RESUMO
In patients with relapsed or refractory neuroblastoma (NB), the limited efficacy of conventional chemotherapies necessitates the exploration of new treatment options. Previous studies have highlighted the anti-tumor properties of arsenic trioxide (ATO) in high-risk NB (HR-NB). This study aims to assess the effectiveness and safety of ATO combined with salvage chemotherapy regimens, featuring cyclophosphamide and topotecan, as a foundational treatment for children with relapsed or refractory NB. Eleven patients (four relapsed, seven refractory NB) were retrospectively analyzed for efficacy and treatment relevance. Salvage treatments, incorporating ATO (0.18 mg/kg daily for 8 h intravenously on days 1 to 10), were administered upon disease progression or relapse, with assessments conducted every two cycles. Treatments had 63.6% efficacy, with six cases of partial response, one case of stable disease, and four cases of disease progression. The overall response rate was 54.5%, and the disease control rate was 63.6%. Importantly, the systemic toxicity experienced by patients following salvage chemotherapy with ATO was mild. Salvage chemotherapy regimens featuring ATO demonstrated potential for prolonging disease stabilization for relapsed or refractory HR-NB patients, exhibiting both favorable efficacy and safety profiles. This suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.
Point 1. The inadequate effectiveness of traditional chemotherapy in individuals with recurrent or resistant neuroblastoma (NB) necessitates the investigation of novel therapeutic approaches. Point 2. Arsenic trioxide (ATO)-based salvage treatments are both effective and less toxic in relapsed or refractory NB. Point 3. Salvage chemotherapy regimens incorporating ATO have shown promise in extending disease stabilization in relapsed or refractory high-risk NB patients, with favorable efficacy and safety profiles, which suggests further clinical exploration and promotion of this therapeutic approach in the treatment of NB.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Trióxido de Arsênio , Recidiva Local de Neoplasia , Neuroblastoma , Terapia de Salvação , Humanos , Trióxido de Arsênio/administração & dosagem , Trióxido de Arsênio/uso terapêutico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Feminino , Masculino , Pré-Escolar , Criança , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Topotecan/administração & dosagem , Topotecan/uso terapêutico , Topotecan/efeitos adversos , Lactente , Resultado do Tratamento , Adolescente , Resistencia a Medicamentos Antineoplásicos , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversosRESUMO
BACKGROUND: Treatment for parameningeal rhabdomyosarcoma (PM-RMS) has been a challenge since local control is difficult. The goal of this study was to analyse the impact of different local treatment approaches on childhood PM-RMS patients and help dispel the doubt that whether secondary radical surgery (SRS) should be encouraged in the management of PM-RMS. METHODS: A total of 17 children with PM-RMS who received unified systemic chemotherapy and individualized local therapy such as radiotherapy (RT) and/or SRS were included in this retrospective study. The overall survival (OS) and event free survival (EFS) were compared between groups adopting different local strategies. RESULTS: The 3-year OS and EFS of our PM-RMS patients was 75.5% and 56.5% respectively. The OS and EFS of patients who received SRS were both significantly lower than that of the non-SRS group (3-year OS: 50.0% vs 90.0%, P = .031; 3-year EFS: 33.3% vs 60.6%, P = .020). The OS and EFS of the patients who received RT was higher than that of the patients of the non-RT group (3-year OS: 85.6% vs 0%, P = .001; 3-year EFS: 64.0% vs 0%, P = .011). CONCLUSION: This study illustrates that SRS was associated with poor prognosis of PM-RMS and should not be routinely performed. Optimized RT strategies along with more intensive chemotherapy may be alternative options to improve the survival of patients with PM-RMS. Multi-center, large sample and prospective studies are needed to further validate these findings.
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Rabdomiossarcoma , Criança , Humanos , Lactente , Estudos Retrospectivos , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/radioterapia , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China/epidemiologiaRESUMO
BACKGROUND: Congenital heart defects (CHDs) are the most common type of birth defects. The genetic aetiology of CHD is complex and incompletely understood. The overall distribution of genetic causes in patients with CHD from neonatal intensive care units (NICUs) needs to be studied. METHODS: CHD cases were extracted from the China Neonatal Genomes Project (2016-2021). Next-generation sequencing results and medical records were retrospectively evaluated to note the frequency of genetic diagnosis and the respective patient outcomes. RESULTS: In total, 1795 patients were included. The human phenotype ontology term of atrial septal defect, patent ductus arteriosus and ventricular septal defect account for a large portion of the CHD subtype. Co-occurring extracardiac anomalies were observed in 35.1% of patients. 269 of the cases received genetic diagnoses that could explain the phenotype of CHDs, including 172 copy number variations and 97 pathogenic variants. The detection rate of trio-whole-exome sequencing was higher than clinical exome sequencing (21.8% vs 14.5%, p<0.05). Further follow-up analysis showed the genetic diagnostic rate was higher in the deceased group than in the surviving group (29.0% vs 11.9%, p<0.05). CONCLUSION: This is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD.
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Cardiopatias Congênitas , Unidades de Terapia Intensiva Neonatal , Recém-Nascido , Humanos , Estudos Retrospectivos , Estudos de Coortes , Variações do Número de Cópias de DNA , Cardiopatias Congênitas/genética , ChinaRESUMO
BACKGROUND Arthroscopic knee surgery (AKS) is minimally invasive, reducing hospital stay compared to traditional surgery, but postoperative pain remains a significant issue. This study compared the analgesic and functional outcomes following AKS following anesthesia using adductor canal block (ACB) with and without anesthesia using the interspace between the popliteal artery and posterior capsule of the knee (IPACK) block under spinal anesthesia (SA). MATERIAL AND METHODS We randomly allocated 120 patients into 3 groups: IPACK+ACB+SA for Group A (n=40), ACB+SA for Group B (n=40), and SA for Group C (n=40). The outcome was the visual analog scale (VAS) score evaluated at rest and during activity at 3 h, 6 h, 12 h, 24 h, and 48 h postoperatively, the frequency of administration of postoperative rescue analgesic, and the maximal walking distance at 24 h and 48 h postoperatively. RESULTS Compared with Group C, the VAS scores in Group A were significantly lower at 48 h postoperatively (P<0.05). There was a significant difference in the frequency of postoperative rescue analgesia use among the 3 groups (P=0.001). In a subgroup analysis of meniscus shaping under arthroscopy, the resting VAS score in Group A was lower than that in Group B and Group C at 48 h postoperatively (P<0.05). The maximum walking distance of Group A was longer than that of Group B and Group C at 24 h and 48 h postoperatively (P<0.01). CONCLUSIONS The effect of postoperative analgesia in the group receiving IPACK combined with ACB after AKS was obviously superior. In arthroscopic meniscus repair surgery, the duration of analgesia was longer, and the maximum walking distance at 48 h postoperatively was longer.
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Artroscopia , Articulação do Joelho , Bloqueio Nervoso , Manejo da Dor , Medição da Dor , Dor Pós-Operatória , Humanos , Dor Pós-Operatória/tratamento farmacológico , Artroscopia/métodos , Artroscopia/efeitos adversos , Feminino , Masculino , Bloqueio Nervoso/métodos , Pessoa de Meia-Idade , Adulto , Manejo da Dor/métodos , Articulação do Joelho/cirurgia , Medição da Dor/métodos , Resultado do TratamentoRESUMO
Rationale: Sustained activation of lung fibroblasts and the resulting oversynthesis of the extracellular matrix are detrimental events for patients with interstitial lung diseases (ILDs). Lung biopsy is a primary evaluation technique for the fibrotic status of ILDs, and is also a major risk factor for triggering acute deterioration. Fibroblast activation protein (FAP) is a long-known surface biomarker of activated fibroblasts, but its expression pattern and diagnostic implications in ILDs are poorly defined. Objectives: The present study aims to comprehensively investigate whether the expression intensity of FAP could be used as a potential readout to estimate or measure the amounts of activated fibroblasts in ILD lungs quantitatively. Methods: FAP expression in human primary lung fibroblasts as well as in clinical lung specimens was first tested using multiple experimental methods, including real-time quantitative PCR (qPCR), Western blot, immunofluorescence staining, deep learning measurement of whole slide immunohistochemistry, as well as single-cell sequencing. In addition, FAP-targeted positron emission tomography/computed tomography imaging PET/CT was applied to various types of patients with ILD, and the correlation between the uptake of FAP tracer and pulmonary function parameters was analyzed. Measurements and Main Results: Here, it was revealed, for the first time, FAP expression was upregulated significantly in the early phase of lung fibroblast activation event in response to a low dose of profibrotic cytokine. Single-cell sequencing data further indicate that nearly all FAP-positive cells in ILD lungs were collagen-producing fibroblasts. Immunohistochemical analysis validated that FAP expression level was closely correlated with the abundance of fibroblastic foci on human lung biopsy sections from patients with ILDs. We found that the total standard uptake value (SUV) of FAP inhibitor (FAPI) PET (SUVtotal) was significantly related to lung function decline in patients with ILD. Conclusions: Our results strongly support that in vitro and in vivo detection of FAP can assess the profibrotic activity of ILDs, which may aid in early diagnosis and the selection of an appropriate therapeutic window.
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Doenças Pulmonares Intersticiais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Doenças Pulmonares Intersticiais/patologia , Pulmão/patologia , Fibrose , Fibroblastos/metabolismoRESUMO
Congenital auricular deformity (CAD) is a complex phenotype that may occur as a single malformation or part of a congenital syndrome. The genetic architecture and utility of next-generation sequencing (NGS) in a sizable cross-sectional study of critically ill neonates with CAD have not yet been systematically investigated. This cross-sectional study investigated the genetic spectrum in critically ill neonates with CADs. Critically ill neonates with CADs (n = 251) were enrolled between August 8, 2016 and October 1, 2022. All neonates underwent NGS. The outcomes were molecular diagnostic yield, spectrum of genetic events, and clinical findings. Genetic findings were obtained in 107 neonates (42.6%), of which 67.3% (72/107) had pathogenic/likely pathogenic/variants of uncertain significance (P/LP/VUS) gene variations and 32.7% (35/107) had P/LP/VUS copy number variations (CNVs). The diagnostic rates of clinical exome sequencing were similar to those of exome sequencing. The logistic regression model revealed that CAD neonates with craniofacial abnormalities (OR = 4.15, 95% CI 2.29-7.53) or cardiovascular malformation (OR = 2.09, 95% CI 1.14-3.84) are more likely to be attributed to genetic causes. Follow-up analysis revealed that, compared to those in the undiagnosed group, the number of neonates whose care was withdrawn or who died was higher in the genetically diagnosed group (P < 0.05). This study identified a high incidence of genetic causes in critically ill neonates with CADs, with a combination of single-nucleotide variations and CNVs among the genetic causes of CAD. These findings highlight potential of NGS in the genetic testing of critically ill neonates with CADs.
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Estado Terminal , Variações do Número de Cópias de DNA , Recém-Nascido , Humanos , Estudos Transversais , Testes Genéticos , FenótipoRESUMO
BACKGROUND: Neuroblastoma (NB) is a childhood malignant tumor,50% of high-risk NB children still have recurrence, and the long-term survival rate is very low. NB tumors expressing high levels of BDNF/TrkB are associated with poor survival outcomes.In this study, we show that the trends of serum concentration of BDNF at different growth stages after birth, and explore the relationship with NB replase. METHODS: In experiment 1, 87 subjects were enrolled and divided into four groups, neonates groupã children groupãadults group and NB patients. The distribution of serum concentration of BDNF by ELISA. In experiment 2, we studied BDNF in stage 4 NB patients to determine their frequency, correlation with clinical parameters, and prognostic impact. RESULTS: First, we identified that serum BDNF concentration decreased from the newborn to childhood in healthy subjects, while it was relatively high in children(age > 1 year) with NB. In the second phase our studies showed no significant increase in serum BDNF concentration in these NB patients, with adverse pathologic features, large tumor maximum diameter, and MYCN amplification. After comprehensive treatment, levels of BDNF gradually increased in children with recurrence and decreased in the remission group. High serum BDNF concentration was associated with relapse. Of 21 stage 4 neuroblastoma patients, adopted a comprehensive treatment approach including ATO-basic modified chemotherapy, traditional radiotherapy,stem cell transplatation and immunotherapy. 76% of alive patients having > 3 years follow-up. CONCLUSION: The aim is to show that BDNF is a predictor of recurrence risk of NB.
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Fator Neurotrófico Derivado do Encéfalo , Neuroblastoma , Criança , Recém-Nascido , Humanos , Recidiva Local de Neoplasia , Neuroblastoma/patologiaRESUMO
PURPOSE: Detecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker. METHODS: We adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies. RESULTS: A considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed. CONCLUSIONS: The measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis.
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Glioma , Humanos , Glioma/patologia , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Autoanticorpos , Fibroblastos/metabolismo , Endopeptidases , Biomarcadores Tumorais/metabolismoRESUMO
BACKGROUND: Nursing experts regularly visited the community to deliver safety education on the prevention of unintentional injuries in children to the parents of children aged 0-6 years and to pregnant women in a maternity school. This was undertaken to explore the effects of the measure on preventing unintentional injuries in children in Chizhou, China. METHODS: Using the convenience sampling method, the guardians(it means mother in this study)of children were investigated. The nursing experts visited communities in which the number of nursing experts is declining. Data on unintentional injuries in children in the previous year were collected retrospectively. RESULTS: After the nursing experts delivered safety education to the community, the scores of the questionnaire on unintentional injury prevention knowledge completed by children's guardians increased significantly (p < 0.01). Among the children whose guardians completed the questionnaire, there were 157 cases of unintentional injury in 2020 and 103 cases in 2021 (p < 0.05). The types of unintentional injuries included scratches, falls, sharp object injuries, swallowing of foreign bodies, burns and traffic accidents; there was no statistical difference (p > 0.05). However, there were significant differences in terms of gender ratio and location (p < 0.05). CONCLUSION: In conjunction with the maternity school for pregnant women and the vaccination programme, nursing experts delivered safety education regarding unintentional injuries in children; this may have promoted safety and protection awareness in the children's guardians and reduced unintentional injuries.
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Lesões Acidentais , Queimaduras , Ferimentos e Lesões , Gravidez , Criança , Humanos , Feminino , Estudos Retrospectivos , Acidentes de Trânsito , Participação da Comunidade , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/etiologia , Ferimentos e Lesões/prevenção & controleRESUMO
OBJECTIVES: To explore the application of whole-genome sequencing (WGS) in the rapid clinical diagnosis of critically ill neonates. METHODS: The critically ill neonates who admitted to the neonatal intensive care unit of Children's Hospital of Fudan University and underwent WGS from August to September, 2019 were enrolled in this prospective study. The genetic testing results and clinical outcome were analyzed with reference to the sequencing data and clinical features of the neonates. RESULTS: A total of 15 neonates were tested, among whom there were 9 boys and 6 girls. The main reason for hospitalization included abnormal breathing in 7 neonates, poor response in 2 neonates, feeding difficulty in 2 neonates, fever in 1 neonate, hypothermia in 1 neonate, preterm birth in 1 neonate, and convulsion in 1 neonate. The mean turn-around time was 4.5 days for WGS. Finally a genetic diagnosis was obtained for 3 neonates, with a positive diagnostic rate of 20% (3/15). Among the 3 neonates, 2 neonates were withdrawn from the treatment due to severe conditions and 1 neonate died on the day when the sample was sent for genetic testing, whose etiology could be explained by the results of genetic testing. CONCLUSIONS: WGS technique can provide a timely and effective diagnosis for critically ill neonates suspected of genetic diseases and provide genetic evidence for clinical treatment of critically ill cases.
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Estado Terminal , Nascimento Prematuro , Recém-Nascido , Masculino , Criança , Feminino , Humanos , Estudos Prospectivos , Dispneia , FebreRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with few treatment options. The poor success in developing anti-IPF strategies has impelled researchers to reconsider the importance of the choice of animal model and assessment methodologies. Currently, it is still not settled whether the bleomycin-induced lung fibrosis mouse model finally returns to resolution. METHODS: This study aimed to follow the dynamic fibrotic features of bleomycin-treated mouse lungs over extended durations through a combination of the latest technologies (micro-computed tomography imaging and histological detection of degraded collagens) and traditional methods. In addition, we also applied immunohistochemistry to explore the distribution of all hydroxyproline-containing molecules. RESULTS: As determined by classical biochemical methods, total lung hydroxyproline contents reached a peak at 4â weeks after bleomycin injury and maintained a steady high level thereafter until the end of the experiments (16â weeks). This result seemed to partially contradict with the changes of other fibrosis evaluation parameters, which indicated a gradual degradation of collagens and a recovery of lung aeration after the fibrosis peak. This inconsistency was well reconciled by our data from immunostaining against hydroxyproline and fluorescent peptide staining against degraded collagen, together showing large amounts of hydroxyproline-rich degraded collagen fragments detained and enriched within the intracellular regions at 10 or 16â weeks rather than at 4â weeks after bleomycin treatment. CONCLUSIONS: Our present data not only offer respiratory researchers a new perspective towards the resolution nature of mouse lung fibrosis, but also remind them to be cautious when using the hydroxyproline content assay to evaluate the severity of fibrosis.
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Bleomicina , Fibrose Pulmonar Idiopática , Animais , Colágeno/metabolismo , Modelos Animais de Doenças , Humanos , Hidroxiprolina/metabolismo , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Microtomografia por Raio-XRESUMO
Emerging evidence demonstrates the clinical utility of genomic applications in newborn intensive care unit (NICU) patients with strong indications of Mendelian etiology. However, such applications' diagnostic yield and utility remain unclear for NICU cohorts with minimal phenotype selection. In this study, focused medical exome sequencing was used as a first-tier, singleton-focused diagnostic tool for 2303 unrelated sick neonates. Integrated analysis of single nucleotide variants (SNVs), small insertions and deletions (Indels), and large copy number variants (CNVs) was performed. The diagnostic rate in this NICU cohort is 12.3% (284/2303), with 190 probands with molecular diagnoses made from SNV/Indel analyses (66.9%), 93 patients with diagnostic aneuploidy/CNVs findings (32.8%), and 1 patient with both SNV and CNV (0.4%). In addition, 54 (2.3%) of patients had a reportable incidental finding. Multiple organ involvements, craniofacial abnormalities, and dermatologic abnormalities were the strongest positive predictors for a molecular diagnosis. Among the 190 cases with SNV/Indel defects, direct impacts on medical management were observed in 46.8% of patients after the results were reported. In this study, we demonstrate that focused medical exome sequencing is a powerful first-line diagnostic tool for NICU patients. Significant number of diagnosed NICU patients can benefit from more focused medical management and long-term care.
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Sequenciamento do Exoma , Estudos de Associação Genética , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Predisposição Genética para Doença , Unidades de Terapia Intensiva Neonatal , Alelos , China , Mapeamento Cromossômico , Variações do Número de Cópias de DNA , Feminino , Estudos de Associação Genética/métodos , Testes Genéticos , Humanos , Mutação INDEL , Masculino , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Neuroblastoma (NB) is the most common extracranial tumor in central nervous system threatening children's health with limited therapeutic options. Arsenic trioxide (ATO) has been identified the cytotoxicity in NB cells but the potential mechanism remains unclear. In this study, we attempted to obtain some insight into the mechanisms of cell death induced by ATO in NB cells. METHODS AND RESULTS: Proteomic analyses found that ATO can affect the signaling pathway associated with ferroptosis, including the upregulation of iron absorption (FTL, FTH1, HO-1), ferritinophagy (LC3, P62, ATG7, NCOA4) and modifier of glutathione synthesis (GCLM); downregulation of glutamine synthetase (GS) and GPX4, which was the critical inhibitor of ferroptosis. Western blot analysis revealing GPX4 expression in SK-N-BE (2) cells decreased after treatment with ATO (7.3 µM), resulting in a loss of GPX4 activity. Furthermore, Ferroptosis inhibitor ferrostatin-1 partially blocked ATO-induced cell death. CONCLUSIONS: Our study revealed that ATO may induce ferroptosis in neuroblastoma cell SK-N-BE (2) by facilitating the downregulation of GPX4, ultimately resulting in iron-dependent oxidative death.
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Ferroptose , Neuroblastoma , Apoptose , Trióxido de Arsênio/farmacologia , Criança , Humanos , Ferro/metabolismo , Neuroblastoma/tratamento farmacológico , ProteômicaRESUMO
Multiple congenital anomalies (MCAs) at birth have emerged as an important cause of neonatal morbidity and mortality. This study aimed to investigate the genetic causes and characteristics of clinical outcomes in a large cohort of neonates with MCAs. Clinical exome sequencing/exome sequencing/genome sequencing were undertaken from December 1, 2016 to December 1, 2019 to detect single nucleotide variations (SNVs) and copy number variations (CNVs) simultaneously in individuals who met the inclusion criteria. A total of 588 neonates with MCAs were enrolled. One hundred sixty-one patients received diagnosis, with 71 CNVs and 90 SNVs detected, the overall diagnostic rate being 27.38%. Cardiovascular malformation was the most common anomaly (60%) and accounted for the top symptomatic proportion in both CNVs and SNVs. As the number of involved system increased from 2 to 3-4, and then to ≥5, the overall diagnostic rate increased gradually from 23.1% to 30.5%, and then to 52.2%, respectively. Patients who received genetic diagnoses were offered better clinical management or were referred to the specific disease clinic. In conclusion, this large cohort study demonstrates that both CNVs and SNVs contribute to the genetic causes of MCAs, and earlier genetic assertion may lead to better clinical management for patients.
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Variações do Número de Cópias de DNA , Sequenciamento de Nucleotídeos em Larga Escala , China , Estudos de Coortes , Humanos , Recém-Nascido , Sequenciamento do ExomaRESUMO
As an effective drug against acute enteritis diarrhea, Gegen Qinlian decoction (GQD) has a history of 2000 years. However, the potential molecular mechanism through which GQD could protect intestinal barrier from ulcerative colitis (UC) still remains undefined. As an important part of the homeostasis of the colon, gut microbiota is closely related to the dynamic evolution of the surrounding environment and the adjustment of dietary structure. At present, the effectiveness and mechanism of Jiawei Gegen Qinlian decoction against UC in different dietary environments are not clear. Here, the main active components of Jiawei Gegen Qinlian Decoction (PBM), were selected to construct a reasonable and effective compound scheme. We adopted "5% dextran sulfate sodium (DSS)" and "high temperature and humidity + high sugar and high fat + alcohol + 5%DSS" to induce UC rat models in general environment and UC rat models in Lingnan area, respectively. Then, we examined the therapeutic effects of PBM (89.96 mg/kg and 179.92 mg/kg) on two kinds of UC rats. The role of gut microbiota in the anti-UC effect of PBM was identified by intestinal flora consumption and fecal microbiota transplantation (FMT) experiments. Subsequently, we monitored the alterations of gut microbiota and fecal metabolism in the rat colon by 16Sr DNA technique and targeted metabonomics, respectively. The colon inflammation of the PBM-treated and the FMT-treated rats both showed significant relief, as evidenced by a reduction in body weight loss, bloody stool, diarrhea, disease activity index (DAI) score, shortening of colon length as well as decreased colon histology damage. Interestingly enough, the depletion of intestinal flora took away the protective effect of PBM, confirming the importance of intestinal flora in the anti-UC effect of PBM. Then our findings suggested that PBM could not only regulate the gut microbiota by increasing Akkermansia and Romboutsia but also decrease Escherichia-Shigella. More importantly, PBM could increase the production of propionate and total short-chain fatty acids (SCFAs) in colitis rats, regulate medium and long chain fatty acids (M-LCFAs), maintain bile acids (BAs) homeostasis, and regulate amino acids (AAs) metabolism. The transformation of intestinal environment might be related to the upregulation of anti-inflammation, anti-oxidation and tight junction protein expression in colonic mucosa. In summary, PBM showed potential for anti-UC activity through gut microbiota dependence and was expected to be a complementary and alternative medicine herb therapy.
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Anti-Inflamatórios/farmacologia , Bactérias/efeitos dos fármacos , Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Gastrointestinais/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Colite Ulcerativa/metabolismo , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Colo/metabolismo , Colo/microbiologia , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Disbiose , Feminino , Mediadores da Inflamação/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Twelve students experienced symptoms of acute respiratory infection (ARI) at a training base in Beijing from August 26 to August 30, 2015. We investigated the cause of this ARI outbreak. METHODS: In partnership with the local center for disease control, we collected a total of twelve pharyngeal swab specimens as well as demographic information for the affected patients. We used multiplex real-time PCR to screen for sixteen common respiratory viruses in these samples. To isolate HAdV, we inoculated Hep-2 cells with the human adenovirus (HAdV)-positive samples and then carried out sequencing and phylogenetic analysis of the hexon, fiber, and penton genes of the isolated adenoviruses. In addition, we analyzed the entire genome of one strain isolated from the index case to identify single-nucleotide substitutions. RESULTS: We identified ten HAdV-positive students using multiplex real-time PCR. None of the students were co-infected with other viruses. We successfully isolated seven HAdV strains from the pharyngeal swab specimens. The coding sequences of the hexon, fiber, and penton genes of these seven HAdV strains were identical, suggesting that they represented seven strains from a single virus clone. One HAdV isolate obtained from the index case, BJDX-01-2015, was selected for whole genome analysis. From this isolate, we obtained a 34,774-nucleotide sequence. The genome of BJDX-01-2015 clustered with HAdV-B55 in phylogenetic analyses and had 99.97% identity with human adenovirus 55 isolate HAdV-B/CHN/BJ01/2011/55 (GenBank accession no. JX491639). CONCLUSIONS: We identified HAdV-B55 as the strain associated with the August 2015 ARI outbreak at a training base in Beijing. This was the first reported outbreak in Beijing due to HAdV-B55. Continuous surveillance of respiratory adenoviruses is urgently needed to understand the epidemiological and evolutionary features of HAdV-B55, and an epidemiological modeling approach may provide further insights into this emerging public health threat. Furthermore, the clinical laboratory data from this outbreak provides important reference for the clinical diagnosis and may ultimately aid in informing the development of strategies to control and prevent respiratory tract infections caused by HAdV-B55.
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Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/genética , Surtos de Doenças , Infecções Respiratórias/epidemiologia , Infecções por Adenovirus Humanos/virologia , Adolescente , Pequim/epidemiologia , Humanos , Incidência , Masculino , Reação em Cadeia da Polimerase Multiplex , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Infecções Respiratórias/virologia , Estudantes , Sequenciamento Completo do GenomaAssuntos
Síndrome da Cauda Equina , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Micobactérias não Tuberculosas , Transplante de Células-Tronco , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMO
BACKGROUND: Burden of Group A streptococcus (GAS) pharyngitis is scarce in developing countries, still unknown in China. The objective of this study was to determine the incidence of clinical cases of pharyngitis and GAS culture-positive pharyngitis, and their outpatient visits among children aged 0-14 years in Beijing, the capital of China. METHODS: Multiplier model was used to estimate the numbers of pharyngitis cases, based on reported numbers of clinical cases and GAS culture-positive rates from GAS surveillances in Beijing, consultation rate, population coverage of GAS surveillances, sampling success rate, and test sensitivity of GAS culture from previous studies, surveys and surveillances. RESULTS: An average of 29804.6 (95 % CI: 28333.2-31276.0) clinical cases of pharyngitis per 100,000 person-years occurred among children aged 0-14 years, resulting in correspondingly 19519.0 (95 % CI: 18516.7-20521.2) outpatient visits per 100,000 person-years from 2012 to 2014 in Beijing. On average, there were 2685.1 (95 % CI: 2039.6-3330.6) GAS culture-positive cases of pharyngitis and 1652.7 (95 % CI: 1256.5-2049.0) outpatient visits per 100,000 person-years during the same period. The estimated burden of GAS pharyngitis was significantly higher than that of scarlet fever. Children aged 5-14 years had a higher burden of GAS pharyngitis than those aged 0-4 years. CONCLUSIONS: The present data suggests that GAS pharyngitis is very common in children in China. Further studies and surveillances are needed to monitor trends and the effectiveness of control measures.
Assuntos
Faringite/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/isolamento & purificação , Adolescente , Pequim/epidemiologia , Criança , Pré-Escolar , China , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Faringite/microbiologia , Infecções Estreptocócicas/diagnósticoRESUMO
BACKGROUND: A(H1N1) 09pdm and A(H3N2) influenza viruses are the main cause of occasional influenza pandemics and seasonal influenza epidemics around the world. Unfortunately, the understanding of long-term genetic variation in these viruses remains limited. METHODS: In this study, hemagglutinin genes from 90 A(H1N1) 09pdm and 48 A(H3N2) influenza viruses in the Beijing area from 2009 to 2014 were sequenced and analyzed. RESULTS: The hemagglutinin genes in A(H1N1) 09pdm and A(H3N2) shared nucleotide similarity that ranged from 93.06% - 99.88% and 98.68% - 99.29%, respectively, compared with current vaccine strains. 10 and 7 amino acid mutations in antigenic sites were identified in these two strains, respectively. In addition, a new site 177 glycosylation, which did not exist in previous circulating strains, was identified in 3 A(H1N1) 09pdm isolates. CONCLUSIONS: This study demonstrated the continued evolution of seasonal influenza viruses in the Beijing area, indicating that an update of the vaccine is needed, especially for A(H1N1) 09pdm influenza virus.