review is limited by the methodological quality of the included trials, and additional studies according to the recommendations of Cochrane Library are appreciated.


Assuntos
Tubos Torácicos , Drenagem/métodos , Pneumonectomia/efeitos adversos , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/terapia , Toracentese/métodos , Exsudatos e Transudatos , Humanos
16.
Acta Trop ; 177: 1-8, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28963064

RESUMO

Parasite infections can cause adverse effects on health, survival and welfare of forest musk deer. However, few studies have quantified the parasite infection status and evaluated the parasite temporal dynamics and differences between breeding centers for captive forest musk deer. The purpose of this study was to assess seasonal and regional effects on the parasite prevalence, shedding capacity, diversity, aggregation and infracommunity to establish baseline data on captive forest musk deer. The McMaster technique was applied to count parasite eggs or oocysts in 990 fecal samples collected at three breeding centers located in Qinling Mountains and Tibetan Plateau during spring, summer, and winter. Five gastrointestinal parasite groups were found in musk deer, and Eimeria spp. were dominant (mean oocysts per gram=1273.7±256.3). A positive correlation between Eimeria spp. and Strongyloides spp. (r=0.336, p<0.001) based on shedding capacity data was found, as well as a negative correlation between Eimeria spp. and Moniezia spp. (r=-0.375, p=0.003). Both seasonal and regional differences in diversity, prevalence, shedding capacity, aggregation and infracommunity were observed for five parasite groups. The low level of aggregation and high shedding capacity of Eimeria spp. and Strongyloides spp. might reflect the contaminated environment, and indicate that host-parasite relationships are unstable. The high degree of aggregation of Trichuris spp., Ascaris spp., and Moniezia spp. also suggests that some individual hosts had less ability to resist pathogens and greater transmission potential than others. These conclusions suggest that a focus on disease control strategies could improve the health of forest musk deer in captivity.


Assuntos
Cervos/parasitologia , Enteropatias Parasitárias/veterinária , Animais , Cruzamento , Fezes/parasitologia , Florestas , Interações Hospedeiro-Parasita , Características de Residência , Estações do Ano
17.
Anim Reprod Sci ; 170: 1-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27091598

RESUMO

The forest musk deer (FMD, Moschus berezovskii) is a threatened species in China. Although crucial for its artificial breeding management and thus protection, to date, gonadal steroidogenic activity data are unavailable in this species. Thus, the objectives of the present study were to characterize ovarian activity throughout the estrous cycle, non-pregnant luteal phase, and gestation in female FMD. These goals were accomplished using an enzyme immunoassay to measure fecal concentrations of estradiol (E2) and progesterone. Fecal samples were collected from female FMD (aged 3-4 years) for one year, including during breeding and non-breeding seasons. Non-pregnant estrous cycles were recorded in females, based on fecal progesterone concentrations, their overall estrous cycle length was (mean±SEM) 24.3±0.5 days, with 21.6±0.5 days in the luteal phase and 2.7±0.3 days in the inter-luteal phase. Fecal progesterone and E2 concentrations were also measured in females that became pregnant and gave birth after gestating approximately 6 months. Two weeks after becoming pregnant, the average fecal progesterone concentration was significantly greater than that during non-pregnancy. The average fecal progesterone concentrations during pregnancy increased 3.2-fold above non-pregnant concentrations, decreasing to non-pregnant concentrations only after parturition. By contrast, average fecal E2 concentrations during gestation and after parturition were not different from average non-pregnant concentration. In addition, no difference was observed between progesterone concentration in the first month after pregnancy and the value during the luteal phase. However, progesterone concentration during the second month of pregnancy was significantly higher than the value during the luteal phase. In conclusion, monitoring fecal progesterone is an effective method for assessing ovarian function in FMD and will be a useful tool for breeding management and development of assisted reproductive techniques, such as artificial insemination, in this species.


Assuntos
Cervos/fisiologia , Fezes/química , Ovário/fisiologia , Progesterona/química , Animais , Estradiol/química , Estradiol/metabolismo , Feminino , Gravidez , Progesterona/metabolismo
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