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INTRODUCTION: Clinical practice showed that patients with haemophilia (PwH) with bony ankylosed end-stage haemophilic arthropathy knees reported milder pain than those with not bony ankylosed knees. AIM: To compare the differences in pain sensation and the histopathological differences in synovial samples of affected knee joints between PwH with bony ankylosed end-stage haemophilic arthropathy knees and those with not bony ankylosed knees. METHODS: From January 2011 to December 2019, the synovial samples of knee joints were collected during total knee arthroplasty (TKA) surgery for end-stage haemophilic arthropathy. The visual analogue scale (VAS, 0-10) pain score was reviewed from the chart data of the patients. The thickness of the inner layer of the synovium in haematoxylin and eosin (H&E) staining sections was measured. The expression levels of Ki67, IL-1ß, TNF-α, CD31, VEGF, NGF and PGP9.5 in the synovium were detected by immunohistochemistry (IHC) method. RESULTS: Fifty-two end-stage haemophilic arthropathy knee synovial samples from 36 male PwH (34 type A and 2 type B) were collected. Fifteen knees had bony ankylosed (BA-group), and 37 were not bony ankylosed (Not-BA-group). The mean age of patients at TKA surgery of BA-group and Not-BA-group was 32 years (15) and 32 years (10), respectively (p = 0.824). Before TKA surgery, the mean VAS pain scores of patients in the Not-BA-group were significantly higher than those in the BA-group (p < 0.001). The mean thickness of the inner layer of the synovium, the mean rate of Ki67+ cells, the mean density of CD31+ vascular endothelial cells and the expression levels of IL-1ß, TNF-α, VEGF and NGF in samples in the Not-BA-group was significantly higher than those in samples in the BA-group (p < 0.001, p = 0.02, p = 0.001, p = 0.117, p < 0.001, p = 0.003 and p = 0.008), respectively. The mean density of PGP9.5+ sensory neural fibres in the Not-BA-group was slightly higher than in the BA-group (p = 0.131). Linear regression analysis showed a significant positive correlation between the VAS pain score and indicators including the synovial thickness, the rate of Ki67+ cells, the expression level of IL-1ß, TNF-α, VEGF, NGF and the densities of CD31+ vascular endothelial cells and PGP9.5+ nerve fibres (p < 0.05). CONCLUSIONS: Worsened hypertrophic synovitis, angiogenesis and sensory nerve sprouting in the synovium may play a critical role in causing worse pain sensation in PwH with not bony ankylosed haemophilic arthropathy knees than in those with bony ankylosed knees.
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Artrite , Hemofilia A , Adolescente , Células Endoteliais , Humanos , Inflamação , Masculino , Membrana SinovialRESUMO
Haemophilic arthropathy (HA), caused by intra-articular haemorrhage, is one of the most common complications in patients with haemophilia. Factor replacement therapy provides missing coagulation factors to prevent children with haemophilia from joint bleeding and decreases their risk for HA. However, haemophilia patients in developing countries are still suffering from HA due to insufficient replacement therapy. Symptoms such as pain and activity limitations caused by HA seriously affect the functional abilities and quality of life of patients with HA, causing a high disability rate in the haemophilia cohort. The pathological mechanism of HA is complicated because the whole pathological mainly involves hypertrophic synovitis, osteopenia, cartilage and bone destruction, and these pathological changes occur in parallel and interact with each other. Inflammation plays an important role in the whole complex pathological process, and iron, cytokines, growth factors and other factors are involved. This review summarizes the pathological mechanism of HA to provide background for clinical and basic research.
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Artrite/patologia , Doenças Ósseas Metabólicas/patologia , Hemartrose/patologia , Hemofilia A/patologia , Osteonecrose/patologia , Sinovite/patologia , Adulto , Artrite/genética , Artrite/imunologia , Artrite/metabolismo , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/imunologia , Doenças Ósseas Metabólicas/metabolismo , Criança , Citocinas/genética , Citocinas/imunologia , Fator VIII/uso terapêutico , Regulação da Expressão Gênica , Hemartrose/genética , Hemartrose/imunologia , Hemartrose/metabolismo , Hemofilia A/genética , Hemofilia A/imunologia , Hemofilia A/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Ferro/imunologia , Ferro/metabolismo , Articulações/imunologia , Articulações/metabolismo , Articulações/patologia , Osteonecrose/genética , Osteonecrose/imunologia , Osteonecrose/metabolismo , Qualidade de Vida , Sinovite/genética , Sinovite/imunologia , Sinovite/metabolismoRESUMO
Sucrose phosphate synthase (SPS), sucrose synthase (SUS) and invertase (INV) are all encoded by multigene families. In tomato (Solanum lycopersicum), a comprehensive analysis of structure characteristics of these family genes is still lacking, and the functions of individual isoforms of these families are mostly unclear under stress. Here, the structure characteristics of the three families in tomato were analyzed; moreover, as a first step toward understanding the functions of isoforms of these proteins under stress, the tissue expression pattern and stress response of these genes were also investigated. The results showed that four SPS genes, six SUS genes and nineteen INV genes were identified in tomato. The subfamily differentiation of SlSPS and SlSUS might have completed before the split of monocotyledons and dicotyledons. The conserved motifs were mostly consistent within each protein family/subfamily. These genes demonstrated differential expressions among family members and tissues, and in response to polyethylene glycerol, NaCl, H2O2, abscisic acid or salicylic acid treatment. Our results suggest that each isoform of these families may have different functions in different tissues and under environmental stimuli. SlSPS1, SlSPS3, SlSUS1, SlSUS3, SlSUS4, SlINVAN5 and SlINVAN7 demonstrated consistent expression responses and may be the major genes responding to exogenous stimuli.
Assuntos
Genes de Plantas , Glucosiltransferases/genética , Proteínas de Plantas/genética , Solanum lycopersicum/enzimologia , Solanum lycopersicum/genética , beta-Frutofuranosidase/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Evolução Molecular , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Família Multigênica , Filogenia , Estresse Fisiológico/genética , SinteniaRESUMO
Silicon (Si) and selenium (Se) can improve the tolerance of plants to NaCl-induced salt stress. However, few studies are available on their regulatory effects on plants' tolerance to calcium nitrate stress, which often occurs in protected facilities, causing secondary soil salinization. In this study, we report the effects of Si (6 mM) and Se (20 µM) applied separately or in combination on the growth, photosynthesis, oxidative damage, and nitrogen metabolism of tomato plants, as well as fruit quality under calcium nitrate stress. The results showed that applications of Si or Se alone or in combination improved the plant growth and photosynthetic performance and reduced oxidative damage of the stressed plants. Applications of Si and Se did not decrease the calcium accumulation in leaves of the stressed plants. Under calcium nitrate stress, the concentrations of NO3-, NO2- and NH4+ in leaves were significantly increased, while the activities of nitrogen assimilation-related enzymes (including nitrate reductase, nitrite reductase, glutamine synthase, glutamine-2-oxoglutarate aminotransferase and glutamate dehydrogenase) were decreased. Applications of Si and Se, especially their combined treatment, decreased the NO3-, NO2-, and NH4+ concentrations and enhanced the activities of nitrogen assimilation-related enzymes in the stressed plants. Applied Si and Se also decreased the nitrate and titratable acid concentrations and increased vitamin levels in tomato fruits under calcium nitrate stress. It is suggested that Si and Se improved the tomato plant growth and fruit quality under calcium nitrate stress by alleviating oxidative damage and promoting both photosynthesis and nitrogen assimilation.
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Compostos de Cálcio , Selênio , Solanum lycopersicum , Nitratos/farmacologia , Nitratos/metabolismo , Selênio/farmacologia , Silício/farmacologia , Dióxido de Nitrogênio , Glutamina , Nitrogênio/metabolismoRESUMO
BACKGROUND: Since there are currently no systematic evidence-based medical data on the efficacy and safety of PECD, this meta-analysis pooled data from studies that reported the efficacy or safety of PECD for cervical disc herniation to examine the efficacy, recurrence and safety of using PECD to treat cervical disc herniation. METHODS: We searched the PubMed, EMBASE and Cochrane Library databases for studies published from inception to July 2022. Nine nonrandomized controlled trials (non-RCTs) that reported the efficacy or safety of percutaneous endoscopic cervical discectomy for cervical disc herniation were included. We excluded duplicate publications, studies without full text, studies with incomplete information, studies that did not enable us to conduct data extraction, animal experiments and reviews. STATA 15.1 software was used to analyse the data. RESULTS: The proportions of excellent and good treatment results after PECD for CDH were 39% (95% CI: 31-48%) and 47% (95% CI: 34-59%), respectively. The pooled results showed that the VAS scores at 1 week post-operatively (SMD = -2.55, 95% CI: - 3.25 to - 1.85) and at the last follow-up (SMD = - 4.30, 95% CI: - 5.61 to - 3.00) after PECD for cervical disc herniation were significantly lower than the pre-operative scores. The recurrence rate of neck pain and the incidence of adverse events after PECD for cervical disc herniation were 3% (95% CI: 1-6%) and 5% (95% CI: 2-9%), respectively. Additionally, pooled results show that the operative time (SMD = - 3.22, 95% CI: - 5.21 to - 1.43) and hospital stay (SMD = - 1.75, 95% CI: - 2.67to - 0.84) were all significantly lower for PECD than for ACDF. The pooled results also showed that the proportion of excellent treatment results was significantly higher for PECD than for ACDF (OR = 2.29, 95% CI: 1.06-4.96). CONCLUSION: PECD has a high success rate in the treatment of CHD and can relieve neck pain, and the recurrence rate and the incidence of adverse events are low. In addition, compared with ACDF, PECD has a higher rate of excellent outcomes and a lower operative time and hospital stay. PECD may be a better option for treating CHD.
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Discotomia Percutânea , Deslocamento do Disco Intervertebral , Animais , Humanos , Deslocamento do Disco Intervertebral/cirurgia , Cervicalgia/etiologia , Discotomia Percutânea/efeitos adversos , Discotomia , Endoscopia/efeitos adversosRESUMO
Buyang Huanwu decoction (BYHWD), as one of the traditional Chinese medicine formulas, is widely used in the clinical treatment of lumbar disc herniation (LDH) with curative effect. It has the characteristics of multi-component, multi-target, and mutual synergy, but the mechanism of action is often unclear. It needs some research to explore the molecular mechanism of BYHWD in the treatment of LDH based on network pharmacology and molecular docking. Screen the active compounds of BYHWD and predict drug-related gene/protein targets, which could determine the specific target of BYHWD in the treatment of LDH. Construct the "Drugs-Compounds-Targets" network and search for the core targets. Use Gene Ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking verification to explore the possible molecular mechanism. Eighty-two effective compounds and 666 targets of BYHWD, 187 targets for LDH treatment, and 20 core candidate targets were excavated. A total of 3414 entries were identified by Gene Ontology enrichment analysis, 173 related signal pathways were identified by Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and 5 core compounds were identified by molecular docking, which had a good affinity with core genes STAT3, JUN, AKT1, MAPK1, RELA, and PIK3CA. BYHWD may play the role of analgesic and improving function by synergistic anti-inflammatory and analgesic compounds, regulating cell metabolic differentiation, regulating immunity, and anticoagulation. BYHWD in the treatment of LDH may play a role in analgesia and improve function through multiple signaling pathways, including PI3K-Akt, mitogen-activated protein kinase, tumor necrosis factor, and interleukin-17. The PI3K-Akt signaling may be one of the key mechanisms.
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Medicamentos de Ervas Chinesas , Deslocamento do Disco Intervertebral , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Deslocamento do Disco Intervertebral/tratamento farmacológico , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-aktRESUMO
BACKGROUND: The impact of Tuina on neonatal jaundice is not yet comprehensively understood, and its clinical application is rather limited. This study systematically assessed the relevant literature and conducted a meta-analysis to study the influence of Tuina on neonatal jaundice and provide convincing clinical evidence for promoting its clinical application. METHODS: We searched Pubmed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM from the establishment of the database up to July 2021. Studies that are randomized controlled trials were included. However, duplicate publications; manuscripts with no full text, incomplete information, or inability to extract data; animal experiments; and reviews and systematic reviews were excluded. STATA 15.1 was used to analyze the data. RESULTS: The pooled results showed that compared with the treatment of neonatal jaundice solely with blue light, Tuina combined with blue light significantly improved the total effective rate and frequency of defecation on days 1, 2, 3, 4, and 5 and significantly decreased the traditional Chinese medicine syndrome score; the third serum total bilirubin on days 3, 4, and 7; and duration of jaundice. Moreover, the incidence of adverse events in neonatal jaundice treated with Tuina combined with blue light was significantly lower than that with blue light alone. CONCLUSION: Tuina combined with blue light for treating neonatal jaundice can increase the effect of clinical treatment and reduce the adverse events caused by blue light therapy. Thus, the clinical application of traditional Chinese medicine Tuina in neonatal jaundice should be further promoted.
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Icterícia Neonatal , Icterícia , Humanos , Recém-Nascido , Icterícia/terapia , Icterícia Neonatal/terapia , Medicina Tradicional Chinesa/métodos , Fototerapia , SíndromeRESUMO
Tumor-derived extracellular vesicles (EVs) are key immune regulators of the tumor microenvironment. They reshape the immune microenvironment and prevent antitumor immune responses via their immunosuppressive cargo, thereby determining cancer responsiveness to treatment. In the immune microenvironment of melanoma, tumor-derived EVs influence tumor progression by regulating innate and adaptive immune responses. Tumor-derived EV-based therapy is a cutting-edge and promising strategy for inhibiting melanoma progression and enhancing antitumor immunity. This review aimed to summarize the regulatory roles of EVs in the immune responses and immunotherapy of patients with melanoma. This paper provided insights into future exploration directions and potential clinical strategies targeting EVs for melanoma treatment.
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Vesículas Extracelulares , Melanoma , Humanos , Vesículas Extracelulares/patologia , Melanoma/patologia , Imunoterapia , Microambiente Tumoral , ImunidadeRESUMO
Non-union is a serious postoperative complication of fracture. Early detection and intervention can avoid revision surgery. Platelet-rich plasma releases many active tissue factors and has potential to promote fracture healing. Percutaneous injection of platelet-rich plasma at the fracture site may avoid surgical treatment when non-union occurs. We present a case of atrophic non-union of an ulna fracture treated conservatively with percutaneous injection of platelet-rich plasma.
Assuntos
Fraturas não Consolidadas/terapia , Plasma Rico em Plaquetas , Fraturas da Ulna/cirurgia , Atrofia/terapia , Criança , Fixação Interna de Fraturas , Fraturas não Consolidadas/diagnóstico por imagem , Fraturas não Consolidadas/patologia , Humanos , MasculinoRESUMO
BACKGROUND: There are still controversies between the curative effect of acupuncture combined with cupping therapy and western medicine for post-herpetic neuralgia (PHN). Our meta-analysis fully incorporates the research of acupuncture combined with cupping therapy versus Western medicine for PHN, aiming to explore the difference in the efficacy of the 2 therapies, so as to provide guidance for clinical treatment. METHODS: We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, CBM, from establishment of the database to September, 2020. Include studies that are clearly defined as PHN or herpes zoster, and exclude duplicate publications; studies with no full text, incomplete information, or inability to extract data; the definition of exposure is quite different from most literature; animal experiments. RESULTS: The total effective rate (relative ratio [RR]â=â1.21, 95% confidence interval [CI]: 1.12-1.31) and the rate of remarkable effect (RRâ=â1.46, 95% CI: 1.30-1.63) of acupuncture and moxibustion combined with cupping in the treatment of PHN were significantly higher than that of conventional western medicine. The visual analogue scale score of acupuncture and moxibustion combined with cupping for PHN was significantly lower than that of conventional western medicine treatment (WMDâ=â-1.77, 95% CI [-2.79, -0.75]). In addition, acupuncture and moxibustion combined with cupping therapy significantly reduced the occurrence of PHN compared with conventional western medicine treatment after treatment of acute herpes zoster (RRâ=â0.30, 95% CI: 0.20-0.45). In order to explore the differences in the efficacy and preventive effects of different types of acupuncture and cupping therapy, we have further conducted a subgroup analysis. CONCLUSION: The effect of acupuncture and moxibustion combined with cupping in the treatment of PHN is significantly higher than that of conventional western medicine, and it can significantly prevent the occurrence of PHN. Chinese medicine should be used more widely in the treatment of PHN.
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Terapia por Acupuntura/normas , Ventosaterapia/normas , Moxibustão/normas , Neuralgia Pós-Herpética/terapia , Terapia por Acupuntura/métodos , Ventosaterapia/métodos , Herpes Zoster/complicações , Humanos , Moxibustão/métodos , Neuralgia Pós-Herpética/etiologiaRESUMO
The purpose of this study was to explore the characteristics and functions of BH3-only proteins Puma, Noxa and Bim in the prognosis, therapy and drug resistance of chronic lymphocytic leukemia (CLL). Puma, Noxa and Bim mRNAs were evaluated by real-time quantitative reverse transcriptase-polymerase chain reaction, and correlations between their expression levels and CLL prognostic markers were analyzed. Primary CLL samples were treated in vitro with fludarabine to investigate the role of Puma, Noxa and Bim in the response to chemotherapeutic drugs which act through activation of the p53 pathway. We found that a low expression level of Puma was associated with some markers of poor prognosis. However, the level of Noxa or Bim was not different in patients with CLL with variant clinical features and prognostic factors. Puma expression was up-regulated after fludarabine treatment in primary CLL cells, but there was no significant difference for Noxa and Bim. Up-regulation of Puma occurred only in CLL cells with functional p53. CLL cells with p53 abnormalities were deficient in the activation of Puma by chemotherapeutics. These results suggest that a lack of Puma induction may contribute to the development of resistance to anticancer agents in CLL.
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Proteínas Reguladoras de Apoptose/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , ADP-Ribosil Ciclase 1/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Apoptose , Proteínas Reguladoras de Apoptose/genética , Proteína 11 Semelhante a Bcl-2 , Linhagem Celular Tumoral , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Proteínas de Transporte da Membrana Mitocondrial , Mutação , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/genética , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Proteína-Tirosina Quinase ZAP-70/metabolismoRESUMO
This study was aimed to investigate the expression level of puma (p53 up-regulated modulator of apoptosis) mRNA in chronic lymphocytic leukemia (CLL) and its significance in evaluation of CLL prognosis. The puma mRNA expressions in 100 CLL patients and 11 normal controls were measured by relative quantification RT-PCR with fluorescent dye SYBR Green I, the beta-actin was used as internal reference. The difference of puma expression rate between groups with different prognostic factors was described using the Mann-Whitney U test. The relative quantitative value of puma expression was calculated by means of 2 (-ΔCt). The results indicated that the correlation coefficients of the standard curves in qRT-PCR were ≥ 0.99. The coefficients of variations (CV) within group or between groups were < 5%, and the sensitivity reached 10² copies/microg RNA. The median puma mRNA expression level was 1.038 x 10⻳ (4.106 x 10â»4 - 2.806 x 10⻳) in CLL patients, which was 1.220 x 10⻳ (7.233 x 10â»4 - 1.405 x 10⻳) in normal controls. There was no difference of puma mRNA expression between CLL patients and normal controls (U = 544.5, p = 0.957). Puma expression was significantly correlated with Binet stages (p < 0.001), expression of CD38 (p = 0.002), ZAP-70 protein (p = 0.012), LDH levels (p = 0.009) and beta2-MG (p = 0.046). The puma expression level in patients with earlier Binet stage (Binet stage A) was obviously higher than that in patients with later Binet stage (Binet stage B, C). The puma expression levels in patients with positive expression of CD38 and ZAP-70 protein, elevating levels of LDH and beta2-MG were sharply lower than those in patients without above-mentioned unfavorable factors. The puma expression was also correlated with molecular cytogenetic abnormalities, the puma expression levels in patients with trisomy 12 (p = 0.003) and 14q32 translocation (p = 0.045) detected by FISH were significantly lower than those in patients without above-mentioned molecular cytogenetic abnormalities. It is concluded that the qRT-PCR assay is reliable and sensitive. Puma mRNA expression is significantly correlated with a great deal of prognostic factors, and may be a prognostic marker of CLL.