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BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.
Assuntos
Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Inibidores da Bomba de Prótons , Pirróis , Sulfonamidas , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/diagnóstico , Pessoa de Meia-Idade , Masculino , Sulfonamidas/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Feminino , Estudos Prospectivos , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Amoxicilina/uso terapêutico , China/epidemiologia , Quimioterapia Combinada/métodos , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Pirróis/administração & dosagem , Resultado do Tratamento , Adulto , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Idoso , População do Leste AsiáticoRESUMO
Although the use of Doxorubicin (Dox) is extensive in the treatment of malignant tumor, the toxic effects of Dox on the heart can cause myocardial injury. Therefore, it is necessary to find an alternative drug to alleviate the Dox-induced cardiotoxicity. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin, which is an active ingredient of Artemisia annua. The study investigates the effects of DHA on doxorubicin-induced cardiotoxicity and ferroptosis, which are related to the activation of Nrf2 and the regulation of autophagy. Different concentrations of DHA were administered by gavage for 4 weeks in mice. H9c2 cells were pretreated with different concentrations of DHA for 24 h in vitro. The mechanism of DHA treatment was explored through echocardiography, biochemical analysis, real-time quantitative PCR, western blotting analysis, ROS/DHE staining, immunohistochemistry, and immunofluorescence. In vivo, DHA markedly relieved Dox-induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes. In vitro, DHA attenuated oxidative stress and cardiomyocyte ferroptosis, activated Nrf2, promoted clearance of autophagosomes, and reduced lysosomal destruction. The changes of ferroptosis and Nrf2 depend on selective degradation of keap1 and recovery of lysosome. We found for the first time that DHA could protect the heart from the toxic effects of Dox-induced cardiotoxicity. In addition, DHA significantly alleviates Dox-induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.
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Artemisininas , Autofagia , Cardiotoxicidade , Doxorrubicina , Ferroptose , Miócitos Cardíacos , Fator 2 Relacionado a NF-E2 , Artemisininas/farmacologia , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Autofagia/efeitos dos fármacos , Doxorrubicina/efeitos adversos , Doxorrubicina/toxicidade , Camundongos , Ferroptose/efeitos dos fármacos , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Cardiotoxicidade/metabolismo , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Linhagem Celular , RatosRESUMO
OBJECTIVES: We aimed to evaluate the association between low-grade inflammation (LGI) and the severity of hypertriglyceridemic acute pancreatitis (HTG-AP). METHODS: We retrospectively reviewed 311 patients with HTG-AP who were admitted to the Department of Gastroenterology, Fujian Provincial Hospital between April 2012 and March 2021. Inpatient medical and radiological records were reviewed to collect the clinical manifestations, disease severity, and comorbidities. C-reactive protein (CRP) level, white blood cell (WBC) count, platelet (PLT) count, and neutrophil-to-lymphocyte ratio (NLR) were considered LGI components and were combined to calculate a standardized LGI score. The association between the LGI score and the severity of HTG-AP was analyzed using univariate and multivariate logistic regression analyses. RESULTS: Of the 311 patients with HTG-AP, 47 (15.1%) had mild acute pancreatitis (MAP), 184 (59.2%) had moderately severe acute pancreatitis (MSAP), and 80 (25.7%) had severe acute pancreatitis (SAP), respectively. Patients with MSAP and SAP had a higher LGI score than those with MAP (1.50 vs -6.00, P < 0.001). Univariate logistic regression analysis revealed that patients with LGI scores in the fourth quartile were more likely to have MSAP and SAP (odds ratio [OR] 21.925, 95% confidence interval [CI] 5.014-95.867, P < 0.001). The multivariate logistic regression analysis confirmed that low calcium (OR 0.105, 95% CI 0.011-0.969, P = 0.047) and high LGI score (OR 1.253, 95% CI 1.066-1.473, P = 0.006) were associated with MSAP and SAP. When predicting the severity of acute pancreatitis, the LGI score had the highest area under the receiver operating characteristic (ROC) curve (0.7737) compared to its individual components. CONCLUSION: An elevated LGI score was associated with a higher risk of SAP in patients with HTG-AP.
Assuntos
Pancreatite , Humanos , Pancreatite/complicações , Pancreatite/diagnóstico , Estudos Retrospectivos , Doença Aguda , Inflamação , Curva ROC , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: This pilot study aimed to evaluate the efficacy and safety of domperidone for the treatment of Chinese patients with functional dyspepsia (FD) who were diagnosed according to the Rome IV criteria and to identify the FD subtypes that potentially responded better to domperidone. METHODS: This multicenter prospective study was conducted in China from August 2018 to July 2020, consisting of a 1-week screening phase and a 2-week double-blind treatment phase. Participants were randomized to receive domperidone 10 mg or matching placebo tablets thrice daily for 14 days. The primary end-point was the overall treatment effect (OTE) response rate after 2-week therapy. RESULTS: Altogether 160 patients were included, with 80 patients in each group. The OTE response rate after 2-week therapy was significantly higher for domperidone compared with placebo (60.7% vs 46.0%; relative risk [RR] 1.318, 95% confidence interval [CI] 0.972-1.787). Moreover, the OTE response rate after 2-week domperidone or placebo treatment was 60.3% versus 54.9% for postprandial distress syndrome (PDS) (RR 1.098, 95% CI 0.750-1.607) and 60.6% versus 35.2% for overlapping PDS-epigastric pain syndrome (EPS) (RR 1.722, 95% CI 0.995-2.980). Adverse events were reported by seven patients in the domperidone group and 12 patients in the placebo group. None of the adverse events in the domperidone group were serious. CONCLUSION: Domperidone showed a positive pattern regarding OTE response rates after 2-week therapy compared to placebo in patients with FD, as well as in subtypes of PDS and overlapping PDS-EPS. No new safety issue was observed.
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Dispepsia , Adulto , Humanos , Dispepsia/tratamento farmacológico , Domperidona/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Método Duplo-Cego , Resultado do TratamentoRESUMO
BACKGROUND: Air pollution is an important and interventionable risk factor for cardiovascular disease. Air pollution exposure, even for a short-term exposure, is conspicuously relevant to increased risk of myocardial infarction (MI) mortality and clinical evidence has shown that air pollution particulate matter (PM) induces the aggravation of AMI. 3,4-benzo[a]pyrene (BaP), an extremely toxic polycyclic aromatic hydrocarbon (PAH) and a common component of PM, is listed as one of the main objects of environmental pollution monitoring. Both epidemiological and toxicological studies suggest that BaP exposure may be associated with cardiovascular disease. Since PM is significantly associated with the increased risk of MI mortality, and BaP is an important component of PM associated with cardiovascular disease, we intend to investigate the effect of BaP on MI models. METHODS: The MI mouse model and the oxygen and glucose deprivation (OGD) H9C2 cell model were used to investigate the effect of BaP in MI injury. The involvement of mitophagy and pyroptosis in regulating deterioration of cardiac function and aggravation of MI injury induced by BaP was comprehensively evaluated. RESULTS: Our study shows that BaP exacerbates MI injury in vivo and in vitro, a result based on BaP-induced NLRP3-related pyroptosis. In addition, BaP can inhibit PINK1/Parkin dependent mitophagy through the aryl hydrocarbon receptor (AhR), thus the mitochondrial permeability transition pore (mPTP) was induced to open. CONCLUSION: Our results suggest a role for the BaP from air pollution in MI injury aggravation and reveal that BaP aggravates MI injury by activating NLRP3-related pyroptosis via the PINK1/Parkin-mitophagy-mPTP opening axis.
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Infarto do Miocárdio , Piroptose , Camundongos , Animais , Mitofagia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Benzo(a)pireno , Proteínas Quinases , Ubiquitina-Proteína LigasesRESUMO
PURPOSE: To investigate the feasibility of percutaneous intrauterine instillation of chilled saline to protect the endometrium during microwave ablation (MWA) treating types 1-3 uterine fibroids. MATERIALS AND METHODS: Twenty-six patients with types 1-3 uterine fibroids were prospectively enrolled in an intrauterine saline instillation group (study group). The same number of patients with types 1-3 uterine fibroids who previously received MWA without endometrial protection were retrospectively included in a control group. Endometrial impairment was evaluated by hysteroscopy and magnetic resonance imaging (MRI). RESULTS: In the study group, hysteroscopy revealed an intact endometrium in 17 patients, congestion and reddening of the endometrium due to heat in 8 patients, and a burnt necrosis with a size < 1 cm on the functional layer of the endometrium in 1 patient. On MRI, in the study group, there were 17 (65.4%), 6 (23.1%), and 3 (11.5%) patients with grades 0, 1, and 2 endometrial impairment, respectively, but no grade 3 endometrial impairment. In the control group, there were 8 (30.8%), 8 (30.8%), 7 (26.9%), and 3 (11.5%) patients with grades 0, 1, 2, and 3 endometrial impairment, respectively. Endometrial impairment in the study group was significantly better than that in the control group (p = 0.006). One patient had puncture tunnel bleeding and no other complications occurred in the study group. CONCLUSION: Intraoperative percutaneous intrauterine instillation of chilled saline may be effective and safe in reducing the thermal damage to the endometrium caused by MWA for treating types 1-3 uterine fibroids.
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Leiomioma , Neoplasias Uterinas , Feminino , Gravidez , Humanos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Endométrio/diagnóstico por imagem , Endométrio/cirurgia , Endométrio/patologia , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Leiomioma/complicações , Histeroscopia , Neoplasias Uterinas/cirurgiaRESUMO
Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[a]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia-reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation-reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53-BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53-BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated.
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Traumatismo por Reperfusão Miocárdica , Camundongos , Animais , Traumatismo por Reperfusão Miocárdica/metabolismo , Piroptose , Benzo(a)pireno/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína Supressora de Tumor p53 , AutofagiaRESUMO
The lateral hypothalamus (LH) is an important brain region mediating sleep-wake behavior. Recent evidence has shown that astrocytes in central nervous system modulate the activity of adjacent neurons and participate in several physiological functions. However, the role of LH astrocytes in sleep-wake regulation remains unclear. Here, using synchronous recording of electroencephalogram/electromyogram in mice and calcium signals in LH astrocytes, we show that the activity of LH astrocytes is significantly increased during non-rapid eye movement (NREM) sleep-to-wake transitions and decreased during Wake-to-NREM sleep transitions. Chemogenetic activation of LH astrocytes potently promotes wakefulness and maintains long-term arousal, while chemogenetic inhibition of LH astrocytes decreases the total amount of wakefulness in mice. Moreover, by combining chemogenetics with fiber photometry, we show that activation of LH astrocytes significantly increases the calcium signals of adjacent neurons, especially among GABAergic neurons. Taken together, our results clearly illustrate that LH astrocytes are a key neural substrate regulating wakefulness and encode this behavior through surrounding GABAergic neurons. Our findings raise the possibility that overactivity of LH astrocytes may be an underlying mechanism of clinical sleep disorders.
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Região Hipotalâmica Lateral , Vigília , Animais , Camundongos , Vigília/fisiologia , Região Hipotalâmica Lateral/fisiologia , Astrócitos , Cálcio , Sono/fisiologia , Neurônios GABAérgicos/fisiologia , HipotálamoRESUMO
The dorsal raphe nucleus (DRN) has previously been proved to be involved in the regulation of the sleep-wake behavior. DRN contains several neuron types, such as 5-HTergic and GABAergic neurons. GABAergic neurons, which are the second largest cell subtype in the DRN, participate in a variety of neurophysiological functions. However, their role in sleep-wake regulation and the underlying neural circuitry remains unclear. Herein, we used fiber photometry and synchronous electroencephalogram (EEG)/electromyography (EMG) recording to demonstrate that DRN GABAergic neurons exhibit high activities during wakefulness and low activities during NREM sleep. Short-term optogenetic activation of DRN GABAergic neurons reduced the latency of NREM-to-wake transition and increased the probability of wakefulness, while long-term optogenetic activation of these neurons significantly increased the amount of wakefulness. Chemogenetic activation of DRN GABAergic neurons increased wakefulness for almost 2 h and maintained long-lasting arousal. In addition, inhibition of DRN GABAergic neurons with chemogenetics caused a reduction in the amount of wakefulness. Finally, similar to the effects of activating the soma of DRN GABAergic neurons, optogenetic stimulation of their terminals in the ventral tegmental area (VTA) induced instant arousal and promoted wakefulness. Taken together, our results illustrated that DRN GABAergic neurons are vital to the induction and maintenance of wakefulness, which promote wakefulness through the GABAergic DRN-VTA pathway.
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Núcleo Dorsal da Rafe , Área Tegmentar Ventral , Área Tegmentar Ventral/metabolismo , Vigília/fisiologia , Sono/fisiologia , Neurônios GABAérgicos/fisiologiaRESUMO
BACKGROUND: The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) has increased yearly, but updated population-based estimates on the incidence of HTG-AP are lacking. Reducing serum triglyceride (TG) levels quickly is crucial in the early treatment of HTG-AP. Decreased serum TG levels are treated by non-invasive methods, which include anti-lipidemic agents, heparin, low-molecular weight heparin, and insulin, and invasive methods, such as blood purification including hemoperfusion (HP), plasmapheresis, and continuous renal replacement therapy. However, authoritative guidelines have not been established. Early selection of appropriate treatment is important and beneficial in controlling the development of HTG-AP. AIM: To evaluate the effect between patients treated with intravenous insulin (INS) and HP to guide clinical treatment. METHODS: We retrospectively reviewed 371 patients with HTG-AP enrolled in the Department of Fujian Provincial Hospital form April 2012 to March 2021. The inpatient medical and radiologic records were reviewed to determine clinical features, severity, complications, mortality, recurrence rate, and treatment. Multivariate logistic regression analyses were used to analyze risk factors for severe HTG-AP. Propensity score matching was used to compare the clinical outcomes of INS and HP. RESULTS: A total of 371 patients met the HTG-AP criteria. The incidence of HTG-AP was increased by approximately 2.6 times during the 10 years (8.4% in April 2012-March 2013 and 22.3% in April 2020-March 2021). The highest incidence rate of acute pancreatitis was observed for men in the age group of 30-39 years. The amylase level was elevated in 80.1% of patients but was only three times the normal value in 46.9% of patients. The frequency of severe acute pancreatitis (26.9%), organ failure (31.5%), rate of recurrence (32.9%), and mortality (3.0%) of HTG-AP was high. Improved Marshall score, modified computed tomography severity index score, baseline TG, baseline amylase, C-reactive protein (CRP), albumin, aspartate aminotransferase, low-density lipoprotein cholesterol, urea nitrogen, creatinine, calcium, hemoglobin, free triiodothyronine, admission to intensive care unit, and mortality were significantly different between patients with different grades of severity (P < 0.050). Multivariate logistic regression analysis confirmed that high CRP [P = 0.005, odds ratio (OR) = 1.011, 95%CI: 1.003-1.019], low calcium (P = 0.003, OR = 0.016, 95%CI: 0.001-0.239), and low albumin (P = 0.023, OR = 0.821, 95%CI: 0.693-0.973) were risk factors of severe HTG-AP. After propensity score matching adjusted by sex, age, severity of HTG-AP, and baseline TG, the serum TG significantly decreased in patients treated with INS (P < 0.000) and HP (P < 0.000) within 48 h. However, the clearance rate of TG (57.24 ± 33.70% vs 56.38 ± 33.61%, P = 0.927) and length of stay (13.04 ± 7.92 d vs 12.35 ± 6.40 d, P = 0.730) did not differ between the two groups. CONCLUSION: The incidence of HTG-AP exhibited a significant increase, remarkable severity, and recurrent trend. Patients with mild and moderately severe acute pancreatitis can be treated effectively with INS safely and effectively without HP.
Assuntos
Hipertrigliceridemia , Pancreatite , Doença Aguda , Adulto , Amilases , Aspartato Aminotransferases , Proteína C-Reativa , Cálcio/uso terapêutico , Colesterol , Creatinina , Heparina/uso terapêutico , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/epidemiologia , Hipertrigliceridemia/terapia , Incidência , Insulina/uso terapêutico , Lipoproteínas LDL , Masculino , Nitrogênio , Pancreatite/diagnóstico , Pancreatite/epidemiologia , Pancreatite/terapia , Estudos Retrospectivos , Triglicerídeos , Tri-Iodotironina/uso terapêutico , UreiaRESUMO
BACKGROUND: The pathogenesis of myocardial ischemia/reperfusion is complex, involving multiple regulatory genes and environmental factors, and requiring the simultaneous regulation of multiple targets. Meanwhile, Traditional Chinese Medicine (TCM) has certain advantages in the comprehensive treatment of multi-site, multi-target conditions and overall regulation of this condition. This study explores the effect of the well-known TCM, the Shexiang Baoxin Pill (SBP) on myocardial ischemia/reperfusion injury in mice. MATERIALS AND METHODS: In vivo, 20 mg/kg/day SBP was administered by gavage for 28 days. In vitro, cardiomyocytes were pretreated with 25 µg/ml SBP for 24 h. Evans blue/TTC double-staining was employed to determine the infarct size. Markers of myocardial injury were detected in the serum and cell supernatants. The changes of pyroptosis and autophagy proteins were detected by western blot. Immunofluorescence, immunohistochemistry and PCR were performed to further illustrate the results. RESULTS: SBP significantly reduced the myocardial infarct size, decreased the myocardial injury markers, inhibited cardiomyocyte pyroptosis and oxidative stress, and promoted autophagy in vivo. In vitro, SBP alleviated cardiomyocyte pyroptosis, inhibited oxidative stress, reduced IL-1ß and IL-18 secretion, and unblocked autophagy flux. Myocardial injury is mitigated by SBP via the rapid degradation of autophagosomes, and SBP promotes the accumulation of autophagosomes by downregulating mmu_circ_0005874, Map3k8 and upregulating mmu-miR-543-3p. CONCLUSION: We found for the first time that SBP can inhibit pyroptosis and oxidative stress, and protect from myocardial I/R injury. In addition, it inhibits pyroptosis and improves H/R injury by promoting autophagosome generation and accelerating autophagic flux. SBP interferes with autophagy through the interaction between mmu_circ_0005874/mmu-miR-543-3p/Map3k8.
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Medicamentos de Ervas Chinesas , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Animais , Autofagia , Medicamentos de Ervas Chinesas/uso terapêutico , MAP Quinase Quinase Quinases , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos , Proteínas Proto-Oncogênicas , RNA/genética , RNA/metabolismoRESUMO
Defensive behavior, a group of responses that evolved due to threatening stimuli, is crucial for animal survival in the natural environment. For defensive measures to be timely and successful, a high arousal state and immediate sleep-to-wakefulness transition are required. Recently, the glutamatergic basal forebrain (BF) has been implicated in sleep-wake regulation; however, the associated physiological functions and underlying neural circuits remain unknown. Here, using in vivo fiber photometry, we found that BF glutamatergic neuron is activated by various threatening stimuli, including predator odor, looming threat, sound, and tail suspension. Optogenetic activation of BF glutamatergic neurons induced a series of context-dependent defensive behaviors in mice, including escape, fleeing, avoidance, and hiding. Similar to the effects of activated BF glutamatergic cell body, photoactivation of BF glutamatergic terminals in the ventral tegmental area (VTA) strongly drove defensive behaviors in mice. Using synchronous electroencephalogram (EEG)/electromyogram (EMG) recording, we showed that photoactivation of the glutamatergic BF-VTA pathway produced an immediate transition from sleep to wakefulness and significantly increased wakefulness. Collectively, our results clearly demonstrated that the glutamatergic BF is a key neural substrate involved in wakefulness and defensive behaviors, and encodes these behaviors through glutamatergic BF-VTA pathway. Overexcitation of the glutamatergic BF-VTA pathway may be implicated in clinical psychiatric diseases characterized by exaggerated defensive responses, such as autism spectrum disorders.
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Prosencéfalo Basal , Vigília , Animais , Prosencéfalo Basal/fisiologia , Eletroencefalografia/métodos , Mesencéfalo , Camundongos , Sono/fisiologia , Vigília/fisiologiaRESUMO
OBJECTIVES: To investigate the clinical effect of Er:YAG laser combined with ethylenediamine tetra acetic acid (EDTA) on three-walled periodontal intrabony defects adjacent to implant sites. METHODS: A total of 30 patients with three-walled periodontal intrabony defects adjacent to implant sites were treated with the combination therapy. Patients with three-walled intrabony defects were divided into two groups according to the depth of the intrabony pocket between the implant and natural teeth. Evaluation of wound healing was performed 10 days after the operation, and bone augmentation was evaluated 6 months after the operation. RESULTS: Primary healing in group 1 was 92.31%, primary healing in group 2 was 82.35%. No significant difference was observed between the two groups (P>0.05). Bone augmentation in group 1 and group 2 were (2.85±1.81), (4.92±2.22) mm. There was significant difference between the two groups (P<0.05). New bone growth occurred more slowly in group 1 (0.70 mm±0.32 mm) than in group 2 (1.25 mm±0.47 mm) (P>0.05). Probe depths (PD), clinical attachment levels (CAL), and sulcus bleeding indices (SBI) showed no statistically significant difference between the two groups (P>0.05). The one-year survival rate of natural tooth in group 1 and group 2 were 100%, 94.2%, and the one-year survival rate of implants in both groups was 100%. CONCLUSIONS: The effect of bone augmentation with combination therapy was more ideal in group 2 than in group 1. Implant placement with combination therapy may be a viable technique to reconstruct three-walled intrabony defects due to the space maintenance provided by implants and bone grafts and the good root surface biocompatibility provided by the Er:YAG laser and EDTA.
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Perda do Osso Alveolar , Implantes Dentários , Lasers de Estado Sólido , Ácido Acético , Etilenodiaminas , Seguimentos , Regeneração Tecidual Guiada Periodontal , Humanos , Perda da Inserção Periodontal , Resultado do TratamentoRESUMO
RATIONALE: Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity. OBJECTIVES: We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis. METHODS: Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6-expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients' final diagnosis. MEASUREMENTS AND MAIN RESULTS: Two hundred and eighty patients with suspected tuberculous meningitis were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6-6.7%), compared with 82.9% (95% confidence interval, 77.4-87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8-80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4-93.8%) and 90.0% (95% confidence interval, 75.4-96.7%), respectively. CONCLUSIONS: Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis.
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Antígenos de Bactérias/líquido cefalorraquidiano , Proteínas de Bactérias/líquido cefalorraquidiano , Leucócitos/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Meníngea/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Estudos Prospectivos , Sensibilidade e Especificidade , Coloração e Rotulagem , Tuberculose Meníngea/líquido cefalorraquidiano , Adulto JovemRESUMO
A family of energetic salts with high thermal stability and low impact sensitivity based on an oxygen-containing cation, 2,4-diamino-1,3,5-triazine-6-one, were synthesized and fully characterized by IR and multinuclear ((1)H, (13)C) NMR spectroscopy, elemental analysis, and differential scanning calorimetry. Insights into their sensitivities towards impact, friction, and electrostatics were gained by submitting the materials to standard tests. The structures of 2,4-diamino-1,3,5-triazine-6-one nitrate, 2,4-diamino-1,3,5-triazine-6-one sulfate, 2,4-diamino-1,3,5-triazine-6-one perchlorate, 2,4-diamino-1,3,5-triazine-6-one 5-nitrotetrazolate were determined by single-crystal X-ray diffraction; their densities are 1.691, 1.776, 1.854, and 1.636â g cm(-3), respectively. Most of the salts decompose at temperatures over 180 °C; in particular, the salts 2,4-diamino-1,3,5-triazine-6-one nitrate and 2,4-diamino-1,3,5-triazine-6-one perchlorate, which decompose at 303.3 and 336.4 °C, respectively, are fairly stable. Furthermore, most of the salts exhibit excellent impact sensitivities (>40â J), friction sensitivities (>360â N), and are insensitive to electrostatics. The measured densities of these energetic salts range from 1.64 to 2.01â g cm(-3) . The detonation pressure values calculated for these salts range from 14.6 to 29.2â GPa, and the detonation velocities range from 6536 to 8275â m s(-1) ; these values make the salts potential candidates for thermally stable and insensitive energetic materials.
RESUMO
By using Penman-Monteith model and Hurst index model, this paper analyzed the spatiotemporal variation patterns of potential evapotranspiration (ET0) in the five provinces of Northwest China in 1960-2011. In the meantime, the dominant factors driving the variations of the ET0 were quantitatively analyzed by using sensitivity analysis method. In 1960-2011, the ET0 in the five provinces presented an overall decreasing trend, with a drop rate of -0.72 mm x a(-1), but the ET0 increased gradually after 1993. An obvious spatial difference was shown in the annual average ET0. The average ET0 in the five provinces was 1158 mm (675-2282 mm), wit the maximum (2282 mm) in Qijiaojing of Xinjiang and the low values (>800 mm) in Qinba Mountains in south Shaanxi. Except in spring, the ET0 in other seasons showed a decreasing trend. In the analysis of future trend, the ET0 in most areas (81.4%) of Northwest China would present a trend from decrease to increase. Therefore, under the background of global warming, the warm and wet degree in Northwest China would be somewhat weakened, but the ET0 in the middle part of Xinjiang would be decreased continuously. Wind speed was the main factor affecting the ET0 in Northwest China at both annual and monthly scales, but the affecting extent of wind speed differed with seasons and areas. The spatial extent affected by the wind speed in winter expanded across the entire five provinces of Northwest China, while the spatial extent affected by the wind speed in summer included the entire Xinjiang and the northwest of Gansu and Qinghai.
Assuntos
Produtos Agrícolas/crescimento & desenvolvimento , Ecossistema , Modelos Teóricos , Transpiração Vegetal , Movimentos da Água , China , Mudança Climática , Análise Espaço-Temporal , Temperatura , Água/metabolismoRESUMO
OBJECTIVE: To investigate the role of Luxs gene on the regulation of virulence factors in Salmonella typhimurium. METHODS: Luxs gene knock-out strain of Salmonella typhimurium of the line 14028S was constructed. Media with Luxs gene knock-out 14028S or wild type 14028S bacteria were added into the media of cultured human intestinal epithelial cells of the line Caco. The numbers of colony formation unit (cfu) were calculated so as to compare the invasion ability. Northern blotting was performed to examine the Luxs gene expression. RESULTS: When the 14028S cells were in the early logarithmic phase the cfu number was 590, and in the middle and late logarithmic, and stationary phases, the cfu numbers were 246, 57, and 13 respectively. The Luxs gene expression levels increased gradually along with the bacterial growth into different phases. The cfu number A600 nm = 0.25 of the Luxs gene knock-out strain was 597, significantly higher than that of the wild type (315, P < 0.05). CONCLUSION: Luxs gene may be a negative regulator on the invasion ability of Salmonella typhimurium.