INTRODUCTION:Human oncostatin M (OSM) is a pleiotropic cytokine that regulates inflammatory and immune responses by binding to the heterodimer receptor complex OSM receptor beta (OSMRβ) and glycoprotein 130 (gp130). The distinct signaling pathways triggered by OSM are involved in multiple chronic inflammatory conditions, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and cancers, making the OSM-bound receptor complex a significant therapeutic target. Currently, no 3D structure of human OSM recognition complex is available, and thus, the molecular mechanisms underlying OSM signaling remain poorly understood. METHODS:In this study, for the first time, we proposed a full-length structural model of the human OSM-OSMRβ-gp130, generated using AlphaFold2 protein structure prediction and all-atom molecular dynamics (MD) simulation (~ 1.12 million atoms with explicit solvent), enabling investigation of the geometric and dynamic profiles of OSM- OSMRβ-gp130 structure at atomic-level. RESULTS:Analysis of the simulation trajectory demonstrated that the structural rearrangements of the heterodimer receptors (i.e., OSMRβ and gp130) initiated by OSM binding mediated the signal transduction from the extracellular to the intracellular domains. In the representative conformation identified through clustering analysis, two main allosteric pathways contributed were found to mediate signal transduction from the allosteric region of OSM to the active sites of OSMRβ and gp130. Finally, two druggable binding sites located on OSM and gp130 were detected by dynamically monitoring pocket flexibility throughout the simulation. A comprehensive analysis of the OSM-OSMRβ-gp130 model was carried out with respect to OSM signaling. CONCLUSION:The findings of this study not only enhance the mechanistic understanding of OSM binding to the heteromeric OSMRβ/gp130 but also identify druggable binding sites for structure-based design of small molecules to inhibit the intracellular signal transduction.

IntroductionThe growing global threat of multidrug-resistant Acinetobacter baumannii (MDR-AB) infections highlights an urgent need for novel and effective therapeutic strategies. Phage therapy has emerged as a promising alternative to conventional antibiotics. This study aimed to isolate and comprehensively characterize a novel lytic bacteriophage (phage), designated AbpL, and evaluate its therapeutic potential against MDR-AB.MethodsAbpL was isolated from sewage samples and characterized in terms of its morphology, growth characteristics, stability, and genome. Comparative genomic classification analysis was also conducted on it. In vitro efficacy was evaluated through time-kill assays and biofilm disruption experiments. To assess in vivo therapeutic potential, a murine model of lethal A. baumannii-induced sepsis was employed, with outcomes including survival rates, bacterial burden, serum levels of inflammatory cytokines, and histopathological evaluation.ResultsAbpL is classified as a member of the genus Friunavirus, subfamily Beijerinckvirinae, family Autoscriptoviridae, order Autographivirales, and class Caudoviricetes. It exhibited an icosahedral head and a short non-contractile tail, and demonstrated a short latent period, a high burst size, and strong stability across a broad range of environmental conditions. AbpL showed lytic activity against 52% of clinical MDR-AB isolates and effectively disrupted pre-existing biofilms. In the murine sepsis model, a single intraperitoneal administration (multiplicity of infection = 10) conferred 100% survival, significantly reduced bacterial loads in the liver and kidneys, and attenuated systemic inflammation compared to treatment with polymyxin B. Histopathological analyses further confirmed the protective effects of AbpL and its favorable safety profile.DiscussionOwing to its strong lytic activity, environmental stability, and robust in vitro and in vivo efficacy, AbpL represents a highly promising candidate for the treatment of MDR-AB infections. Furthermore, its unique 400-bp terminal redundancy may serve as a valuable platform for future engineering via synthetic biology approaches.

BackgroundVenous thromboembolism (VTE) prophylaxis frequently falls short of ideal standards in current clinical practice. Based on China’s policy-oriented quality evaluation indicators for VTE management, this study explored the role of pharmacists in VTE prophylaxis quality management and conducted preliminary verification among cardiothoracic surgery inpatients.MethodsWe retrospectively analyzed patients hospitalized in the cardiothoracic surgery department of our hospital between 1 January 2025 and 30 June 2025. The primary outcome measures included the implementation rates of pharmacological, mechanical, combined, and standardized prophylaxis. The secondary outcomes included the incidence of hospital-associated VTE, in-hospital major bleeding events, and the mortality attributable to hospital-associated VTE. Patients were categorized into the baseline group, pilot intervention group, and pharmacist intervention group based on the time series and the extent of pharmacist involvement. We compared the outcome measures for each group within both the original study cohort and the propensity score matching (PSM) cohort. We also performed stratified analyses by baseline VTE risk category (moderate vs. high risk) to assess potential effect modification.ResultsA total of 1813 patients were enrolled in this study, with a mean age of 62.1 ± 11.8 years. Among them, 1171 (64.6%) were identified as being at moderate or high risk of VTE. Progressive pharmacist intervention coincided with increases in the implementation of mechanical prophylaxis (54.6% vs. 74.2% vs. 79.7%, p < 0.001, Cramer’s V = 0.224, 95% CI [0.182, 0.266])) and standardized prophylaxis (57.1% vs. 74.8% vs. 77.8%, p < 0.001, Cramer’s V = 0.188, 95% CI [0.146, 0.228]) compared to the baseline period. Conversely, no statistically significant alterations were observed in the rates of pharmacological (43.9% vs. 45.7% vs. 49.1%, p = 0.351) and combined prophylaxis implementation (70.7% vs. 70.3% vs. 69.5%, p = 0.976). This finding was corroborated by the PSM cohort. The reduction in hospital-associated VTE were observed, though the analysis was based on very few events (9 vs. 1), which limits interpretability.ConclusionThe pharmacist-participated VTE management model was associated with improved implementation rates of mechanical and standardized prophylaxis, generating hypotheses about its potential utility in optimizing quality control for in-hospital VTE prevention and management, which remain to be validated through concurrent controlled trials.

BACKGROUND:MicroRNAs (miRNAs) play a pivotal role in various physiological and pathological processes. In particular, miRNA-21 holds significant potential as a novel biomarker for the diagnosis of heart failure. The development of miRNA detection methods is rapidly advancing, with point-of-care testing (POCT) platforms garnering considerable attention. However, traditional methods are often hampered by their reliance on expensive instruments and complex procedures, limiting clinical applicability. Therefore, there is an urgent need to develop a simple, portable, sensitive, and rapid POCT platform for miRNA-21 detection. RESULTS:In this work, we proposed a portable POCT platform using a colorimetric biosensor specifically sensitive for miRNA-21. The platform utilized 3,3',5,5'-tetramethylbenzidine as the signaling molecule, and a Linear G-quadruplex loaded with Blocker Nanostructures (LGBN) generated by the RCA reaction as the probe. Furthermore, changes in primary color channels (R/G/B) of TMB for miRNA-21 detection were analyzed via smartphone-based digital image recognition. Under optimal conditions, the platform showed a linear detection range between 0.01 nM and 1 nM, with limits of detection of 8.3 pM (colorimetric methods) and 9.5 pM (digital image colorimetry). Moreover, the colorimetric biosensor exhibited excellent specificity and resistance to interference, successfully detecting miRNA-21 in serum samples from heart failure patients. SIGNIFICANCE:This detection method has an accuracy consistent with RT-qPCR results, providing a novel and practical approach with POCT for miRNA-21 detection.

Objective: We conducted a pharmacovigilance analysis of mesalazine-related adverse events (AEs) in the realworld using the America's FAERS and Japan's JADER databases. Methods: We extracted reports of mesalazine-associated AEs from FAERS and JADER spanning the first quarter of 2004 to the third quarter of 2024. In the disproportionality analysis, we applied the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma-Poisson shrinker (MGPS) algorithms for signal detection. The time to onset of AEs was assessed using Kaplan-Meier curves and the Weibull distribution test. Results: The analysis encompassed 40,265 AEs reports from FAERS and 4,330 from JADER. Mesalazine-related preferred terms (PTs) mapped to 27 System Organ Classes (SOCs) in FAERS and 25 SOCs in JADER. Gastrointestinal disorders emerged as the most frequently reported SOC in both databases. Three SOCs demonstrated significant signal strength across both datasets: (1) gastrointestinal disorders, (2) general disorders and administration site conditions, and (3) respiratory, thoracic, and mediastinal disorders. Common AEs including diarrhœa, pancreatitis, gastroenteritis, asmyopericarditis, proctitis ulcerative, and glutamate dehydrogenase level abnormal aligned with established drug labeling. Notably, novel pharmacovigilance signals were detected for organizing pneumonia (FAERS: n = 113, ROR = 35.21, 95%CI 29.21-42.46; JADER: n = 32, ROR = 7.90, 5.56-11.22) and eosinophilic pneumonia (FAERS: n = 77, ROR = 41.25, 32.87-51.76; JADER: n = 179, ROR = 57.69, 49.26-67.56), both requiring urgent clinical attention. AEs mainly occurred within 30 days (58.36%) with a median onset of 17 days, and the median onset time of female patients (12 days) was shorter than male patients (25 days). Conclusion: This pharmacovigilance study provides clinically significant evidence regarding safety-associated adverse events (AEs) of mesalazine in real-world settings. The detection of novel safety signals, particularly organizing pneumonia and eosinophilic pneumonia, highlights the necessity for enhanced post-marketing surveillance through longitudinal AE monitoring. Our findings contribute to the evolving safety profile of mesalazine and warrant further clinical investigations to validate their clinical relevance and establish causal relationships.

ObjectiveTo identify predictors of all-grade, grade ≥ 3, and onset time of immune-related adverse events (irAEs) in cancer patients undergoing immune checkpoint inhibitors (ICIs) therapy.MethodsThis retrospective analysis included cancer patients treated with ICIs at Chongqing Medical University Second Affiliated Hospital from 2018 to 2024. Logistic regression and Cox regression analyses were used to identify predictors of all-grade and grade ≥ 3 irAEs and the time of irAE onset.ResultsAmong the 3,795 patients analyzed, 1,101 (29.0%) developed all-grade irAEs, and 175 (4.6%) experienced grade ≥ 3 irAEs. Multivariate logistic regression revealed that female (OR = 1.37, p < 0.001), combination therapy (OR = 1.87, p < 0.001), pre-existing autoimmune diseases (AIDs) (OR = 5.15, p < 0.001), pre-existing cirrhosis (OR = 1.34, p = 0.001), antibiotic use during ICIs treatment (OR = 1.51, p < 0.001), and a higher baseline prognostic nutritional index (PNI) (OR = 1.23, p = 0.01) were significant predictors for the development of all-grade irAEs. The predictors for grade ≥ 3 irAEs included age ≥ 60 (OR = 1.49, p = 0.023) and pre-existing AIDs (OR = 2.09, p = 0.005), For the onset time, predictors included female (HR = 1.26, p = 0.001), combination therapy (HR = 1.80, p < 0.001), pre-existing AIDs (HR = 2.25, p < 0.001), and pre-existing infection (HR = 1.20, p = 0.008).ConclusionsFemales, combination therapy, pre-existing AIDs and cirrhosis, antibiotics, and a higher baseline PNI are associated with a higher risk of developing all-grade irAEs. Those aged ≥ 60 and with pre-existing AIDs face a higher risk of severe irAEs. Females, undergoing combination therapy, with pre-existing AIDs and infection generally experience a shorter time to irAEs onset. Multicentric prospective studies are warranted to validate these findings.

Objective: This study aimed to investigate the effects of polymyxin B (PMB) in combination with other antibiotics on delaying resistance in Klebsiella pneumoniae and to explore the mechanisms underlying PMB-induced resistance. Methods: In vitro continuous induction experiments were performed to observe changes in drug susceptibility with PMB alone vs. in combination. RNA-seq, quantitative reverse transcription PCR, and proteomic analyses were utilized to evaluate differential gene and protein expression between induced-resistant strains and those exhibiting delayed resistance. Then, gene knockout experiments were performed to validate the functional roles of relevant genes. Results: These findings indicated that PMB alone could induce resistance within 1–2 d, whereas the combination with amikacin (AMK) or tigecycline delayed the onset of resistance by 6 d. RNA-seq, quantitative reverse transcription PCR, and proteomic analyses revealed significant upregulation of nlpE, two-component systems, and AcrAB-TolC efflux pump-associated genes in PMB-induced resistant strains, whereas these genes were downregulated in the delayed resistant strains of PMB combined with AMK. Deletion and complementation experiments demonstrated that the expression levels of two-component systems and efflux pump-related genes were downregulated in nlpE knockout strains. Furthermore, PMB induction experiments revealed a significant upregulation of PmrA, PhoP, PhoQ, PagP, and AcrB proteins associated with cationic antimicrobial peptide pathways in the wild-type and nlpE complemented strains, whereas no differential change was observed in the nlpE knockout strain. Conclusions: nlpE contributes to PMB resistance by modulating the AcrAB-TolC efflux pump and the PhoP/Q and PmrA/B two-component systems. The combined use of PMB with AMK effectively delays the development of resistance in K. pneumoniae through the regulation of nlpE and its associated signalling pathways.

The laboratory standard MRSA strain WHO-2 and clinical isolate S1 were used to establish a pneumonia infection model. The results showed that methicillin increased the expression of Hla and PVL protein at subminimum inhibitory concentration, while artesunate decreased the secretion of Hla and PVL protein. Artesunate alone reduced hemolysin expression and reversed methicillin-induced increases in Hla and PVL proteins. In addition, the study found that the combination of artesunate and methicillin had the best therapeutic effect, with survival rates of 70 % and 40 % at seven days, respectively (corresponding to the WHO-2 and S1 strains). The combination treatment was able to reduce cell mortality, showing a 65 % and 46 % reduction in cell mortality, respectively. The study also found that the combination therapy decreased the expression of alpha-hemolysin and pantone valentin leukin in the culture medium and significantly reduced the activation of NF-kB. This is caused by a significant decrease in the expression of inflammatory factors.

Based on synthetic methodology-based library, a new class of tricyclic spiroindole derivatives as potent P-glycoprotein inhibitors with excellent tumor multidrug resistance reversal activity was discovered.

Excessive stress leads to disruptions of the central nervous system. Individuals' responses to stress and trauma differ from person to person. Some may develop various neuropsychiatric disorders, such as post-traumatic stress disorder, major depression, and anxiety disorders, while others may successfully adapt to the same stressful events. These two neural phenotypes are called susceptibility and resilience. Previous studies have suggested resilience/susceptibility as a complex, non-specific systemic response involving central and peripheral systems. Emerging research of mechanisms underlying resilience is mostly focussing on the physiological adaptation of specific brain circuits, neurovascular impairment of the blood-brain barrier, the role of innate and adaptive factors of the immune system, and the dysbiosis of gut microbiota. In accordance with the microbiota-gut-brain axis hypothesis, the gut microbiome directly influences the interface between the brain and the periphery to affect neuronal function. This review explored several up-to-date studies on the role of gut microbiota implicated in stressful events-related resilience/susceptibility. We mainly focus on the changes in behavior and neuroimaging characteristics, involved brain regions and circuits, the blood-brain barrier, the immune system, and epigenetic modifications, which contribute to stress-induced resilience and susceptibility. The perspective of the gut-brain axis could help to understand the mechanisms underlying resilience and the discovery of biomarkers may lead to new research directions and therapeutic interventions for stress-induced neuropsychiatric disorders.

目的 构建重庆市社区药学服务评价指标体系.方法 通过文献研究法、实地调研法和专家讨论法拟订社区药学服务评价指标,采用德尔菲法向41名相关专家进行两轮函询,确立评价指标体系,利用层次分析法确定最终评价指标权重.结果 第一轮、第二轮函询专家积极系数分别为97.62％和100.00％;专家意见变异系数分别为0.08～0.24和0.07～0.21,肯德尔和谐系数分别为0.142和0.130(P＜0.001);专家权威程度(Cr)为0.91;所有指标重要程度评分均数＞4.0,变异系数＜0.25.最终建立的评价指标体系包括3个一级指标(社区患者服务、社区医院服务、服务满意度,权重分别为0.524 7,0.333 8,0.141 6),13个二级指标(综合权重为0.011 0～0.2753,其中占比最高的为社区患者服务的用药情况),55个三级指标(综合权重为0.002 2～0.083 9,其中占比最高的为用药情况的用药依从性).结论 所构建的评价指标体系可用于初步评价重庆市社区药学服务.

BackgroudThe high or low inferior mesenteric artery (IMA) ligation in rectal cancer remains a great debate. This study retrospectively discussed the outcomes of the perioperative period, defecation and urinary function and long-term prognosis in rectal cancer patients with high or low IMA ligation.MethodsThis study enrolled 220 consecutive rectal cancer cases, including 134 with high IMA ligation and 86 with low ligation. A comparison between the two groups was made for anastomotic leakage, low anterior resection syndrome (LARS), international prostate symptom score (IPSS), 5-year disease-free survival (DFS) and 5-year overall survival (OS).ResultsLow-ligation group had a longer operative time, and larger intraoperative blood loss. No significant difference was noted in anastomotic leakage incidence. In multivariable analysis, the male gender and tumor located at the lower rectum were identified as risk factors for anastomotic leakage. No significant differences were observed between groups in their LARS and IPSS questionnaire responses. The high-ligation vs. the low-ligation 5-year OS and DFS were 78.3% vs. 82.4% and 72.4% vs. 76.6%, respectively, which were not statistically different.ConclusionThe ligation level of the IMA had no significant effect on the anastomotic leakage incidence, defecation, urinary function, and long-term prognosis.

《医疗机构制剂管理标准》规范了医疗机构制剂管理工作中的基本条件、生产过程、质量管理与持续改进等要素.该标准内容借鉴《药品生产质量管理规范》(GMP)要求,兼顾各级各类医疗机构,覆盖医疗机构制剂管理的全流程.标准由中国医院协会药事专业委员会牵头编制,编制方法及流程包括问题梳理、框架建立、初稿撰写、意见征集、专家论证审议和标准形成等.该文阐述《医疗机构制剂管理标准》制订过程,并对该标准内容进行解析,以期为医疗机构制剂管理标准化、同质化提供指导.

Small molecule inhibitors (SMIs) targeting oncostatin M (OSM) signaling pathway represent new therapeutics to combat cancer, inflammatory bowel disease (IBD) and CNS disease. Recently, the first-in-class SMI named SMI10B that target OSM and block its interaction with receptor (OSMR) were reported. However, the binding pocket and interaction mode of the compound on OSM remain poorly understood, which hampering the rational design of SMIs that target OSM. Here, using SMI-10B as a probe, the multiple pockets on OSM for small molecules binding were extensively explored by unbiased molecular dynamics (MD) simulations. Then, the near-native structure of the complex was identified by molecular mechanics generalized Born surface area (MM/GBSA) binding energy funnel. Moreover, the binding stabilities of the protein-ligand complexes in near- and non-native conformations were verified by additional independent MD runs and absolute free energy perturbation (FEP) calculation. In summary, the unique feature of SMI-10B spontaneously binds to OSM characterized here not only provide detailed information for understanding the molecular mechanism of SMI-10B binding to OSM, but also will facilitate the rational design of novel and more potent SMIs to block OSM signaling.

随着抗生素的大量使用,肺炎克雷伯菌呈现出多药耐药性趋势,尤其是耐碳青霉烯类肺炎克雷伯菌的出现,意味着可用于治疗肺炎克雷伯菌感染的抗生素越来越少.多黏菌素以其独特的抗菌机制已成为治疗耐碳青霉烯类肺炎克雷伯菌感染的最后一道防线,但随着其使用增加,国内外肺炎克雷伯菌耐药株的报道也呈上升趋势,严重危害着患者的生命安全.笔者就肺炎克雷伯菌对多黏菌素的耐药机制进行总结,发现肺炎克雷伯菌对多黏菌素的耐药机制主要包括细菌外膜脂多糖的结构修饰、荚膜多糖的过表达、多药外排泵的过表达等,可为该药的合理使用及耐药肺炎克雷伯菌的防治提供依据.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a serious threat to health, and the detection rate in intensive care units (ICUs) is relatively high. We compared regional differences in the clinical and molecular characteristics of CRKP from three ICUs in different hospitals, to make a reference and contribution for infection control and clinical medication. Methods: A total of 150 CRKP strains from Chongqing, Beijing, and Nantong, as well as the clinical data of the infected patients, were collected between 2019 and 2021. The carbapenemase phenotype was determined by CarbaNP test, and the outer membrane porin (OMP) genes (ompK35/ompK36), multi-locus sequence typing (MLST) and resistance genes were identified by polymerase chain reaction (PCR) amplification and sequencing. Results: Patients infected with CRKP were mainly elderly, with comorbidity, and had undergone invasive operation and multiple antibiotic therapy. All strains exhibited high-level resistance to most antibiotics except for polymyxin B and tigecycline. Among the CRKP strains, 100 had the blaKPC-2 gene and 8 had bla(NDM-1) gene, which were distributed in all of the hospitals. Nearly all the strains harbored extended-spectrum beta-lactamase (ESBL) genes (bla(SHV), bla(CTX-M), and bla(TEM)). Class C carbapenemase genes (bla(CIT), bla(DHA)), and deletion and mutation of ompK35/ompK36 existed in some strains. ST11 was the main MLST type, followed by ST15. Conclusions: There were a few significant differences in the molecular epidemiology and clinical characteristics, but generally the features of CRKP from the three ICUs aligned fairly well, which might have resulted from dissemination through frequent personnel exchanges between regions.

Objective To investigate the use of anticoagulant drugs in hospitalized patients with nonvalvular atrial fibrillation (NVAF), and to explore the relevant factors that affect the efficacy of drug treatment in the patients. Methods A retrospective analysis was conducted on the NVAF inpatients admitted in our department from January 1, 2016 to December 31, 2019. Their clinical characteristics and usage of oral anticoagulants were collected and analyzed. According to the stratification of stroke risk, the patients with CHA2DS2-VASc score≥2 were selected to explore their use of anticoagulants. Logistic regression analysis was used to analyze the influencing factors of anticoagulation therapy. Results Among the 3 984 patients included, there were 2 438 (61.2%) anticoagulant patients, including 247 (39.0%), 316 (42.6%), 736 (65.3%), and 1 139 (76.9%) patients, respectively during the year of 2016 to 2019. The number of patients with CHA2DS2-VASc≥2 was 3 418, and 60.4% (2 065) of them took anticoagulants. Logistic regression analysis showed that age≥75 years (OR=0.494), vascular diseases (OR=0.838), acute coronary syndrome (ACS) (OR=0.583), history of percutaneous coronary intervention (PCI) (OR=0.651), bleeding history (OR=0.436), renal insufficiency (OR=0.625), drugs (OR=0.634), and before price reduction of new oral anticoagulants (NOAC) (OR=0.22) were influencing factors to reduce the rate of anticoagulation treatment (P < 0.05); While, atrial fibrillation ablation (OR=2.093) and stroke history (OR=1.351) were influencing factors to increase the treatment rate (P < 0.05). Conclusion Though the rate of anticoagulation treatment for NVAF patients is increasing year by year, but it is still lower than that in the European and American countries. Bleeding history, combined use of antiplatelet drugs, renal insufficiency, before NOAC price reduction, age ≥75 years, accompanied with vascular diseases, ACS, and post-PCI are influencing factors to reduce the rate, and atrial fibrillation ablation and stroke history are factors increasing the rate of anticoagulant treatment.

Pseudomonas aeruginosa (PA) is a common gram-negative bacterium. Imipenem (IMP) is considered to be the most effective clinical drug for the treatment of PA infection. IMP-resistant ceftazidime-susceptible PA is relatively rare in clinical practice; so far, there have been no clinical reports regarding the treatment of IMP-resistant PA with piperacillin/tazobactam alone. This paper will report the case of a severe pneumonia patient with IMP-resistant ceftazidime-susceptible PA infection that was successfully treated with piperacillin/tazobactam monotherapy after initial therapy with biapenem (BIP) according to the drug sensitivity test. The patient was a 75-year-old female, her main symptom was drowsiness. She was admitted to hospital due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and pulmonary encephalopathy. After admission, endotracheal intubation was performed immediately, and the lavage fluid was sent to the laboratory for sputum culturing for several times. BIP was selected for the initial anti-infection regimen, and other symptomatic treatments were performed at the same time. On the day 8, the sputum culture drug sensitivity test results showed PA (sensitive to: piperacillin/tazobactam sodium, ceftazidime, aminoglycoside, and fluoroquinolones; resistant to IMP; and intermediate sensitivity to: cefoperazone-sulbactam and meropenem), so we adjusted the anti-infection regimen as piperacillin/tazobactam sodium. After that, the infection index of the patient declined steadily, and the patient was discharged from hospital after continuous treatment with piperacillin tazobactam until the 24th day. For severe pneumonia patients with IMP-resistant ceftazidime-susceptible PA infection, piperacillin/tazobactam is still an option specially when the MIC of piperacillin/tazobactam is very low.

Background Atherosclerosis is the main cause of many cardiovascular diseases and the second leading cause of death in elderly people. The formation of intimal macrophage-derived foam cells is a major feature of early atherosclerotic lesions. Little is known about the effects of artesunate (ART) on macrophage-derived foam cell formation. Methods Oil red O staining was employed to detect foam cell formation; colorimetric analysis was employed for cholesterol measurement; quantitative real time polymerase chain reaction (qRT-PCR) and western blot analysis were employed to assess messenger RNA (mRNA) and protein expression, respectively; enzyme-linked immunosorbent assay (ELISA) analyses were used to observe interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) release; and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to examine cell viability. Results It was revealed that ART attenuated oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation from THP-1-derived macrophages by decreasing cholesterol accumulation, and the effect might have occurred via enhanced cholesterol efflux. Additionally, ART decreased toll-like receptor 4 (TLR4) expression, increased adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) expression, and reduced the secretion of IL-6 and TNF-α. Conclusions This study showed that ART attenuated the ox-LDL-induced formation of foam cells from THP-1-derived macrophages by increasing ABCA1 and ABCG1 expression via inhibiting TLR4 expression and reducing TNF-α and IL-6 secretion from macrophages induced by ox-LDL, which ultimately decreased the accumulation of cholesterol. It is worthwhile further investigate ART as a potential drug for the treatment of atherosclerosis.