Risk Factors for Artificial Kidney Failure During Continuous Renal Replacement Therapy

Objective To explore the influencing factors of artificial kidney failure (AKF) during continuous renal replacement therapy (CRRT). Methods We conducted a retrospective observational study on 70 patients undergoing 199740 minutes of CRRT comprising 143 circuits at the Department of Intensive Care Medicine of First Affiliated Hospital of Chongqing Medical University from August 2021 to August 2022. Results The occurrence rate and total time of access outflow dysfunction (AOD) in AKF group increased significantly than those in nAKF group. Receiver Operating Characteristic (ROC) Curve analysis showed the optimal cutoff value of AOD total time (AODTT) was 7 minutes. Logistic regression analysis further showed that AODTT≥7 min was an independent predictor of AKF. Conclusion The presence of AOD was related to AKF. AODTT≥7 min during CRRT was an independent risk factor for AKF

Preparation, evaluation, and pharmacokinetics in beagle dogs of a taste-masked flunixin meglumine orally disintegrating tablet prepared using hot-melt extrusion technology and D-optimal mixture design

Flunixin meglumine (FM) is a nonsteroidal anti-inflammatory drug limited by irritation of the respiratory tract and mucosa in veterinary tissue. This study aimed to develop a taste-masked FM solid dispersion (SD) by hot-melt extrusion (HME) and formulate an orally disintegrating tablet (ODT) with selected excipients by direct compression. Eudragit® E PO was chosen as the matrix, and HME parameters were optimized: extrusion temperature, 135℃; screw speed, 100 rpm; and drug loading, 20%. Characterization techniques proved that FM was rendered amorphous in the HME extrudate. In vitro dissolution studies showed that FM SD released significantly slower than the corresponding physical mixture in artificial saliva. Excipients were selected based on compression formability, disintegration, and solubility. A D-optimal mixture design was used to optimize the composition: 25% FM SD, 18.75% microcrystalline cellulose, 52.5% mannitol, 3.75% low-substituted hydroxypropyl cellulose, and 1% magnesium stearate. Taste-masked FM ODT had a tensile strength of 0.7 ± 0.01 MPa and a disintegration time of 17.6 ± 0.1 s. E-tongue and E-nose analysis showed that FM ODT had a better taste-masked effect than commercial granules. Finally, a pharmacokinetic study proved that the main pharmacokinetic parameters of FM ODT were not significantly different from those of commercial granules, which indicated that these formulations had similar pharmacokinetic behaviours in beagles

Preparation and in vitro/in vivo evaluation of orally disintegrating/modified-release praziquantel tablets

This study was designed to develop orally disintegrating/sustained-release praziquantel (PZQ) tablets using the hot-melt extrusion (HME) technique and direct compression, and subse-quently evaluate their release in in vitro and in vivo pharmacokinetics. For the extrusion process, hypromellose acetate succinate (HPMCAS)-LG was the carrier of pure PZQ, with a standard screw configuration used at an extrusion temperature of 140◦ C and a screw rotation speed of 100 rpm. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopy (FTIR) were performed to characterize the extru-date. Orally disintegrating/sustained-release praziquantel tablets (PZQ ODSRTs) were prepared by direct compression after appropriate excipients were blended with the extrudate. The release amount was 5.10% in pH 1.0 hydrochloric acid at 2 h and over 90% in phosphoric acid buffer at 45 min, indicating the enteric-coating character of PZQ ODSRTs. Compared with the pharmacokinetics of marketed PZQ tablets (Aipuruike®) in dogs, the times to peak (Tmax), elimination half-life (t1/2λ) and mean residence time (MRT) were extended in PZQ ODSRTs, and the relative bioavailability of PZQ ODSRTs was up to 184.48% of that of Aipuruike®. This study suggested that PZQ ODSRTs may have potential for the clinical treatment of parasitosis

Effect of Zhishenyuanhu Anticoagulant Formula on Hypercoagulability in Rats with Qi Stagnation and Blood Stasis and Arterial and Venous Thrombosis in Rats

Background: Tumor patients present with hypercoagulable blood and are at risk of venous thromboembolism (VTE). We explored the effect of Zhishenyuanhu anticoagulant formula（ZSYH）on hypercoagulability in rats with qi stagnation and blood stasis and thrombosis in rats.Methods: Part I. Epinephrine (0.6 mg/kg, hypodermic injection, h.i.) was administered every day for 7 days. Six groups were gavaged with saline, saline, rivaroxaban, low-dose, medium-dose, and high-dose ZSYH every day. We collected rats’ daily body weight, food intake, clotting time (CT), coagulation and hemorheology results. Part II. Six groups of rats were given the same drugs as in part I for 7 days. Half of rats in each group were used to construct a common carotid artery thrombusis model, while the other half were used to construct an inferior vena cava thrombusis model. Results: ZSYH caused decreases in FIB, shear rate 1, whole blood low shear relative index, and RE. The high dose of ZSYH caused decreases in wet and dry weight of arterial and venous thrombosis.Conclusion: ZSYH is effective in treating hypercoagulability in rats with qi stagnation and blood stasis. The high dose of ZSYH prevent the development of arterial thrombosis and venous thrombosis

A Novel Mutation in the NBD Domain of NLRC4 Causes Mild Autoinflammation With Recurrent Urticaria

BackgroundNOD-like receptor family CARD-containing 4 protein (NLRC4) is a cytosolic protein that forms an inflammasome in response to flagellin and type 3 secretion system (T3SS) proteins from invading Gram-negative bacteria. NLRC4 mutations have been recently identified in early-onset severe autoinflammatory disorders. In this study, we reported a novel mutation in NLRC4 in two Chinese patients, who manifested with recurrent urticaria and arthralgia.MethodsWe summarized the clinical data of the two patients. Gene mutations were identified by whole-exome sequencing (WES). Swiss-PdbViewer was used to predict the pathogenicity of the identified mutations. Cytokine levels and caspase-1 activation were detected in the patient PBMCs with lipopolysaccharide (LPS) stimulation. All previously published cases with NLRC4 mutations were reviewed.ResultsWe identified a missense heterozygous mutation (c.514G>A, p.Gly172Ser), which was located in the highly conserved residue of nucleotide-binding domain (NBD) of NLRC4. The mutation did not alter the expression of NLRC4 protein, but induced considerably much higher production of IL-1β and IL-6 in patient PBMCs than in healthy controls after LPS stimulation. Four NLRC4 inflammasomopathy phenotypes have been described, with severe inflammatory diseases including macrophage activation syndrome, enterocolitis and NOMID in patients with mutations in the NBD and HD1 domains, whereas a mild clinical phenotype was associated with two mutations in the WHD domain of NLRC4.ConclusionWe identified a novel mutation in the NBD domain, and the patients just presented with a mild inflammatory phenotype. Thus, our findings reinforce the diversity of NLRC4 mutations and expand the clinical spectrum of associated diseases

Estimating seasonal aboveground biomass of a riparian pioneer plant community:An exploratory analysis by canopy structural data

The aboveground biomass (AGB) of vegetation is of central importance for ecosystem services by providing a measure of productivity. Models have been developed for estimating AGB via canopy structural variables in both fundamental and applied ecological studies. However, the potential of canopy structural variables for describing AGB dynamics throughout a growing season are still unclear. This study focuses on the AGB seasonal dynamics of a pioneer community, Cynodon dactylon (L.) Pers. (Bermuda grass), in a newly-formed riparian habitat at China’s Three Gorges Reservoir. The objectives are (1) to determine the most important structural variable for estimating AGB at different growing stages during the season, and (2) to develop a model that can estimate AGB at the different growing stages and using multiple structural variables. We sampled the C. dactylon community six times during the growing season from May to September 2016. Six variables were engaged in the analysis, including five canopy structural variables, i.e., canopy height (H), canopy cover (CC), leaf area index (LAI), the volume related variables VLAI (H × LAI) and VCC (H × CC), and one seasonal growth effect variable (SV). We conducted univariate linear regression analysis to determine the most important estimator of AGB and the best subset regression analysis were used to develop the AGB estimation model. The detected most important AGB estimator changed with different growing stages throughout a season. Canopy structural characteristics of the community are key factors for determining such changes. Cover was the most important variable for AGB estimation during the early growing season and VLAI was the most important variable in the mid and end of the growing season. The developed best multivariate models explained an additional 11% in AGB variance on average for the different growing stages compared with the univariate models using the most important estimators. SV was found to be useful in developing an acceptance general AGB estimation model appropriate for the entire growing season. The findings of this study are expected to provide knowledge for guiding sampling work and to assist with modeling AGB and understanding the AGB seasonal dynamics in the future

Activation of Testosterone-Androgen Receptor Mediates Cerebrovascular Protection by Photobiomodulation Treatment in Photothrombosis-Induced Stroke Rats

RATIONALE: Numerous epidemiological studies have reported a link between low testosterone levels and an increased risk of cerebrovascular disease in men. However, there is ongoing controversy surrounding testosterone replacement therapy due to potential side effects. PBMT has been demonstrated to improve cerebrovascular function and promote testosterone synthesis in peripheral tissues. Despite this, the molecular mechanisms that could connect PBMT with testosterone and vascular function in the brain of photothrombosis (PT)-induced stroke rats remain largely unknown. METHODS: We measured behavioral performance, cerebral blood flow (CBF), vascular permeability, and the expression of vascular-associated and apoptotic proteins in PT-induced stroke rats treated with flutamide and seven consecutive days of PBM treatment (350 mW, 808 nM, 2 min/day). To gain further insights into the mechanism of PBM on testosterone synthesis, we used testosterone synthesis inhibitors to study their effects on bEND.3 cells. RESULTS: We showed that PT stroke caused a decrease in cerebrovascular testosterone concentration, which was significantly increased by 7-day PBMT (808 nm, 350 mW/cm CONCLUSIONS: Our study provides evidence that PBMT attenuates cerebrovascular injury and behavioral deficits associated with testosterone/AR following ischemic stroke. Our findings suggest that PBMT may be a promising alternative approach for managing cerebrovascular diseases

Influence of Yb:YAG laser beam parameters on Haynes 188 weld fusion zone microstructure and mechanical properties

The weldability of 1.2 mm thick Haynes 188 alloy sheets by a disk Yb:YAG laser welding was examined. Butt joints were made, and the influence of parameters such as power, size, and shape of the spot, welding speed, and gas flow has been investigated. Based on an iconographic correlation approach, optimum process parameters were determined. Depending on the distribution of the power density (circular or annular), acceptable welds were obtained. Powers greater than 1700 W, welding speeds higher than 3.8 m mm1, and spot sizes between 160 and 320 lm were needed in the circular (small fiber) configuration. By comparison, the annular (large fiber) configuration required a power as high as 2500 W, and a welding speed less than 3.8 m min�1. The mechanical properties of the welds depended on their shape and microstructure, which in turn depended on the welding conditions. The content of carbides, the proportion of areas consisting of cellular and dendritic substructures, and the size of these substructures were used to explain the welded joint mechanical properties