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Xiuying Li,1 Xin Wang,1 Xiuwu Qu,1 Ningning Shi,1 Qinqing Li,1 Zhifang Yan,1 Yandong Li,2 Yingli Wang3 1Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of China; 2Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China; 3Shanxi Modern Traditional Chinese Medicine Engineering Laboratory, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of ChinaCorrespondence: Yandong Li; Yingli Wang, Email liyandongzhongnan@163.com; wyl@sxtcm.edu.cnPurpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients.Methods: Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed.Results: The developed micelles had a particle size of (89.62 ± 1.33) nm and a zeta potential of (− 4.9 ± 0.53) mV. The IC50 value of PVGLIG-MTX-Que-Ms (185.90 ± 6.98) μmol/L was significantly lower than that of free Que (141.10 ± 6.39) μmol/L. The synthesized micelles exhibited slow-release properties, low cytotoxicity, strong targeting abilities, and significant anti-inflammatory effects in vitro. In vivo, the drug-loaded micelles accumulated at the joint site for a long time. PVGLIG-MTX-Que-Ms significantly reduced joint swelling, improved bone destruction, and decreased the expression of serum inflammatory factors in CIA rats.Conclusion: The smart-targeting micelles PVGLIG-MTX-Que-Ms with strong targeting, anti-inflammatory, cartilage-protective, and other multiple positive effects are a promising new tool for RA treatment.Keywords: matrix metalloproteinases, quercetin, macrophages, methotrexate, anti-inflammatory

Jia-Guang Song,1,2,* Zi-Xin Yang,2,* Na Shi,3 Mei Zhu2 1Department of Ultrasound, Shandong Provincial Hospital, Shandong University, Jinan, 250021, People’s Republic of China; 2Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 3Department of Ultrasound, Linyi Mental Health Center, Linyi, 276001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mei Zhu, Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +86 15653101616, Fax +86 53168778113, Email zhumei75@126.comAbstract: Mycotic pseudoaneurysm of the ascending aorta is extremely uncommon, particularly in children with no prior cardiac surgery or trauma. We report a rare case of a mycotic pseudoaneurysm of the ascending aorta in a 2-year-old girl with no history of cardiac surgery. Investigations revealed a methicillin-resistant Staphylococcus aureus infection and significant pericardial effusion in the child who presented with persistent fever and altered mental state. Cardiac ultrasound revealed a disruption in the aortic wall and a tumor-like structure. Contrast-enhanced computed tomography confirmed an ascending aortic pseudoaneurysm with thrombus. The child underwent successful surgical treatment without implants. This case emphasizes the diagnostic significance of imaging, particularly the advantages of ultrasound in pediatric settings, and the need for timely and accurate diagnosis using appropriate imaging modalities in children.Keywords: aorta, mycotic, pseudoaneurysm

Zhe-Feng Zhao,1,* Bing-Bing Liu,1,* Jian-Nan Zhang,2,* Ni Shi,3,* Ping Zhang,1,* Gang-Zhi Yang,4 Yu-Fu Cao,4 Long-He Tian,4 Cheng-Cai Qiu,5 Yang Gao6,7 1Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 4Department of Neurosurgery, People’s Hospital of Hegang City, Hegang, Heilongjiang, People’s Republic of China; 5Department of Neurosurgery, Traditional Chinese Medicine Hospital of Jixi City, Jixi, Heilongjiang, People’s Republic of China; 6Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 7Institute of Critical Care Medicine, The Sino Russian Medical Research Center of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhe-Feng Zhao, Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email know810512@163.com Yang Gao, Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email gaoyang0312@126.comObjective: In this study, we aimed to explore the demographic and clinical factors that could determine short- and long-term complete pain relief (CPR) in adult patients with primary trigeminal neuralgia (PTN) after microvascular decompression (MVD) to guide clinical practice.Methods: This single-center retrospective study included adult patients with PTN who underwent MVD as their initial neurosurgical procedure in the Department of Neurosurgery at the Second Affiliated Hospital of Harbin Medical University from January 2017 to December 2019 and completed a 3-year post-surgery follow-up. Demographic and clinical information was obtained from medical records. Pain relief of adult patients with PTN at various time points after sufficient decompression of trigeminal nerve (TN) during MVD was determined and classified by the patient’s subjective response and medications use. Pain relief of local patients was evaluated by outpatient follow-up at various time points, whereas that of local cases who could not return to outpatient or non-local cases was assessed through telephone or WeChat.Results: In univariate analysis, compression degree of TN and type of conflicting vessels constantly showed significant differences between the two groups at 3 months, 6 months, 1 year, 2 years, and 3 years after MVD. Compression degree of TN and type of conflicting vessels at various time points after MVD were always the related factors to CPR in logistic regression analysis, with the former having the greatest impact. The areas under the receiver operating characteristic (ROC) curve of CPR at various time points after MVD were 0.937, 0.874, 0.879, 0.864, and 0.869, respectively.Conclusion: In summary, compression degree of TN and type of conflicting vessels can determine short- and long-term CPR in adult patients with PTN after MVD.Keywords: compression degree of trigeminal nerve, type of conflicting vessels, microvascular decompression, sufficient decompression of trigeminal nerve, complete pain relief, primary trigeminal neuralgia

Shuyun Wang,1 Yan Song,1 Nan Shi,1,2 Donghong Yin,1 Jianbang Kang,1 Wanni Cai,2 Jinju Duan1 1Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Jinju Duan, Department of Pharmacy, Second Hospital of Shanxi Medical University, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People’s Republic of China, Tel +86 13834653172, Email duanjinju@163.comPurpose: The aim of this study was to investigate the current epidemiology, its changes during the study years, and inflammatory biomarkers of bacterial bloodstream infections (BSIs) in neutropenic patients with hematological malignancies. We assessed mortality risk factors and multidrug-resistant (MDR) gram-negative BSI predictors.Patients and Methods: We conducted a retrospective study from January 2015 to December 2021, which included adult neutropenic oncohematological patients with confirmed BSIs. We used univariable and multivariable analyses to analyze the risk factors. Each index’s reliability for bacterial BSI diagnosis was assessed using the receiver-operating characteristic curve and area under the curve.Results: A total of 514 isolates were obtained from the 452 patients. The average mortality was 17.71%. Gram-negative organisms were the predominant causes of BSI. Escherichia coli was the most common microorganism (49.90%). The overall variation trend of the isolation rate of MDR and carbapenem-resistant gram-negative bacteria increased. Multivariate analysis indicated that: 1) neutropenia that lasted for more than 7 days, patients ≥ 60 years of age, septic shock, hospitalization for > 20 days, BSI with a carbapenem-resistant strain, and treatment with linezolid or vancomycin in infections lasting less than 30 days were independent mortality risk factors; 2) severe neutropenia exceeding 7 days, unreasonable empirical therapy, and receipt of aminoglycosides or 3rd or 4th generation cephalosporins in infections lasting less than 30 days were independent risk factors of MDR gram-negative bacteria. Procalcitonin, absolute neutrophil count, and white blood cell indicate higher diagnostic accuracy for BSIs. Moreover, bacteria time to detection was better at differentiating Gram-negative and Gram-positive bacterial infections.Conclusion: We analyzed the risk factors for BSI neutropenic patients with hematological malignancies, the distribution of bacteria, antibiotic resistance, and the changes in clinical parameters. This single-center retrospective study may provide clinicians with novel insights into the diagnosis and treatment of BSI to improve future clinical outcomes.Keywords: bloodstream infection, neutropenia, hematological malignancy, pathogens distribution, antibiotic susceptibility, risk factors

Nan Shi,1,2,&ast; Jianbang Kang,2,&ast; Shuyun Wang,2 Yan Song,2 Donghong Yin,2 Xiaoxia Li,2 Qian Guo,2 Jinju Duan,2 Shuqiu Zhang1 1Department of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinju Duan; Shuqiu Zhang, Email duanjinju@163.com; shuqiu.zhang@126.com; shuqiu.zhang@sxmu.edu.cnObjective: The aim of this study was to analyze the epidemiological of gram-negative bloodstream infection (GNBSI) and establish a risk prediction model for mortality and acquiring multidrug resistant (MDR), the extended spectrum beta-lactamases (ESBLs) producing and carbapenem-resistant (CR) GNBSI.Methods: This retrospective study covered five years from January 2015 to December 2019. Data were obtained from Hospital Information System (HIS) and microbiology department records. The risk factors for mortality and acquiring MDR, ESBLs-producing and CR GNBSI were analyzed by univariable and multivariable analysis.Results: A total of 1018 GNBSI cases were collected. A majority of GNBSI patients were in hematology ward (23.77%). There were 38.61% patients who were assigned in the 41– 60 age group. Escherichia coli was the most common gram-negative organism (49.90%). Among isolates of GNBSI, 40.47% were found to be MDR strains, 34.09% were found to be ESBLs-producing strains and 7.06% were found to be CR strains. Escherichia coli was the most common MDR (71.36%) and ESBLs-producing strain (77.81%). Acinetobacter baumannii was the most common CR isolate (46.15%). Multivariate analysis indicated that diabetes mellitus, solid organ tumor, non-fermentative bacteria, MDR strain, central venous cannula, urinary catheter, therapy with carbapenems or tigecycline prior 30 days of infection were independent mortality risk factors for GNBSIs. Over all, therapy with tigecycline prior 30 days of infection was the mutual predictor for mortality of GNBSI, acquiring MDR, ESBLs-producing and CR GNBSI (OR, 8.221, OR, 3.963, OR, 3.588, OR, 9.222, respectively, all p < 0.001).Conclusion: Collectively, our study implies that patients who were diagnosed as GNBSI had a younger age. Therapy with tigecycline was the mutual and paramount predictor for mortality of GNBSI, acquiring MDR, ESBLs-producing and CR GNBSI. Our investigation had provided a theoretical basis for the use of antibiotics and prevention and control of hospital infection in our region.Keywords: gram-negative bloodstream infection, epidemiology, risk prediction model, MDR, ESBL, carbapenem resistance

Xinyuan Feng,1,* Zhiqi Zhang,2,* Xiaoxia Li,3 Yan Song,3 Jianbang Kang,3 Donghong Yin,3 Yating Gao,3 Nan Shi,1 Jinju Duan3 1Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pharmacy, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China *These authors contributed equally to this work Purpose: To investigate the main molecular resistance mechanisms to fluoroquinolones (FQs) in Pseudomonas aeruginosa and also to investigate the effect of time and concentration on mutations in resistance genes.Materials and methods: The clinical isolates of P. aeruginosa which are sensitive to ciprofloxacin (CIP) or levofloxacin (LEV) were collected. The isolates were incubated with different concentrations of CIP or LEV for 5 days and the minimal inhibitory concentrations (MICs) of CIP, LEV and ofloxacin (OFX) were measured. The MIC of FQs to P. aeruginosa was measured by the agar dilution method. FQ resistance determining regions of gyrA, gyrB, parC and parE were amplified by PCR, and mutations in four genes were explored using sequence analysis with the Snapgene software. The relative expression levels of two efflux pumps genes (mexA and mexE) were measured by quantitative reverse transcription PCR.Results: A total of eleven isolates were collected from the Second Hospital of Shanxi Medical University. Amino acid alterations in gyrA and gyrB were mainly detected in resistant mutants, and the percentage of strains with amino acid alterations in gyrB was significantly higher than that in gyrA (P0.05). No amino acid alterations were detected in genes of parC and parE. In both gyrA and gyrB, the number of amino acid alterations increased with incubation time prolonged and increased with increasing incubation concentration.Conclusion: CIP was more competent than LEV in making P. aeruginosa resistant to in vitro selection. Mutations occurring in gyrB played an important role in FQ resistance of P. aeruginosa in vitro selection. Keywords: Pseudomonas aeruginosa, fluoroquinolones, molecular resistance mechanisms, in vitro

Objective: Middle ear myoclonic tinnitus (MEMT) is a disease caused by myoclonus or abnormal contractive movement of middle ear muscles (MEMs). This translational study was conducted to propose intratympanic botulinum toxin (IT‐BTX) injection as a new therapeutic modality to treat MEMT. Study Design: Animal experiment and nonrandomized controlled clinical trial. Setting: Laboratory and medical center of an academic tertiary medical institution. Methods: For the animal study, male Sprague‐Dawley rats were divided into 4 subgroups according to the sacrificing day after IT‐BTX injection. After initial hearing tests, randomly assigned experimental ears were intratympanically injected with 1 unit/100 μL of BTX‐A, whereas control ears were injected with normal saline. Changes in the hearing thresholds, morphometry of the cochleae, electron microscopy study, and immunofluorescence analysis of MEMs were evaluated. For the human study, 10 intractable MEMT patients were enrolled. The hearing thresholds and the degree of tinnitus distress were observed for changes after IT‐BTX injection. All patients were followed up for 3 months. Results: As for the animal study, there were no significant changes in hearing thresholds and cochlear morphologies in all 4 subgroups of the rats. Significant MEM degenerations and immuno‐detection of cleaved synaptosome‐associated protein of 25 kDa (cSNAP‐25) indicated the efficacy of IT‐BTX. MEMT patients enrolled for the pilot clinical trial showed statistically significant improvement in tinnitus after IT‐BTX injection. No major complications were noted. Conclusion: The new therapeutic modality of IT‐BTX injection for the treatment of MEMT seems highly promising with an excellent result. [ABSTRACT FROM AUTHOR]

We have developed an innovative workflow, Stability, Transport, Equilibrium, and Pedestal (STEP)-zero-dimensional (0D), within the OMFIT integrated modeling framework. Through systematic validation against the International Tokamak Physics Activity global H-mode confinement database, we demonstrated that STEP-0D, on average, predicts the energy confinement time with a mean relative error of less than 19%. Moreover, this workflow showed promising potential in predicting plasmas for proposed fusion reactors such as the affordable, robust, compact (ARC) reactor, the European demonstration power plant (EU-DEMO), and the China fusion engineering test reactor (CFETR) indicating moderate H-factors between 0.9 and 1.2. STEP-0D allows theory-based prediction of tokamak scenarios, beginning with 0D quantities. The workflow initiates with the PRO-create module, generating physically consistent plasma profiles and equilibrium using the same 0D quantities as the IPB98(y,2) confinement scaling. This sets the starting point for the STEP module, which further iterates between theory-based physics models of equilibrium, core transport, and pedestal to yield a self-consistent solution. Given these attributes, STEP-0D not only improves the accuracy of predicting plasma performance but also provides a path toward a novel fusion power plant design workflow. When integrated with engineering and costing models within an optimization, this new approach could eliminate the iterative reconciliation between plasma models of varying fidelity. This potential for a more efficient design process underpins STEP-0D's significant contribution to future fusion power plant development. [ABSTRACT FROM AUTHOR]

A technique for remediating and protecting ground-water and drinking-water wells from contamination is presented. A ground-water remediation well design is proposed in which ground water is drawn into the well bottom, treated in the well casing, and returned clean to the aquifer at the well top. The hydraulics of ground-water circulation around imperfectly penetrating wells were examined experimentally in pilot-scale tanks and mathematically with numerical models in a two-dimensional domain. Ambient ground-water velocities of from 1 to 3 m/day, typical for coarse sand and gravel aquifers, were simulated in combination with in-well vertical velocities of from 2 to 16 m/day. Under some of these flow conditions, contaminants were intercepted and drawn into the wells for treatment. Hydraulic problems identified with the experimental apparatus and simulated by the computer models included blow through of contaminant at the well intake by high ambient ground-water velocities and submergence by the well hydraulics of surface contaminant plumes without interception. Both types of problems were corrected by adjusting internal well velocities. Important design parameters include ambient ground-water velocity and well pumping rate.

Aims: To extract and identify the metabolites of strain A217 as well as its antifungal spectrum and control effect on various plant pathogens. Methods and Results: Strain A217 was identified as a Streptomyces sp. which was most similar to Streptomyces lienomycini. An antimicrobial spectrum test indicated that strain A217 inhibited several plant pathogenic fungi and strong antibacterial effect such as Phytophthora capsici, Botrytis cinerea, Sclerotinia sclerotiorum, Fusarium oxysporum, Pseudomonas syringae and Xanthomonas campestris. An in vivo tissue test demonstrated that the fermentation broth of strain A217 exerted therapeutic and protective effects of 49·47 and 61·60% respectively, on S. sclerotiorum. Additionally, the fermentation broth of A217 exerted control effects on walnut black spot disease in walnut leaves and branches amounting to 79·33 and 81·52% respectively. In a pot experiment, the fermentation broth exhibited a stronger protective and control effect (68·29%), as well as better bacteriostatic and disease control effects on Phytophthora blight of pepper, compared with Metalaxyl. Compounds possessing antifungal and antibacterial activities were obtained from the fermentation broth of strain A217, using column chromatography and HPLC. Chemical and structural analyses conducted using MS and nuclear magnetic resonance confirmed that these compounds were 1H‐pyrrole‐2‐carboxylic acid and 1H‐pyrrole‐2‐carboxamide. The EC50 values of compound 1H‐pyrrole‐2‐carboxylic acid1 for S. sclerotiorum and P. capsici were 20·13 and 50·36 μg ml−1 respectively. Compound 1H‐pyrrole‐2‐carboxamide2 showed significant antibacterial activity against different plant pathogenic bacteria. The MIC values of P. syringae, X. campestris and X. campestris pv. jugiandis were 7·5, 30 and 15·0 μg ml−1 respectively. Conclusions: Actinomyces A217 fermentation products have a broad spectrum of bacteriostasis, and have good bacteriostasis activity to many plant pathogenic fungi and bacteria. Significance and Impact of the Study: The present study revealed a new antimicrobial producing strain of Streptomyces and its potential application as a biological control agent for plant diseases. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) patients experience a premature and more severe presentation of coronary artery disease. The underlying mechanisms of accelerated coronary artery disease in SLE patients remain to be elucidated. Methods: By using atherosclerosis combining a SLE murine model, we proved that the onset of SLE aggravates atherosclerosis. Although the onset of SLE reduced blood lipids slightly, immune deviation contributed to aggravated atherosclerosis in lupus mice. Lupus atheroma were characterized by inflammatory cell infiltration, such as gathered dendritic cells, macrophages, and IgG deposition. Results: Decreased lymphocytes and magnified dendritic cells in the spleen were also observed in lupus mice. Hydroxychloroquine prevented atherosclerosis progression mainly by reversing immune status abnormality caused by SLE. Serum interferon alfa levels were not changed in lupus mice. Conclusion: These findings strongly suggested that anti-inflammatory therapies and hydroxychloroquine provide a new possible strategy for treating SLE patients with atherosclerosis. [ABSTRACT FROM AUTHOR]