Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder characterized by mental manifestations, abdominal pain, and alterations in defecation habits. The incidence rate in some areas even exceeds 20%. Secondary to chronic, recurrent gastrointestinal motility dysfunction, for patients with IBS, upon oral administration of drugs, the fluctuation of bioavailability is typically far more significant than that of healthy individuals. Nevertheless, at present, few studies have put forward targeted drug delivery systems addressing this aspect. In this study, an oral spirulina nanotechnology System (SP@TIIAn) is developed that integrates tanshinone IIA liposome with spirulina for enhanced IBS treatment. Owing to the passive targeting of intestinal villi and enhanced adhesion by spirulina and nanoparticles, it is discovered that, in contrast to enteric-coated capsules, this system is more beneficial for guaranteeing the pharmacokinetic stability of IBS. SP@TIIAn effectively treats multiple gut-brain symptoms of IBS, contributing to providing new alternatives for the development of clinical medications for IBS.

Abstract Increased plasma homocysteine (Hcy) has been identified as one of the important risk factors for cardiovascular disease. However, the association between plasma Hcy and peripheral artery disease (PAD) is still controversial. This study aimed to investigate the association between plasma Hcy and PAD and the potential modifier factors in Chinese hypertensive adults. A total of 25 300 hypertensive patients aged 18 years or older were included in the analysis in this cross‐sectional study. The outcome was PAD, which defined as an ankle‐brachial index ≤0.90 in either limb. Multiple logistic regression was used to analyze the relationship between plasma Hcy and PAD. The median plasma Hcy was 14.00 (interquartile range: 11.60–17.80) μmol/L. There was a significant positive association between plasma Hcy and PAD (per SD increment; OR: 1.13; 95% CI: 1.06–1.19). Patients in the upper plasma Hcy tertile (≥16.16 μmol/L) were associated with a 53% increased risk of PAD compared with patients in the lower tertile (<12.33 μmol/L) after adjustment for multiple potential confounders. Subgroup analyses showed the association between Hcy and PAD was robust among various strata. Among Chinese adults with hypertension, plasma Hcy is an independent risk factor for PAD. This finding may improve the risk stratification of PAD.

Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety. To assess the liability of candidate drugs, we developed an artificial intelligence model for the precise prediction of compound off-target interactions, leveraging multi-task graph neural networks. The outcomes of off-target predictions can serve as representations for compounds, enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity. Furthermore, the predicted off-target profiles are employed in adverse drug reaction (ADR) enrichment analysis, facilitating the inference of potential ADRs for a drug. Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs.

AbstractRNAs play essential roles in diverse physiological and pathological processes by interacting with other molecules (RNA/protein/compound), and various computational methods are available for identifying these interactions. However, the encoding features provided by existing methods are limited and the existing tools does not offer an effective way to integrate the interacting partners. In this study, a task-specific encoding algorithm for RNAs and RNA-associated interactions was therefore developed. This new algorithm was unique in (a) realizing comprehensive RNA feature encoding by introducing a great many of novel features and (b) enabling task-specific integration of interacting partners using convolutional autoencoder-directed feature embedding. Compared with existing methods/tools, this novel algorithm demonstrated superior performances in diverse benchmark testing studies. This algorithm together with its source code could be readily accessed by all user at: https://idrblab.org/corain/ and https://github.com/idrblab/corain/.

Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase and selective inhibitors for fibroblast growth factor receptors demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape.

Chronic active Epstein-Barr virus infection (CAEBV) progresses rapidly in the later stage and has a poor prognosis. The treatments of CAEBV have no unified standard and a bad effect. Only few person could cure. It is important to diagnosis early. Metagenomic next-generation sequencing (mNGS) offers an effective means for the diagnosis of difficult, critical and rare pathogenic microbial infections. Here, we report a case of viral pleurisy caused by CAEBV identified by mNGS in an 88-year-old Chinese male patient.

A typical output of a metabolomic experiment is a peak table corresponding to the intensity of measured signals. Peak table processing, an essential procedure in metabolomics, is characterized by its study dependency and combinatorial diversity. While various methods and tools have been developed to facilitate metabolomic data processing, it is challenging to determine which processing workflow will give good performance for a specific metabolomic study. NOREVA, an out-of-the-box protocol, was therefore developed to meet this challenge. First, the peak table is subjected to many processing workflows that consist of three to five defined calculations in combinatorially determined sequences. Second, the results of each workflow are judged against objective performance criteria. Third, various benchmarks are analyzed to highlight the uniqueness of this newly developed protocol in (1) evaluating the processing performance based on multiple criteria, (2) optimizing data processing by scanning thousands of workflows, and (3) allowing data processing for time-course and multiclass metabolomics. This protocol is implemented in an R package for convenient accessibility and to protect users’ data privacy. Preliminary experience in R language would facilitate the usage of this protocol, and the execution time may vary from several minutes to a couple of hours depending on the size of the analyzed data.

Individual variations in drug efficacy, side effects and adverse drug reactions are still challenging that cannot be ignored in drug research and development. The aim of pharmacometabonomics is to better understand the pharmacokinetic properties of drugs and monitor the drug effects on specific metabolic pathways. Here, we systematically reviewed the recent technological advances in pharmacometabonomics for better understanding the pathophysiological mechanisms of diseases as well as the metabolic effects of drugs on bodies. First, the advantages and disadvantages of all mainstream analytical techniques were compared. Second, many data processing strategies including filtering, missing value imputation, quality control-based correction, transformation, normalization together with the methods implemented in each step were discussed. Third, various feature selection and feature extraction algorithms commonly applied in pharmacometabonomics were described. Finally, the databases that facilitate current pharmacometabonomics were collected and discussed. All in all, this review provided guidance for researchers engaged in pharmacometabonomics and metabolomics, and it would promote the wide application of metabolomics in drug research and personalized medicine.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a severe and rapidly evolving epidemic. Now, although a few drugs and vaccines have been proved for its treatment and prevention, little systematic comments are made to explain its susceptibility to humans. A few scattered studies used bioinformatics methods to explore the role of microRNA (miRNA) in COVID-19 infection. Combining these timely reports and previous studies about virus and miRNA, we comb through the available clues and seemingly make the perspective reasonable that the COVID-19 cleverly exploits the interplay between the small miRNA and other biomolecules to avoid being effectively recognized and attacked from host immune protection as well to deactivate functional genes that are crucial for immune system. In detail, SARS-CoV-2 can be regarded as a sponge to adsorb host immune-related miRNA, which forces host fall into dysfunction status of immune system. Besides, SARS-CoV-2 encodes its own miRNAs, which can enter host cell and are not perceived by the host’s immune system, subsequently targeting host function genes to cause illnesses. Therefore, this article presents a reasonable viewpoint that the miRNA-based interplays between the host and SARS-CoV-2 may be the primary cause that SARS-CoV-2 accesses and attacks the host cells.

Copeptin has been identified as a biomarker of disease severity and is associated with mortality risk in several common diseases. This study sought to determine the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. PubMed, Web of Science, and Wanfang Medicine Database were searched for studies assessing the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. The pooled hazard ratio (HR) of mortality was calculated and presented with 95 % confidence interval (95 % CI). Data from 1332 intracerebral hemorrhage patients were derived from 9 studies. Meta-analysis showed that intracerebral hemorrhage patients with poor prognosis had much higher copeptin levels than those survivors (standardized mean difference = 1.68, 95 % CI 1.26–2.11, P < 0.00001). Meta-analysis of 8 studies with HRs showed that high circulating copeptin level was associated with higher risk of mortality in patients with intracerebral hemorrhage (HR = 2.42, 95 % CI 1.60–3.65, P < 0.0001). Meta-analysis of 6 studies with adjusted HRs showed that high circulating copeptin level was independently associated with higher risk of mortality in patients with intracerebral hemorrhage (HR = 1.67, 95 % CI 1.26–2.22, P = 0.0003). Our study suggests that there is an obvious association between circulating copeptin level and mortality in patients with intracerebral hemorrhage. High circulating copeptin level is independently associated with higher risk of mortality in patients with intracerebral hemorrhage.

近一个世纪以来，抗菌药物在人类战胜各种感染性疾病的过程中发挥了关键作用，但日益突出的多重耐药菌问题已给临床抗感染治疗带来了严峻挑战。如何有效减缓多重耐药菌的产生，阻断多重耐药菌传播，已引起医学界、政府与社会的广泛关注。为加强多重耐药菌的医院感染管理，有效预防和控制多重耐药菌在医院内的产生和传播，保障患者的安全，由中国感染控制杂志组织，58位国内知名专家共同发起，邀请全国165位专家参与，历时10个月，召开了9场专题讨论会，在充分收集意见和讨论的基础上，最终形成了《多重耐药菌医院感染预防与控制中国专家共识》。共识荟萃了国内外多重耐药菌医院感染防控的最新进展，总结了我国大多数权威专家防控方面的宝贵经验，旨在规范和指导我国多重耐药菌医院感染的防控，提高我国多重耐药菌感染防控水平。

Objective To investigate the effect of quercetin on proliferation and apoptosis of human lung cancer cellline A- 549 in vitro. Methods The cultured A- 549 cells were treated with different concentrations of quercetin, and cellproliferation and apoptosis were detected by MTT and flow cytometry, respectively. The morphological changes of the apoptotic cells were observed by invert microscopy, transmission electron microscopy and Heochst33258 fluorescence staining. The expression of survivin was analyzed by Western blot. Results After treatment of quercetin for 24 h the proliferation of A- 549 cells was inhibited in a dose- dependent manner, and cells were arrested at the G2/M phase. The apoptosis rates of quercetin treatment groups (15, 30, 60μmol/L) were(7.24±1.73)%, (12.57±2.72)%and (26.02±1.67)%, respectively, significantly higher than that of control group [(2.67±2.32)%, P<0.01]. Apoptosis or necrosis of A- 549 cells were morphological y observed after quercetin treatment for 24h. The expression of survivin protein in quercetin- treated A- 549 cells was decreased in a dose- dependent manner. Conclusion Quercetin can inhibit proliferation and induce apoptosis of human lung cancer A- 549 cells, which is associated with cellcycle ar-rest and down- regulation of survivin expression.

INTRODUCTION:Curcumin has remarkable anti-inflammatory and antioxidant properties. However, its effects on bacterium-induced acute lung injury (ALI) are not fully understood.OBJECTIVE:To investigate the protective effects of curcumin on a mouse model of S. aureus-induced ALI.METHODS:Mice were pretreated with intraperitoneal injection of curcumin or vehicle 2 h before Staphylococcus aureus instillation. The survival rate and bacterial burden after infection were recorded. Mice were sacrificed for the analyses of severity of pneumonia, integrity of lung barrier, disorder of coagulation cascades and extent of inflammation 12 h postinfection. The production of proinflammatory cytokines and chemokines in the lung and bronchoalveolar lavage fluid was detected.RESULTS:Pretreatment with curcumin markedly attenuated S. aureus-induced pneumonia, barrier disruption, lung edema and vascular leakage. Activation of plasminogen activator inhibitor-1 and infiltration of neutrophils were reduced by curcumin, together with lower levels of proinflammatory cytokines and chemokines.CONCLUSION:Curcumin can alleviate S. aureus-induced ALI through multiple pathways.

Human infection with avian influenza A H7N9 virus has emerged in China with high morbidity rates. Patients usually present with severe and rapidly progressive pneumonia. Therefore, radiological findings are important to diagnose and evaluate disease severity. The clinical characteristics of three new cases of H7N9 virus infection were analyzed, especially the radiological findings, and previously published studies regarding H7N9 virus infection were summarized. Ground-glass opacification and areas of consolidation were the most common image features. Although drug resistance has been found in some H7N9 viruses, oseltamivir administration is still recommended as soon as possible. Moreover, timely epidemiological surveillance is needed, and a new vaccine is expected for the management of avian influenza.

目的观察利福平、异烟肼在肺结核合并糖尿病患者中的血药浓度,同时观察其疗效。方法收集肺结核合并糖尿病患者46例(观察组)及单纯肺结核患者53例(观察组)。两组患者均口服利福平0.45g,1次/d;异烟肼0.3 g,1次/d;同服乙胺丁醇和吡嗪酰胺。采用高效液相色谱法分别测定利福平和异烟肼的血药浓度,并复查痰涂片找抗酸杆菌及胸部X片。结果两组患者痰菌阴转率、病灶显著吸收率及利福平血清药物浓度低于治疗浓度比例差异均有统计学意义(均<0.05),但异烟肼血清药物浓度低于治疗浓度所占比例差异无统计学意义(>0.05)。结论肺结核合并糖尿病患者的抗结核治疗疗效较单纯肺结核要差,可能与利福平血清药物浓度低于正常治疗范围有关。

Objective To analyze the expression of four important molecules of CD4+CD25+ regulatory T cells(Tregs) in peripheral blood of chronic hepatitis B patients and asymptomatic HBV carriers,and to investigate their potential functions.Methods 50 patients with chronic hepatitis B(CHB),28 asymptomatic HBV carriers(ASC) and 24 healthy blood donators were enrolled in this study.Peripheral blood mononuclear cells(BMC) from CHB,ASC and healthy blood donators were isolated by Ficoll-Hypaque density gradient centrifugation.CD4+CD25+ Tregs were isolated by using CD4+CD25+ regulatory T cell isolation kit,and auto MACS separator(Miltenyi Biotec Inc.).Then their total RNA was extracted.After reverse transcription,we developed and evaluated a rapid and reliable real-time PCR approach using Applied Biosystems 7500 Real-Time PCR technology for validation of this partial results of hybridization.Results The results of real-time PCR demonstrated that the expression of ICAM-1,neuropilin-1 and TLR5 showed no significant difference in circulating CD4+CD25+ Tregs from different groups.ASC presented a lower expression of TLR8 of circulating CD4+CD25+ Tregs than those in CHB patients and normal controls(P<0.05),but there was no significant difference of TLR8 expression in circulating CD4+CD25+ Tregs between CHB and normal controls(P>0.05).Conclusion The results of real-time PCR demonstrated that there is difference of TLR8 expression in circulating CD4+CD25+ Tregs among different groups.TLR8 may play an important role in dominant immunological self-tolerance maintained by CD4+CD25+ Tregs after HBV infection.

国外文献报道:长期服用甲氨蝶呤与淋巴瘤存在一定关联[1].现报道1例. 临床资料:患者,女性,65岁,因咳嗽气急2个月,右胸痛6 d于2008年8月入院.既往有RA病史22年,11年前开始服用MTX 7.5 mg qw至今.

Methotrexate is effective in treating rheumatoid arthritis (RA). Some reports have discussed the possible association between methotrexate and lymphoma. Here, we report a case of pulmonary non-Hodgkin’s lymphoma (NHL) developed after 11 years’ methotrexate therapy for RA. Biopsy of the pulmonary mass demonstrated a diffuse large B-cell lymphoma. After withdrawal of methotrexate without any other intervention for 4 weeks, a significant reduction in the size of the lymphoma was observed. The causative relationship between methotrexate and pulmonary lymphoma is suggested by the persistent remission after stopping methotrexate therapy.

This paper introduces the design and development of a teleimaging diagnosis system by using B/S mode. A detailed design on the telediagnosis process and telediagnosis management is presented, focusing on resolving medical image transmission, management and display in the internet, and is trying to integrate the teleimaging diagnosis system with PACS.

Statins are HMG-CoA reductase inhibitors that have been used for many years in the treatment of hypercholesterolemia.Statins,however,have additional pleiotropic pharmacologic properties,including anti-inflammatory,antioxidant,antithrombogenic,and vascular function-restoring actions.The effects of statins on prevention and treatment for chronic obstructive plumonary diseases have been supported by the animal experiment and clinic research.