Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

The functional microbiota of on- and off-year moso bamboo (Phyllostachys edulis) influences the development of the bamboo pest Pantana phyllostachysae.

BACKGROUND: Development of Pantana phyllostachysae, a moso bamboo pest, is affected by its diet. Understanding the mechanism underlying the different insect-resistant capacities of on- and off-year moso bamboo fed by P. phyllostachysae is crucial for managing pest outbreaks. As microbes were proven to influence plant immunity, we compared gut microbial communities of P. phyllostachysae with different diets by metabarcoding sequencing. By using sterilization assay, microbes were removed from leaf surfaces, and thus we confirmed that microbes inhabiting moso bamboo leaves impact the weight of P. phyllostachysae larva. Furthermore, the gut microbial communities of P. phyllostachysae fed on on- and off-year bamboo leaves were compared, to identify the functional microbial communities that impact the interaction between bamboo leaves and P. phyllostachysae. RESULTS: We found that species from orders Lactobacillales and Rickettsiales are most effective within functional microbiota. Functional prediction revealed that gut microbes of larva fed on on-year leaves were related to naphthalene degradation, while those fed on off-year leaves were related to biosynthesis of ansamycins, polyketide sugar unit biosynthesis, metabolism of xenobiotics, and tetracycline biosynthesis. Most functional microbes are beneficial to the development of larva that feed on on-year bamboo leaves, but damage the balance of intestinal microenvironment and immune systems of those larva that feed on off-year leaves. CONCLUSIONS: This work developed an efficient strategy for microbiome research of Lepidopteran insects and provided insights into microbiota related to the interaction between host plants and P. phyllostachysae. We provided microbial candidates for the ecological control of P. phyllostachysae according to the function of effective microbiota.

[Short-term memory characteristics of vibro-tactile perception in human fingertips].

This paper discusses the short-term memory of vibro-tactile perception of human fingertips. By using a self-developed vibro-tactile expression device, a recall experiment was firstly carried out among 20 subjects aged 20-30 (10 males and 10 females) to discover the memory span about the vibro-tactile perception of human fingertips. Within this memory span, a cognitive experiment analyzing the recognition accuracy and the reaction time was carried out. The results showed: (1) The vibro-tactile memory span of human fingertip is 4 ± 1; (2) The vibro-tactile memory span increases as the discrete intensity between vibration stimuli increases; (3) Too long or too short vibration duration will reduce the vibro-tactile memory span, and the optimal vibration duration for men is 400 ms, for women is 300 ms; (4) The more the number of vibration stimuli is perceived by the human fingertip, the lower the recognition accuracy and the longer the reaction time it needs; (5) Compared with the vibration stimuli in disorder, people are more likely to remember the vibration stimuli in increasing/decreasing order; (6) The information extraction mechanism of the short-term memory about fingertip vibro-tactile perception bases a point to point scanning process among these stimuli. These results help to understand the human fingertip tactile characteristics and provide a physiological basis for the study of tactile feedback technologies.

Complete Genome of a Novel Pseudoalteromonas Phage PHq0.

We isolated and purified a novel virulent Pseudoalteromonas bacteriophage PHq0 and the host bacterium Pseudoalteromonas BQ0 from seawater collected in a coastal area of the Yellow Sea of China. (36°06'N, 120°32'E). Transmission electron microscopy revealed that the phage had an icosahedral head of 50 nm in diameter with a long tail of 100 nm. The one-step growth curve showed the latent period of about 15 min, a rise period of 15 min, and a burst size of about 363 virions. The genome of phage PHq0 was found to consist of a linear, double-stranded 33,399-bp DNA molecule with a GC content of 40.29 % and 56 putative open reading frames (ORFs). Among these genes, 23 conserved domains were detected by BLASTP, 17 were functionally known, leaving 39 unknown putative genes, BLASTP results show that 57.14 % of the 56 predicted ORFs were not found to have any matches of putative functions or conserved domains in the BLASTP database which should be classified as a new member of the Siphoviridae family. The phage PHq0 genome adds a new Siphoviridae-family phage genome for marine bacteriophages which will provide useful basic information for further molecular research on interaction mechanism between bacteriophages and their hosts.

[Combination of Jianpi Liqi Yiliu Formula with Cytokine-induced Killer Cell Treatment for Advanced Hepatocellular Carcinoma].

OBJECTIVE: To evaluate the clinical efficacy of Jianpi Liqi Yiliu Formula (JLYF) combined with cytokine-induced killer (CIK) cells for treating patients with advanced hepatocellular carcinoma (HCC). METHODS: Between January 2011 and January 2014, 60 advanced HCC patients were enrolled in this study, who were assigned to the treatment group and the control group according to their willingness for taking JLYF, 30 cases in each group. All patients received CIK cell treatment: 1 x 109-3 x 109 each time, by intravenous dripping from the 1st day to the 3rd day, once per day. Besides, patients in the treatment group took JLYF decoction, while those in the control group took Chinese medical decoction by syndrome typing. All patients received treatment of at least two cycles. The time to progression (TTP) , overall survival (OS), disease control rate (DCR), performance status scale (PS), Child-Pugh scale, and adverse reactions were observed, and subgroup analyzed. RESULTS: To May 31, 2014, all patients reached the clinical endpoint. TTP was 3.5 months (95% Cl: 3.30-4.10) in the treatment group, better than that (2.5 months, 95% CI: 2.32-2.68) of the control group (P < 0.05). DCR was 36.7% in the treatment group and 30.0% in the control group (P > 0.05). OS was 5.2 months (95% CI: 4.53-5.87) in the treatment group and 4.6 months (95% CI: 4.06-5.14) in the control group (P > 0.05). The PS scale was 1.60 ± 0.10 after treatment, lower than that (1.80 ± 0.09) before treatment in the treatment group (P < 0.05). When the PS scale was 0-2 or Child-Pugh scale was class A, TTP was longer in the treatment group than in the control group (P < 0.05). No adverse reaction occurred in the two groups during the treatment course. CONCLUSIONS: The combination of JLYF with ClK cell treatment could prolong advanced HCC patients' TTP, improve PS scale, as compared with syndrome typed Chinese medical decoction treatment group. Besides, when the PS scale was 0-2 or Child-Pugh scale was class A, it was a better treatment program for advanced HCC patients.

Extended Kalman filter algorithm for non-roughness and moving damage identification.

It is a promising method to identify structural damage using bridge dynamic response under moving vehicle excitation, but the lack of accurate information about road roughness and vehicle parameters will lead to the failure of this method. The paper proposed a step-by-step EKF damage identification method, which transforms the inversion problem of unknown structural parameters under unknown loads (vehicle and road roughness) into two separate inversion problems: moving contact force identification and damage parameters identification. Firstly, the VBI model is converted into bridge vibration model under a moving contact force, and the moving contact force covering the information of road roughness and vehicle parameters can be calculated by EKF iteration. Secondly, the moving contact force identified in the first step is loaded on the bridge as a known condition, and the bridge damage problem is also solved by the EKF method. Numerical analyses of a simply-supported bridge under the moving vehicle are conducted to investigate the accuracy and efficiency of the proposed method. Effects of the vehicle speed, the damage cases, the measurement noise, and the roughness levels on the accuracy of the identification results are investigated. The results demonstrate the proposed algorithm is efficient and robust, and the algorithm can be developed into an effective tool for structural health monitoring of bridges.

Biomimetic bone tissue engineering hydrogel scaffolds constructed using ordered CNTs and HA induce the proliferation and differentiation of BMSCs.

The use of bone tissue engineering scaffolds has become a promising potential treatment for bone defects as they expedite bone healing. A carbon nanotube-hydroxyapatite (CNT-HA) composite can accelerate the growth of cells. However, the molecular organized arrangement of organic and inorganic components is one of the most important biochemical phenomena in the formation of bones. This study aimed to prepare ordered CNT-HA scaffolds by applying agarose gel electrophoresis to imitate a biomimetic parallel pattern of collagens and hydroxyapatite hydrogel scaffolds (AG-Col-o-CNT). Significant improvements were presented in the mechanical properties of the scaffolds and cell growth in vitro or in vivo. The results showed that the AG-Col-o-CNT scaffolds accelerated the proliferation and differentiation of bone mesenchymal stem cell lines. In addition, the bone defects were repaired when the scaffolds were transplanted after 28 and 56 days in vivo. The superior performance of the ordered AG-Col-o-CNT scaffolds indicates that they have an enormous potential for bone tissue engineering.