Efficacy and Safety of Different Dosing Regimens of Colchicine in Patients With Coronary Artery Disease: A Network Meta-analysis of 15 Randomized Controlled Trials.

ABSTRACT: Several meta-analyses have investigated the effects of different doses of colchicine in treating coronary artery disease, but all dosing regimens were never compared in a single study. We aimed to compare the efficacy and safety of 3 dosing regimens of colchicine in patients with coronary artery disease. PubMed, EMBASE, the Cochrane Library, and SCOPUS were searched for randomized controlled trials involving different colchicine doses. Major adverse cardiac events (MACE), all-cause and cardiovascular mortality, recurrent myocardial infarction (MI), stroke, gastrointestinal adverse events (AEs), discontinuation, and hospitalization were evaluated using risk ratio (RR) with 95% confidence interval (CI). A total of 15 randomized controlled trial involving 13,539 patients were included. Pooled results calculated with STATA 14.0 showed that low-dose colchicine significantly reduced MACE (RR, 0.51; 95% CI, 0.32-0.83), recurrent MI (RR, 0.56; 95% CI, 0.35-0.89), stroke (RR, 0.48; 95% CI, 0.23-1.00), and hospitalization (RR, 0.44; 95% CI, 0.22-0.85), whereas high and loading doses significantly increased gastrointestinal AEs (RR, 2.84; 95% CI, 1.26-6.24) and discontinuation (RR, 2.73; 95% CI, 1.07-6.93), respectively. Sensitivity analyses confirmed that 3 dosing regimens did not reduce all-cause and cardiovascular mortality but significantly increased the gastrointestinal AEs, and high dose significantly increased AEs-related discontinuation; loading dose resulted in more discontinuation than low dose. Although differences between 3 dosing regimens of colchicine are not significant, low dose is more effective in reducing MACE, recurrent MI, stroke, and hospitalization than the control, whereas high and loading doses increase gastrointestinal AEs and discontinuation, respectively.

Persistent proliferation of keratinocytes and prolonged expression of pronociceptive inflammatory mediators might be associated with the postoperative pain in KK mice.

Epidermal keratinocytes play a vital role in restoration of the intact skin barrier during wound healing. The negative effect of hyperglycemia may prolong the wound healing process. Epidermal keratinocytes have been demonstrated to modulate and directly initiate nociceptive responses in rat models of fractures and chemotherapy-induced neuropathic pain. However, it is unclear whether epidermal keratinocytes are involved in the development and maintenance of incisional pain in nondiabetic or diabetic animals. In the current study, using behavioral tests and immunohistochemistry, we investigated the differential keratinocytes proliferation and expression of pronociceptive inflammatory mediators in keratinocytes in C57BL/6J mice and diabetic KK mice. Our data showed that plantar incision induced postoperative pain hypersensitivity in both C57BL/6J mice and KK mice, while the duration of postoperative pain hypersensitivity in KK mice was longer than that in C57BL/6J mice. Moreover, plantar incision induced the keratinocytes proliferation and expression of IL-1ß and TNF-α in keratinocytes in both C57BL/6J mice and KK mice. Interestingly, compared to C57BL/6J mice, the slower and more persistent proliferation of keratinocytes and expression of IL-1ß and TNF-α in keratinocytes were observed in KK mice. Together, our study suggested that plantar incision may induce the differential keratinocytes proliferation and expression of IL-1ß and TNF-α in kertinocytes in diabetic and nondiabetic animals, which might be associated with the development and maintenance differences in diabetic and nondiabetic postoperative pain.

Anti-Inflammatory and Antioxidant Effects of Acetyl-L-Carnitine on Atherosclerotic Rats.

BACKGROUND The purpose of the present study was to evaluate the regulatory effects of acetyl-L-carnitine (ALCAR) on atherosclerosis in Wister rats and to explore its anti-atherosclerotic mechanism. MATERIAL AND METHODS We randomly divided 32 Wister rats into 4 groups: a normal diet group (control group, n=8), a normal diet+ALCAR group (ALCAR group, n=8), an atherosclerosis group (AS group, n=8), and an atherosclerosis+ALCAR group (AS+ALCAR group, n=8). The serum lipid distribution, oxidative stress, inflammatory factors and adiponectin (APN) in the blood, and heart and aortic tissues were determined using the standard assay kits, xanthine oxidase method, and ELISA, respectively. HE staining was performed to observe aortic pathology structure change, and the level of angiotensin II (AngII) in the aorta was assessed using radioimmunoassay. In addition, real-time quantitative PCR and Western blot analysis were applied to detect the expression of iNOS, IL-1ß, TNF-alpha, and CRP in the aortic and heart tissues. RESULTS Compared with the AS group, the levels of serum TC, TG, LDL, and VLDL in rats decreased significantly, while HDL level significantly increased in the AS+ALCAR group. ALCAR administration enhanced the SOD and GSH-Px activities and decreased MDA activity. APN level was significantly elevated in the AS group, but ALCAR had no significant effect on APN. Further, ALCAR reduced the expressions of inflammation factors TNF-alpha, IL-1ß, iNOS, and CRP, and the concentration of AngII in serum, aortic, and heart tissues. CONCLUSIONS ALCAR can inhibit the expressions of inflammatory factors and antioxidation to suppress the development of atherosclerosis by adjusting blood lipid in the myocardium of AS rats.

Optimization of ultrasonic-assisted supramolecular solvent microextraction of coumarins from Cortex fraxini using response surface methodology combined with artificial neural network-genetic algorithm.

A simple, fast, and efficient ultrasonic-assisted supramolecular solvent microextraction combined with high performance liquid chromatography method was developed for the determination of coumarins in Cortex fraxini, including esculin, esculetin and fraxetin. In this study, a novel supramolecular solvent was prepared with 1-octanol, tetrahydrofuran and water for the first time, and its composition, viscosity, density, structure, and micromorphology were characterized. The prepared supramolecular solvent exhibited vesicular structures and had the characteristics of low viscosity. Through single-factor experiments, response surface methodology and artificial neural network-genetic algorithm, the optimal extraction conditions were obtained as follows: NaCl concentration of 1 mol mL-1, pH value of 10, solid-liquid ratio of 10:1, vortex time of 30 s, ultrasonic power of 100 W, ultrasonic temperature of 60 °C, ultrasonic time of 15 min, centrifugation speed of 5000 rpm, and centrifugation time of 1 min. The results demonstrated that the artificial neural network model exhibited maximum R-values of 0.98703, 0.97440, 0.99836, and 0.95447 for training, testing, validation, and all dataset, respectively. The minimum mean square errors were 0.75, 10.15, 1.99, and 2.63, respectively. This indicated that the predicted values were almost consistent with the actual values. Under the optimal conditions, the total extraction yields of target analytes reached 2.80 %. The calibration curves for each analyte exhibited excellent linearity within the linear range (r > 0.9993). The limits of detection and quantification ranged from 4.87 to 6.55 ng mL-1 and 16.24 to 21.84 ng mL-1, respectively. The recoveries ranged from 98.71 % to 111.01 % with relative standard deviations of less than 3.6 %. The present method had the advantages of short extraction time (15 min) and less solvent consumption (0.5 mL). The prepared supramolecular solvent was proved to have great potential in extracting coumarins from medicinal plants.

Effect of Sevoflurane on the Deep Neuromuscular Blockade in Obese Patients Undergoing Laparoscopic Sleeve Gastrectomy: A Single Center Prospective Randomized Controlled Study.

Objective: Our study aimed to demonstrate that the combination of sevoflurane inhalation with continuous intravenous anesthesia can effectively reduce the dosage of muscle relaxants, shorten extubation time under anesthesia while meeting the requirements of laparoscopic deep neuromuscular block (dNMB) in obese patients. Additionally, we sought to assess the potential reduction in postoperative residual muscle relaxants. Methods: Fifty-nine patients were randomly assigned. Anesthesia-related variables, such as anesthetics dosages, muscle relaxant effective time, clinical muscle relaxant time, muscle relaxant in vivo action time, muscle relaxant recovery time, body movement times, and extubation duration were recorded. Surgery-related variables (the Leiden-Surgical Rating Scale (L-SRS), duration of the procedure) were recorded. Pain was measured using the visual analog scale (VAS) score before leaving the PACU. The duration of the PACU stay and patients' satisfaction levels in the PACU were also recorded. Results: Patients who inhaled sevoflurane during the operation required a lower dosage of muscle relaxant to achieve the same deep neuromuscular block (dNMB) effect. The time from stopping the rocuronium pump to T1 recovery of 90% was shorter, and the time for T1 to recover from 25% to 75% was faster among patients who inhaled sevoflurane during the operation. Furthermore, the sevoflurane combined with continuous intravenous anesthesia group exhibited a shorter extubation time for obese patients undergoing laparoscopic bariatric surgery, along with a reduced risk of experiencing hypoxemia and a shorter observation time in the PACU. Conclusion: Inhaling sevoflurane combined with continuous intravenous anesthesia during the operation effectively reduces the dosage of muscle relaxant required to achieve the same deep neuromuscular block (dNMB) effect. Additionally, this approach significantly shortens the extubation time for obese patients undergoing laparoscopic bariatric surgery and reduces the risk of experiencing hypoxemia, along with reducing the observation time in the PACU.

Poly(vinylidene Fluoride-Hexafluoropropylene) Porous Membrane with Controllable Structure and Applications in Efficient Oil/Water Separation.

Poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) porous membranes are fabricated via thermally induced phase separation (TIPS) with mixed diluent (dibutyl phthalate (DBP)/dioctyl phthalate (DOP)). The effects of mixed diluent are discussed in detail in term of morphology, mean pore size, selective wettability, etc. The results show that the membrane structure changes from spherulitic to bicontinuous with the change of DBP/DOP ratio. It is also found that the degree of crystallization decreases with the decrease of DBP/DOP ratio in mixed diluent. When liquid-liquid (L-L) phase separation precedes solid-liquid (S-L) phase separation, the obtained membranes have outstanding hydrophobicity and lipophilicity, excellent mechanical property. Additionally, the PVDF-HFP hybrid membranes are prepared with silica (SiO2) particles and the effect of SiO2 content on structure and properties is discussed. It is found that the PVDF-HFP hybrid membrane with 2 wt % SiO2 (M3-S2) has better properties and higher filtration rate and separation efficiency for surfactant-stabilized water-in-oil emulsion separation. Moreover, the membrane M3-S2 also exhibits excellent antifouling performance for long-running.

In situ reduced graphene oxide-based polyurethane sponge hollow tube for continuous oil removal from water surface.

Graphene oxide (GO) was prepared by using the natural graphite as raw materials via the modified Hummers' method and ultrasonic stripping method. GO was reduced online after its anchoring on the surface of polyurethane sponges by a dip-coating method, then in situ reduced graphene oxide-based polyurethane (IRGOPU) sponges were fabricated. The characterizations of IRGOPU sponges were investigated using Field emission scanning electron microscope (FESEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and contact angle measurement. The IRGOPU sponges had an adsorption capacity for a broad range of oils up to 21.7 ~ 55 g/g. A simulation experiment of large-scale oil spill using a simple IRGOPU sponge hollow tube component was designed. The process of continuous oil removal from water surface was quick and effective, and the oil/water separation efficiency could be up to 99.6%. The results indicated that the IRGOPU sponge hollow tube may be an optimum candidate for the oil/water separation of large-scale oil spill.

A study on fabrication of PVDF-HFP/PTFE blend membranes with controllable and bicontinuous structure for highly effective water-in-oil emulsion separation.

In this study, poly(vinylidene fluoride-co-hexafluropropylene) (PVDF-HFP)/polytetrafluoroethylene (PTFE) blend membranes for water-in-oil emulsion separation were prepared via a thermally induced phase separation (TIPS) method using dibutyl phthalate (DBP) and dioctyl phthalate (DOP) as a mixed diluent. The effects of PTFE content on the obtained membranes' structure and properties were studied. The results showed that the surface structure of the obtained membranes without addition of PTFE particles was denser and the surface pores got smaller. The porosity, pore size and hydrophobicity obviously increased with the increase in PTFE content. However, the breaking elongation and breaking strength decreased with the increase of PTFE content. When the PTFE content was 10 wt%, the obtained membrane showed the highest separation efficiency for different kinds of water-in-oil emulsions. In addition, the antifouling performance of the obtained membranes was also studied for many times of reuse. This paper introduces an effective and facile method to prepare hydrophobic-oleophilic membranes for water-in-oil emulsion separation.

Preparation of PSF/FEP mixed matrix membrane with super hydrophobic surface for efficient water-in-oil emulsion separation.

Polysulfone (PSF)/fluorinated ethylene propylene (FEP) mixed matrix membranes (MMMs) with super hydrophobic surface were successfully fabricated via non-solvent induced phase separation (NIPS) method. The effects of FEP content on the morphology, roughness, wettability, pore size, and mechanical property of PSF/FEP MMMs were characterized by scanning electron microscope, confocal microscopy, contact angle goniometer, mercury porosimetry, and tensile testing instrument, respectively. When the FEP content was 9 wt%, the average roughness of M-4 reached 0.712 µm. Meanwhile, the water contact angle (CA) and the water sliding angle (SA) was 153.3° and 6.1°, respectively. M-4 showed super hydrophobicity with a micro- and nanoscale structure surface. Then, M-4 was used for separating of water-in-oil emulsion, showing high separation efficiency for water-in-kerosene and water-in-diesel emulsions of 99.79% and 99.47%, respectively. The flux and separation efficiency changed slightly after 10 cycles. Therefore, this study indicated that the obtained PSF/FEP MMM with super hydrophobic surface could be used for efficient water-in-oil emulsion separation.