System Pharmacology-Based Strategy to Decode the Synergistic Mechanism of Zhi-zhu Wan for Functional Dyspepsia

Functional dyspepsia (FD) is a widely prevalent gastrointestinal disorder throughout the world, whereas the efficacy of current treatment in the Western countries is limited. As the symptom is equivalent to the traditional Chinese medicine (TCM) term “stuffiness and fullness,” FD can be treated with Zhi-zhu Wan (ZZW) which is a kind of Chinese patent medicine. However, the “multi-component” and “multi-target” feature of Chinese patent medicine makes it challenge to elucidate the potential therapeutic mechanisms of ZZW on FD. Presently, a novel system pharmacology model including pharmacokinetic parameters, pharmacological data, and component contribution score (CS) is constructed to decipher the potential therapeutic mechanism of ZZW on FD. Finally, 61 components with favorable pharmacokinetic profiles and biological activities were obtained through ADME (absorption, distribution, metabolism, and excretion) screening in silico. The related targets of these components are identified by component targeting process followed by GO analysis and pathway enrichment analysis. And systematic analysis found that through acting on the target related to inflammation, gastrointestinal peristalsis, and mental disorder, ZZW plays a synergistic and complementary effect on FD at the pathway level. Furthermore, the component CS showed that 29 components contributed 90.18% of the total CS values of ZZW for the FD treatment, which suggested that the effective therapeutic effects of ZZW for FD are derived from all active components, not a few components. This study proposes the system pharmacology method and discovers the potent combination therapeutic mechanisms of ZZW for FD. This strategy will provide a reference method for other TCM mechanism research

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis:Erase

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.</p

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis:Erase

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The Use of Bolted Side Plates for Shear Strengthening of RC Beams: A Review

Reinforced concrete (RC) beams may need to be strengthened because of material deterioration, structure aging, change of building function, defective design, and the decrease of structural reliability caused by accidental disasters such as earthquake and fire. Thus, the retrofitting of RC beams has become a crucial problem, especially for the old buildings constructed before 1980 in mainland China. A variety of studies have proven that the bolted side-plating (BSP) method is feasible and effective for rehabilitating RC beams in existing buildings and infrastructures. The aim of this paper is mainly to review the previous studies conducted by the authors on the shear performance of reinforced concrete (RC) beams retrofitted using the BSP technique, including experimental, theoretical, and numerical studies

Two new species of Henckelia (Gesneriaceae) from Southeastern Yunnan, China

Two new species of Gesneriaceae, Henckelia nanxiheensis Lei Cai & Z.L.Dao, sp. nov. and H. multinervia Lei Cai & Z.L.Dao, sp. nov. from southeastern Yunnan, China, are described with color photos. The diagnostic characters of the two new species, together with photographs, detailed descriptions, distribution and habitat, as well as comparisons with morphologically similar species, are also provided

Two new species of Oreocharis (Gesneriaceae) from karst regions in Yunnan and notes on O. tetraptera and O. brachypoda from China

Two new species of Gesneriaceae, Oreocharis aimodisca and O. longipedicellata, from the limestone area of Yunnan Province, China, are described and illustrated. Their morphological relationship with similar species is discussed and colour photographs, detailed descriptions, distribution and habitat, as well as the IUCN endangered status are provided. We also discuss the accuracy of the scientific names of the described species O. tetrapterus from Guangxi, China in 2019 and O. brachypodus from Guizhou, China, in 2015, and put forward corrections related to name form

Oreocharis wumengensis, a new species of Gesneriaceae from northeastern Yunnan, China

A new species of Gesneriaceae, Oreocharis wumengensis Lei Cai & Z.L.Dao from Wumeng Mountain area, Yanjin County, Yunnan Province, China, is described. The new species is morphologically similar to O. panzhouensis Lei Cai, Y.Guo & F.Wen in the shape of corolla, number of stigma and stamens, but it can be easily distinguished from this species by the leaf shape and indumentum characters of leaf blade, calyx and stamens. Detailed descriptions with photographs of the plant and holotype, and comparisons with morphologically similar species, are also provided

Numerical Study on the Local Buckling Behaviour of Bolted Steel Plates in Steel Jacketing

A numerical simulation was conducted to investigate the local buckling behaviour of the bolted steel plates in steel jacketing technique. The numerical model was firstly validated by the results of a previous experimental study. Then a parametric study was conducted to investigate the influence of different restraint measures on the local buckling behaviour and the sensitivity of the buckling behaviour to the initial imperfection. Fitted formulae were developed to calculate the structural field capacity of the bolted steel plates, and recommended values of stiffener size were also provided to facilitate the strengthening design of steel jacketing

Strengthening of RC Structures by Using Engineered Cementitious Composites: A Review

This paper presents a review of the recent work assessing the performance of building structures strengthened with engineered cementitious composite (ECC). ECC characterizes tensile strain hardening and multiple cracking properties, as well as strong interfacial bonding performance with substrate concrete, which makes it a promising retrofitting material. A lot of researches have been conducted on reinforced concrete (RC) structures, including beams, columns, beam&ndash;column joints, and fire-damaged slabs, strengthened with ECC material, and an extensive collection of valuable conclusions were obtained. These strengthening systems usually combine ECC with FRP textiles or steel bars to form a composite strengthening layer. The review demonstrates that ECC strengthening can greatly improve the performance of RC structures