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To effectively alleviate acute severe ulcerative colitis (ASUC), we developed a colon-specific delivery system-PLGA-KPV/MMT/CS multifunctional medicinal nanoparticles loaded with cyclosporine A (CyA). The lysine-proline-valine (KPV) tripeptide, which possesses anti-inflammatory properties and high affinity to peptide transporter 1 (PepT1), can target therapy-related cells (colonic epithelial cells and macrophages) via overexpression of PepT1. Montmorillonite (MMT)/chitosan (CS) coating can reduce CyA leakage in the upper gastrointestinal tract (GIT) and enhance nanoparticle adhesion to the inflamed colon. The bio-distribution demonstrated that nanoparticles can specifically accumulate in the inflamed tissues and can be retained for up to 36 h. After being treated with the CyA-PLGA-KPV/MMT/CS nanoparticles (PKMCN), the mice with DSS-induced ulcerative colitis exhibited significant improvements in body weight, colon length, and disease activity index. Moreover, biochemistry and immunohistochemical analysis showed that the PKMCN treatment group performed as well as the healthy group. Intriguingly, PKMCN without CyA also presented marked therapeutic effects. Our results suggested that PKMCN could be a promising drug delivery system for ASUC therapy by targeting inflamed cells, prolonging curative time, and mitigating colitis.

Recent studies indicated obvious impacts of nano-carriers on cytochrome P450 enzymes (CYP450s) in vitro, but the effects in vivo are still unknown. In the present research, mPEG 2k -PCL x micelles with different length of hydrophobic block (2000-10,000 Da) were intravenously administrated into rats for 14 days to evaluate the sub-chronic influences in the metabolic function of hepatic CYP450s. Although CYP1A1/B2 was susceptible to mPEG 2k -PCL x micelles compared with other CYP isoenzymes, induction was mainly observed and varied with micelle type, administration dose, and CYP isoform. Interestingly, mPEG 2k -PCL 3.5k micelles at 5 mg/kg increased the activity of CYP1A2, CYP2B1, CYP2C6, CYP2C11, and CYP3A1/2 while mPEG 2k -PCL 5k micelles only induced the latter three enzymes at 75 mg/kg. The mRNA expression of corresponding CYPs was mostly up-regulated by mPEG 2k -PCL 3.5k micelles whilst less effect in protein level except for CYP3A1/2. Moreover, mPEG 2k -PCL 3.5k micelles could affect the pharmacokinetic properties of phenacetin (CYP1A2), tolbutamide (CYP2C6), omeprazole (CYP2C11), and midazolam (CYP3A1/2) with a decrease of 19.6% in C max , 20.5% in AUC 0-t , 31.6% in AUC 0-t , and 40.1% in C max at 5 mg/kg, respectively (P < 0.05 or P < 0.01). These results unveiled nano-DDS might be involved in nanocarrier-drug interaction by intervening in the activity of CYP450s., (Copyright © 2019 Elsevier B.V. All rights reserved.)

One of the most common upper limb dysfunction seen among cerebral palsy children is the limited supination or pronation of the forearm, thus training forearm axial rotation is a common demand for interventions. We propose a method to estimate forearm axial rotation using commercially available tracking device HTC Vive tracker to support interaction with serious games with forearm axial rotation movement for rehabilitation in clinic or home environment. The proposed method provides an easy-to-access and affordable way for forearm axial angle estimation when arm is at different positions relative to torso and when tracking devices are worn in different orientations. Effectiveness of the proposed method is examined, and a serious game system that uses the method for interaction is designed which was installed in The First Hospital of Jilin University as an option of forearm movement practices for children with cerebral palsy.

This study investigated the value and clinical significance of ultrasound combined with CT in the diagnosis of cystic renal cell carcinoma. A total of 85 patients with cystic renal cell carcinoma, who were admitted to the Oncology Department of Yantai Yuhuangding Hospital Affiliated to Qingdao University from December 2015 to April 2017, were selected as the study group, and 70 patients with benign renal cyst, who were examined in Yantai Yuhuangding Hospital Affiliated to Qingdao University, were selected as the benign group. The patients in the two groups were examined by ultrasound and CT. The diagnostic value of ultrasound, CT, and ultrasound combined with CT in cystic renal cell carcinoma was analyzed. The sensitivity of ultrasound combined with CT was significantly higher than that of CT and ultrasound (P<0.05). The specificity and diagnostic coincidence rate of ultrasound combined with CT were significantly higher than those of CT (P<0.05). For unicapsular kidney cancer, there was no significant difference among ultrasound, CT and ultrasound combined with CT in the diagnosis of septum and wall nodule (P>0.05). For polycystic kidney cancer, there was no significant difference among ultrasound, CT and ultrasound combined with CT in the diagnosis of the presence or absence of septum (P>0.05). Ultrasound was significantly better than CT in cyst wall confounding (P<0.05). Ultrasound combined with CT was significantly better than ultrasound in calcification and blood supply of tumors (P<0.05). In conclusion, the accuracy of ultrasound combined with CT is higher than that of ultrasound or that of CT in the diagnosis of cystic renal cell carcinoma, which can be beneficial in accurately carrying out clinical diagnosis, reduce the incidence of missed diagnosis and misdiagnosis caused by a single diagnosis and treatment. Ultrasound combined with CT is good for clinical screening and can guide clinical symptomatic treatment, which is worthy of generalizing in clinic.

Bee pollen (BP) collected from different floras possesses various potential bioactivities, but the mechanism-related research on anti-inflammatory effects is limited. Here, three types of BP originating from Camellia sinensis L. (BP-Cs), Nelumbo nucifera Gaertn. (BP-Nn), and Brassica campestris L. (BP-Bc) were assessed using molecular and metabolomics methods to determine their anti-inflammatory effects. The differences in polyphenolic abundance of three types of BP extracts were determined by HPLC-DAD/Q-TOF-MS. In vitro anti-inflammatory effects of three BP extracts were evaluated in a lipopolysaccharide (LPS)-induced RAW 264.7 cells model. BP-Cs extract with the most abundant polyphenols was found to be the most effective in reducing inflammation by downregulating inflammatory-related genes expression and blocking the activation of MAPK and NF-κB signaling pathways. Polyphenol-rich BP-Cs was further evaluated for their in vivo anti-inflammatory effect in a LPS-induced acute lung injury mouse model. An UPLC-Q-TOF/MS-based metabolomics approach was applied to analyze metabolite changes in mouse serum. Weshowed that the pretreated BP-Cs extract alleviated inflammation and regulated glycerophospholipid metabolism significantly. Our findings provide a foundation for developing and justifying BP as a potential anti-inflammatory ingredient in functional foods or nutraceutical formulations.

This work aims to investigate the impact of different amount of oil or surfactant included in self-microemulsifying drug delivery systems on the intestinal lymphatic transport of sirolimus using the single-pass intestinal perfusion (SPIP) technique and a chylomicron flow blocking approach. Male Sprague-Dawley rats were pretreated intraperitoneally with 3.0mg/kg cycloheximide or saline. One hour later, single-pass intestinal perfusion experiments in jejunum and ileum and in vivo bioavailability studies were carried out to calculate the effective permeability coefficient and pharmacokinetic parameters, respectively. Drug absorption from oil-free formulation was mostly via the portal blood. In contrast, for the SMEDDS formulations containing ≥25% MCT, the lymphatic transport of sirolimus was a major contributor to oral bioavailability. The formulation including more content of oil presented higher lymphatic transport of drug and further exhibited the increased oral bioavailability. Besides, distal ileum presented much more lymphatic transport of drug compared to proximal jejunum. Furthermore, even though the smaller droplet size of resultant microemulsions and more surfactant content also can positively influence the intestinal absorption of drug, their influences on the drug intestinal lymphatic transport were relatively weaker than that of more oil content. In addition, there was a high linear correlation between the AUC values and the mean of P(eff) values in jejunum and ileum., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The aim of the current study was to compare pharmacokinetics of local chemotherapy by pelvic intra-arterial administration with intravenous injection in dogs. A total of 18 female dogs (weight: 10-15 kg) were randomly divided into 3 groups: the peripheral vein administration (group A, n = 6), the abdominal aorta administration (group B, n = 6), and the internal iliac artery administration (group C, n = 6). Carboplatin at a dose of 1.2 mg/kg was administered by infusing into the arteries or the vein. For analysis, plasma and uterine tissue samples were collected at different times following infusion. The peak local concentration of platinum in the uterus of dogs in group C was significantly higher than those of groups A and B (P < .05). The area under the tissue concentration-time curve (AUC) of uterine tissues was significantly higher in dogs of group C compared to those of the other 2 groups (P < .05). There was no significant difference in the AUC of the uterine tissues of dogs between groups A and B (P > .05). The peak concentration of platinum in plasma was significantly higher in group A compared to those of the other 2 administration routes (P < .05). We observed the pharmacokinetic advantages of local chemotherapy by internal iliac artery perfusion with the chemotherapeutic agent, carboplatin, to the uterus, thereby leading to a high-drug concentration that may be more effective in treating cervical cancer.

In order to study the modulatory effects of compound polysaccharide Erweikang on the immune function of the immunosuppressive mice, the positive immune modulation of Erweikang at different doses and different time points was compared when normal saline and cyclophosphamide served as controls. The results showed that different doses of Erweikang could effectively reverse the decreased induction levels of NK, IL-2, gamma-IFN and the contents of TNF and IgF of the immunosuppressive mice after administration of Erweikang for 7 to 14 days. It was suggested that compound polysaccharide Erweikang presents positive immune modulation in dose- and time-dependent manners.