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PURPOSE: To clarify the predictive performance of different measures of frailty, including Clinical Frailty Scale (CFS), 11-factor modified Frailty Index (mFI-11), and 5-factor modified Frailty Index (mFI-5), on adverse outcomes. METHODS: PubMed, Embase, Web of Science, and other databases were retrieved from the inception of each database to June 2023. The pooled sensitivity, specificity, and the area under the summary receiver operating curve (SROC) values were analyzed to determine the predictive power of CFS, mFI-11, and mFI-5 for adverse outcomes. RESULTS: A total of 25 studies were included in quantitative synthesis. The pooled sensitivity values of CFS for predicting anastomotic leakage, total complications, and major complications were 0.39, 0.57, 0.45; pooled specificity values were 0.70, 0.58, 0.73; the area under SROC values were 0.58, 0.6, 0.66. The pooled sensitivity values of mFI-11 for predicting total complications and delirium were 0.38 and 0.64; pooled specificity values were 0.83 and 0.72; the area under SROC values were 0.64 and 0.74. The pooled sensitivity values of mFI-5 for predicting total complications, 30-day mortality, and major complications were 0.27, 0.54, 0.25; pooled specificity values were 0.82, 0.84, 0.81; the area under SROC values were 0.63, 0.82, 0.5. CONCLUSION: The results showed that CFS could predict anastomotic leakage, total complications, and major complications; mFI-11 could predict total complications and delirium; mFI-5 could predict total complications and 30-day mortality. More high-quality research is needed to support the conclusions of this study further.
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Neoplasias Colorretais , Delírio , Fragilidade , Humanos , Fragilidade/complicações , Fatores de Risco , Medição de Risco , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicaçõesRESUMO
Colorectal cancer (CRC) is a global health challenge, and patient education plays a crucial role in its early detection and treatment. Despite progress in AI technology, as exemplified by transformer-like models such as ChatGPT, there remains a lack of in-depth understanding of their efficacy for medical purposes. We aimed to assess the proficiency of ChatGPT in the field of popular science, specifically in answering questions related to CRC diagnosis and treatment, using the book "Colorectal Cancer: Your Questions Answered" as a reference. In general, 131 valid questions from the book were manually input into ChatGPT. Responses were evaluated by clinical physicians in the relevant fields based on comprehensiveness and accuracy of information, and scores were standardized for comparison. Not surprisingly, ChatGPT showed high reproducibility in its responses, with high uniformity in comprehensiveness, accuracy, and final scores. However, the mean scores of ChatGPT's responses were significantly lower than the benchmarks, indicating it has not reached an expert level of competence in CRC. While it could provide accurate information, it lacked in comprehensiveness. Notably, ChatGPT performed well in domains of radiation therapy, interventional therapy, stoma care, venous care, and pain control, almost rivaling the benchmarks, but fell short in basic information, surgery, and internal medicine domains. While ChatGPT demonstrated promise in specific domains, its general efficiency in providing CRC information falls short of expert standards, indicating the need for further advancements and improvements in AI technology for patient education in healthcare.
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Neoplasias Colorretais , Medicina Interna , Humanos , Reprodutibilidade dos Testes , Manejo da Dor , Benchmarking , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapiaRESUMO
The p38 mitogen-activated protein kinase (p38 MAPK) is a multifunctional molecule that is involved in cellular response to various stressful stimuli. In the present study, the full-length cDNA sequence of p38 MAPK (Lcp38 MAPK) was identified from the large yellow croaker Larimichthys crocea, which encoded a polypeptide of 361 amino acid residues. The predicted Lcp38 MAPK protein contained a highly conserved Thr-Gly-Tyr (TGY) motif, a glutamate and aspartate (ED) site, a substrate binding site (Ala-Thr-Arg-Trp < ATRW>), and a serine/threonine kinase catalytic (S_TKc) domain characteristic of the MAPK family. The constitutive expression of Lcp38 MAPK was detected in most of the tissues examined with the strongest expression in intestine. Subcellular localization in LCK cells (kidney cell line from a L. crocea) revealed that Lcp38 MAPK existed in both the cytoplasm and cell nucleus. The expression of Lcp38 MAPK after temperature stress was tested in LCK cells. The results indicated that Lcp38 MAPK transcripts were significantly upregulated under both cold (10 °C) and heat stress (35 °C) (P < 0.05). Furthermore, the phosphorylation levels of p38 MAPK as well the transcriptional levels of heat shock protein 27 (HSP27) and caspase3 in LCK cells were significantly induced under thermal exposure (P < 0.05). However, the cold- and heat induced HSP27 and caspase3 expression was significantly suppressed by SB203580, a specific inhibitor of p38-MAPK (P < 0.05). These findings indicated that Lcp38 MAPK might be involved in the cellular stress response via HSP27 and caspase3 in large yellow croaker.
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Perciformes , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas de Choque Térmico HSP27/metabolismo , Fosforilação , Temperatura , Perciformes/genética , Perciformes/metabolismoRESUMO
Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , RimRESUMO
Inflammation is a crucial pathological feature in cancers and kidney diseases, playing a significant role in disease progression. Cyclin-dependent kinases CDK4 and CDK6 not only contribute to cell cycle progression but also participate in cell metabolism, immunogenicity and anti-tumor immune responses. Recently, CDK4/6 inhibitors have gained approval for investigational treatment of breast cancer and various other tumors. Kidney diseases and cancers commonly exhibit characteristic pathological features, such as the involvement of inflammatory cells and persistent chronic inflammation. Remarkably, CDK4/6 inhibitors have demonstrated impressive efficacy in treating non-cancerous conditions, including certain kidney diseases. Current studies have identified the renoprotective effect of CDK4/6 inhibitors, presenting a novel idea and potential direction for treating kidney diseases in the future. In this review, we briefly reviewed the cell cycle in mammals and the role of CDK4/6 in regulating it. We then provided an introduction to CDK4/6 inhibitors and their use in cancer treatment. Additionally, we emphasized the importance of these inhibitors in the treatment of kidney diseases. Collectively, growing evidence demonstrates that targeting CDK4 and CDK6 through CDK4/6 inhibitors might have therapeutic benefits in various cancers and kidney diseases and should be further explored in the future.
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Antineoplásicos , Nefropatias , Neoplasias , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Terapias em Estudo , Divisão Celular , Inflamação , Nefropatias/tratamento farmacológico , Mamíferos , Neoplasias/tratamento farmacológicoRESUMO
RATIONALE: The standardization, individualization, and rationalization of intensive care and treatment for severe patients have improved. However, the combination of corona virus disease 2019 (COVID-19) and cerebral infarction presents new challenges beyond routine nursing care. PATIENT CONCERNS AND DIAGNOSES: This paper examines the rehabilitation nursing of patients with both COVID-19 and cerebral infarction as an example. It is necessary to develop a nursing plan for COVID-19 patients and implement early rehabilitation nursing for cerebral infarction patients. INTERVENTIONS: Timely rehabilitation nursing intervention is essential to enhance treatment outcomes and promote patient rehabilitation. After 20 days of rehabilitation nursing treatment, patients showed significant improvement in visual analogue scale score, drinking test, and upper and lower limb muscle strength. OUTCOMES: Treatment outcomes for complications, motor function, and daily activities also improved significantly. LESSONS: Critical care and rehabilitation specialist care play a positive role in ensuring patient safety and improving their quality of life by adapting measures to local conditions and the timing of care.
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COVID-19 , Humanos , COVID-19/complicações , Qualidade de Vida , Infarto Cerebral/complicações , Resultado do Tratamento , Cuidados CríticosRESUMO
Peritoneal dialysis (PD) is a widely accepted renal replacement therapy for patients with end-stage renal disease (ESRD). Morphological and functional changes occur in the peritoneal membranes (PMs) of patients undergoing long-term PD. Peritoneal fibrosis (PF) is a common PD-related complication that ultimately leads to PM injury and peritoneal ultrafiltration failure. Autophagy is a cellular process of "self-eating" wherein damaged organelles, protein aggregates, and pathogenic microbes are degraded to maintain intracellular environment homeostasis and cell survival. Growing evidence shows that autophagy is involved in fibrosis progression, including renal fibrosis and hepatic fibrosis, in various organs. Multiple risk factors, including high-glucose peritoneal dialysis solution (HGPDS), stimulate the activation of autophagy, which participates in PF progression, in human peritoneal mesothelial cells (HPMCs). Nevertheless, the underlying roles and mechanisms of autophagy in PF progression remain unclear. In this review, we discuss the key roles and potential mechanisms of autophagy in PF to offer novel perspectives on future therapy strategies for PF and their limitations.
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NEMO (nuclear factor-κB
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NF-kappa B , Perciformes , Animais , NF-kappa B/metabolismo , Transdução de Sinais , Regulação da Expressão Gênica , Fator de Necrose Tumoral alfa/genéticaRESUMO
Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.
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Humanos , Vírus da Hepatite B , Encefalopatia Hepática/complicações , Insuficiência Hepática Crônica Agudizada/diagnóstico , Doença Hepática Terminal/complicações , Índice de Gravidade de Doença , Fatores de Risco , Curva ROC , Prognóstico , Estudos RetrospectivosRESUMO
Children's fever is often accompanied by food accumulation. Traditional Chinese medicine believes that removing food stagnation while clearing heat of children can effectively avoid heat damage. To systematically evaluate the efficacy of Xiaoer Chiqiao Qingre Granules(XRCQ) in clearing heat and removing food accumulation and explore its potential mechanism, this study combined suckling SD rats fed with high-sugar and high-fat diet with injection of carrageenan to induce rat model of fever and food accumulation. This study provided references for the study on the pharmacodynamics and mechanism of XRCQ. The results showed that XRCQ effectively reduced the rectal temperature of suckling rats, improved the inflammatory environment such as the content of interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ(IFN-γ), white blood cells, and monocytes. XRCQ also effectively repaired intestinal injury and enhanced intestinal propulsion function. According to the confirmation of its efficacy of clearing heat, the thermolytic mechanism of XRCQ was further explored by non-targeted and targeted metabolomics methods based on LTQ-Orbitrap MS/MS and UPLC-QQQ-MS/MS. Non-target metabolomics analysis of brain tissue samples was performed by QI software combined with SIMCA-P software, and 22 endogenous metabolites that could be significantly regulated were screened out. MetaboAnalyst pathway enrichment results showed that the intervention mechanism was mainly focused on tyrosine metabolism, tricarboxylic acid cycle, inositol phosphate metabolism, and other pathways. At the same time, the results of targeted metabolomics of brain tissue samples showed that XRCQ changed the vitality of digestive system, and inhibited abnormal energy metabolism and inflammatory response, playing a role in clearing heat and removing food stagnation from multiple levels.
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Animais , Ratos , Ratos Sprague-Dawley , Temperatura Alta , Espectrometria de Massas em Tandem , Metabolômica , Alimentos , Febre , Interferon gamaRESUMO
OBJECTIVE@#This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase (DGC) in Vibrio cholerae and how its transcription is regulated by Fur and HapR.@*METHODS@#The roles of VCA0560 was investigated by utilizing various phenotypic assays, including colony morphological characterization, crystal violet staining, Cyclic di-GMP (c-di-GMP) quantification, and swimming motility assay. The regulation of the VCA0560 gene by Fur and HapR was analyzed by luminescence assay, electrophoretic mobility shift assay, and DNase I footprinting.@*RESULTS@#VCA0560 gene mutation did not affect biofilm formation, motility, and c-di-GMP synthesis in V. cholerae, and its overexpression remarkably enhanced biofilm formation and intracellular c-di-GMP level but reduced motility capacity. The transcription of the VCA0560 gene was directly repressed by Fur and the master quorum sensing regulator HapR.@*CONCLUSION@#Overexpressed VCA0560 functions as an active DGC in V. cholerae, and its transcription is repressed by Fur and HapR.
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Vibrio cholerae/genética , Biofilmes , Percepção de Quorum , Mutação , Regulação Bacteriana da Expressão Gênica , Proteínas de Bactérias/genéticaRESUMO
ObjectiveTo explore the neuromuscular control mechanism of training strategies based on mirror neuron system (MNS): action observation (AO), action execution (AE) and action imitation (AO+AE) using functional Near Infrared Spectroscopy (fNIRS) and surface electromyography (sEMG). MethodsFrom July, 2022 to February, 2023, 64 healthy adults were asked to finish four tasks: watching landscape video (control), watching landscape video and acting right wrist and hand extension (AE), watching right wrist and hand extension video (AO), and watching right wrist and hand extension video and acting right wrist and hand extension (AO+AE). A block design was adopted, five times a task in a block, eight cycles, random orders in videos and tasks. The activation of each channel and regions of interest (ROI, namely BA40, BA44, BA45, BA46, BA6 and BA7) in left MNS regions was detected with fNIRS synchronously, as well as the average electromyography (AEMG) of extensor digitorum and extensor carpi radialis with sEMG. ResultsCompared with the control condition, MNS activated in AO, AE and AO+AE conditions, and the intensities mildly increased in turn. Compared with the control condition, 15 channels activated in AO condition, 15 channels activated in AE condition, and all 20 channels activated in AO+AE condition; and the activation intensities of most channels were AO+AE > AE > AO. Four ROI, BA40, BA46, BA6 and BA7, activated in AO condition, all the six ROI activated in AE and AO+AE conditions, and the activation intensities of most ROI were AO+AE > AE > AO. The standardized AEMG of extensor digitorum and extensor carpi radialis were higher in AO+AE condition than in AE condition (|t| > 4.24, P < 0.001). ConclusionMNS has been activated during action observation, execution and imitation, and the ranges and intensities of activation increase in turn. The target muscles activate more during imitation than during execution. Synchronous application of fNIRS and sEMG is feasible in the study of neural mechanism of rehabilitation strategies based on mirror neuron theory.
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ß-Thalassemia (ß-thal), a highly prevalent disease in tropical and subtropical regions of Southern China, is caused mainly by point mutations in the ß-globin gene cluster. However, large deletions have also been found to contribute to some types of ß-thal. We identified a novel 5 kb deletion in the ß-globin cluster in a Chinese patient using multiplex ligation-dependent probe amplification (MLPA), and characterized it with single molecule real-time (SMRT) sequencing, gap-polymerase chain reaction (gap-PCR) and Sanger sequencing. The deletion was located between positions 5226189 and 5231091 on chromosome 11 (GRCh38), extending from 4 kb upstream of the 5' untranslated region (5'UTR) to the second intron of the ß-globin gene. The patient with this deletion presented with microcytosis and hypochromic red cells, as well as relatively high Hb F and Hb A2 levels. Our research indicated that SMRT sequencing is a useful tool for accurate detection of large deletions. Our study broadens the spectrum of deletional ß-thalassemias and provides a perspective for further study of the function of the ß-globin cluster.
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Globinas beta , Talassemia beta , Humanos , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Deleção de Genes , Família Multigênica , Reação em Cadeia da Polimerase Multiplex , Deleção de SequênciaRESUMO
Toll-interacting protein (Tollip) plays an important role in the innate immune response by negative regulation of the TLR-IL-1R signaling pathway. MyD88 serves as a universal adaptor in TLR-mediated NF-κB activation. However, the regulation mechanisms of Tollip in piscine MyD88-mediated NF-κB activation is largely unknown. In the present study, the cDNA sequence of LcTollip was identified from the large yellow croaker (Larimichthys crocea). The putative LcTollip protein encoded 275 amino acid residues, containing a N-terminal TBD domain, a central C2 domain, and a C-terminal CUE domain. Quantitative PCR showed that the most predominant constitutive expression of LcTollip was detected in spleen. In addition, LcTollip transcripts enhanced significantly after LPS and poly I:C challenge (P < 0.05). Cellular localization revealed that LcTollip existed in the cytoplasm and nucleus. Furthermore, the overexpression plasmids of wild type LcTollip as well as its six domain truncated mutants of LcTollip were constructed by overlap PCR. Dual luciferase analysis showed that NF-κB activation could not be induced by overexpression of LcTollip or its domain truncated mutants alone. However, the LcMyD88-induced-NF-κB activation was significantly suppressed by overexpression with LcTollip, and the truncated mutants LcTollip-ΔTBD, LcTollip-ΔC2, LcTollip-ΔCUE and LcTollip-ΔTBDΔCUE while not by LcTollip-ΔLR and LcTollip-ΔTBDΔC2. Moreover, co-immunoprecipitation (Co-IP) assay revealed that the interaction between LcTollip and LcMyD88 was through CUE domain. More interesting, IP and immunoblotting examination of HEK293T cells co-transfected with LcMyD88, LcTollip and HA-ubiquitin showed that LcMyD88 induced a dose-dependent de-ubiquitination of LcTollip while LcTollip enhanced a dose-dependent ubiquitination of LcMyD88. However, protein degradation investigation displayed that the proteolysis and ubiquitination of LcMyD88 were not connected. Our findings suggested that the LcTollip might involve in negative regulation TLR pathway by suppressing LcMyD88-mediated immune activation and improving the ubiquitination level of LcMyD88.
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Fator 88 de Diferenciação Mieloide , Perciformes , Proteínas Adaptadoras de Transdução de Sinal/genética , Sequência de Aminoácidos , Aminoácidos/metabolismo , Animais , DNA Complementar/genética , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Luciferases/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Poli I-C/farmacologia , Transdução de Sinais , Ubiquitinação , Ubiquitinas/genéticaRESUMO
Background: Gastrointestinal cancers are the most common malignant tumors worldwide. As the improvement of survival by surgical resection alone for cancers is close to the bottleneck, recent neoadjuvant therapy has been emphasized and applied in the treatment. Despite the advantage on improving the prognosis, some studies have reported neoadjuvant therapy could reduce skeletal muscle and therefore affect postoperative outcomes. However, the conclusions are still controversial. Methods: PubMed, CINAHL, Embase, and Cochrane Library were searched from inception to September 2, 2021. The inclusion criteria were observational studies, published in English, of individuals aged ≥18 years who underwent neoadjuvant therapy with gastrointestinal cancers and were assessed skeletal muscle mass before and after neoadjuvant therapy, with sufficient data on skeletal muscle change or the association with clinical outcomes. Meta-analysis was conducted by using the STATA 12.0 package when more than two studies reported the same outcome. Results: A total of 268 articles were identified, and 19 studies (1,954 patients) were included in the review. The fixed effects model showed that the risk of sarcopenia increased 22% after receiving neoadjuvant therapy (HR=1.22, 95% CI 1.14, 1.31, Z=4.286, P<0.001). In the random effects model, neoadjuvant therapy was associated with skeletal muscle loss, with a standardized mean difference of -0.20 (95% CI -0.31, -0.09, Z=3.49, P<0.001) and a significant heterogeneity (I2 = 62.2%, P<0.001). Multiple meta regression indicated that population, neoadjuvant therapy type, and measuring tool were the potential sources of heterogeneity. The funnel plot revealed that there was no high publication bias in these studies (Begg's test, P=0.544) and the sensitivity analysis showed stable results when separately excluding studies. For the postoperative outcomes, the results revealed that muscle loss during neoadjuvant therapy was significantly related to overall survival (HR=2,08, 95% CI =1.47, 2.95, Z=4.12, P<0.001, I2 = 0.0%), but not related to disease-free survival and other short-term outcomes. Conclusions: This systematic review and meta-analysis revealed that skeletal muscle decreased significantly during neoadjuvant therapy in patients with gastrointestinal cancers and skeletal muscle loss was strongly associated with worse overall survival. More high-quality studies are needed to update and valid these conclusions in a more specific or stratified way. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier PROSPERO (CRD42021292118).
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Lupus nephritis (LN) is the most common serious complication of systemic lupus erythematosus (SLE). The pathogenesis of LN is complex, and the majority causes of LN are the renal deposition of circulating or/and in situ-formed immune complexes. These immune complexes trigger glomerular and tubulointerstitial inflammation, which finally leads to proteinuria and loss of renal function. Despite the emergence of new biological agents, cyclophosphamide (CY), an alkylating agent, is still the first-line drug widely used to treat patients with severe LN. In this review, we outline the application history, molecular structure, and pharmacokinetics of CY in the treatment of LN. We also detail its latest known immunopharmacological mechanisms, with a focus on supplemental regulation and inhibition of CD4 and CD8 positive T cells, differences in the use of various guidelines, and the combination with other drugs. The side effects of CY are also mentioned in this review.
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Complexo Antígeno-Anticorpo , Ciclofosfamida/uso terapêutico , Humanos , Glomérulos Renais/patologia , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologiaRESUMO
Toll like receptor 5 (TLR5) plays a crucial role in the innate immune response by recognizing bacterial flagellin proteins. In the present study, the genomic and 5'-flanking sequences of LcTLR5M (membrane) and LcTLR5S (soluble) were cloned from the large yellow croaker, Larimichthys crocea. Then, their promoter activities were determined in human embryonic kidney (HEK293T) cells. LcTLR5M contained 4 exons and 3 introns, and LcTLR5S contained 2 exons and 1 intron. Bioinformatic prediction of transcription factor binding sites (TFBSs) indicated that the promoter structures were different between LcTLR5M and LcTLR5S. A dual luciferase assay showed that the deletion mutant -471 to +189 of LcTLR5M promoter possessed the greatest activity with 36 times activity of the control (P < 0.05). For LcTLR5S, two deletion mutants, -1687 to +106 and - 720 to +106, showed high promoter activity. Furthermore, site-directed mutation demonstrated that a -392 to -391 AT/GG substitution in Oct-1 binding site, and a -104 to -103 GG/TT and a -98 to -97 CC/AA substitution in the NF-κB binding site of TLR5S caused a significant decline of luciferase activity (P < 0.05). Moreover, the co-transfection of an NF-κB/p65 over-expression plasmid with wild type TLR5S (-720 to +106) resulted in an extremely significant increase of promoter activity by more than 9 times compared with the NF-kB mutant (P < 0.01). Our findings suggest that the genomic organization and promoter structure may differ between LcTLR5M and LcTLR5S. Oct1 and NF-κB binding sites might be cis-regulatory elements in the LcTLR5S promoter. NF-κB/p65 plays an important role in LcTLR5S promoter activation through binding with the NF-κB binding site.
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NF-kappa B , Perciformes , Animais , Sítios de Ligação , Proteínas de Peixes/genética , Células HEK293 , Humanos , Imunidade Inata , NF-kappa B/genética , NF-kappa B/metabolismo , Perciformes/genética , Perciformes/metabolismoRESUMO
Objective@#This study conducts a Meta analysis on the epidemiological studies of obesity and autism spectrum disorder (ASD) in order to explore the relationship between autism spectrum disorder and obesity in children and adolescents, and to provide some guidance for improving the quality of daily life of children and adolescents with ASD.@*Methods@#PubMed and CNKI (January,2010-January,2022) were systematically searched for literature related to autism spectrum disorders reported the or value by Meta analysis, and compared the weight, BMI acquisition method.@*Results@#A total of 11 literatures were selected for analysis. The total sample included 336 830 participants, including 58 187 patients with ASD and 278 643 patients with normal development. Through Meta analysis, children and adolescents with ASD had a higher risk of obesity than normal people ( OR=1.80, 95%CI = 1.74 -1.86). when stratified by BMI acquisition, autistic patients with BMI obtained from objective measurement, medical records and parents reports had a higher risk of obesity than normal people, and the OR value (95% CI ) was 1.43(1.04-1.96),5.23( 4.44- 6.16),2.57(1.79-3.69). When stratified by age, children and adolescents with ASD aged 14 to 20 years had a higher risk of obesity than normal people. The OR value (95% CI ) was 2.19(1.21-3.94).@*Conclusion@#Compared with healthy peers, children and adolescents with ASD have a higher risk of obesity. ASD patients need guidance in diet and physical activity, especially in adolescence, to prevent obesity or diseases caused by obesity.
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OBJECTIVE: To analyze the hematological characteristics of Chinese Gγ+(Aγδß)0-thalassemiaï¼SEA-HPFH and Taiwan type ß-thalassemia. METHODS: Hemoglobin electrophoresis and blood routine test were used to analyze the hematological indexes of all peripheral blood samplesï¼PCR-Flow fluorescent hybridization and Gap-PCR were used to detect the globin gene mutations and the data were analyzed statistically. RESULTS: The 3 types of deletion ß- Thalassemia patients were showed as hypochromic small cell anemia. The MCH and MCV values of Taiwan type ß-thalassemia patients were the lowest. The results of hemoglobin electrophoresis showed that the increasing of HbF was found in all of the 3 types. Except for the decreasing of Hb A2 in Chinese Gγ+(Aγδß)0-thalassemiaï¼the levels of Hb A2 in the other two deletion ß-thalassemia patients were significantly increased. Except for Hb, there were significant differences in MCV, MCH, Hb A2 and HbF between Chinese Gγ+(Aγδß)0-thalassemia and SEA-HPFH(P<0.001). CONCLUSION: Through analyze the hematological characteristics, it can be provide that the guidance for the differential diagnosis and genetic consultation of the three commonest deletion ß-thalassemia in Chinese.
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Talassemia , Talassemia beta , China , Diagnóstico Diferencial , Hemoglobina Fetal , Humanos , Mutação , Talassemia beta/diagnóstico , Talassemia beta/genéticaRESUMO
OBJECTIVE: To investigate whether ß-globin gene 3'UTR+101G>C (HBB:c.*233G>C) variant has genetic effect and provide basis for gene diagnosis and genetic counseling. METHOD: Whole blood cell analysis and capillary zone electrophoresis (CZE) were used to analyze the hematological indexes. The most frequent 23 mutations in southern Chinese individuals were routinely measured by PCR-flow fluorenscence immunmicrobeads assay. Sanger sequencing was used to detect the other variants of ß-globin gene (HBB). RESULTS: In 463 cases, a total of 7 cases with HBB:c.*233G>C variant were detected, among them 4 cases carried other pathogenic variants of HBB gene (2 cases were in trans, 2 cases were in cis), who had typical hematological characteristics of mild ß-thalassemia, and 3 cases also carried abnormal hemoglobin variation, but did not have hematological characteristics of ß-thalassemia. CONCLUSION: The study shows that HBB:c.*233G > C variant has no obvious genetic effect and should be a benign polymorphism.