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A chemotherapeutic drug exerts favorable antitumor activity and simultaneously exhibits expectable inhibition on wound healing process. Phenanthroimidazole derivatives possess potent anticancer activity. However, only a few studies focused on the discovery of its potential effects on promoting tissue regeneration. In this study, four novel phenanthroimidazole derivatives were synthesized and characterized, and they exhibited evident inhibition on different tumor cells; compound 3 is the most active one. Moreover, 3 can promote wound healing of zebrafish in a dose-dependent manner. Further study demonstrated that 3 promoted the recruitment of inflammatory cells, formation of angiogenesis, and generation of reactive oxygen species and also influenced the motor behavior of zebrafish. Results indicated that 3 can accelerate the occurrence of pro-inflammation, angiogenesis, oxidative stress, and innervation, which play key roles in the facilitation of wound healing. Therefore, 3 can act as a bifunctional drug in inhibiting tumor and promoting tissue regeneration.
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Nadadeiras de Animais/efeitos dos fármacos , Antineoplásicos/farmacologia , Imidazóis/farmacologia , Regeneração/efeitos dos fármacos , Nadadeiras de Animais/fisiologia , Animais , Animais Geneticamente Modificados , Antineoplásicos/toxicidade , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Embrião não Mamífero/irrigação sanguínea , Embrião não Mamífero/efeitos dos fármacos , Proteínas de Fluorescência Verde/genética , Humanos , Imidazóis/toxicidade , Inflamação/imunologia , Larva/efeitos dos fármacos , Larva/imunologia , Locomoção/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Espécies Reativas de Oxigênio/imunologia , Cicatrização/efeitos dos fármacos , Peixe-Zebra/genéticaRESUMO
CONTEXT: The DNAN/DNB eutectic is a high-energy explosive eutectic with superior safety and thermal stability compared to traditional melt-cast explosives. However, the addition of polymer binders can effectively enhance its mechanical properties, allowing for continued production demands without the need for changes to existing factory equipment. In this paper, a model of the DNAN/DNB eutectic explosive was established, and five different types of polymers-cis-1,4-polybutadiene (BR), ethylene-vinyl acetate copolymer (EVA), polyethylene glycol (PEG), fluorinated polymer (F2603), and polyvinylidene fluoride (PVDF)-were added to the (1 0 - 1), (1 0 1), and (0 1 1) cleavage planes, respectively, to form polymer-bonded explosives (PBXs). The stability, trigger bond length, mechanical properties, and detonation performance of the various polymer-bound PBXs were predicted retrogressively. Among the five PBX models, the DNAN/DNB/PEG model exhibited the highest binding energy and the shortest trigger bond length, indicating a significant improvement in stability, compatibility, and sensitivity compared to the original eutectic. Additionally, although the detonation performance of DNAN/DNB decreased after the addition of binders, the final results were still satisfactory. Overall, the DNAN/DNB/PEG model demonstrated excellent comprehensive performance, proving that among the many polymer binders, PEG is the optimal choice for DNAN/DNB. METHODS: Within the Materials Studio software, molecular dynamics (MD) simulations were employed to predict the properties of the DNAN/DNB eutectic PBX. The MD simulation timestep was set to 1 fs, with a cumulative simulation duration of 2 ns. A 2 ns MD simulation was conducted using the isothermal-isobaric ensemble (NPT). The COMPASS force field was applied, and the temperature was fixed at 295 K.
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CONTEXT: Thermal decomposition of 1-methyl-3,4,5-trinitropyrazole (MTNP), a melt-cast explosive, was investigated at different temperatures (2500, 2750, 3000, 3250, and 3500 K) and pressures (3000 K/0.5 GPa, 3000 K/1 GPa) using the ReaxFF/lg force field. The study aimed to analyze the changes in reactant quantities, initial reaction pathways, and final product yields. The results demonstrated that complete decomposition of MTNP molecules occurred within a timeframe of 200 ps, with shorter decomposition times observed as the temperature increased. The high-temperature thermal decomposition of MTNP was found to follow two primary reaction pathways. Reaction 1 involved denitration, while reaction 2 proceeded with nitro group isomerization. DFT calculations indicated that nitro group isomerization was the most favorable reaction. During the initial stages, higher quantities of NO2, NO, and N2 were observed compared to other species. This can be attributed to the relatively higher nitrogen and oxygen content in the MTNP structure. Among the five reaction temperatures, it was observed that the quantities of small molecules followed the order of NO2 > NO > N2 > CO. Moreover, with increasing temperature, the quantities of all four small molecules increased, indicating that higher temperatures promoted the progression of the reactions. However, as the pressure increased, there was a trend of initially increasing and then decreasing to zero for the quantities of NO2 and NO. This suggests that high temperature accelerated the high-temperature thermal decomposition of NO2 and NO, leading to a significant increase in the content of N2. METHODS: A 3 × 5 × 5 supercell model of MTNP was constructed in Materials Studio, consisting of 75 unit cells and 300 MTNP molecules. The model was then subjected to a 20 ps geometric optimization using the Polak-Ribiere version of the conjugate gradient (CG) algorithm in the large-scale atomic/molecular massively parallel simulator (LAMMPS) under the isothermal-isobaric (NPT) ensemble at 1 atm pressure and 300 K temperature. Following the optimization, molecular dynamics simulations were performed on the model at five temperatures (2500, 2750, 3000, 3200, and 3500 K) under 1 atm using the NPT ensemble for a total duration of 1 ns. During the simulations, atomic trajectories, as well as information on atomic and molecular species, were output every 500 steps. Subsequently, a custom script was utilized to analyze the thermal decomposition pathways and products. A time step of 0.1 fs was employed for the calculations, and periodic boundary conditions were applied to eliminate boundary effects.
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CONTEXT: CL-20/DNDAP cocrystal is a promising new type of explosive with exceptional energy density and detonation parameters. However, compared to TATB, FOX-7 and other insensitive explosives, it still has higher sensitivity. In order to decrease the sensitivity of CL20/DNDAP cocrystal explosive, in this article, a CL20/DNDAP cocrystal model was established, and six different types of polymers, including butadiene rubber (BR), ethylene-vinyl acetate copolymer (EVA), polyethylene glycol (PEG), hydroxyl-terminated polybutadiene (HTPB), fluoropolymer (F2603), and polyvinylidene difluoride (PVDF), were added to the three cleaved surfaces of (1 0 0), (0 1 0) and (0 0 1) to obtain polymer-bonded explosives (PBXs). Predict the effects of different polymers on the stability, trigger bond length, mechanical properties, and detonation performance of PBXs. Among the six PBX models, CL-20/DNDAP/PEG model exhibited the highest binding energy and the lowest trigger bond length, indicating that CL-20/DNDAP/PEG model had the best stability, compatibility, and the least sensitivity. Furthermore, although the CL-20/DNDAP/F2603 model demonstrated superior detonation capabilities, it should be noted that this model displayed low levels of compatibility. Overall, CL-20/DNDAP/PEG model exhibited the superior comprehensive properties, thereby demonstrating that PEG is a more suitable binder option for PBXs based on the CL20/DNDAP cocrystal. METHODS: The properties of CL-20/DNDAP cocrystal-based PBXs were predicted by molecular dynamics (MD) method under Materials Studio software. The MD simulation time step was set at 1fs and the total MD simulation time was 2ns. The Isothermal-isobaric (NPT) ensemble was used for the 2ns of MD simulation. The COMPASS force field was used, and the temperature was set at 295K.
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BACKGROUND: In 2016, the Chinese government issued the Healthy China 2030 plan, which also produced the initiative practice for health (IPFH) concept. However, people's knowledge and awareness of the IPFH are unclear. AIM: To investigate awareness of IPFH in the Chinese population and explore the relevant influential factors. METHODS: An internet-based self-designed questionnaire survey was used to collect respondents' demographic characteristics and awareness of health and the IPFH from March 26 to April 18, 2020. IPFH consciousness was assessed by the scores for different related questions. The Student's t test, the Chi-square test, and multiple logistic regression analysis were performed to analyze the differences and influencing factors. RESULTS: A total of 2678 valid questionnaires were collected. Of the respondents, 973 (36.3%) had heard of the IPFH concept. In addition, 89.5% of participants agreed with the view that the IPFH is beneficial to improving quality of life, and over half thought that a regular schedule, a reasonable diet, tobacco and alcohol control, a cheerful mood, specific life goals and plans, taking the initiative to accept health-related education and implement health knowledge, good interpersonal relationships, and regular physical examinations were closely related to the IPFH. The majority of respondents paid attention to their health and usually obtained health-related knowledge via social media and were also willing to promote the IPFH. Most of the participants underestimated the role of hospitals, family doctors, and health managers in promoting the IPFH. Age, monthly income, and medical-related work experience were the influencing factors for IPFH awareness. CONCLUSION: The Chinese population has limited knowledge of the IPFH. People with strong IPFH awareness are older, earn more, and have medical-related work experience.
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Poly(ethylene oxide) (PEO)-based solid electrolyte suffers from limited anodic stability and an intrinsic flammable issue, hindering the achievement of high energy density and safe all-solid-state lithium batteries. Herein, we surprisingly found out that a bromine-rich additive, decabromodiphenyl ethane (DBDPE), could be preferably oxidized at an elevated voltage and decompose to lithium bromide at an elevated potential followed by inducing an organic-rich cathode/electrolyte interphase (CEI) on NCM811 surface, enabling both high-voltage resistance (up to 4.5 V) and flame-retardancy for the PEO-based electrolyte. On the basis of this novel solid electrolyte, all-solid-state Li/NCM811 batteries deliver an average reversible capacity of 151.4 mAh g-1 over the first 150 cycles with high capacity retention (83.0%) and high average Coulombic efficiency (99.7%) even at a 4.5 V cutoff voltage with a unprecedented flame-retardant properties. In view of these exploration, our studies revealed the critical role of LiBr in inducing an organic-rich thin and uniform CEI passivating layer with enhanced lithium ion surface diffusion and high-voltage resistant properties, which provides a new protocol for the further design of a high-voltage PEO-based all-solid-state electrolyte.
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OBJECTIVE: To investigate the correlation between the pain rating index (PRi), which is an index derived from processed electroencephalography signals, and the end-tidal sevoflurane concentration (ETsevo). METHODS: This study involved 50 adults with a body mass index of 18 to 25 kg/m2 who were undergoing elective surgery under general anesthesia. Thyrocricocentesis was performed with 2.5 mL of 2% tetracaine for endotracheal surface anesthesia, and intravenous injections of midazolam, etomidate, and rocuronium were then administered. The patients' tracheas were intubated and their ventilatory rate was adjusted to maintain the partial pressure of end-tidal carbon dioxide at 30 to 35 mmHg. Anesthesia was maintained with sevoflurane. The ETsevo was adjusted to maintain anesthesia at 0.6, 0.8, 1.0, and 1.2 minimum alveolar concentration for 15 minutes each, and the PRi, mean arterial pressure (MAP), and heart rate were recorded at each concentration. RESULTS: A negative correlation was found between the PRi and ETsevo (-0.882) and between the MAP and ETsevo (-0.571). A low positive correlation was found between the PRi and MAP (0.484). CONCLUSIONS: The PRi showed a high negative correlation with the ETsevo. Therefore, the PRi can be used to guide the depth regulation of sevoflurane anesthesia.Clinical trial registration number: ChiCTR-IPR-17012092.
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Anestésicos Inalatórios , Éteres Metílicos , Adulto , Anestesia Geral , Humanos , Dor , Pressão Parcial , SevofluranoRESUMO
BACKGROUND: Tuberculosis (TB) is an important public health problem in China and environmental and genetic factors have an impact on its occurrence and development. We explored the relationship between environmental factors, genetic susceptibility genes and gene-environment interactions and the incidence of TB, as well as their high-risk combination, which can provide a scientific basis for prevention of the disease. METHODS: The 242 individuals, which included 82 TB patients, 67 family genetically related patients and 93 healthy controls, all of whom were of the Han population in Guangdong Province. The basic information of subjects was collected, including general conditions, behaviour habits, family environmental factors and blood samples. Two single nucleotides with potential functions (interleukin-10 [IL-10] rs1800896, interferon-γ [IFN-γ] rs2430561) were screened by bioinformatics tools and identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We found that gender, education, TB exposure history, fitness activities, residential areas and indoor hygiene conditions were all associated with the occurrence of TB. In the dominant model, AG+GG of IL-10 and AA of IFN-γ are high-risk genotypes. Multifactor dimensionality reduction (MDR) analysis of TB-prone families shows that a combination of male sex, IL-10 AA and AG genotypes and smoking history are elements of high risk for TB infection (prediction accuracy 62.45%, cross-validation consistency 10/10). The MDR analysis of the TB patients group and the healthy control group showed that the combination of low education level, history of TB exposure, and IFN-γ AA genotype represented a higher risk of TB infection (prediction accuracy 80.34%, cross-validation consistency 10/10). CONCLUSIONS: The occurrence of TB in TB-prone families in the Han population of Guangdong Province is related to environmental factors as well as cytokines IL-10 and IFN-γ. We also found high-risk combinations of genes and environmental factors, providing clues for the timely detection of high-risk groups.
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Polimorfismo de Nucleotídeo Único , Tuberculose , Estudos de Casos e Controles , China/epidemiologia , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Tuberculose/epidemiologia , Tuberculose/genéticaRESUMO
BACKGROUND: Wavelet index (WLi) and pain rating index (PRi) are new parameters for regulating general anesthesia depth based on wavelet analysis. AIM: To investigate the safety and efficacy of using WLi or PRi in sevoflurane anesthesia. METHODS: This randomized controlled trial enrolled 66 patients scheduled for elective posterior lumbar interbody fusion surgery under sevoflurane anesthesia between September 2017 and February 2018. A random number generator was used to assign the eligible patients to three groups: Systolic blood pressure (SBP) monitoring group, WLi monitoring group, and PRi monitoring group. The main anesthesiologist was aware of the patient grouping and intervention used. The primary endpoint was anesthesia recovery time. Secondary endpoints included extubation time, sevoflurane consumption, number of unwanted events/ interventions, number of adverse events and postoperative visual analogue scale for pain. RESULTS: A total of 62 patients were included in the final analysis (SBP group, n = 21; WLi group, n = 21; and PRi group, n = 20). There were no significant differences among the three groups in patient age, gender distribution, body mass index, American Society of Anesthesiologists class, duration of surgery, or duration of anesthesia. Anesthesia recovery time was shorter in the WLi and PRi groups than in the SBP group with no significant difference between the WLi and PRi groups. Extubation time was shorter in the WLi and PRi groups than in the SBP group. Sevoflurane consumption was lower in the WLi and PRi groups than in the SBP group. Nicardipine was more commonly needed to treat hypertension in the WLi and PRi groups than in the SBP group. CONCLUSION: Regulation of sevoflurane anesthesia depth with WLi or PRi reduced anesthesia recovery time, extubation time and sevoflurane consumption without intraoperative unwanted events.
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Chemotherapy drugs exerts beneficial antitumor activity before and after cancer surgery. Post-injury complications are a potential hazard after surgical tumor resection. Inflammation caused by surgical stress is known to promote the progression of post-injury complications. Recent studies have found that chemotherapy drugs can promote post-injury inflammatory response, leading to increased post-injury complications. Imidazole derivatives have effective anticancer activity. However, the impact of post-operative inflammation caused by imidazole derivatives is unclear. In this study, two novel phenanthroimidazole derivatives (L082 and L142) were synthesized and characterized. These compounds showed significant inhibitory effects on different tumor cells. The compound L082 also inhibited liver cancer in vivo. In addition, L082 played a significant role in inhibiting the accumulation of inflammatory cells and promoting the elimination of inflammatory cells at the incision, which may be related to inhibiting the production of ROS and NO in oxidative and nitric stress. These results suggest that L082 can be used as a bifunctional drug to suppress tumors and reduce post-injury inflammation complications.
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Anti-Inflamatórios/síntese química , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Fenantrenos/síntese química , Fenantrenos/uso terapêutico , Células A549 , Animais , Animais Geneticamente Modificados , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Relação Dose-Resposta a Droga , Células HeLa , Células Hep G2 , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Fenantrenos/farmacologia , Peixe-ZebraRESUMO
In order to introduce effectively the external electric fields into the explosive systems, the change trends of the strengths of trigger linkages, nitro group charges, and explosive sensitivities of 1,4-dinitroimidazole-N-oxide (1,4-DNIO) were investigated in the external electric fields at the B3LYP/6-311++G(2d,p) and M06-2X/aug-cc-pVTZ levels. The formulas for calculating the impact sensitivity by the surface electrostatic potentials were discussed. The results show that the N-NO2 bond is always the most likely trigger linkage, followed by N â O. This is the very valuable information for the researchers engaged in the molecular design or synthesis of the energetic explosives: The influences of the weak N â O coordination bond attached to the aromatic ring on the explosive sensitivity can be ignored when the N-NO2 bond exists. In the external electric fields along the positive directions of the N â O and C-NO2 bond axes as well as the negative direction of the N-NO2 bond axis, the dissociation energies (BDEs) of the N-NO2 bond and h50 values are increased, leading to the decreased impact sensitivities. The changes of the bond lengths, AIM electron density values, nitro group charges, BDEs of the trigger linkages, and impact sensitivities correlate well with the external electric field strengths, respectively. The effects of the fields on the electric spark sensitivities and shock initiation pressures are not obvious. The essence of the low BDEs of the N-NO2 bond was revealed by the resonance theory of the aromatic ring. Graphical abstract Changes of the impact sensitivities versus field strengths.
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The preparation of efficient and low-cost bifunctional catalysts with superior stability for water splitting is a topic of significant current interest for hydrogen generation. A facile strategy has been developed to fabricate highly active electrodes with hierarchical porous structures by using a two-step electrodeposition method, in which NiFe layered double hydroxide is grown in situ on a three-dimensional hierarchical Ni mesh (NiFe/Ni/Ni). The as-prepared NiFe/Ni/Ni electrodes demonstrate remarkable structural stability with high surface areas, effective gas transportation, and fast electron transfer. Benefiting from the unique structure, the self-supported NiFe/Ni/Ni electrodes exhibit overpotentials of 190â mV and 300â mV for the oxygen evolution reaction (OER) at current densities of 10 and 500â mA cm-2 , respectively. Furthermore, the self-supported NiFe/Ni/Ni electrodes also exhibit high performance in the hydrogen evolution reaction (HER) and excellent stability at a current density of 500â mA cm-2 for both OER and HER. Remarkably, using NiFe/Ni/Ni as both the cathode and anode for alkaline water electrolysis, a current density of 500â mA cm-2 is attained at a cell voltage of 1.96â V. Additionally, the water electrolyzer demonstrates superior stability even at a large current density (500â mA cm-2 ) when subjected to high temperatures.
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OBJECTIVE: To explore the correlation of tip perfusion index (TPI) with the hemodynamics and catecholamines and to assess the value and meaning of TPI for monitoring stress responses in general anesthesia. METHODS: Twenty patients who were to receive selective neurosurgery underwent induction and maintenance of propofol and remifentanil by target controlled infusion (TCI). A 60 mA-50 Hz-5 s electrostimulus was applied before tracheal intubation and head holder setting respectively. TPI, SBP, diastolic blood pressure (DBP), heart rate (HR), and bispectral index (BIS) were recorded at nine time points: before induction (baseline), before and after electrostimulation, before and after tracheal intubation, before and after electrostimulation, and before and after head holder setting. The changes of parameters (DeltaTPI, DeltaSBP, DeltaDBP, DeltaHR, and DeltaBIS) were calculated after each stimulation. Five out of 20 patients were selected randomly to monitor the plasma concentration of catecholamine at the above time points. The responses to tracheal intubation and head holder setting were defined as the SBP increasing > 15 mm Hg over the baseline value. RESULTS: DeltaTPI was significantly correlated with DeltaSBP and DeltaDBP (r = 0.623 and 0.317, P <0.01 and 0.05). The responses to tracheal intubation and head holder setting were inhibited effectively when the DeltaTPI caused by electrostimulus was less than 10% of the pre-electrostimulus TPI. TPI was significantly negatively correlated with the plasma concentrations of norepinephrine and epinephrine (r = -0.679, and r = -0.364, P < 0.05 and 0.01). CONCLUSION: (1) The TPI change is correlated well with the blood pressure change during stresses, and the TPI change caused by electrostimulus can predict the blood pressure change caused by tracheal intubation and head holder setting. (2) The TPI change reflects the norepinephrine plasma level indirectly.
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Anestesia Geral , Catecolaminas/sangue , Hemodinâmica/fisiologia , Adolescente , Adulto , Anestésicos Intravenosos/administração & dosagem , Estimulação Elétrica , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Monitorização Intraoperatória/métodos , Neurocirurgia/métodos , Perfusão/métodos , Piperidinas/administração & dosagem , Propofol/administração & dosagem , Remifentanil , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To observe the hemodynamic changes, recovery profiles, and side effects of propofol and remifentanil anesthesia by target controlled infusion (TCI). At different neurosurgical stages in patients undergoing neurosurgical operations. METHODS: 230 patients were scheduled for elective craniotomy in five hospitals in Beijing, Changsha, and Guangzhou. During the general anesthesia the plasma target-concentration of propofol remained unchangeable and the dose of remifentanil changed at different stages before skin incision, during skull opening, during intracranial procedure, and at skull closing. The hemodynamics changes and anesthetic recovery profiles were recorded. RESULTS: The plasma target-concentrations of remifentanil were set to 3.0, 3.5, 3.6 and 3.4 ng/ml respectively. The time of consciousness loss during induction was (2.0 +/- 0.9) min. The mean arterial pressure (MAP) and heart rate (HR) decreased after induction (both P < 0.05) and increased after intubation. The hemodynamic changes were stable at different surgical stages and the HR was significantly lower than the baseline value (P < 0.01). MAP and HR increased gradually when the spontaneous breathing was recovered. 80, 41, 9, and 12 patients received nicardipine, atropine, esmolol, and ephedrine respectively during the operation. The times of recovery of spontaneous breathing, eye opening, extubation, and orientation were (12 +/- 9) min, (13 +/- 7) min, (16 +/- 8) min, and (21 +/- 8) min respectively. CONCLUSION: When combined with 3 microg/ml propofol, the plasma target-concentrations of remifentanil, 3.0, 3.5, 3.6, and 3.4 ng/ml before skin incision, during skull opening, during intracranial procedure, and at skull closing respectively, can provide rapid induction, faster emergence , and better hemodynamic stability.
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Anestésicos Intravenosos/administração & dosagem , Procedimentos Neurocirúrgicos/métodos , Piperidinas/administração & dosagem , Adolescente , Adulto , Idoso , Anestesia Intravenosa , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Propofol/administração & dosagem , Remifentanil , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To investigate the role of Toll-like receptor 4 (TLR4) inflammatory signal pathway in brain ischemic tolerance induced by hypoxia preconditioning (HP). METHODS: 160 Wistar rats were randomly divided into 4 groups: asphyxial cardiac arrest (ACA) group (n = 54, subjected to ACA for 4 min and then resuscitation), HP + ACA group [n = 44, subjected to apnea and ventilation (HP) for 1 min 4 times with an interval of 5 min between each 2 times, and then subjected to apnea for 4 min and resuscitation 24 h later), HP group (n = 42, subjected to HP 4 times only), and sham operation group (Group C, n = 20). The mortality within 24 h after resuscitation and circulatory functions were observed. Neurodeficit score (NDS) was recorded 24, 48, and 72 hours after successful resuscitation. Rats were killed 1, 3, 6, 12, 24, 48, and 72 h after preconditioning or operation to take out the left brain cortex. RT-PCR was used to detect the mRNA expression of TLR4. The levels of nuclear factor-kappaB (NFkappaB), tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-6 were detected by relevant kits. RESULTS: The mortality of the HP + ACA group was 5%, significantly lower than that of ACA group (30%, P < 0.01). The NDS levels at different time points of the HP group and Group C were all 100 +/- 0. The NDS levels of the HP + ACA group and ACA group at different time points were all significantly lower than those of the control group and HP group (all P < 0.01). The NDS levels at different time points of the ACA group were all significantly lower than those of the HP + ACA group (all P < 0.05). The NDS levels 72 h later of the HP + ACA and ACA groups were both significantly higher than those 24 h later of the corresponding groups (both P < 0.05). The TLR4 mRNA expression of the control group at any time points were all very weak, and the TLR4 mRNA expression level of the other groups increased since 1 h after hypoxia gradually and decreased 72 h later. The NFkappaB expression levels of the control group at any time points were all very weak, and the NFkappaB expression level of the other groups increased time-dependently since 1 h later, peaked 3 - 6 h later, and began to decrease 24 h later. There was a tendency of increase of NFkappaB expression level in the order of HP group < HP + ACA group < ACA group. The expression of TNF-alpha and IL-6 showed the same tendency as seen in the expression of TLR2 and NFkappaB. CONCLUSION: HP induces brain ischemic tolerance via a possible mechanism of activating TLR4 signal pathway and then inhibiting inflammatory response induced by ACA.
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Isquemia Encefálica/fisiopatologia , Precondicionamento Isquêmico/métodos , Transdução de Sinais , Receptor 4 Toll-Like/fisiologia , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/prevenção & controle , Reanimação Cardiopulmonar , Ensaio de Imunoadsorção Enzimática , Interleucina-6/metabolismo , Masculino , NF-kappa B/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Changes in N-NO2 bond strength, ring strain energy and electrostatic potential upon formation of intermolecular H-bonds between HF and the nitro group in nitrogen heterocyclic rings C n H2n N-NO2 (n = 2-5), RDX and HMX were investigated using DFT-B3LYP and MP2(full) methods with the 6-311++G(2df,2p) and aug-cc-pVTZ basis sets. Analysis of electron density shifts was also carried out. The results indicate that H-bonding energy correlates well with the increment of ring strain energy. Upon complex formation, the strength of the N-NO2 trigger-bond is enhanced, suggesting reduced sensitivity, while judged by the increased ring strain energy, sensitivity is increased. However, some features of the molecular surface electrostatic potential, such as a local maximum above the N-NO2 bond and ring, σ + (2) and electrostatic balance parameter ν, remain essentially unchanged upon complex formation, and only a small change in the impact sensitivity h 50 is suggested. It is not sufficient to determine sensitivity solely on the basis of trigger bond or ring strain; as a global feature of a molecule, the molecular surface electrostatic potential is available to help judge the change of sensitivity in H-bonded complexes. Graphical Abstract The strengthened N-NO2 bond suggests reduced sensitivity, while it is reverse by theincreased ring strain energy upon the complex formation. However, the molecular surfaceelectrostatic potential (V S) shows the little change of h 50. The V S should be taken into accountin the analysis of explosive sensitivity in the H-bonded complex.
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OBJECTIVE: To study the correlation of polymorphisms of CYP1A1 MSPI and glutathiones S-transferase (GST-M1) independently and in combination with the risk of lung cancer. METHODS: A case control study which included 91 cases of lung cancer and 138 controls collected from the First Affiliated Hospital of Sun Yat-sen University of Medical Sciences, Guangzhou Tumor Hospital and The Red Cross Hospital of Guangzhou or conmunity area. All subjects were investigated with a uniform questionnaire. Blood samples were collected from all cases and controls for detecting CYP1A1 MSPI and GST-M1 polymorphisms which were analyzed by PCR and RFLP. RESULTS: It showed that there was no significant difference in frequencies of this genotypes of CYP1A1 MSPI between the two groups. The frequency of GST-M1 null (0/0) genotype was higher in the case group than in the control group, with an OR of 1.38 (95% CI 0.81 - 2.38), but there was no statistical significance. However, combination of several genotypes was strongly associated with lung cancer. There was a synergistic interaction between the m2m2 genotype of CYP1A1 MSPI and GST-M1 (0/0) genotype, with an OR of 2.47 (95% CI 1.03 - 5.90). CONCLUSION: The combination of two genetic polymorphisms significantly increases the risk of lung cancer.
Assuntos
Citocromo P-450 CYP1A1/genética , Glutationa Transferase/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Risco , Fumar/efeitos adversosRESUMO
OBJECTIVE: To evaluate whether isoflurane induced hypotension increases the incidence of cerebral vasospasm in intracranial aneurysm surgery. METHODS: Thirty consecutive patients undergoing intracranial aneurysmal surgery without preexisting cerebral ischemia were prospectively randomized into 2 groups: isoflurane induced hypotension group (group A, n = 15) and isoflurane maintained anesthesia group (group B, n = 15). The patients in the group A were performed isoflurane induced hypotension after dura opening by increasing the inhaled concentration of isoflurane to decrease the mean arterial pressure (MAP) by 30 - 40 percent of that of baseline value. After the aneurysm was clipped, the concentration of inhaled isoflurane was decreased so as to stop blood pressure reduction. The patient in group B was given 1 minimum alveolar concentration (MAC) of isoflurane during the whole procedure. The indicators of blood circulation were measured before blood pressure reduction, 30 minutes after blood pressure reduction, just after the clipping of the aneurysm, and 30 minutes after stopping blood pressure reduction. The S100B protein level in cerebrospinal fluid was observed before the controlled hypotension and 0, 2, and 4 h after the aneurysm was clipped. Assessment of the mean blood flow velocity of parent artery and its main branches was performed by microvascular ultrasonics before and after the aneurysm was clipped. The patients were followed-up for one week after the operation to observe the neurological complication. RESULTS: The MAP was decreased from 95 mm Hg +/- 12 mm Hg to 59 mm Hg +/- 5 mm Hg 30 minutes after the induced hypotension, and resumed to 75 mm Hg +/- 8 mm Hg 30 minutes after the aneurysm was clipped. Compared with those in the group B, both the total systemic vascular resistance and myocardial contract acceleration were decreased in group A, whereas the cardiac output and heart rate remained stable. (2) 4 hours after the aneurysm was clipped the S100B protein level in CSF was increased significantly in both groups, and that in the group A being significantly higher than that in the group B (t = 2.854, P < 0.01). (3) In the group A, the mean arterial flow velocity of distal parent vessels increased by more than 30 percent in 8 out of the 15 patients and 3 of these 8 patients suffered from neurological deficits postoperatively. However, the mean arterial flow velocity of distal parent vessels in the group B increased by more than 30 percent in only 3 of the 15 patients and 2 of these 3 patients suffered from neurological deficits postoperatively. CONCLUSION: Isoflurane controlled hypotension may increase the incidence of cerebral vasospasm. Isoflurane induced hypotension for intracranial aneurysm surgery should be cautioned.
Assuntos
Hipotensão/complicações , Aneurisma Intracraniano/cirurgia , Isoflurano/administração & dosagem , Vasoespasmo Intracraniano/etiologia , Adulto , Idoso , Anestésicos Inalatórios/administração & dosagem , Pressão Sanguínea/fisiologia , Feminino , Seguimentos , Humanos , Hipotensão/induzido quimicamente , Hipotensão/fisiopatologia , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Prospectivos , Proteínas S100/líquido cefalorraquidiano , Resultado do Tratamento , Vasoespasmo Intracraniano/líquido cefalorraquidianoRESUMO
OBJECTIVE: To evaluate the efficacy of Integrative Chinese and western medicine (ICWM) in treating SARS. METHODS: By controlled paralled design, 49 patients of SARS were studied, they were divided into the control group (n = 29) and the ICWM group (n = 20). The former was treated according to the "Recommended Program for Treatment of SARS" provided by Health Ministry, by administering of such drugs as Ribavirin, Levofloxacin, Thymopentin, Azithromycin, etc, the latter was treated with the ICWM protocol for SARS of "Special Technological Action to Prevent and Treat SARS" provided by Science and Technology Ministry. RESULTS: (1) The time for improving symptom in the ICWM group was 5.10 days and that in the control group was 7.62 days, the difference between them was significant (P < 0.05); (2) The days and amount for use hormone before subtract in the two group were similar, with insignificant difference (P > 0.05); (3) The days and amount for use hormone after subtract in the two groups were significantly different (P < 0.05); (4) The time for improving peripheral WBC count and absolute value of lymphocyte, as well as for absorption time of shadow in chest film were not different significantly between the two groups (P > 0.05). CONCLUSION: In treating SARS, ICWM was superior to the treatment with western medicine alone in aspects of improving clinical symptom, promoting recovery of immune function and absorption of lung inflammation, decreasing the dosage of hormone used and shortening the therapeutic course.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Metilprednisolona/uso terapêutico , Fitoterapia , Ribavirina/uso terapêutico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Adolescente , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Levofloxacino , Masculino , Pessoa de Meia-Idade , Ofloxacino/uso terapêutico , Síndrome Respiratória Aguda Grave/imunologiaRESUMO
OBJECTIVE: To evaluate the effect of intraoperative continuous nimodipine infusion on cerebral vasospasm during intracranial aneurysm surgery. METHODS: Thirty consecutive patients under-going intracranial aneurysmal surgery were prospectively randomized into two groups: Isoflurane (group A, n = 15) and nimodipine (group B, n = 15). The patients in group A were maintained with 1 minimum alveolar concentration (MAC) isoflurane anesthesia during the whole procedure. The patients in group B were given nimodipine infusion continuously (20 microg.kg(-1).h(-1)) after induction of anesthesia and anesthetized with 1 MAC isoflurane. S100B levels in cerebrospinal fluid were determined before aneurysm clipping and 0, 2, 4 h after aneurysm clipping by enzyme linked immunosorbent assay. Assessment of mean blood flow velocity of parent arterial and arterial branches were performed before and after aneurysm clipping. RESULTS: (1) S100B in cerebrospinal fluid was increased significantly at 4 h after aneurysm was clipped in group A (F = 4.11, P < 0.05). However, S100B in cerebrospinal fluid was stable in group B in the whole procedure. (2) Mean arterial flow velocity of parent vessels in group B was lower significantly than that in group A (t = 2.08, P < 0.05). However, mean arterial flow velocity of distal vessels in both groups has no significant difference. CONCLUSION: Intraoperative nimodipine infusion may prevent cerebral vasospasm during intracranial aneurysm surgery.