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In this study, we designed and prepared a trastuzumab-coupled drug delivery system with pH response characteristics using mesoporous zeolitic imidazolate framework-8 (ZIF-8) as the carrier, Trastuzumab@ZIF-8@DOX. As results, the targeted drug delivery system (TDDS) ultimately showed high drug loading and good biocompatibility. The cumulative curve of drug release indicated that the early leakage levels were low under neutral pH conditions. However, under acidic pH conditions, there was an effective enhancement in drug release, indicating the presence of an explicit pH-triggered drug release mechanism. The results indicate that the prepared nanoparticles have the potential to serve as drug delivery systems, as they can release the loaded drug in a controlled manner. The results of cellular uptake tests showed that the uptake of the nanoparticles was greatly enhanced by the internalization mediated by the HER2 antibody. This finding indicates that the prepared nanoparticles can selectively target cancer cells that overexpress HER2. When the doxorubicin dose was 5 µg/ml, the survival rate of SK-BR-3 cells (cancer cells) was 47.75 %, and the survival rate of HaCaT cells (healthy cells) was 75.25 % when co-cultured with both cells. The therapeutic efficacy of Trastuzumab@ZIF-8@DOX was assessed on BALB/c nude mice to validate its potential as an effective drug delivery system for tumor inhibition in vivo. In conclusion, these findings demonstrate the specificity-targeted and pH-responsive nature of this smart drug delivery system, highlighting its promising prospects for efficient and controllable cancer treatment applications.
Subject(s)
Metal-Organic Frameworks , Nanoparticles , Animals , Mice , Mice, Nude , Drug Delivery Systems , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Trastuzumab/pharmacology , Drug Carriers , Hydrogen-Ion ConcentrationABSTRACT
In COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO), our primary objective was to determine the frequency of intracranial hemorrhage (ICH). Secondary objectives were to estimate the frequency of ischemic stroke, to explore association between higher anticoagulation targets and ICH, and to estimate the association between neurologic complications and in-hospital mortality. DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, Cochrane, and MedRxiv databases from inception to March 15, 2022. STUDY SELECTION: We identified studies that described acute neurological complications in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring ECMO. DATA EXTRACTION: Two authors independently performed study selection and data extraction. Studies with 95% or more of its patients on venovenous or venoarterial ECMO were pooled for meta-analysis, which was calculated using a random-effects model. DATA SYNTHESIS: Fifty-four studies (n = 3,347) were included in the systematic review. Venovenous ECMO was used in 97% of patients. Meta-analysis of ICH and ischemic stroke on venovenous ECMO included 18 and 11 studies, respectively. The frequency of ICH was 11% (95% CI, 8-15%), with intraparenchymal hemorrhage being the most common subtype (73%), while the frequency of ischemic strokes was 2% (95% CI, 1-3%). Higher anticoagulation targets were not associated with increased frequency of ICH (p = 0.06). In-hospital mortality was 37% (95% CI, 34-40%) and neurologic causes ranked as the third most common cause of death. The risk ratio of mortality in COVID-19 patients with neurologic complications on venovenous ECMO compared with patients without neurologic complications was 2.24 (95% CI, 1.46-3.46). There were insufficient studies for meta-analysis of COVID-19 patients on venoarterial ECMO. CONCLUSIONS: COVID-19 patients requiring venovenous ECMO have a high frequency of ICH, and the development of neurologic complications more than doubled the risk of death. Healthcare providers should be aware of these increased risks and maintain a high index of suspicion for ICH.
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OBJECTIVE: To determine the association between delay in transfer to a central stroke unit from peripheral institutions and outcomes. METHODS: We conducted a retrospective cohort study of all patients with acute stroke, admitted to a comprehensive stroke center (CSC) from three emergency departments (EDs), between 2016 and 2018. The primary outcomes were length of stay, functional status at 3 months, discharge destination, and time to stroke investigations. RESULTS: One thousand four hundred thirty-five patients were included, with a mean age of 72.9 years, and 92.4% ischemic stroke; 663 (46.2%) patients were female. Each additional day of delay was associated with 2.0 days of increase in length of stay (95% confidence interval [CI] 0.8-3.2, p = 0.001), 11.5 h of delay to vascular imaging (95% CI 9.6-13.4, p < 0.0001), 24.2 h of delay to Holter monitoring (95% CI 7.9-40.6, p = 0.004), and reduced odds of nondisabled functional status at 3 months (odds ratio 0.98, 95% CI 0.96-1.00, p = 0.01). Factors affecting delay included stroke onset within 6 h of ED arrival (605.9 min decrease in delay, 95% CI 407.9-803.9, p < 0.0001), delay to brain imaging (59.4 min increase in delay for each additional hour, 95% CI 48.0-71.4, p < 0.0001), admission from an alternative service (3918.7 min increase in delay, 95% CI 3621.2-4079.9, p < 0.0001), and transfer from a primary stroke center (PSC; 740.2 min increase in delay, 95% CI 456.2-1019.9, p < 0.0001). CONCLUSION: Delay to stroke unit admission in a system involving transfer from PSCs to a CSC was associated with longer hospital stay and poorer functional outcomes.
Subject(s)
Hemorrhagic Stroke , Stroke , Humans , Female , Aged , Male , Retrospective Studies , Treatment Outcome , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Stroke refers to a group of cerebrovascular diseases associated with organic brain injury. It is characterized by the sudden and rapid onset of focal or diffuse dysfunction. In recent years, in addition to routine treatment, Chinese medicine acupuncture has been administered to patients with hemiplegia, and it can be considered a new treatment for rehabilitation. AIM: To investigate the effects of eye acupuncture needle retention and body acupuncture combined with routine rehabilitation on gait performance and plantar pressure in patients recovering from stroke. METHODS: Thirty-two stroke patients who met the inclusion criteria were randomly divided into an experimental group and a control group, with 16 patients in each group. Both groups underwent routine rehabilitation. The experimental group was treated by eye acupuncture needle retention, and the control group was treated by body acupuncture. Before and after 4 wk of treatment, both groups underwent kinematic and plantar pressure synchronous tests to assess gait performance. RESULTS: The step length, gait speed, step frequency, joint angles of the lower limbs, and ground reaction force impulse in the anterior region of the affected foot in both groups significantly increased from before to after treatment (P < 0.05); the center of mass displacement, peak pressure values, and impulse in the anterior region of the healthy foot and posterior regions of both the affected and healthy feet significantly decreased from before to after treatment (P < 0.05). The patients in the experimental group showed greater improvement in the following parameters than the control group: Step length, gait speed, step frequency, lower extremity joint angles, center of gravity displacement, and peak pressure values and impulse in the anterior and posterior regions of both the affected and healthy feet (P < 0.05). CONCLUSION: Eye acupuncture needle retention and body acupuncture combined with routine rehabilitation can effectively improve the gait performance of patients recovering from stroke. Between these two treatments, eye acupuncture needle retention combined with routine treatment is better than body acupuncture, and it can be considered a practical and effective clinical treatment.
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OBJECTIVE: To investigate the long-term effect of posterior lumbar pedicle screw fixation combined with isthmus bone grafting and fusion in young patients with spondylolysis. METHODS: A retrospective study was carried out, consisting of 16 young patients with lumbar spondylolysis without spondylolisthesis treated by lumbar posterior pedicle screw fixation combined with isthmic bone grafting fusion from January 2006 to July 2014. There were 11 males and 5 females, aged from 18 to 21 years old, with an average age of 19.3 years old, and the course of disease ranged from 12 to 26 months, with an average of 22 months. All the patients suffered from lumbar pain and difficulty in getting out of bed. Preoperative CT confirmed 12 cases of L5 isthmus fissure and 4 cases of L4 isthmus fissure. Bone graft fusion was confirmed and internal fixation was removed after operation. Lumbar spondylolysis was evaluated by lumbago visual analogue scoring method at preoperative and postoperative time points. Lumbar isthmic fusion was evaluated by lumbar CT, and degeneration of fixed and adjacent segments of lumbar intervertebral disc was evaluated by lumbar MRI. RESULTS: Of the 16 patients, 13 patients (26 sides) were followed up, with a mean duration of 96 months. The operation time ranged from 80 to 105 minutes, with an average of 95 minutes. The intraoperative bleeding volume ranged from 150 to 300 ml, with an average of 225 ml. All the patients were successfully operated without any complications related to the operation. VAS scores at each time point after operation were improved compared with those before operation(P<0.01). Postoperative CT scans of lumbar spine showed osseous fusion at 6 to 14 months, with an average of 12 months. There were no changes of adjacent segment degeneration, fixed segment disc degeneration and protrusion on lumbar spine MRI, and no symptomatic recurrence or recurrent spondylolysis in the long term. CONCLUSIONS: The posterior lumbar pedicle screw fixation combined with isthmic bone grafting and fusion is safe and effective in the treatment of young spondylolysis. The fusion rate is high and the interference of normal physiological range is reduced. The long-term effect is satisfactory.
Subject(s)
Pedicle Screws , Spinal Fusion , Spondylolysis , Adolescent , Bone Transplantation , Female , Humans , Lumbar Vertebrae , Male , Retrospective Studies , Spondylolysis/surgery , Treatment Outcome , Young AdultABSTRACT
A highly sensitive quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor based on a custom quartz tuning fork (QTF) with a small-gap of 200 μm was demonstrated. With the help of the finite element modeling (FEM) simulation software COMSOL, the change tendency of the QEPAS signal under the influence of the laser beam vertical position and the length of the micro-resonator (mR) were calculated theoretically. Water vapor (H2O) was selected as the target analyte. The experimental results agreed well with those of the simulation, which verified the correctness of the theoretical model. An 11-fold signal enhancement was achieved with the addition of an mR with an optimal length of 5 mm in comparison to the bare QTF. Finally, the H2O-QEPAS sensor, which was based on a small-gap QTF, achieved a minimum detection limit (MDL) of 1.3 ppm, indicating an improvement of the sensor performance when compared to the standard QTF that has a gap of 300 μm.
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The physics of combusting flows consists of a complex interaction between chemical reactions, fluid mechanics and radiation. Temperature is one of the most important parameters for the processes. Laser-based imaging techniques are frequently used to assess temperature information from reactive systems without perturbing the system under study. To verify the feasibility of the temperature measurement of UV tunable absorption spectroscopy technology the methane/air premix flat flame was selected as the target of test because of the combustion stability of this kind of flame. Before the temperature measurement the distribution of OH radical in the premix flat flame under different operating conditions were obtained by using planar laser induced fluorescence (PLIF). At the low equivalence ratio the OH radicals distribute uniformly in the flame for the adequate oxygen in the premix gas. The condition with uniform distribution of OH in the flame was selected for the UV tunable absorption spectroscopy measurement. For the selection of absorption lines of the measurement the spectrum of OH A-X(0,0) band have been simulated by LIFBASE. Considering the slope sensitivity and SNR of the test the transitions P1(2) and Q1(8) were suitable for the temperature measurement of the flame. A dye laser pumped by a frequency doubled Nd:YAG laser was used to generated the UV laser. The dye laser was operated with the mixed dye of DCM and PM580 for high conversion efficiency at 310 nm. To investigate the transitions of Q1(8) and P1(2) of OH A-X(0,0) the laser was tuned from 309.225~309.255 and 308.625~308.655 nm separately with the step of 0.4 pm, 30 pulses were recorded at each step. The laser pulses reflected by the beam splitter were collected by detector A, and the pulses passed the flame were collected by detector B. The signal of these two detectors were recorded by the oscilloscope and acquired by the computer automatically. The line shape of these transitions can be obtained after fitting the experimental data with the Voigt function. The integral ratio between the fitting results of these two lines was calculated. Then temperature of the flame could be deduced by the integral ratio. The temperatures of different positions above the surface of burner and varied heights of the flame center were obtained by measuring the integrated absorption ratio of these two transitions. The test results of this method are compared with the report in reference, in which temperature of the burner with the same structure was measured by other ways. The results of these two tests agree well. It shows that this method has the potential to be a calibration for the two-dimension thermometry in flame such as two-line PLIF.
ABSTRACT
Quartz-enhanced photoacoustic spectroscopy (QEPAS) technology was invented lately. Therefore it's an innovative method for trace gas detection compared with other existed technologies. In this paper, we studied the trace gas detection system based on QEPAS, and the atmospheric H2O was selected as the target analyte. In theory, the principles of laser wavelength modulation and signal harmonic detection were analyzed firstly, and the realizing solutions for the gas concentration retrieving and laser wavelength locking were obtained. Furthermore, the selection principle of absorption line for high sensitivity gas detection was discussed. In experiments, a continuous-wave distributed feedback(DFB) single mode diode laser emitting at 1.39 µm was used as the exciting source for the H2O vapor measurement. Using wavelength modulation spectroscopy and 2nd harmonic detection, the influence of laser wavelength modulation depth on QEPAS signal level was investigated, and the acoustic wave enhancement of the addition of micro-resonator in the acoustic detection module was analyzed as well. After optimization of the QEPAS system, a detection limit of 5.9 ppm for H2O vapor was obtained. We measured the H2O vapor with different concentrations, and the R-Square of 0.98 was achieved after the experimental data was linear fitted, indicated that the QEPAS system had an excellent linear response ability. Finally, continuous monitoring of atmospheric H2O concentration levels for a period of 12 hours was performed when the line locking mode was employed with the help of 3rd harmonic detection. The experimental results showed that this QEPAS scheme had a stable performance and outstanding continuous measuring capacity, and it can be widely used in high sensitivity on-line measurement for other trace gases detection fields.
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Solid complexes of terbium and europium nitrates with an amino-alkenone type ligand, 1-[2-(6-methylpyridin-2-ylamino)-5,6-dihydro-4H-pyran-3-yl]ethanone (L) have been prepared and characterized by elemental analysis, conductivity measurements, and IR spectra. The crystal and molecular structures of the complexes [TbL(2)(NO(3))(3)(H(2)O)]·CHCl(3) (1) and [EuL(2)(NO(3))(3)(H(2)O)]·CH(3)CO(2)C(2)H(5) (2) have been determined by single crystal X-ray diffraction. And the coordination spheres of the complexes are similar. At the same time, the luminescent properties of the Tb(3+) complex in solid state and in solvents were investigated at room temperature. Under the excitation of UV light, Tb(III) complex exhibited characteristic emissions but not for the Eu(III) complex. The lowest triplet state energy level of the ligand in the complex matches better to the resonance level of Tb(III) than Eu(III) ion.
Subject(s)
Alkenes/chemistry , Europium/chemistry , Terbium/chemistry , Crystallography, X-Ray , Ligands , Magnetic Resonance Spectroscopy , Molecular Structure , Ultraviolet RaysABSTRACT
Two new highly luminescent Tb(III) coordination complexes of beta-diketone ligands, [TbL(capital I, Ukrainian)(NO(3))(3)(H(2)O)] 1 [L(capital I, Ukrainian)=N-(2-pyridinyl)ketoacetamide] and [TbL(capital I, Ukrainiancapital I, Ukrainian) (2)(NO(3))(2)(C(3)H(6)O)][TbL(capital I, Ukrainiancapital I, Ukrainian)(NO(3))(4)] 2 [L(capital I, Ukrainiancapital I, Ukrainian)=N-(6-(4-methylpyridinyl))ketoacetamide], were synthesized and characterized by single crystal X-ray diffraction, and incorporated into SiO(2)/polymer hybrid material by sol-gel method resulting in a novel ternary molecular hybrid material. The Tb(III) complexes display characteristic metal-centered luminescence while the ligands emission are completely quenched, showing that efficient ligand-to-metal energy transfer (antenna effect) occurs. The gels can exhibit the characteristic emission bands of terbium ion. In addition, terbium ions present longer fluorescence lifetime in gels than in the corresponding pure complexes powders. Compared with the complexes, the unit mass luminescence intensities of the gels are enhanced. And the increase extent of luminescence intensity of the gel is influenced by the substituent of the ligands. At the same time, concentration effects on the luminescence intensity were investigated. The photo stabilities of the gels under UV radiation are much better than those of the pure terbium complexes.