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Ferroptosis is a novel, iron-dependent cell death characterized by the excessive accumulation of ferroptosis lipid peroxides ultimately leading to oxidative damage to the cell membrane. Iron, lipid, amino acid metabolism, and other signaling pathways all control ferroptosis. Numerous bodily tissues experience hypoxia under normal and pathological circumstances. Tissue cells can adjust to these changes by activating the hypoxia-inducible factor (HIF) signaling pathway and other mechanisms in response to the hypoxic environment. In recent years, there has been increasing evidence that hypoxia and ferroptosis are closely linked, and that hypoxia can regulate ferroptosis in specific cells and conditions through different pathways. In this paper, we review the possible positive and negative regulatory mechanisms of ferroptosis by hypoxia-inducible factors, as well as ferroptosis-associated ischemic diseases, with the intention of delivering novel therapeutic avenues for the defense and management of hypoxic illnesses linked to ferroptosis.
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Ferroptose , Transdução de Sinais , Humanos , Animais , Hipóxia/metabolismo , Ferro/metabolismo , Hipóxia CelularRESUMO
BACKGROUND: Severe heart failure (HF) has a higher mortality during vulnerable period while targeted predictive tools, especially based on drug exposures, to accurately assess its prognoses remain largely unexplored. Therefore, this study aimed to utilize drug information as the main predictor to develop and validate survival models for severe HF patients during this period. METHODS: We extracted severe HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database and local hospital (as external validation cohorts). Three algorithms, including Cox proportional hazards model (CoxPH), random survival forest (RSF), and deep learning survival prediction (DeepSurv), were applied to incorporate the parameters (partial hospitalization information and exposure durations of drugs) for constructing survival prediction models. The model performance was assessed mainly using area under the receiver operator characteristic curve (AUC), brier score (BS), and decision curve analysis (DCA). The model interpretability was determined by the permutation importance and Shapley additive explanations values. RESULTS: A total of 11,590 patients were included in this study. Among the 3 models, the CoxPH model ultimately included 10 variables, while RSF and DeepSurv models incorporated 24 variables, respectively. All of the 3 models achieved respectable performance metrics while the DeepSurv model exhibited the highest AUC values and relatively lower BS among these models. The DCA also verified that the DeepSurv model had the best clinical practicality. CONCLUSIONS: The survival prediction tools established in this study can be applied to severe HF patients during vulnerable period by mainly inputting drug treatment duration, thus contributing to optimal clinical decisions prospectively.
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Insuficiência Cardíaca , Modelos de Riscos Proporcionais , Humanos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Feminino , Masculino , Idoso , Reprodutibilidade dos Testes , Prognóstico , Análise de Sobrevida , Pessoa de Meia-Idade , Curva ROC , Algoritmos , Área Sob a Curva , Bases de Dados Factuais , Aprendizado Profundo , Índice de Gravidade de DoençaRESUMO
PURPOSE: To investigate the association between proton pump inhibitors (PPIs) administration during hospitalization and mortality and length of stay in critically ill pediatric patients. MATERIALS AND METHODS: This is a retrospective observational cohort study on pediatric ICU patients (0 to 18 years). Propensity score matching (PSM), Kaplan-Meier curves, Cox proportional hazards model and Linear regression model was applied for assessing the effects of PPIs on mortality and other outcomes during hospitalization. RESULTS: A total of 2269 pediatric ICU patients were included, involving 1378 omeprazole (OME) users and 891 non-OME users. The results showed significant association between OME exposure and decreased ICU stay (ß -0.042; 95% CI -0.073--0.011; P = 0.008) but prolonged non-ICU hospital stay (ß 0.121; 95% CI 0.097-0.155; P = 0.040). No statistical significance was observed between OME exposure and reduced mortality, but the OME group had a slightly decreased tendency in 28-day mortality (HR 0.701; 95% CI 0.418-1.176) and in-hospital mortality (HR 0.726; 95% CI 0.419-1.257). Furthermore, subgroup analyses revealed that the decreased tendency of mortality were more obvious in patients less than 1 year old compared with older pediatric patients, although not statistically significant. In addition, we also observed that OME exposure was significantly associated with reduced mortality of general ICU subgroup. CONCLUSIONS: This study provided a sign that PPIs used only in the ICU, rather than throughout hospital stay, might provide more benefit for critically ill pediatric patients. Additionally, younger pediatric patients might gain relatively more benefit than older children when receiving PPIs.
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Estado Terminal , Omeprazol , Humanos , Criança , Adolescente , Lactente , Tempo de Internação , Estudos de Coortes , Omeprazol/uso terapêutico , Estado Terminal/terapia , Mortalidade Hospitalar , Inibidores da Bomba de Prótons/uso terapêutico , Unidades de Terapia Intensiva , Estudos RetrospectivosRESUMO
BACKGROUND: Recently, increasing evidence has demonstrated that IL-10 single nucleotide polymorphisms (SNPs) are associated with the risk of acute leukemia (AL), but the findings of different articles remain controversial. Thus, we performed a meta-analysis to further investigate the exact roles of IL-10 SNPs in AL susceptibility. METHODS: Six common Chinese and English databases were utilized to retrieve eligible studies. The strength of the association was assessed by calculating odds ratios and 95 % confidence intervals. All analyses were carried out using Review Manager (version 5.3) and STATA (version 15.1). The registered number of this research is CRD42022373362. RESULTS: A total of 6391 participants were enrolled in this research. The results showed that the AG genotype of rs1800896 increased AL risk in the heterozygous codominant model (AG vs. AA, OR = 1.41, 95 % CI = 1.04-1.92, P = 0.03) and overdominant model (AG vs. AA + GG, OR = 1.32, 95 % CI = 1.04-1.70, P = 0.03). In the subgroup analysis, associations between the G allele, GG genotype, AG genotype, AG + GG genotype of rs1800896 and increased AL risk were also observed in the mixed population based on allelic, homozygote codominant, heterozygous codominant, dominant, and overdominant models. Furthermore, an association between the AC genotype of rs1800872 and increased AL risk was observed in the Caucasian population in the overdominant model. However, the rs1800871, rs3024489 and rs3024493 polymorphisms did not affect AL risk. CONCLUSION: IL-10 rs1800896 and rs1800872 affected the susceptibility of AL and therefore may be biomarkers for early screening and risk prediction of AL.
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Interleucina-10 , Leucemia Mieloide Aguda , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença/genética , Genótipo , Interleucina-10/genética , Leucemia Mieloide Aguda/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
OBJECTIVES: The current world witnesses a greatly increased prevalence and incidence of hyperuricemia and gout with unfortunately the comparative efficacy and safety of present available uricosuric agents remaining uncertain. We herein aimed to investigate the most appropriate uricosuric agent for gout or hyperuricemia patients. METHOD: PubMed, Embase, Cochrane Library databases, and ClinicalTrials.gov from inception to 2 July 2022 were searched to retrieve eligible studies assessing efficacy and safety of uricosuric drugs in hyperuricemia or gout patients. Network meta-analysis was carried out using the Stata 16.0 software. RESULTS: Twelve randomized controlled trials comprising 1851 patients were eventually included. Network meta-analysis showed that dotinurad 4 mg once daily, verinurad, dotinurad 2 mg once daily, dotinurad 1 mg once daily, and benzbromarone were the top 5 effective treatments to achieve target serum uric acid. Furthermore, dotinurad 4 mg once daily was more effective at achieving urate-lowering targets (RR of dotinurad 4 mg once daily vs. probenecid: 1.68, 95% CI [1.13; 2.50]) and safer (RR of probenecid vs. dotinurad 4 mg once daily: 1.77, 95% CI [0.69; 4.56]) than probenecid. CONCLUSIONS: This network meta-analysis demonstrated an important absolute benefit of dotinurad 4 mg once daily to achieve target serum uric acid and low risk of adverse events for drug treatment of gout or hyperuricemia patients. Additionally, verinurad might be used as an alternative uricosuric therapeutic option to dotinurad. These findings provided further comprehensive insight into the treatment value of current uricosuric agents for gout or hyperuricemia. Key Points 1. This is the first systematic review and network meta-analysis examining the efficacy and safety of currently available uricosuric agents in gout or hyperuricemia patients. 2. Recommended doses of dotinurad 4mg once daily used for the treatment of gout or hyperuricemia patients can significantly decrease serum uric acid levels. 3. The present findings will provide further comprehensive insight into the treatment value of certain uricosuric agents for gout or hyperuricemia.
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Gota , Hiperuricemia , Uricosúricos , Humanos , Gota/tratamento farmacológico , Supressores da Gota/efeitos adversos , Hiperuricemia/tratamento farmacológico , Metanálise em Rede , Probenecid , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Úrico , Uricosúricos/efeitos adversosRESUMO
Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta-analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty-six individual meta-analyses were identified, including 29 meta-analyses of observation studies with 32 unique outcomes and 19 meta-analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non-H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta-analyses showed that 4 of 46 meta-analyses were assigned as high scores, 3 were assigned as "moderate," and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as "moderate," 9 outcomes were rated as "low," and 17 outcomes were rated as "very low." We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.
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Enterocolite Necrosante , Pneumonia , Humanos , Recém-Nascido , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversosRESUMO
Background: Although numerous studies confirmed the marked efficacy of chimeric antigen receptor T cells (CAR-T cells) in many hematologic malignancies, severe cardiovascular toxicities remain to be a major obstacle when incorporating this technology. Furthermore, previous individual investigations regarding the cardiovascular toxicities of CAR-T cell therapy also reported controversial conclusions. Therefore, a meta-analysis was performed to further evaluate the impacts of CAR-T cell therapy on cardiovascular toxicities. Methods: The PubMed, Embase, Web of Science, and ClinicalTrials.gov databases were searched for eligible studies up to April 2022. All analyses were carried out using the R 4.1.0 software. Results: Eventually, 25 related studies consisting of 2,059 patients were enrolled in the current meta-analysis. We discovered that the pooled incidence rate of the all-cause mortality rate was 14.1% and that the pooled incidence rates of overall cardiovascular (CV) events and CV events with cytokine release syndrome (CRS) grade ≥ 2 were 25.6% and 14.2%, respectively. The pooled incidence of hypotension was 28.6%. Further analysis showed that the incidence rates of arrhythmias, cardiovascular dysfunction, heart failure (HF), CV deaths, acute coronary syndrome (ACS), cardiomyopathy, cardiac arrest, and other CV events were 19.2%, 8.0%, 5.3%, 1.8%, 2.5%, 2.9%, 1.3%, and 1.9%, respectively. Conclusion: Cancer patients treated with CAR-T cell therapy were at risk for cardiovascular toxicities, of which the most common cardiovascular events were arrhythmias, cardiovascular dysfunction, and heart failure. These findings would contribute to achieving more rational and individualized use of CAR-T cells in clinical treatment.
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PURPOSE: To analyze the clinical effect of digital impression combined with all-ceramic denture restoration on patients with dental defects. METHODS: A study was conducted on 120 patients with dental defects admitted to Dongfeng Stomatological Hospital from June 2018 to June 2020. The two groups of patients were randomly divided into digital imprinting modules and silicone rubber imprinting modules using a random number table method. There were 60 cases in each group. The silicone rubber imprint module used traditional silicone impression combined with all-ceramic denture restoration, while the digital imprint module used digital impression combined with all-ceramic denture restoration.The clinical efficacy of the two groups was observed. Gingival index (GI), periodontal index (PI) before dental restoration, during dental restoration and 6 monthes after dental restoration were compared. The adjacent surface contact conditions, occlusion and adverse reactions of the two groups were compared. SPSS 22.0 software package was used for statistical analysis. RESULTS: The two groups of patients selected grade A and grade B for the evaluation of the restoration when the restoration was completed. The number of patients who chose grade A for the digital imprint module was more than that of the silicone rubber imprint module,but there was no significant difference(Pï¼0.05). Six months after the tooth was worn, GI and PI indexes of the two groups of patients increased. GI and PI indexes of the silicone rubber stamping module were significantly higher than those of the digital stamping module(Pï¼0.05). When dental restoration was completed and 6 months after the tooth was replaced, the pass rate of contact between the adjacent surfaces of the imprinting module patients was significantly higher than that of the silicone rubber imprinting module(Pï¼0.05). When dental restoration was completed, the occlusion of the digital imprinting module patients was significantly better than that of the silicone rubber imprinting module(Pï¼0.05). Six months after wearing the denture, there was no significant difference in occlusion between the two groups of patients(Pï¼0.05). When dental models of the two groups of patients were taken, the incidence of adverse reactions in patients with digital imprints was significantly lower than that of silicone rubber imprints(Pï¼0.05). CONCLUSIONS: The use of digital impressions combined with all-ceramic restorations to repair patients with dental defects can effectively improve the treatment effect, improve prognostic GI and PI indexes of the patients, increase the pass rate of the adjacent surface contact and occlusion of the tooth, and reduce the process of dental restoration. The incidence of adverse reactions are minimal, with good prognostic effects. It is worthy of clinical application.
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Coroas , Porcelana Dentária , Cerâmica , Desenho Assistido por Computador , Técnica de Moldagem Odontológica , Planejamento de Prótese Dentária/métodos , Dentaduras , Humanos , Elastômeros de SiliconeRESUMO
Background and objectives: Patients with chronic obstructive pulmonary disease (COPD) suffer from impaired pulmonary function and dyspnea, which result in limited levels of physical activity, and impaired quality of life. Exercise and regular physical activity have been proven to break the vicious circle. The aim of this pilot study is to investigate the effects of a walking program on exercise capacity and quality of life in patients with COPD. Materials and Methods: Patients with COPD were randomly assigned to a pedometer group (PG) or control group (CON). Subjects in the PG walked target steps daily with a pedometer for six weeks. Before and after the program, the following measurements were performed: pulmonary function test (PFT), daily steps, Six-Minute Walk Test (6 MWT), COPD Assessment Test (CAT), and quality of life questionnaire (SF-12). Results: After this walking program, PG (n = 15) significantly improved their daily steps from 4768.4 ± 2643.3 steps to 7042.7 ± 4281.9 steps (p = 0.01). Forced vital capacity (FVC) increased from 2.5 ± 0.7 L to 2.8 ± 0.9 L (p = 0.02). CAT scores decreased from 14.9 ± 8.8 points to 11.5 ± 7.5 points (p = 0.03). In the control group (n = 11), there were no differences in any outcomes after this daily walking program. Conclusions: For patients with COPD, a daily walking program with a pedometer is beneficial in the improvement of pulmonary function, daily steps, and quality of life.
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Actigrafia , Doença Pulmonar Obstrutiva Crônica , Humanos , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , CaminhadaRESUMO
Metazoans harbor a wealth of symbionts that are ever-changing the environment by taking up resources and/or excreting metabolites. One such common environmental modification is a change in pH. Conventional wisdom holds that symbionts facilitate the survival and production of their hosts in the wild, but this notion lacks empirical evidence. Here, we report that symbiotic bacteria in the genus Enterococcus attenuate the oviposition avoidance of alkaline environments in Drosophila. We studied the effects of alkalinity on oviposition preference for the first time, and found that flies are robustly disinclined to oviposit on alkali-containing substrates. This innate repulsion to alkaline environments is explained, in part, by the fact that alkalinity compromises the health and lifespan of both offspring and parent Drosophila. Enterococcus dramatically diminished or even completely reversed the ovipositional avoidance of alkalinity in Drosophila. Mechanistically, Enterococcus generate abundant lactate during fermentation, which neutralizes the residual alkali in an egg-laying substrate. In conclusion, Enterococcus protects Drosophila from alkali stress by acidifying the ovipositional substrate, and ultimately improves the fitness of the Drosophila population. Our results demonstrate that symbionts are profound factors in the Drosophila ovipositional decision, and extend our understanding of the intimate interactions between Drosophila and their symbionts.
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Fenômenos Fisiológicos Bacterianos , Drosophila melanogaster/microbiologia , Drosophila melanogaster/fisiologia , Repelentes de Insetos/química , Oviposição , Simbiose , Animais , Concentração de Íons de HidrogênioRESUMO
BACKGROUND: Several studies have explored the association between the use of proton pump inhibitors (PPIs) and the risk of developing hepatic encephalopathy (HE) in patients with advanced liver disease. However, the evidence-based conclusions are controversial. We hypothesized that using PPIs may increase the risk of HE in patients with advanced liver disease. If confirmed, clinicians must strictly adhere to the indications for PPI treatment in this population. AIM: To evaluate the pooled risk of HE in patients with advanced liver disease who use PPIs. METHODS: Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from the date of database inception through January 8, 2019 to identify comparative studies evaluating the association between PPI use and the risk of HE. Data from the included studies were extracted. The random-effects model was used for pooling risk estimates and the corresponding 95% confidence intervals (CIs). Subgroup and sensitivity analyses were also performed. RESULTS: In total, 4342 patients from five case-control studies and 188053 patients from four cohort studies were included in this analysis. In patients with advanced liver disease, PPI use was associated with an elevated risk of developing HE, with significant heterogeneity. The pooled odds ratio for case-control studies was 2.58 (95%CI: 1.68-3.94, I 2 = 72%). The pooled RR for cohort studies was 1.67 (95%CI: 1.30-2.14, I 2 = 67%). The results of the subgroup analyses suggested that the heterogeneity may be the result of differences in the study designs and the definitions of PPI use. The sensitivity and subgroup analyses did not alter our findings. CONCLUSION: In patients with advanced liver disease, PPI use is associated with an elevated risk of HE. Future large prospective studies are needed to confirm this association.
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Encefalopatia Hepática/epidemiologia , Cirrose Hepática/complicações , Inibidores da Bomba de Prótons/efeitos adversos , Progressão da Doença , Encefalopatia Hepática/etiologia , Humanos , Cirrose Hepática/patologia , Estudos Observacionais como Assunto , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: The risk of lower extremity arterial disease (LEAD) is increased in diabetic patients. LEAD in diabetic patients occurs earlier and is often more severe and diffuse; however, it is largely underdiagnosed and untreated. The purposes of this study were to investigate and analyze LEAD situation of hospitalized elderly type 2 diabetic patients. METHODS: The ankle-brachial index (ABI) was used to screen LEAD in hospitalized elderly type 2 diabetic patients. The patients were divided into 5 groups based on the screening results: non-LEAD group and LEAD group; the LEAD group was divided into mild stenosis group, moderate stenosis group, and severe stenosis group. RESULTS: The percentage of patients who had LEAD was 43%. Significant difference in age, diabetes duration, peak velocity, microalbuminuria, and vibratory sensory neuropathy was observed between patients with and without LEAD; regression analysis showed that urinary albumin and vibratory sensory neuropathy were independent risk factors for LEAD. Significant difference in age, body mass index (BMI), peak velocity, urinary albumin, and high-density lipoprotein cholesterol (HDL-C) was observed between mild stenosis group, moderate stenosis group, and severe stenosis group; regression analysis showed that urinary albumin, BMI, and HDL-C were independent risk factors for accelerating vascular stenosis. CONCLUSIONS: The incidence of LEAD in hospitalized elderly type 2 diabetic patients is high; age, diabetes duration, peak velocity, BMI, urinary microalbumin, vibratory sensory neuropathy, and HDL-C are the major risk factors for LEAD. Active control of risk factors is helpful to reduce or delay LEAD.
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Ultrasound-assisted extraction (UAE), using petroleum ether as the solvent, was systematically applied to extract main macamides and macaenes from Maca hypocotyls. Extraction yield was related with four variables, including ratio of solution to solid, extraction temperature, extraction time, and extraction power. On the basis of response surface methodology (RSM), the optimal conditions were determined to be the ratio of solution to solid as 10:1 (mL/g), the extraction temperature of 40 °C, the extraction time of 30 min, and the extraction power of 200 W. Based on the optimal extraction method of UAE, the total contents of ten main macamides and two main macaenes of Maca cultivated in twenty different areas of Tibet were analyzed by HPLC and UHPLC-ESI-Q-TOF-MS/MS. This study indicated that UAE was able to effectively extract macamides alkaloids from Maca hypocotyls. Quantitative analysis showed that geographical origins, not ecotypes, played a more important role on the accumulation of active macamides in Maca.
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Lepidium/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Temperatura , TibetRESUMO
In the present study, the removal of p-nitrophenol (p-NP) from aqueous solution through the adsorption on water-quenched blast furnace slag (WBFS) was investigated. The physicochemical properties of the slag were characterized by SEM, XRD, FTIR and BET. Batch experiments were conducted to investigate the mechanism, kinetics and thermodynamics of adsorption process. The results showed that the experimental data could fit to Freundlich model. The enthalpy change (ΔH) and entropy change (ΔS) were 3.29 kJ·mol-1 and 4.66 J·(mol·K)-1, respectively. It indicated that the adsorption of p-NP on WBFS was an endothermic and entropy-increasing process. The values of ΔG decreased with increasing temperature, indicating the spontaneous adsorption proportional to the temperature. The adsorption could be divided into two parts, one was high-speed surface coverage, and the other was slow-speed internal diffusion adsorption. It was also found that the adsorption process followed the pseudo-second-order kinetic model. The fractal dimensions of WBFS surface calculated by Freundlich adsorption fractal model were 2.78, 2.80, 2.84 and 2.87 at different temperatures, respectively. It indicated the existence of fractal phenomenon with higher fractal dimension of WBFS at higher temperature.
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Resíduos Industriais , Nitrofenóis/metabolismo , Poluentes Químicos da Água/metabolismo , Adsorção , Fractais , Concentração de Íons de Hidrogênio , Cinética , Temperatura , Termodinâmica , ÁguaRESUMO
OBJECTIVE: To compare the efficacy differences between acupuncture-moxibustion and physiotherapy interventions in improving proprioception of athletes with lateral collateral ligament injury of the ankle joint. METHODS: Thirty patients with injured lateral collateral ligament of ankle joint were randomly divided into acupuncture group (n = 15) and physiotherapy group (n = 15). Patients of the acupuncture group were treated by acupuncture and moxibustion stimulation of Qiuxu (GB40), Kunlun (BL 60), Shenmai (BL 62), Jiexi (ST 41), and Ashi-points, etc., and those of the physiotherapy group treated with TDP irradiation of the regional lateral malleolus. The treatment of the two groups was conducted once the other day, 3 times each week, continuously for 8 weeks. Before and after the treatment, the ankle-joint's active and passive repositioning error angles were measured by using a joint angle ruler. RESULTS: The average error angle values of active and passive reposition tests of the injured ankle-joint were 4.98 +/- 1.11 and 4.78 +/- 1.3 before the treatment, and 3.67 +/- 0.58 and 3.51 +/- 0.64 after the treatment, respectively in the acupuncture group, being reduced significantly after the treatment (both P < 0.01). No significant changes of the average error angle values of both active and passive reposition tests of the ankle-joint were found after the treatment in the physiotherapy group (P > 0.05). Comparison between two groups showed that the average error angle, average active and passive reposition angles of the injured ankle in the acupuncture group were evidently lower than those in the physiotherapy group (P < 0.01). CONCLUSION: Acupuncture and moxibustion can effectively improve the proprioception of the injured lateral collateral ligament of the ankle joint in athletes, which is superior to conventional physiotherapy in the therapeutic effect.
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Pontos de Acupuntura , Terapia por Acupuntura , Traumatismos do Tornozelo/terapia , Ligamentos Colaterais/lesões , Moxibustão , Propriocepção , Adolescente , Traumatismos do Tornozelo/fisiopatologia , Atletas , Terapia Combinada , Feminino , Humanos , Masculino , Resultado do Tratamento , Adulto JovemAssuntos
Neoplasias do Sistema Nervoso Central/patologia , Granulomatose Linfomatoide/patologia , Ataxia/etiologia , Ataxia/patologia , Biópsia , Encéfalo/patologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Imuno-Histoquímica , Pulmão/patologia , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética , Exame Neurológico , Remissão Espontânea , Adulto JovemRESUMO
Monoesters of ginsenoside metabolite M1 at the 3-OH, 4-OH and 6-OH positions of the glucose moiety at M1 were synthesized via the reaction of M1 with acyl chloride, or acid-N,N'-diisopropylcarbodiimide in the presence of DMAP. Their structures were fully characterized by spectral methods. The cytotoxicity of these compounds against then MGC80-3 human gastric cancer cell line was also assessed. High inhibitory effects were found at a concentration of 100 µg/mL.
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Antineoplásicos/síntese química , Ginsenosídeos/síntese química , Ginsenosídeos/farmacologia , Antineoplásicos/farmacologia , Carbodi-Imidas/análise , Carbodi-Imidas/química , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Piridinas/análise , Piridinas/químicaRESUMO
AIMS: To investigate epidermal growth factor receptor (EGFR) expression and amplification in gliomas and to assess their association with survival. METHODS AND RESULTS: Immunohistochemistry and fluorescence in-situ hybridization were performed to analyse EGFR status in 158 cases of primary glioma. Kaplan-Meier survival and Cox regression analyses were performed to analyse the prognosis of patients. Overexpression of EGFR and expression of EGFR variant III (EGFRvIII) were found in 102 cases (64.6%) and 47 cases (29.7%), respectively. Overexpression of EGFR was significantly correlated with World Health Organization (WHO) grade and Karnofsky performance score (KPS) (both P < 0.05). Expression of EGFRvIII was significantly correlated with WHO grade, gender, age, and KPS (all P < 0.05). EGFR amplification was found in 46 cases (29.1%), and was significantly correlated with WHO grade, age, KPS and EGFR overexpression (all P < 0.05). Cox multifactor analysis showed that EGFR amplification was an independent unfavourable prognostic factor for human gliomas at all ages, and EGFRvIII was an independent prognostic factor in patients older than 60 years. CONCLUSION: EGFR amplification and EGFRvIII expression were associated with an unfavourable prognosis for patients of all ages, and for those older than 60 years, respectively. The differing significance of EGFR status in young and old glioma patients and its impact on prognosis needs further study.
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Neoplasias Encefálicas/patologia , Receptores ErbB/biossíntese , Receptores ErbB/genética , Glioma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Receptores ErbB/análise , Feminino , Amplificação de Genes , Genes erbB-1 , Glioma/genética , Glioma/metabolismo , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies in China and epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane. The aim of this study was to investigate the protein overexpression and gene copy number of EGFR in ESCC, and help to identify patients who may benefit from EGFR targeted therapies. METHODS: Immunohistochemistry (IHC) was performed to analyze the expression of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 cases of normal esophageal tissue. Fluorescence in situ hybridization (FISH) was performed to analyze the gene copy number in 80 cases of ESCC, eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue. RESULTS: The IHC-positive rates of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 normal esophageal tissues were 97% (102/105), 44% (7/16), and 18% (2/11) respectively. The difference in the expression of EGFR among different esophageal tissue groups had statistically significance (P < 0.05). Among the 105 cases of ESCC, overexpression of EGFR was found in 90 cases (86%), of which 55 cases scored 3+ for EGFR staining and 35 cases scored 2+. In ESCC, the expression of EGFR was significantly correlated with depth of invasion and TNM stage (P < 0.05), but not with other parameters. The FISH-positive rates of EGFR in 80 cases of ESCC, the eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue were 31.3% (25/80), 0 (0/8) and 0 (0/8) respectively. In ESCC, EGFR gene amplification was found in 17 (21%) cases, high polysomy in 8 (10%) cases, disomy in 34 cases, low trisomy in 17 cases, and high trisomy in four cases. EGFR FISH-positive was significantly correlated with depth of invasion and lymph node metastasis (P < 0.05). EGFR FISH-positive was significantly associated with overexpression of EGFR. CONCLUSION: Protein overexpression and/or increased gene copy number of EGFR is common in ESCC, and EGFR targeted therapy may be appropriate for ESCC patients.
Assuntos
Receptores ErbB/metabolismo , Neoplasias Esofágicas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas , Receptores ErbB/genética , Neoplasias Esofágicas/genética , Feminino , Dosagem de Genes/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-IdadeRESUMO
Expression profiling of microRNAs (miRNAs) in most diseases might be popular and provide the possibility for diagnostic implication, but few studies have accurately quantified the expression level of dysregulated miRNAs in acute myeloid leukemia (AML). In this study, we analyzed the peripheral blood mononuclear cells (PBMCs) from 10 AML patients (subtypes M1 to M5) and six normal controls by miRNA microarray and identified several differentially expressed miRNAs. Among them miR-29a and miR-142-3p were selectively encountered in Northern blot analysis and their significantly decreased expression in AML was further confirmed. Quantitative real-time PCR in 52 primarily diagnosed AML patients and 100 normal controls not only verified the expression properties of these 2 miRNAs, but also established that the expression level of miR-142-3p and miR-29a in PBMCs could be used as novel diagnostic markers. A better diagnostic outcome was achieved by combining miR-29a and miR-142-3p with about 90% sensitivity, 100% specificity, and an area under the ROC curve (AUC) of 0.97. Our results provide insights into the involvement of miRNAs in leukemogenesis, and offer candidates for AML diagnosis and therapeutic strategy.