Using part of the initial analgesic dose as the epidural test dose did not delay the onset of labor analgesia: a randomized controlled clinical trial.

BACKGROUND: Epidural test dose for labor analgesia is controversial and varies widely in clinical practice. It is currently unclear whether using a portion of the initial dose for analgesia as the test dose delays the onset time of analgesia, compared to the traditional test dose. METHODS: One hundred and twenty-six parturients who chose epidural analgesia during labor were randomly assigned to two groups. The first dose in group L was 3 ml 1.5% lidocaine, and in the RF group was 10 ml 0.1% ropivacaine combined with 2 µg/ml fentanyl. After 3 min of observation, both groups received 8 ml 0.1% ropivacaine combined with 2 µg/ml fentanyl. The onset time of analgesia, motor and sensory blockade level, numerical pain rating scale, patient satisfaction score, and side effects were recorded. RESULTS: The onset time of analgesia in group RF was similar to that in group L (group RF vs group L, 7.0 [5.0-9.0] minutes vs 8.0 [5.0-11.0] minutes, p = 0.197). The incidence of foot numbness (group RF vs group L, 34.9% vs 57.1%, p = 0.020) and foot warming (group RF vs group L, 15.9% vs 47.6%, p < 0.001) in group RF was significantly lower than that in group L. There was no difference between the two groups on other outcomes. CONCLUSIONS: Compared with 1.5% lidocaine 3 ml, 0.1% ropivacaine 10 ml combined with 2 µg/ml fentanyl as an epidural test dose did not delay the onset of labor analgesia, and the side effects were slightly reduced. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn (ChiCTR2100043071).

Comparison of diagnostic performance of X­ray, CT and MRI in patients with surgically confirmed subtle Lisfranc injuries.

The present study aimed to compare the diagnostic performance of three imaging tests: X-ray, computed tomography (CT) and magnetic resonance imaging (MRI), for subtle Lisfranc injuries and three anatomical subtype injuries. The non-weight-bearing X-ray, CT and MRI imaging results of patients with subtle Lisfranc injuries from September 2013 to March 2022 were retrospectively reviewed. Subtle Lisfranc injuries and three anatomical subtypes (first, second and cuneiform rays) were diagnosed based on the surgical reports. The diagnostic performance of X-ray, CT and MRI was compared. The sensitivity (Sn), specificity (Sp), positive predictive value, negative predictive value, area under the receiver operating characteristic curve (AUC) and κ coefficient were reported. A total of 31 patients were included in the study. The correct diagnosis was made in 48.4% (15/31), 87.1% (27/31) and 96.8% (30/31) of patients by X-ray, CT and MRI, respectively. A total of 54 different anatomical injuries were found intraoperatively in all patients, with MRI and CT having high agreement (Sn, 72.2 and 87.0%; κ, 0.69 and 0.78, respectively) and X-ray having a low agreement (Sn, 29.6%; κ, 0.26) with the surgical findings. Regarding the first-ray injuries, CT had the highest Sn (76.9%), Sp (100%) and AUC (0.885) in diagnosing subtle Lisfranc injuries. MRI showed the best Sn (88.5 and 93.3%, respectively) and AUC (0.942 and 0.904, respectively) in both second and cuneiform rays. In conclusion, non-weight-bearing X-rays had poor diagnostic accuracy for subtle Lisfranc injuries and their subtypes. CT was superior to X-rays and MRI in diagnosing first-ray injuries. Although not significantly different from CT in terms of overall diagnosis, MRI was superior to X-ray and CT in diagnosing second and cuneiform-ray injuries.

Discovery of novel antibacterial agent for the infected wound treatment: all-hydrocarbon stapling optimization of LL-37.

Rationale: Antimicrobial peptide LL-37 has been recognized as a favorable alternative to antibiotics due to its broad antibacterial spectrum, low resistance development and diverse biological activities. However, its high manufactory cost, poor proteolytic stability, and unpredictable cytotoxicity seriously hindered its medical translation. Methods: To push the frontiers of its clinical application, all-hydrocarbon stapling strategy was exploited here for the structural modification of KR-12, the core and minimal fragment of LL-37. Results: Based on a library of KR-12 derivatives that designed and synthesized to be stapled at positions of either i, i+4 or i, i+7, structure to activity relationship was investigated. Among them, KR-12(Q5, D9) with the glutamine and aspartic acid residues stapled displayed increased helical content and positive charge. The reinforced α-helical conformation not only protected it from proteolytic hydrolysis but also improved its antibacterial efficacy via effective membrane perturbation and anti-inflammatory efficacy via compact LPS binding. Besides, the increased positive charge endowed it with an enhanced therapeutic index. On infected wound mouse model, it was demonstrated to eliminate bacteria and promote wound closure and regeneration effectively. Conclusion: Overall, the all-hydrocarbon stapling was proven to lay the foundation for the future development of antibacterial agents. KR-12(Q5, D9) could serve as a lead compound for the clinical treatment of bacterial infections.

Simultaneous determination of 58 glucocorticoid residues in milk by ultra-high performance liquid chromatography-tandem mass spectrometry.

Abuse of glucocorticoid veterinary drugs in dairy industry can potentially threat milk safety and consequently influence human health. Here a reliable method for determination of 58 glucocorticoid drug residues in milk was established by combining solid phase extraction with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The analytes were extracted with acetonitrile and cleanup with EMR-Lipid lipid removal column. The analytes were chromatographically separated using Poroshell EC-C18 column and acquired by electrospray ionization with multiple-reaction monitoring (MRM) mode. The limit of quantification (S/N ≥ 10) ranged from 0.2 to 2.0 µg/kg and the limit of detection (S/N ≥ 3) ranged from 0.1 to 1.0 µg/kg. Average recoveries were from 71% to 113%, the relative standard deviations (RSDs) were less than 15%, and the correlation coefficients (R2) of calibration curves exceeded 0.99. The method was applied to detect twenty milk products obtained from local supermarkets including ten pasteurized milk and ten UHT milk. Two endogenous glucocorticoids, i.e. hydrocortisone and cortisone were detected but not exceed the maximum residue limits (MRLs).

Comparative pharmacokinetics of free doxorubicin and a liposomal formulation in cats following intravenous administration.

Doxorubicin, a potent chemotherapeutic agent used extensively in cancer treatment, displays complex pharmacokinetic behavior, especially across various formulations. With a rising incidence of cancer cases in cats, understanding the drug's pharmacokinetics in feline subjects remains a critical yet unexplored area. Hence, this study investigated the pharmacokinetic profile of doxorubicin after slow intravenous administration of doxorubicin hydrochloride (DOX·HCl) or doxorubicin hydrochloride pegylated liposome (DOX·HCl-PLI) in twelve cats at a single dose of 20 mg/m2. Blood samples collected at pretreatment time (0 h) and over 192 h were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The obtained pharmacokinetic parameters of doxorubicin revealed significant differences between the two formulations and were as follows: elimination half-life (T1/2λz) of 5.00 ± 3.20 h (DOX·HCl) and 17.62 ± 8.13 h (DOX·HCl-PLI), area under the concentration/time curve from 0 to last point (AUClast) of 0.67 ± 0.12 µg hr./mL (DOX·HCl) and 783.09 ± 267.29 µg hr./mL (DOX·HCl-PLI), and total body clearance (CL_obs) of 27098.58 ± 5205.19 mL/h/m2 (DOX·HCl) and 28.65 ± 11.09 mL/h/m2 (DOX·HCl-PLI). Additionally, differences were also detected in the apparent volume of distribution (Vz_obs) with 178.56 ± 71.89 L/m2 (DOX·HCl) and 0.64 ± 0.20 L/m2 (DOX·HCl-PLI), and the maximum plasma concentration (Cmax) with 2.25 ± 0.30 µg/mL (DOX·HCl) and 24.02 ± 5.45 µg/mL (DOX·HCl-PLI). Notably, low concentration of doxorubicinol, the metabolite of doxorubicin, was detected in plasma after administration of DOX·HCl, with even less present when DOX·HCl-PLI was administered. This investigation provides valuable insights into the distinct pharmacokinetic behaviors of DOX·HCl and DOX·HCl-PLI in cats, contributing essential groundwork for future studies and potential clinical applications in feline oncology.

Achilles tendon thickening does not affect elasticity and functional outcome after surgical repair of Achilles rupture: A retrospective study.

PURPOSE: Previous studies have confirmed that Achilles tendon occurs Achilles thickening after repair surgery of the rupture. Although this mechanism has been elucidated in the laboratory, there are few reports on its impact on clinical function. We designed a retrospective study to investigate the Achilles thickening after Achilles tendon rupture repair and its correlation between the elasticity and postoperative function. METHODS: In this retrospective analysis, patients who underwent surgical treatment for acute Achilles tendon rupture from April 2016 to April 2020 were included. All the patients were regularly followed up at 3 months, 1 year, and 2 years after surgery. American Orthopaedic Foot Ankle Surgeon (AOFAS) scale and Leppilahti score were used to evaluate functional outcomes. Achilles elasticity was measured by ultrasound shear wave of elasticity. Achilles thickening was calculated as maximal transverse and longitudinal diameter in cross-sectional plane of magnetic resonance scan. Sample t-tests was used for different follow-up periods. Correlation between Achilles thickening and other factors were analyzed using Pearson's method. p < 0.05 indicates a statistically significant difference. RESULTS: AOFAS scale and Leppilahti score at 1 year were significantly higher than at 3 months postoperatively (both p < 0.001). These functional scales were also improved at 2-year follow-up significantly (both p < 0.001). The dorsiflexion difference showed gradually recovery in each follow-up period (t = -17.907, p < 0.001). The elasticity of the Achilles appeared to continuously decreases during the postoperative follow-up period in all position sets (p < 0.001). In thickening evaluation, the cross-sectional area of the thickest plane of Achilles was significantly higher at 1 year postoperatively (310.5 ± 25.2) mm2 than that at 3 months postoperatively ((278.0 ± 26.2) mm2, t = -8.219, p < 0.001) and became thinner in 2-year magnetic resonance scan ((256.1 ± 15.1) mm2, t = 16.769, p < 0.001). The correlations between Achilles thickening, elasticity, and functional outcome did not show statistical significance (p > 0.05) in every follow-up period. CONCLUSION: Achilles tendon thickens after surgery in the 1st year, but begins to gradually return to thinning about 2 years after surgery. There was no significant correlation between the increase and decrease of thickening and the patients' clinical function scores, Achilles elasticity, and bilateral ankle dorsiflexion difference.

Evaluation of milk photooxidation based on peptidomics.

Photooxidation is one of the main causes of the deterioration of milk quality during processing and marketing. This study aimed to investigate the variation in peptides after photooxidation using peptidomic techniques, and how cow species, oxygen content, and light intensity affect photooxidation. The different peptides were identified and quantified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Eighteen milk samples were subjected to light treatment. Seven types of peptides were identified as photooxidation markers. Subsequently, the effects of milk variety, oxygen content, and light intensity on photooxidation were studied, and sensory evaluations were performed. Dairy cow breed, oxygen content, and light intensity all affect photooxidation. Sensory evaluation verified that light and oxygen are necessary for the photooxidation of milk. The peptide m/z+ 529.2783 (LLDEIKEVV), both in different varieties of milk and in different brands of commercially available milk, showed a large variation in multiplicity, and its content was closely related to oxygen and light. This peptide was not produced in the absence of oxygen and light, and its relative content increased with the duration of light exposure. These results suggest that the peptidomics method is an effective tool for distinguishing between normal and photooxidized milk.