Alpha-lipoic acid, epalrestat, and mecobalamin are widely used as monotherapies for diabetic peripheral neuropathy. However, whether a triple-combination therapy with these three drugs is superior to ...monotherapy or dual therapy remains debatable.
Nine randomized controlled trials were identified through a search on electronic databases such as PubMed, Web of Science, and Cochrane Library. The trial participants (N = 1153) were divided into the experimental group who received the triple-combination therapy and the control group who received conventional or dual therapy with the aforementioned drugs.
Therapeutic outcomes were better in the experimental group than in the control group (odds ratio: 3.74; 95 % confidence interval: 2.57–5.45; I2 = 0 %; p < 0.00001). No statistic difference was noted in adverse effects. Compared with the control group, the experimental group exhibited significant improvements in median motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and vibration perception thresholds (VPT) in the left and right lower limbs. In the control group, a subgroup analysis by treatment strategy revealed similar improvements in total efficacy, MNCV, and SNCV.
For diabetic peripheral neuropathy, the triple-combination therapy may be more effective than monotherapy or dual therapy.
•DPN is the most common complication of DM.•ALA + MC + epalrestat might be an effective and safety treatment procedure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The conjugation of small molecular hydrophobic anticancer drugs onto a short peptide with overall hydrophilicity to create self- assembling drug amphiphiles offers a new prodrug strategy, producing ...well-defined, discrete nanostructures with a high and quantitative drug loading. Here we show the detailed synthesis procedure and how the molecular structure can influence the synthesis of the self-assembling prodrugs and the physicochemical properties of their assemblies. A series of camptothecin-based drug amphiphiles were synthesized via combined solid- and solution-phase synthetic techniques, and the physicochemical properties of their self-assembled nanostructures were probed using a number of imaging and spectroscopic techniques. We found that the number of incorporated drug molecules strongly influences the rate at which the drug amphiphiles are formed, exerting a steric hindrance toward any additional drugs to be conjugated and necessitating extended reaction time. The choice of peptide sequence was found to affect the solubility of the conjugates and, by extension, the critical aggregation concentration and contour length of the filamentous nanostructures formed. In the design of self-assembling drug amphiphiles, the number of conjugated drug molecules and the choice of peptide sequence have significant effects on the nanostructures formed. These observations may allow the fine-tuning of the physicochemical properties for specific drug delivery applications, ie systemic vs local delivery.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this study, we measure the absolute isotope ratios of ytterbium (Yb) by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) using an optimized regression model for mass bias ...correction. A rhenium (Re) reference material (NIST SRM 3143), which has been characterized previously, is selected as a primary calibrator to calibrate the absolute Yb isotope ratios for three Yb materials (GSB, Alfa Yb, and GBW). The three-isotope plot for all collected data indicates that the results of Yb isotope ratios obtained are not affected by any polyatomic interferences and the mass-independent isotopic fractionation. Furthermore, the recalibrated Hf historical isotope ratios by using the absolute Yb isotopic composition obtained in this study for the isobaric interference correction on Hf isotopes are in agreement with the original historical values. This work has further demonstrated the applicability of the regression model for the calibrated measurements of absolute isotope ratios using MC-ICP-MS. The three mono-elemental Yb standard solutions are thus proposed as the reference materials for Yb isotope ratio measurements in environmental and geoscience applications.
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IJS, KILJ, NUK, PNG, UL, UM
Background
The effective dose of perampanel in status epilepticus (SE), refractory SE (RSE), and super-refractory SE (SRSE) in humans is unknown, and the potential of perampanel in treating SE has ...not been evaluated in a large cohort.
Methods
Data of intensive care patients with RSE and SRSE treated with perampanel were retrospectively reviewed and analyzed.
Results
Eighty-one patients received perampanel, including 39 females with median age 64 17–91 years, perampanel responders (
n
= 27), and non-responders (
n
= 54). The initial perampanel dose was positively associated with treatment response in patients with RSE or SRSE (OR = 1.27, 95% CI 1.03–1.57,
p
= 0.025), while the maximum dose was negatively associated with treatment response (OR = 0.74, 95% CI 0.58–0.96,
p
= 0.022). Hypoxia caused seizures in six patients; five died in hospital and one had severe disability. A statistically non-significant tendency toward better response was found in patients with unique SE type and cause, particularly in nonconvulsive status epilepticus (NCSE) without coma (NCSE without coma vs. generalized tonic–clonic seizure: OR = 4.14, 95% CI 0.98–17.47,
p
= 0.053). In the high-dose (≥ 16 mg/day) groups, although distributions of modified Rankin Scale (mRS) scores were similar between perampanel responders and non-responders at discharge, a greater proportion of perampanel responders had less change in mRS scores from baseline than did perampanel non-responders (median mRS: 0 vs 4,
p
= 0.064). No cardiorespiratory adverse events or laboratory abnormalities were noted with perampanel treatment.
Conclusions
Perampanel is effective and has a satisfactory safety profile in the emergency treatment of established RSE and SRSE.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aim
To determine the effect of safranal on diabetic retinopathy
in vitro
and its possible mechanisms.
Methods
We used human retinal microvascular endothelial cells (HRMECs) to test the influence of ...safranal
in vitro
. High glucose damage was established and an safranal was tested at various concentrations for its potential to reduce cell viability using the MTT assay. We also employed apoptosis detection, cell cycle detection, a transwell test, and a tube formation assay to look into safranal’s inhibitory effects on high glucose damage at various doses. Furthermore, mRNA transcriptome sequencing was performed. mRNA expression levels in a high glucose damage model, a high glucose damage model treated with safranal, and a blank control were compared to find the possible signaling pathway. Western blotting was used to confirm the expressions of several molecules and the levels of phosphorylation in each for the newly discovered pathway.
Results
Cell proliferation was inhibited under a high glucose condition but could be protected by safranal at different concentrations (P<0.001). Flow cytometry results suggested safranal also protected cells from apoptosis (P=0.006). A transwell test demonstrated reduced invasiveness of safranal-treated cells in a high glucose condition (P<0.001). In a tube formation investigation, there were noticeably more new branches in the high gloucose group compared to a high glucose treated with safranal group (P<0.001). In mRNA expression patterns on transcriptome sequencing, the MAPK signaling pathway showed an expression ratio. With western blotting, the phosphorylation level of p38-AKT was elevated under a high glucose condition but could be inhibited by safranal. The expression of molecules associated with cell adhesion, including E-cadherin, N-cadherin, Snail, Twist, and fibronectin also changed significantly after safranal treatment under a high glucose condition.
Conclusion
Safranal can protect diabetic retinopathy
in vitro
, and the p38-AKT signaling pathway was found to be involved in the pathogenesis of diabetic retinopathy and could be inhibited by safranal. This pathway may play a role by influencing cell migration and adhesion.
Abstract
In-flight icing detectors are important for the flight safety of aircraft. Detectors based on ultrasonic pulse-echo can be used for detecting ice thickness. To study the influencing factors ...of ultrasonic pulse-echo detection performance, a simulation model of elastic wave-piezoelectric coupling was established, which was used to analyze the influence of different types of piezoelectric ceramics, matching layers with different acoustic impedances, and different substrate materials on ultrasonic pulse-echo signals. It was found that when aluminum is used as the substrate material, the ultrasonic echo signal has a higher signal-to-noise ratio. Furthermore, the influence of aluminum substrate materials with different thicknesses on ultrasonic pulse-echo was analyzed. The ice thickness can be identified by measuring the time of flight between the aluminum-ice interface echo and the ice-air interface echo. The results indicate that when the thickness of the aluminum substrate is 25mm, the upper detection limit of ice layer thickness can reach about 10mm. Therefore, the detection upper limit of ice layer thickness can be extended by appropriately increasing the thickness of the aluminum substrate material.
Abstract
Lamb wave is one of the most used ultrasonic guided waves, which has a wide application prospect in the field of aircraft icing detection. The platform of Lamb wave propagation based on ...piezoelectric wafer was used as the physical model, and COMSOL software was used as the numerical calculation tool to simulate the propagation of Lamb wave in different thickness, length and types of ice. The results showed that the attenuation of voltage amplitude increases with the thickness of ice in a certain range. The time delay of Lamb wave B
1
mode at the receiving end increases linearly with the increase of ice length. As the mechanical parameters of ice layer decrease, the attenuation of voltage amplitude and the time delay of Lamb wave B
1
mode increase gradually. The propagation characteristics of Lamb wave in ice are preliminarily proved, which provides a theoretical reference for the subsequent propagation experiments of Lamb wave in ice.
The ribosome, a 2.6 megadalton biomolecule measuring approximately 20 nm in diameter, coordinates numerous ligands, factors, and regulators to translate proteins with high fidelity and speed. ...Understanding its complex functions necessitates multiperspective observations. We developed a dual-FRET single-molecule Förste Resonance Energy Transfer method (dual-smFRET), allowing simultaneous observation and correlation of tRNA dynamics and Elongation Factor G (EF-G) conformations in the same complex, in a 10 s time window. By synchronizing laser shutters and motorized filter sets, two FRET signals are captured in consecutive 5 s intervals with a time gap of 50–100 ms. We observed distinct fluorescent emissions from single-, double-, and quadruple-labeled ribosome complexes. Through comprehensive spectrum analysis and correction, we distinguish and correlate conformational changes in two parts of the ribosome, offering additional perspectives on its coordination and timing during translocation. Our setup’s versatility, accommodating up to six FRET pairs, suggests broader applications in studying large biomolecules and various biological systems.
We examined the seroprevalence change of anti‐hepatitis D virus (HDV) antibodies in Taiwan from 2006 to 2019. A total of 1147 patients who had chronic hepatitis B virus (HBV) infection were assessed. ...Of them, 51 (4.4%) were positive for anti‐HDV antibodies. Comparison between anti‐HDV‐positive and negative groups was performed to examine clinical and virological factors related to anti‐HDV positivity. It was found that the median HBV‐DNA concentration was 1.6 × 105 IU/mL (range, <20‐4.5 × 1010 IU/mL) and <20 IU/mL (range, <20‐2.0 × 109 IU/mL) for patients with negative and positive anti‐HDV antibodies, respectively (P < .001). In addition, a progressive year‐to‐year decrease of anti‐HDV seroprevalence was unveiled. For patients who had HBV‐DNA >15 000 IU/mL, the year‐to‐year (calculated every 2 years) seropositive rates of anti‐HDV were 10.0%, 7.9%, 0.7%, 0.3%, 0%, 0%, and 0% (P < .001). For patients who had HBV‐DNA <15 000 IU/mL, the year‐to‐year seropositive rates were 18.6%, 12.8%, 7.8%, 5.0%, 7.3%, 8.0%, and 3.7% (P < .001). In conclusion, seropositive of anti‐HDV was inversely associated with HBV‐DNA levels. A progressive decrease of anti‐HDV seroprevalence was found with no anti‐HDV‐positive cases detected in high HBV‐DNA patient group after 2014.
Highlight
Seroprevalence of anti‐HDV is decreasing in Taiwan.
From 2006‐2019, 4.4% of chronic hepatitis B patients were anti‐HDV positive.
Seroprevalence of anti‐HDV is inversely correlated with HBV‐DNA levels.
No anti‐HDV‐positive cases were found after 2014 in high HBV DNA patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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