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Background: Sepsis and continuous renal replacement therapy (CRRT) are both responsible for the alterations of the pharmacokinetics of antibiotics. For patients with sepsis receiving CRRT, the serum concentrations of meropenem in the early phase (< 48 h) was significantly lower than that in the late phase (> 48 h). This current trial aimed to investigate whether administration of a loading dose of meropenem results in a more likely achievement of the pharmacokinetic (PK)/pharmacodynamics (PD) target (100% fT > 4 × MIC) and better therapeutic results in the patients with sepsis receiving CRRT.Methods: This is a single-blinded, single-center, randomized, controlled, two-arm, and parallel-group trial. This trial will be carried out in Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangdong, China. Adult patients (age ≥ 18 years) with critical sepsis or sepsis-related shock receiving CRRT will be included in the study. The subjects will be assigned to the control group and the intervention group (LD group) randomly at a 1:1 ratio, the estimated sample size should be 120 subjects in each group. In the LD group, the patient will receive a loading dose of 1.5-g meropenem resolved in 30-ml saline which is given via central line for 30 min. Afterward, 0.75-g meropenem will be given immediately for 30 min every 8 h. In the control group, the patient will receive 0.75-g meropenem for 30 min every 8 h. The primary objective is the probabilities of PK/PD target (100% fT > 4 × MIC) achieved in the septic patients who receive CRRT in the first 48 h. Secondary objectives include clinical cure rate, bacterial clearance rate, sepsis-related mortality and all-cause mortality, the total dose of meropenem, duration of meropenem treatment, duration of CRRT, Sequential Organ Failure Assessment (SOFA), C-reactive protein levels, procalcitonin levels, white blood cell count, and safety.Discussion: This trial will assess for the first time whether administration of a loading dose of meropenem results in a more likely achievement of the PK/PD target and better therapeutic results in the patients with sepsis receiving CRRT. Since CRRT is an important therapeutic strategy for sepsis patients with hemodynamic instability, the results from this trial may help to provide evidence-based therapy for septic patients receiving CRRT.Trial Registration: Chinese Clinical Trials Registry, ChiCTR2000032865 . Registered on 13 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=53616 . [ABSTRACT FROM AUTHOR]

Shape-memory polymers (SMPs) have attracted enormous attention in recent years, but most of the research has been focused on the nature of the shape change itself. Actually, there is great potential as well as a big challenge to develop a new class of smart materials with the assistance of shape-memory technology (SMT). Herein, by integrating SMT and photo-imaging in one system, we proposed SMPs as a high-security storage medium featuring information storage, masking and dual-anticounterfeiting. In this work, an anthracene-containing polymer embedded with shape-memory component and photoactive moiety was elaborately designed. The shape-memory component determines the shape-change, that is, produces a three-dimensional (3D) signal, while the localized photo-cross-linking of the anthracene-containing film under 365 nm UV with a photomask generates a photo-image on the surface of the SMP, that is, a two-dimensional (2D) signal, due to the distinct boundaries of areas of strong and weak fluorescence. The stored information, the 2D image produced by photo-imaging, could only be verified by 254 nm UV resource, and with the integrated SMT-generated 3D signal, the safety level of the information could be improved. By implementing sequential photo-imaging and SMT, the high-security information storage medium was proved by a model of a scroll and a practical example of a label. [ABSTRACT FROM AUTHOR]

Multistimuli-responsive shape-memory polymers are highly desirable in various applications, and numerous modes have been developed in recent years. However, most of them need to reprogram before they are ready to respond to another stimulus while one is triggered. Here, a new strategy is developed to achieve dual-stimuli-responsive triple-shape memory with non-overlapping effect in one programming cycle. Here, a series of poly( l-lactide)-poly(tetramethylene oxide) glycol copolymers (PLA-PTMEG-A) is prepared by selected dangling photoresponsive anthracene moieties on the crystalline PTMEG backbone. The architectures of the copolymers are well-controlled in order to keep a good balance between the crystallinity of the soft segment and the mobility of the anthracene moieties. Thus, PLA-PTMEG-A's can respond to heat and light with non-overlapping effect. The thermally-induced shape-memory effect (TSME) is realized by the crystallization-melting transition of PTMEG soft segments, while the light-induced shape-memory effect (LSME) is achieved by the reversible photodimerization of anthracene groups. In view of the non-overlapping effect of TSME and LSME in the copolymers, a triple-shape-memory effect triggered by dual-stimuli is realized in one programming and recovery cycle. [ABSTRACT FROM AUTHOR]

A novel light-induced shape-memory material based on poly(l-lactide)-poly(ethylene glycol) copolymer is developed successfully by dangling the photoresponsive anthracene group on the PEG soft segment selectively. For synthesis strategy, the preprepared photoresponsive monomer N,N-bis(2-hydroxyethyl)-9-anthracene-methanamine (BHEAA) is first embedded into PEG chains; then, we couple this anthracene-functionalized PEG precursor with PLA precursor to result in PLA-PEG-A copolymer. The composition of target product can be well-defined by simply adjusting the feed ratio. The chemical structures of intermediate and final products are confirmed by (1)H NMR. Differential scanning calorimetry analysis of material reveals that the PEG soft segment became noncrystallizable when 4% or more BHEAA is introduced, and this feature is beneficial to the mobility of anthracene groups in polymer matrix. The static tensile tests show that the samples exhibit rubberlike mechanical properties except for the PLA-dominant one. The reversibility of [4 + 4] cycloaddition reaction between pendant anthracene groups in PLA-PEG-A film is demonstrated by UV-vis. Eventually, the light-induced shape-memory effect (LSME) is successfully realized in PLA-PEG-A. The results of cyclic photomechanical tests also reveal that the content of PLA hard segment as well as photosensitive anthracene moieties plays a crucial role in LSME.

Mycophenolate mofetil (MMF), a widely used immunosuppressant, is characterized by highly variable pharmacokinetics. UGT1A8, UGT1A9, UGT2B7 and ABCC2 have been proved to be critical genes associated with inter-individual variation of MMF pharmacokinetics. In this study, we investigated the genetic polymorphisms of UGT1A8*2, UGT1A8*3, UGT1A9 C-2152T, UGT1A9 T-275A, UGT1A9 T98C, UGT2B7*2, ABCC2 C-24T and ABCC2 C3972T in 200 Chinese renal transplant recipients and compared them with those in other ethnic groups reported in the literature, to start the exploration of a better use of MMF in Chinese. A much higher frequency of UGT1A8*2 variant allele was found in Chinese than in Caucasians and Africans, while the UGT2B7*2 variant allele was significantly rarer in Chinese than in Caucasians and Africans. For ABCC2, -24T allele was more common and 3972T allele was less common in Chinese than in Caucasians and Africans. However, none of the SNPs in UGT1A9 were present in our study population. The findings of this study suggest that Chinese renal transplant recipients may exhibit a response profile to MMF that is different from those of other ethnic groups.

The pregnane X receptor (PXR/NR1I2) gene is a master regulator for a number of cytochrome P450s (CYPs) and drug transporters. This study aimed to detect the single nucleotide polymorphisms (SNPs) of the PXR gene in Han Chinese (n = 186) and to compare the frequencies of polymorphisms of the PXR gene with those in Caucasian and African Americans reported in the literature. The SNPs of the PXR gene were analyzed using the polymerase chain reaction (PCR) and direct sequencing analysis. The mutant frequencies of A11156C and T11193C in Han Chinese were 55% (95% confidence interval (CI): 0.49-0.61) and 59% (95% CI: 0.52-0.64), respectively, higher than those of Caucasian Americans (16 and 16%, respectively) and African Americans (33 and 30%, respectively). However, the reported SNPs in exons 2 and 4 (PXR*2,*3,*4,*6,*9,*10,and *11) were not detected in Han Chinese. These results indicate that there are marked differences in the mutant frequencies of A11156C and T11193C of PXR between Han Chinese and other ethnic groups. The mutant frequency in the coding region (exons 2 and 4) of PXR was very low in Han Chinese. Further studies are needed to determine the impact of common SNPs of PXR in Han Chinese and other ethnic populations on the phenotypic activity of cytochrome P450s and drug transporters transactivated by PXR., ((c) 2008 S. Karger AG, Basel)

The pregnane X receptor (PXR/NR1I2) gene is a critical transcriptional regulator of a number of important drug metabolizing enzymes and transporters. This study was undertaken to determine the frequencies of single nucleotide polymorphisms (SNPs) and haplotypes and to detect yet unknown SNPs in the NR1I2 gene in 210 unrelated healthy Han Chinese in comparison with other ethnic groups. We also characterized the functional impact of two SNPs, -24622A>T in the 5'-untranslated region and -24446C>A in exon 1 of NR1I2, by constructing three recombinants and monitoring promoter activity using the dual luciferase reporter gene assay. Genomic DNA was isolated from peripheral leukocytes and subjected to polymerase chain reaction (PCR) amplification, followed by direct DNA sequencing. Sixteen SNPs in NR1I2 with frequencies of 0.3-90.3% were found in Han Chinese, two of which (-25439A>G in the 5'-untranslated region and 7637C>T in intron 5) are previously unknown. The mutant allelic frequencies varied from 0.3% to 90.3%. Most of the detected SNPs were located in introns. A total of 15 linkage disequilibriums were detected; and positive linkage disequilibriums were found between -24381A>C in exon 1 and -24113G>A in intron 1, and 252A>G in intron 2 and 275A>G in intron 2 (rho(2) = 1, P<0.001). A total of 42 haplotypes were inferred and the two most frequent haplotypes were H1 (TCAGGGGCCACC) and H2 (CCGAAAACTAAT) with a frequency of 15.1%. The activity of the recombinants with alleles containing the -24622A>T in the 5'-untranslated region or -24446C>A in exon 1 was 30-40% higher than that in the wild-type (reference genotype). These results indicate that there are marked ethnic differences in the frequency between Han Chinese and other ethnic groups and that alleles with -24622A>T in the 5'-untranslated region and -24446C>A in exon 1 of the NR1I2 gene result in an increased activity compared to the wild-type. Further studies are warranted to explore the clinical and toxicological impact of SNPs and haplotypes of NR1I2 in various ethnic groups.