[Systemic disseminated nocardiosis in a patient with normal immune function: a case report].

Nocardiosis, characterized by poor prognosis and high mortality, is a local or systemic suppurative or granulomatous disease caused by Nocardia that is common in immunosuppressed individuals but rare in populations with normal immune function. This paper described one case of Nocardia gipuzkoensis disseminated infection in a patient with normal immune function by outlining the process of treatment, conducting literature review and by outlining the clinical characteristics, diagnostic criteria and standardized treatments of nocardia disease, in the hope of providing reference for subsequent treatment of rare Nocardia subspecies infections.

[Progress in preserved ratio impaired spirometry].

Preserved ratio impaired spirometry (PRISm) refers to the mode of a decrease in forced expiratory volume in 1 second (FEV1) while the FEV1/forced vital capacity (FVC) remains constant. PRISm was prevalent in the study population, but it is underreported in the current research. The cohort studies in European-American have found that the PRISm has a higher risk of developing chronic obstructive pulmonary disease (COPD), cardiovascular-related deaths and all-causes death than the normal lung function. PRISm may be one of the pre-COPD population, so early detection and prevention are crucial. In this review, we summarized the recent advances in the research of PRISm with the aim to increase understanding of PRISm, and to provide comprehensive evaluation and management for PRISm population.

[A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in adult patients with hematological disease during the period 2014-2018].

Objective: To investigate the distribution of pathogens and the antibiotic resistance profile of bloodstream infections in adult patients with hematological diseases in the period 2014-2018 to provide evidence for the rational use of antibiotics. Methods: We retrospectively analyzed the bloodstream infections in patients with hematological diseases from January 2014 to December 2018 at the institute of Hematology & Blood Diseases Hospital; this included an assessment of the clinical characteristics, distribution of pathogens, and antibiotic resistance data. Results: There were 1935 episodes of BSIs in the 1478 patients who were studied; among these, 1700 episodes occurred in the neutropenic phase. The 7-day and 30-day all-cause mortality rates were 5.5% and 8.2%, respectively. Bloodstream infection was usually accompanied by respiratory tract, perianal zone mucositis, and digestive tract symptoms; the respective proportions were 12.4%, 12.3%, and 9.1%, respectively. Total 2025 strains were isolated; 1551 (76.6%) of the pathogens were gram-negative bacteria, mainly Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa; 423 (20.9%) were gram-positive bacteria, mainly Staphylococcus spp. and Streptococcus spp. Viridans; 51 (2.5%) were fungi, mainly Candida tropicalis. The resistance rates of Enterobateriaceae to piperacillin/tazobactam, carbapenems, amikacin were <10%. The resistance rates of K. pneumoniae to cefepime, piperacillin/tazobactam and meropenem increased annually. The resistance rates of Pseudomonas aeruginosa to piperacillin/tazobactam, quinolones, Aminoglycosides were <5% even when compared to carbapenems. Eleven stains of methicillin-resistant S. aureus and 1 stain of vancomycin-resistant Enterococcus faecium were detected. Conclusion: The pathogens of bloodstream infection in adult patients with hematological diseases are widely distributed. The resistance rates of different strains vary; the rates in some species had a tendency to increase. Antibiotics should be selected rationally as per the distribution of pathogens and resistance to antibiotics in different patient groups.

[Analysis of pathogens and clinical characteristics of bloodstream infection in neutropenic children with hematological malignancies from 2014 to 2018].

Objective: To investigate the microbiologic and clinical characteristics of bloodstream infection in neutropenic pediatric patients with hematological malignancies and provide data support for the rational use of antimicrobial agents in these patients. Methods: A retrospective analysis was performed on the clinical data, pathogen species distribution, and drug sensitivity data of bloodstream infection in neutropenic pediatric patients with hematological malignancies from the Institute of Hematology & Blood Diseases Hospital from January 2014 to December 2018. Results: Total 537 episodes of bloodstream infections occurred in 427 neutropenic children with hematological malignancies; the 30-day all-cause mortality rate was 3.7%. The clinical feature of 44.7% patients with bloodstream infection was only fever, and the pathogenic bacteria were mainly enterobacteriaceae bacteria. Bloodstream infection was usually accompanied by oral mucosa (20.7%) , respiratory tract (20.5%) , and digestive tract (14.3%) symptoms. The distribution of pathogens in patients with different symptoms of bloodstream infection varied (χ(2)=40.561, P=0.001) . Total 550 strains of pathogens were isolated, and the top 5 bacteria were Streptococcus aureus (109 strains, 19.8%) , Escherichia coli (99 strains, 18.0%) , Staphylococcus epidermidis (75 strains, 13.6%) , Klebsiella pneumoniae (67 strains, 12.2%) , and Staphylococcus aureus (32 strains, 5.8%) . The resistance rates of Enterobacteriaceae and Pseudomonas aeruginosa to piperacillin/tazobactam and carbapenems were <5%. The proportion of methicillin-resistant Staphylococcus aureus (MRSA) in Staphylococcus aureus was 9.7%. Conclusion: The proportion of pathogenic bacteria gram-positive cocci and gram-negative bacilli in the bloodstream infection of neutropenic children with hematological malignancies was approximately the same, suggesting that the use of antimicrobial agents should be broad-spectrum. Carbapenems, glycopeptides, and enzyme inhibitor complexes still have good effects.

MicroRNA-544 inhibits inflammatory response and cell apoptosis after cerebral ischemia reperfusion by targeting IRAK4.

OBJECTIVE: Stroke remains the most common malignant cerebrovascular event in the world. The correlation between the expression of miR-544 and the degree of cerebral ischemia reperfusion (CIR) injury has not been well recognized in recent years. This study focuses on the effect of miR-544 on inflammation and apoptosis after CIR. PATIENTS AND METHODS: Plasma expression of miR-544 in ischemic stroke (IS) patients and healthy controls was determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The effects of miR-544 on cerebral infarction and neurological deficits were verified in vitro by tail vein injection of Ago-miR-544. Western blotting was utilized to examine protein expressions of key proteins involving in inflammation and apoptosis in mouse brain. Western blotting, immunofluorescence staining and luciferase assays were used to demonstrate whether miR-544 influences the expression of interleukin-1 receptor-associated kinase 4 (IRAK4), downstream inflammatory and apoptosis-related proteins. RESULTS: MiR-544 was found decreased in peripheral blood of IS patients compared with healthy controls. MiR-544 has been shown to relieve neurological deficits and reduce the volume of cerebral infarction in mice. Overexpression of miR-544 ameliorated the inflammation and apoptotic responses in brain tissue after ischemia reperfusion by down-regulating the expression of IRAK4, whereas the low expression was opposite in vivo and in vitro. CONCLUSIONS: We found that miR-544 may participate in controlling inflammation and apoptosis after ischemia-reperfusion by targeting IRAK4, providing possible diagnostic indicators and therapeutic targets for IS.

Correlations of neuronal apoptosis with expressions of c-Fos and c-Jun in rats with post-ischemic reconditioning damage.

OBJECTIVE: Transcription factors (c-Fos and c-Jun) have been considered to play roles in the initiation of programmed nerve cell death. However, the roles of c-Fos and c-Jun protein expressions in neuronal apoptosis of rats with post-ischemic reconditioning damage were not clarified. Therefore, the aim of this study was to investigate the correlations of protein expressions of c-Fos and c-Jun with neuronal apoptosis of rats with post-ischemic reconditioning damage. MATERIALS AND METHODS: Rat models of post-ischemic reconditioning were established firstly. Then, apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay, and the gene expression levels of apoptosis-related proteins [cytochrome c (Cyt c), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax)] were detected by reverse transcription-polymerase chain reaction (RT-PCR). Lastly, Western blotting was used to determine the protein expression levels of c-Fos and c-Jun, and the expressions of c-Fos and c-Jun in brain tissues of models were measured by immunohistochemistry. RESULTS: Treatment group had significantly increased malonaldehyde (MDA) level and significantly decreased superoxide dismutase (SOD) activity in rat cortex compared with those in control group (p<0.05). The number of TUNEL positive cells in the right cortex of rats in the treatment group was clearly higher than that in control group. Among them, post-ischemic reperfusion group had reduced level of Bax in the cytoplasm, but increased Bax level in the mitochondrion, and lowered expression level of Bcl-2 in both mitochondrion and cytoplasm in comparison with control group. Dynamic detection results of c-Jun were in synchronization with those of apoptosis proteins, and maximum expression occurred at 24 h after treatment. CONCLUSIONS: c-Jun may play a role in the initiation of apoptotic cell death in these neurons.

Research on the nutrition and cognition of high-risk stroke groups in community and the relevant factors.

OBJECTIVE: To investigate the prevalence rate of nutritional risk in high-risk stroke groups in community, analyze its influencing factors, and analyze and compare the relationship between nutritional risk or malnutrition assessed by different nutritional evaluation methods and cognitive function, so as to provide the basis and guidance for clinical nutritional assessment and support. PATIENTS AND METHODS: A cross-sectional survey was performed for 1196 cases in high-risk stroke groups in community from December 2015 to January 2017. At the same time, the nutritional status of patients was evaluated using the mini nutritional assessment (MNA) and MNA-short form (MNA-SF), and the cognitive status of patients was evaluated using the mini-mental state examination (MMSE). Moreover, the relevant influencing factors of nutritional risk and MMSE score were analyzed and compared. RESULTS: High-risk stroke groups in community suffered from a high risk of malnutrition. MNA-SF had a higher specificity and lower false positive rate than MNA. Nutritional risk occurred more easily in high-risk stroke groups in community with a history of diabetes mellitus, less physical exercise or light manual labor, daily use of multiple drugs, and higher age. Those with a higher nutritional risk were more prone to cognitive impairment. High-risk stroke groups in community, complicated with hyperhomocysteinemia, daily use of three or more kinds of prescription drugs, and a previous history of stroke, were accompanied by cognitive impairment easily. CONCLUSIONS: MNA-SF can be used for the nutritional screening of high-risk stroke groups in community. For the high-risk stroke groups in community, the rational nutritional diet should be publicized, blood sugar should be controlled in a scientific manner and physical exercise should be moderately increased.

Series of new ß-cyclodextrin-cored starlike carriers for gene delivery.

The development of safe and effective ß-cyclodextrin (ß-CD)-cored cationic star gene carriers has attracted considerable attention. In this work, a series of star-shaped hemocompatible CD-PGPP, CD-PGAEPP, and CD-PGAPP vectors composed of ß-CD cores and piperazine (PP)-, N-(aminoethyl)piperazine (AEPP)-, or N-(3-aminopropyl)-2-pyrrolidinone (APP)-functionalized poly(glycidyl methacrylate) arms were successfully proposed and compared for highly efficient gene delivery. Such star carriers possess plentiful secondary amine, tertiary amine, and nonionic hydroxyl groups. CD-PGPP, CD-PGAEPP, and CD-PGAPP were effective in condensing plasmid DNA into nanoparticles, whose sizes were 100-200 nm and positive ζ potentials were 25-40 mV at nitrogen/phosphate (N/P) ratios of 10 and above. CD-PGPP, CD-PGAEPP, and CD-PGAPP showed significantly lower cytotoxicity than control poly(ethylenimine) (PEI; ∼25 kDa). At most N/P ratios, CD-PGAPP exhibited better gene transfection performance than CD-PGPP and CD-PGAEPP particularly in HepG2 cells. More importantly, in comparison with PEI, all of the CD-PGPP, CD-PGAEPP, and CD-PGAPP vectors did not cause undesirable hemolysis.

Different types of degradable vectors from low-molecular-weight polycation-functionalized poly(aspartic acid) for efficient gene delivery.

Poly(aspartic acid) (PAsp) has been employed as the potential backbone for the preparation of efficient gene carriers, due to its low cytotoxicity, good biodegradability and excellent biocompatibility. In this work, the degradable linear or star-shaped PBLA was first prepared via ring-opining polymerization of ß-benzyl-L-aspartate N-carboxy anhydride (BLA-NCA) initiated by ethylenediamine (ED) or ED-functionalized cyclodextrin cores. Then, PBLA was functionalized via aminolysis reaction with low-molecular-weight poly(2-(dimethylamino)ethyl methacrylate) with one terminal primary amine group (PDMAEMA-NH2), followed by addition of excess ED or ethanolamine (EA) to complete the aminolysis process. The obtained different types of cationic PAsp-based vectors including linear or star PAsp-PDM-NH2 and PAsp-PDM-OH exhibited good condensation capability and degradability, benefiting gene delivery process. In comparison with gold standard polyethylenimine (PEI, ∼ 25 kDa), the cationic PAsp-based vectors, particularly star-shaped ones, exhibited much better transfection performances.

Bioreducible comb-shaped conjugates composed of secondary amine and hydroxyl group-containing backbones and disulfide-linked side chains with tertiary amine groups for facilitating gene delivery.

Comb-shaped polymeric vectors (SS-PGEADMs) consisting of ethanolamine/cystamine-functionalized poly(glycidyl methacrylate) (SS-PGEA-NH2) backbones and bioreducible poly((2-dimethyl amino)ethyl methacrylate) (PDMEAMA) side chains were prepared by a combination of the ring-opening reaction and atom transfer radical polymerization (ATRP). The SS-PGEA-NH2 backbones, which were prepared via the ring-opening reaction of the pendant epoxide groups of poly(glycidyl methacrylate) with the amine moieties of ethanolamine/cystamine, possess plentiful flanking secondary amine and hydroxyl groups and some flanking disulfide bond-containing cystamine derivatives. The primary amine groups of the cystamine derivatives were activated to produce bromoisobutylryl-terminated SS-PGEA (SS-PGEA-Br) as multifunctional initiators for subsequent ATRP of DMAEMA. The resultant disulfide-linked short PDMEAMA side chains possess pendant tertiary amine groups and are biocleavable. Such SS-PGEADMs can effectively condense pDNA. The cytotoxicity of SS-PGEADMs could be controlled by adjusting the grafting amount of PDMEAMA side chains. In comparison with the pristine SS-PGEA-NH2, the moderate introduction of PDMEAMA side chains can further enhance the gene transfection efficiency in different cell lines. The present approach to well-defined comb-shaped vectors with multifunctional groups could provide a versatile means for tailoring the functional structures of advanced gene/drug vectors.

Relationships between biochemical and physiological changes induced by exercise in postmyocardial infarction patients.

AIM: AIM of the study was to examine the relationships between biochemical and physiological changes induced by exercise in postmyocardial infarction patients (PMIP) during the early stages of cardiac rehabilitation. METHODS: Forty-nine male non-blockade recent PMIP, aged 63.8 ± 4.7 years, performed a graded exercise test on a motorised treadmill until volitional cessation or reaching any of the American College of Sports Medicine criteria. Blood pressure and rate-pressure product (RPP) were recorded every three minutes. A 12-lead electrocardiogram was monitored continuously and heart rate (HR) was taken from this. Blood samples were obtained by two methods; those used for testing blood lactate (BL) were taken from an already warmed finger tip before and during exercise, and the others used for enzymatic analysis based on lactate dehydrogenase (LDH), lactate dehydrogenase isoenzyme 1 (LDH-1), creatine kinase (CK) and creatine kinase polypeptide sub-unit MB (CK-MB) were collected by venipuncture from the antecubital vein pre and immediate post exercise test. RESULTS: Highly significant correlations existed between exercise-induced changes in HR, RPP, BL and ST segment level with increased enzymes activity in serum, and 73.1% to 90.1% of the variance in percentage increase of the enzyme activity could be predicted from the variance in percentage increase of HR during exercise. However, the mechanism of these relationships may differ. CONCLUSION: Since the rise in serum enzymes during submaximal exercise is primarily attributed to changes in membrane permeability in fatigued muscle, these relationships provide useful guidance to health professionals obtaining biochemical information about muscle fatigue.

Multiarm cationic star polymers by atom transfer radical polymerization from ß-cyclodextrin cores: influence of arm number and length on gene delivery.

Controlled ß-cyclodextrin (ß-CD) core-based cationic star polymers have attracted considerable attention as non-viral gene carriers. Atom transfer radical polymerization (ATRP) could be readily used to produce the star-shaped polymers. The precise control of the number of initiation sites on the multifunctional core was of crucial importance to the investigation of the structure-property relationship of the functional star gene carriers. Herein, the controlled multiarm star polymers consisting of a ß-CD core and various arm lengths of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) were prepared via ATRP from the chloroacetylated ß-CD with well-designed initiation sites. Generally, these star polycations can condense plasmid DNA into 100-150 nm nanoparticles with positive zeta potentials of 30-40 mV at N/P ratios (star polymer to DNA ratios) of 17 or higher. The effects of arm numbers and lengths on gene delivery were investigated in detail. With a fixed length of the PDMAEMA arm, the fewer the number of arms, the lower the toxicity. The star polycations with suitable arm numbers possess the best transfection ability. On the other hand, with the fixed molecular weights, the shorter the arms, the lower the toxicity. The polymers with 21 arms possess the lowest transfection efficiency.