A Multifunctional Nanocomposite Hydrogel Delivery System Based on Dual-Loaded Liposomes for Scarless Wound Healing.

Increased inflammatory responses and oxidative stress at the wound site following skin trauma impair healing. Furthermore, skin scarring places fibroblasts under severe mechanical stress and aggravates pathological fibrosis. A novel liposomal composite hydrogel is engineered for wound microenvironment remodeling, incorporating dual-loaded liposomes into gelatin methacrylate to create a nanocomposite hydrogel. Notably, tetrahydrocurcumin (THC) and hepatocyte growth factor (HGF) are encapsulated in the hydrophobic and hydrophilic layers of liposomes, respectively. The composite hydrogel maintains porous nanoarchitecture, demonstrating sustainable THC and HGF release and enhanced mechanical properties and biocompatibility. This system effectively promotes cell proliferation and angiogenesis and attenuates apoptosis. It decreases the expression of the inflammatory factors by inhibiting the high-mobility group box /receptor for advanced glycation end product/NF-κB (HMGB1/RAGE/NF-κB)pathway and increases macrophage polarization from M1 to M2 in vitro, effectively controlling inflammatory responses. It exhibits remarkable antioxidant properties by scavenging excess reactive oxygen species and free radicals. Most importantly, it effectively prevents scar formation by restraining the transforming growth factor beta (TGF-ß)/Smads pathway that downregulates associated fibrotic factors. It demonstrates strong therapeutic effects against inflammation and fibrosis in a rat skin wound model with biosafety, advancing the development of innovative hydrogel-based therapeutic delivery strategies for clinical scarless wound therapy.

Use of carbon dioxide fractional laser in the management of lower limb ischemia in patients with diabetes: a case report : CO2 fractional laser in the treatment of diabetic foot.

Treatment of lower limb ischemia in patients with diabetes is challenging because of the location of the ulcers and the complexity of their pathogenesis. Carbon dioxide fractional laser (CO2FL) therapy in conjunction with tibial periosteum distraction could become a substitute for conventional methods. We herein describe a patient diagnosed with ischemic diabetic foot with a complex ulcer in the upper third of the tibia. Laser irradiation (Deep FX mode with 30 mJ of energy and 10% density) was applied to the entire region of skin below the knee after surface anesthesia, and this treatment was performed twice a week until the ulcer healed. Computed tomography angiography showed successful establishment of a blood supply to the back of the right foot after treatment. Skin grafting was successfully performed, with only a few wounds remaining on the foot 8 months after treatment. The pain score was significantly decreased at the last follow-up. No complications occurred. This case report provides guidance for the performance of CO2FL, a fast, easy, accurate treatment in patients with diabetes. CO2FL can target lower limb arterial occlusive disease accompanied by refractory ulcers, addressing the underlying vascular occlusion and dysfunction as well as promoting microcirculation and wound healing.

Establishment and validation of a risk prediction model incorporating concentrations of linezolid and its metabolite PNU142300 for linezolid-induced thrombocytopenia.

BACKGROUND: Linezolid-induced thrombocytopenia is the main factor restricting the clinical application of linezolid. OBJECTIVES: To investigate the relationship between PNU-14230 concentration and linezolid-induced thrombocytopenia and further develop and validate a risk model for predicting linezolid-induced thrombocytopenia. METHODS: A regression model was constructed to predict the occurrence of linezolid-induced thrombocytopenia, and further externally validated. The predictive performance was evaluated by receiver operating characteristic curve and Hosmer-Lemeshow test. Linezolid Cmin and PNU-142300 concentrations were compared for different kidney function groups. The Kaplan-Meier method was used to estimate the difference in cumulative incidence of linezolid-induced thrombocytopenia among different kidney function patients. RESULTS: In the derivation (n = 221) and validation (n = 158) cohorts, 28.5% and 24.1% of critically ill patients developed linezolid-induced thrombocytopenia. Logistic regression analysis indicated that the independent risk factors were linezolid Cmin, PNU-142300 concentration, baseline platelet count, renal insufficiency (RI) and continuous venovenous haemofiltration (CVVH). The AUC for the risk model was 0.901, and the model was good (P = 0.633). The model also showed good discrimination (AUC 0.870) and calibration (P = 0.282) in the external validation cohort. Compared with normal kidney function patients, patients with RI and CVVH had higher linezolid Cmin and PNU-142300 concentrations (P < 0.001) and higher cumulative incidence of linezolid-induced thrombocytopenia (P < 0.001). CONCLUSIONS: PNU142300 concentration, as well as linezolid Cmin, might identify patients at risk of linezolid-induced thrombocytopenia. The risk prediction model had good predictive performance for linezolid-induced thrombocytopenia development. Concentrations of linezolid and PNU-142300 accumulated in patients with RI and CVVH.

Dietary supplementation with 2-hydroxy-4-methyl(thio) butanoic acid and DL-methionine improves productive performance, egg quality and redox status of commercial laying ducks.

This experiment aimed to study the effects of supplemental methionine sources, 2-hydroxy-4 methyl(thio) butanoic acid (HMTBa) and DL-Methionine (DL-Met), on productive performance, egg quality, and redox status of laying ducks. A total of 792 healthy 25-wk-old Longyan laying ducks with similar body weights were randomly allotted to 11 treatment groups. Each treatment group had 6 replicates of 12 ducks. The trial lasted for 16 wk. Ducks were fed a basal deficient diet (Met: 0.24%; Met + Cys: 0.51%) or supplemented with DL-Met or HMTBa at 0.05%, 0.12%, 0.19%, 0.26%, and 0.33% of diet, respectively. Compared with the basal diet, supplementation with either DL-Met or HMTBa increased the average egg weight, egg mass, and decreased feed to egg ratio during the whole trial period (P < 0.05). Albumen weight and its ratio to total egg weight were increased, but yolk and shell ratio, albumen height, Haugh unit and shell breaking strength were decreased (P < 0.05). Dietary DL-Met or HMTBa supplementation increased taurine, methionine, leucine, tryptophan and arginine content, and decreased serine and lysine content in plasma (P < 0.05). The redox status of laying ducks was improved by enhancing the glutathione peroxidase and catalase activities, glutathione content and its ratio relative to glutathione (oxidized) content and decreasing malondialdehyde content and increasing mRNA expression of superoxide dismutase-1, glutathione peroxidase-1, hemeoxygenase-1 and nuclear factor-like 2 in liver and ileum with the supplementation of DL-Met or HMTBa (P < 0.05). Liver health status measured by average area proportion lipid droplet was improved with supplementation of DL-Met or HMTBa (P < 0.05). Villus height and villus height to crypt depth ratio in the ileum and the ileal gene expression of tight junction protein and occludin were increased with DL-Met or HMTBa supplementation (P < 0.05). Taken together, these results suggested that the efficacy of dietary supplementation of HMTBa was similar to DL-Met, and it ranged from 98% to 100% for productive performance and egg albumen ratio in laying ducks (25 to 41 wk).

Dose optimisation of linezolid in critically ill patients based on a population pharmacokinetic model: A two-centre prospective interventional study.

OBJECTIVES: This study evaluated the intervention effect of clinical pharmacist-mediated optimisation of a linezolid regimen using a population pharmacokinetic (PPK) model. METHODS: Patients treated with linezolid in two medical centres from January 2020 to June 2021 were retrospectively included in the control group; those treated from July 2021 to June 2022 were prospectively enrolled in the intervention group. Clinical pharmacists optimised the dosage regimen according to a published linezolid PPK model in the intervention group. An interrupted times series approach was used to analyse the data. The incidence of linezolid-induced thrombocytopenia (LIT), target attainment of pharmacokinetic/pharmacodynamic parameters and other adverse drug reactions (ADRs) were compared between the two groups. RESULTS: In total, 77 and 103 patients were enrolled in the control and intervention groups, respectively. The intervention group had a lower incidence of LIT and other ADRs than the control group (10.7% vs. 23.4%, P = 0.002; 1.0% vs. 7.8%, P = 0.027). The intervention group exhibited a considerably lower trough concentration (Cmin) and area under the concentration-time curve/MIC ratio (AUC24/MIC) (P = 0.001 and P < 0.001). Cmin and AUC24/MIC rates within the target range were substantially higher in the intervention group (49.6% vs. 20.0%, adjusted P < 0.05; 48.1% vs. 25.6%, adjusted P < 0.05). CONCLUSION: Interventions by clinical pharmacists reduced the incidence of LIT and other ADRs. Implementation of model-informed precision dosing (MIPD) for linezolid markedly increased the Cmin and AUC24/MIC rates within the target range. We recommend MIPD-guided linezolid dose reduction for patients with renal impairment.

Physiological and clinical variables identify ARDS classes and therapeutic heterogeneity to glucocorticoids: a retrospective study.

OBJECTIVE: We aimed to identify new classes in acute respiratory distress syndrome (ARDS) using physiological and clinical variables and to explore heterogeneity in the effects of glucocorticoid therapy between classes. METHODS: Using the Medical Information Mart for Intensive Care-IV database, we identified patients with ARDS. Potential profile analysis was used to identify classes with physiological and clinical data as delineating variables. Baseline characteristics and clinical outcomes were compared between classes. The effect of glucocorticoid treatment was explored by stratifying by class and glucocorticoid treatment. RESULTS: From 2008 to 2019, 1104 patients with ARDS were enrolled in the study. The 2-class potential analysis model had the best fit (P < 0.0001), with 78% of patients falling into class 1 and 22% into class 2. Additional classes did not improve the model fit. Patients in class 2 had higher anion gap, lactate, creatinine, and glucose levels and lower residual base, blood pressure, and bicarbonate compared with class 1. In-hospital mortality and 28-day mortality were significantly higher among patients in class 2 than those in class 1 (P < 0.001). Heterogeneity of glucocorticoid treatment was observed, stratified by class and treatment, with no significant effect in class 1 (P = 0.496), increased mortality in class 2 (P = 0.001), and a significant interaction (P = 0.0381). In class 2, 28-day survival was significantly lower with glucocorticoid treatment compared with no hormone treatment (P = 0.001). CONCLUSION: We used clinical and physiological variables to identify two classes of non-COVID-19-associated ARDS with different baseline characteristics and clinical outcomes. The response to glucocorticoid therapy varied among different classes of patients.

Continuous infusion versus intermittent infusion of vancomycin in critically ill patients undergoing continuous venovenous hemofiltration: a prospective interventional study.

BACKGROUND: A prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR) with PK/PD indices. METHODS: This prospective interventional study was conducted in two independent intensive care units (ICUs) from February 2021 to January 2022. Patients in one ICU were assigned to receive CI (intervention group) of vancomycin, whereas patients in the other ICU were assigned to receive II regimen (control group). The primary outcome was to compare the PK/PD target attainment, including target concentration and target area under the curve over 24 h to minimum inhibitory concentration (AUC24/MIC). RESULTS: Overall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.7% vs. 40.5%; P < 0.05) or AUC24/MIC (53.2% vs. 28.6%; P < 0.05). There were no significant differences in clinical success (72.2% vs. 50.0%; P = 0.183) and microbiological success (83.3% vs. 75.0%, P = 0.681) between the patients treated with CI or II of vancomycin. Adverse reactions occurred at similar rates (0.0% vs. 4.4%; P = 0.462), and mortality between the two modalities was also not significant different (21.7% vs. 17.9%; P = 0.728). Correlation analysis showed a weak to moderately inverse correlation of EFR with observed concentration (r = - 0.3921, P = 0.01) and AUC24/MIC (r = - 0.3811, P = 0.013) in the II group, whereas the correlation between EFR and observed concentration (r = - 0.5711, P < 0.001) or AUC24/MIC (r = - 0.5458, P < 0.001) in the CI group was stronger. CONCLUSION: As compared to II, CI of vancomycin in critically ill patients undergoing CVVH was associated with improved attainment of PK/PD indices. Furthermore, the inverse correlation of PK/PD indices with EFR was stronger among patients treated with CI of vancomycin. Trial registration The trial was registered in the Chinese clinical trial registration center (21/01/2021-No. ChiCTR2100042393).

Dose Optimization of Teicoplanin for Critically Ill Patients With Renal Dysfunction and Continuous Renal Replacement Therapy: Experience From a Prospective Interventional Study.

Background: Due to the lack of updated information on teicoplanin (TEI) for continuous renal replacement therapy (CRRT), no exact dosage regimen has been recommended. The aim of this study was to optimize the dosage regimen of TEI in renal dysfunction patients with or without CRRT, evaluate the influence factors of the eradication of Gram-positive bacteria, and evaluate the effect of CRRT on the clearance of TEI. Methods: Patients with renal dysfunction receiving TEI treatment in the ICU were prospectively recruited and divided into CRRT and non-CRRT groups. Logistic regression analysis was used to screen the factors affecting the eradication of Gram-positive bacteria. The filtrate concentration of the CRRT group was measured at the time of TEI Cmin, and the filtration coefficient of TEI was calculated to evaluate the effect of CRRT on the clearance of TEI. Results: A total of 106 patients were included, 40 cases in the CRRT group and 66 cases in the non-CRRT group. After giving high-loading doses of TEI, 75.8 and 70% of TEI Cmin in the non-CRRT and CRRT groups reached the range of 10-30 mg/L before the 3rd dose, respectively. The risk of G+ bacteria being uneradicated was higher while the APACHEⅡscore was higher than 22.5. The albumin level before the start of TEI administration and before the 6th-8th dose was lower than 32.8 g/L and 29.3 g/L, respectively, and Cmin before the 3rd dose and 6th-8th dose was lower than 13.2 mg/L and 17.1 mg/L, respectively, with the duration of TEI therapy shorter than 10.5 days. The correlation coefficient (r) was 0.6490 between Cmin before the 3rd dose and the albumin level (p < 0.001). The filtration coefficient of TEI was 10.7 ± 2.4% at Cmin and 11.1 ± 2.5% at Cmax. The GFR had no correlation with the filtration coefficient (r = -0.06204; r = -0.08059). The clearance of TEI in CRRT patients was negatively correlated with the albumin level (r = -0.6305, p = 0.0013). Conclusion: The early stage of the albumin level can significantly affect the initial Cmin and clinical efficacy of TEI, and also had effect on the clearance of TEI by CRRT. The filtration coefficient of TEI was stable, even with a higher ultrafiltration rate.

Predictive performance of reported vancomycin population pharmacokinetic model in patients with different renal function status, especially those with augmented renal clearance.

BACKGROUND: There is a significant correlation between augmented renal clearance (ARC) and lower serum trough concentrations of vancomycin (VCM) during therapy. There is a need to evaluate the predictive performance of the population pharmacokinetic (PPK) model used for individual calculation of dosage regimens in ARC patients. OBJECTIVE: Our study aimed to estimate the predictive performance differences of the reported VCM PPK software JPKD-vancomycin and SmartDose in patients with varying renal function status, especially those with ARC. METHODS: Patients receiving VCM treatment from May 2014 to December 2019 were enrolled, and divided into the ARC group, the normal renal function (NRF) group, and the impaired renal function (IRF) group. VCM dosage, trough concentration, area under the curve (AUC) and pharmacokinetic parameters were compared among the three groups. The predictive performance of PPK software was expressed using absolute prediction error (APE), sensitivity, specificity, and regression coefficient (r2) of linear regression analysis between the measured VCM trough concentration and the predicted trough concentration. RESULTS: A total of 388 patients were included: 86 patients in the ARC group, 241 patients in the NRF group, and 61 patients in the IRF group. The daily dose of the adjusted regimen in the ARC group was higher than in the NRF group, but the trough concentration was significantly lower than in the NRF group (2.8±0.6 g vs 1.9±0.6 g, p<0.001; 10.5±5.1 mg/L vs 12.9±6.8 mg/L, p=0.030). The percentage of trough concentrations lower than 10 mg/L was 84.9% in the ARC group. Compared with the APE of the initial dosage regimen, the APE of the adjusted regimen calculated by JPKD was lower in the ARC group (p=0.041) and the NRF group (p＜0.001). Specificity of JPKD and SmartDose in the ARC group was higher than in the NRF group (p<0.001; p<0.001). According to the linear regression analysis, the coefficients of determination (r2) were all >0.6 for the initial regimen and adjusted regimen of VCM in the ARC and NRF groups, and the r2 of the adjusted regimen of JPKD was >0.8 in the ARC and NRF groups. In the IRF group, 31.1% of patients had a change in serum creatinine (Scr) level of >50%. The r2 increased from 0.527 to 0.7347 in SmartDose and from 0.55 to 0.7802 in JPKD when using Scr at the sampling time. The ARC group showed a significant decrease in AUC (p<0.001) and an increase in clearance rate (p<0.001) when compared to the NRF group. CONCLUSION: ARC was significantly associated with subtherapeutic serum VCM concentration. The pharmacokinetic parameters of VCM were diverse in patients with different renal function status. The PPK model JPKD and SmartDose had a good predictive performance for predicting VCM trough concentrations of the ARC and NRF patients, especially using JPKD for prediction of the adjusted regimen. The change of Scr is a main factor affecting the accuracy of software prediction.

Dietary zinc supplementation affects eggshell quality and ultrastructure in commercial laying ducks by influencing calcium metabolism.

This study evaluated dietary Zn supplementation on productive performance, eggshell quality and ultrastructure, and calcium metabolism during eggshell formation in laying ducks. A total of 360 Longyan laying ducks (45-wk) were randomly divided into 5 treatment groups with 6 replicates of 12 birds each and fed for 20 wk. The 6 treatments fed the basal diet supplemented with 0 (control), 20, 40, 80, or 160 mg Zn/kg (ZnSO4·H2O). Dietary supplemental level at 80 mg/kg increased egg production (4.3%) and mass (5.7%), and decreased FCR (2.9%) compared to the basal diet, and these indices increased quadratically with increasing Zn supplemental levels (P < 0.05). The shell breaking strength (15.8%) and fracture toughness (10.6%) were higher with the supplementation of Zn at 80 mg/kg than the basal diet, and increased quadratically with Zn supplementation (P < 0.05). Dietary supplementation of Zn at 80 mg/kg improved shell ultrastructure by increasing total (9.0%) and effective thickness (14.2%) and decreasing mammillary thickness (12.0%), and their responses were quadratic with increasing Zn levels (P < 0.05). The supplementation of Zn affected the calcium contents in plasma, tibias and ulna, ulna phosphorus content, and linear and quadratic effects were observed, and higher values were observed with 160 mg/kg Zn supplementation than control (P < 0.05). The supplemental Zn level at 80 mg/kg increased shell effective thickness in growth stage (P < 0.05), and shell calcium and phosphorus content in initial and growth stages (P < 0.05). Dietary Zn supplementation did not affect the gene expression of Ca2+ transporters in the eggshell gland, but affected the expression of HCO3- exchanger in initial and growth stage (P < 0.05). Overall, dietary Zn supplementation could improve productive performance and shell quality in laying ducks at late phase of production, and calcium metabolism and deposition were modulated by Zn influencing HCO3- secretion and thus affecting shell ultrastructure and quality. A supplemental level of 80 mg/kg Zn in the diet with a basal content of 34.0 mg/kg was optimal, and higher level (160 mg/kg) decreased shell calcium deposition by depressing its metabolism.

A Regression Model to Predict Augmented Renal Clearance in Critically Ill Obstetric Patients and Effects on Vancomycin Treatment.

Background: Augmented renal clearance (ARC) risk factors and effects on vancomycin (VCM) of obstetric patients were possibly different from other populations based on pathophysiological characteristics. Our study was to establish a regression model for prediction of ARC and analyze the effects of ARC on VCM treatment in critically ill obstetric patients. Methods: We retrospectively included 427 patients, grouped into ARC and non-ARC patients. Logistic regression analysis was used to analyze the factors related to ARC. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the model for ARC. Patients who received VCM therapy were collected. The published VCM population pharmacokinetic (PPK) model was used to calculate pharmacokinetic parameters. A linear regression analysis was made between the predicted and measured concentrations. Results: Of the 427 patients, ARC was present in 201 patients (47.1%). The independent risk factors of ARC were heavier, greater gestational age, higher albumin level, fewer caesarean section, severe preeclampsia and vasoactive drug; more infection, hypertriglyceridemia and acute pancreatitis. We established the above nine-variable prediction regression model and calculated the predicted probability. ROC curve showed that the predicted probability of combined weight, albumin and gestational age had better sensitivity (70.0%) and specificity (89.8%) as well as the maximal area under the curve (AUC, AUC = 0.863). 41 cases received VCM; 21 cases (51.2%) had ARC. The initial trough concentration in ARC patients was lower than in non-ARC patients (7.9 ± 3.2 mg/L vs 9.5 ± 3.3 mg/L; p = 0.033). Comparing the predicted trough concentration of two published VCM PPK models with the measured trough concentration, correlation coefficients (r) were all more than 0.8 in the ARC group and non-ARC group. AUC was significantly decreased in the ARC group (p = 0.003; p = 0.013), and clearance (CL) increased in the ARC group (p < 0.001; p = 0.008) when compared with the non-ARC group. Conclusion: ARC is a common state in critically ill obstetric patients. The regression model of nine variables had high predictive value for predicting ARC. The published VCM PPK models had good predictive performance for predicting trough concentrations of obstetric patients. Pharmacokinetic parameters of VCM are different in ARC obstetric patients, which results in enhanced VCM clearance and decreased trough concentration.

Hypothermic properties of dexmedetomidine provide neuroprotection in rats following cerebral ischemia-reperfusion injury.

Dexmedetomidine (Dex) is a sedative and analgesic agent that is widely administered to patients admitted to the intensive care unit, and has been demonstrated to result in hypothermia. Many patients have been revealed to benefit from therapeutic hypothermia, which can mitigate cerebral ischemia/reperfusion (I/R) injury following successful cardiopulmonary resuscitation. However, studies investigating the efficacy of Dex in I/R treatment is lacking. The present study aimed to investigate the efficacy of Dex in mitigating neuronal damage, and to determine the possible mechanism of its effects in a rat model of cardiac arrest (CA). CA was induced in Sprague-Dawley rats by asphyxiation for 5 min. Following successful resuscitation, the surviving rats were randomly divided into two treatment groups; one group was intraperitoneally administered with Dex (D group), whereas the control group was treated with normal saline (N group). Critical parameters, including core temperature and blood pressure were monitored following return of spontaneous circulation (ROSC). Arterial blood samples were collected at 10 min after surgery (baseline) 30 and 120 min post-ROSC; and neurological deficit scores (NDS) of the rats were taken 12 or 24 h after ROSC prior to euthanasia. The hippocampal tissue was then removed for analysis by histology, electron microscopy and western blotting. Rats in the D group exhibited a lower core temperature and higher NDS scores compared with the N group (P<0.05). In addition, Dex injection resulted in reduced expression of apoptotic and autophagy-associated factors in the hippocampus (P<0.05). Dex treatment induced hypothermia and improved neurological function in rats after ROSC following resuscitation from CA by inhibiting neuronal apoptosis and reducing autophagy, which suggested that Dex may be a potential therapy option for patients with CA.

Effects of silymarin on p65 NF-κB, p38 MAPK and CYP450 in LPS-induced hoof dermal inflammatory cells of dairy cows.

BACKGROUND: Laminitis is considered as one of the most important causes of hoof lameness in dairy cows, which can lead to enormous economic losses. However, the etiology and pathogenesis of laminitis have not been clarified yet. Besides, it is of great significant to find alternative herbs for the prevention and treatment of dairy hooves to avoid the antibiotic abuse. In this study, the primary hoof dermal cells of dairy cows were isolated, the inflammatory model was induced by LPS, and treated with silymarin to find whether silymarin has protective effect on the inflammatory dermal cells. The viability of dermal cells, the levels of IL-1ß and TNF-α, the degree of p65 NF-κB and p38 MAPK phosphorylation, the expressions of CYP3A4 and CYP1A1 were measured. RESULTS: Hoof dermal cells of dairy cows were successfully isolated and cultured by tissue adherent culture method. Certain concentrations of LPS can increase the levels of IL-1ß and TNF-α, promote the phosphorylation of p65 NF-κB and p38 MAPK, and inhibit the mRNA expressions of CYP3A4 and CYP1A1. The optimal concentration for LPS to establish a hoof dermal cells inflammatory model was 10 µg/mL. Certain concentrations of silymarin can markedly decrease the secretions of IL-1ß and TNF-α, inhibit the phosphorylation of p65 NF-κB and p38 MAPK, and promote the mRNA expressions of CYP3A4 and CYP1A1 in LPS-induced dermal inflammatory model. CONCLUSIONS: LPS can be used for inducing the hoof dermal cells inflammatory model of dairy cows. Silymarin has protective effects on the LPS-induced inflammatory model.

Cloning, Expression and Characterization of a Novel Cold-adapted ß-galactosidase from the Deep-sea Bacterium Alteromonas sp. ML52.

The bacterium Alteromonas sp. ML52, isolated from deep-sea water, was found to synthesize an intracellular cold-adapted ß-galactosidase. A novel ß-galactosidase gene from strain ML52, encoding 1058 amino acids residues, was cloned and expressed in Escherichia coli. The enzyme belongs to glycoside hydrolase family 2 and is active as a homotetrameric protein. The recombinant enzyme had maximum activity at 35 °C and pH 8 with a low thermal stability over 30 °C. The enzyme also exhibited a Km of 0.14 mM, a Vmax of 464.7 U/mg and a kcat of 3688.1 S-1 at 35 °C with 2-nitrophenyl-ß-d-galactopyranoside as a substrate. Hydrolysis of lactose assay, performed using milk, indicated that over 90% lactose in milk was hydrolyzed after incubation for 5 h at 25 °C or 24 h at 4 °C and 10 °C, respectively. These properties suggest that recombinant Alteromonas sp. ML52 ß-galactosidase is a potential biocatalyst for the lactose-reduced dairy industry.

[Clinical verification of vancomycin population pharmacokinetics in patients with augmented renal clearance].

OBJECTIVE: To evaluate the predictive value and to verify the clinical effect of JPKD-vancomycin for the trough concentration of vancomycin in patients with augmented renal clearance (ARC), and to provide a reference for clinical individualized drug therapy. METHODS: A retrospective analysis was conducted. The clinical data of 48 adult patients with ARC using vancomycin and monitoring steady-state trough concentration of vancomycin admitted to Suzhou Hospital Affiliated to Nanjing Medical University from July 2013 to July 2017 were collected. A combination of classical Vancomycin Calculator software and JPKD-vancomycin software was used. Based on the individual conditions of patients [gender, age, height, weight, serum creatinine (SCr), disease status], Vancomycin Calculator software was used to obtain the recommended regimen and its steady-state trough concentration, and then JPKD-vancomycin software was used to predict the steady-state trough concentration of initial regimen. If the regimen was adjusted during the treatment, JPKD-vancomycin software was used to predict the steady-state trough concentration of the adjusted regimen. The measured values of steady-state trough concentration were recorded. The weight deviation between predicted concentration and measured concentration (WRES) was calculated. WRES < 30% was considered as good prediction, and the predictive value of JPKD-vancomycin software was evaluated for vancomycin trough concentration. RESULTS: Forty-eight patients with ARC were enrolled, of whom 24 patients had adjusted the dosing regimen during the treatment. The initial concentration of blood samples was 48, after adjusting the dosage regimen, 24 blood samples were collected. The initial and adjusted daily dose of vancomycin was (2 000±500) mg/d and (2 500±600) mg/d, respectively, and the initial trough concentrations and adjusted trough concentrations was (8.4±7.3) mg/L and (9.1±4.3) mg/L, respectively. Only 14.6% and 25.0% of initial and adjusted trough concentrations reached the target range (10-20 mg/L) without significant difference (P > 0.05). The WRES value of adjusted trough concentrations predicted by JPKD-vancomycin software was significantly lower than that of initial regimen [10.6% (3.0%, 16.4%) vs. 14.3% (10.5%, 38.2%), P < 0.05], and the percentage of WRES < 30% also tended to increase [95.8% (23/24) vs. 70.8% (34/48), P < 0.05]. The well predictive rate of JPKD-vancomycin software for vancomycin trough concentration was 79.2% (57/72), but there were 15 patients with WRES > 30%. CONCLUSIONS: JPKD-vancomycin software has good predictive value for the vancomycin trough concentration of ARC patients, especially for the trough concentration after adjusting the treatment regimen. JPKD-vancomycin can provide a reference for the design of clinical individualized application of vancomycin.