Aims:The invasive intramyocardial injection of mesenchymal stromal cells (MSCs) allows for limited repeat injections and shows poor therapeutic efficacy against ischemic heart failure.Intravenous injection is an alternative method because this route allows for repeated, noninvasive, and easy delivery.However, the lack of targeting of MSCs hinders the ability of these cells to accumulate in the ischemic area after intravenous injections.We investigated whether and how the overexpression of colony-stimulating factor 2 receptor beta subunit (CSF2RB) may regulate the cardiac homing of MSCs and their cardioprotective effects against ischemic heart failure.Methods and Results: Adult mice were subjected to myocardial ischemia/reperfusion (MI/R) or sham operations.We observed significantly higher CSF2 protein expression and secretion by the ischemic heart from 1 day to 2 weeks after MI/R.Mouse adipose tissue-derived MSCs (ADSCs) were infected with adenovirus harboring CSF2RB or control adenovirus.Enhanced green fluorescent protein (EGFP)-labeled ADSCs were intravenously injected into MI/R mice every three days for a total of 7 times.Compared with ADSCs infected with control adenovirus, intravenously delivered ADSCs overexpressing CSF2RB exhibited markedly increased cardiac homing.Histological analysis revealed that CSF2RB overexpression significantly enhanced the ADSC-mediated proangiogenic, antiapoptotic, and antifibrotic effects.More importantly, ADSCs overexpressing CSF2RB significantly increased the left ventricular ejection fraction and cardiac contractility/relaxation in MI/R mice.In vitro experiments demonstrated that CSF2RB overexpression increases the migratory capacity and reduces the hypoxia/reoxygenation-induced apoptosis of ADSCs.We identified STAT5 phosphorylation as the key mechanism underlying the effects of CSF2RB on promoting ADSC migration and inhibiting ADSC apoptosis.RNA sequencing followed by cause-effect analysis revealed that CSF2RB overexpression increases the expression of the ubiquitin ligase RNF4.Coimmunoprecipitation and coimmunostaining experiments showed that RNF4 binds to phosphorylated STAT5.RNF4 knockdown reduced STAT5 phosphorylation as well as the antiapoptotic and promigratory actions of ADSCs overexpressing CSF2RB.
Yaks provide necessities such as meat and milk for Tibetans living at high altitudes on and around the Qinghai-Tibetan Plateau. Enterococci are ubiquitous members of the animal gut microbiota that can cause biofilm-associated opportunistic infections. Meanwhile, multidrug-resistant Enterococcus also poses a serious threat to public health. This study aims to characterize antibiotic resistance, virulence genes, and biofilm formation of enterococci from yaks. From April 2018 to July 2019, we collected 395 fecal samples of yaks in Aba Tibetan Autonomous Prefecture, China. Enterococci isolated from the samples were identified and classified according to the 16S rDNA sequence. The antibiotic resistance of each isolate was detected according to the Kirby-Bauer disk diffusion method, and antibiotic resistance genes were detected by polymerase chain reaction (PCR) and sequencing. Enterococcal biofilms were assessed using standard procedures. Different virulence genes were detected by PCR and sequencing. In total, 381 enterococci strains were recovered, with Enterococcus faecalis (41.99%) and Enterococcus faecium (37.80%) being the predominant species. Many isolates were multidrug- resistant (60.37%) and showed a high resistance rate to rifampicin (64.30%) and tetracycline (61.54%). We also detected various antimicrobial resistance genes in the tested strains. The E. faecalis strains had higher frequency of biofilm formation and virulence genes than other enterococcal species. This is the first report that shows yaks are repositories for drug-resistant enterococci with virulent determinants and biofilms that may spread into humans and to environment. This study also provides useful data suggesting that enterococci may pose a potential health risk to yaks. Therefore, active surveillance of antimicrobial resistance and pathogenesis in enterococci from yaks is urgently warranted.
Previous studies have shown that postoperative cognitive dysfunction (POCD) is related to multiple factors including age, postoperative trauma, inflammation, postoperative pain, and anesthesia, among which postoperative pain is thought to play an important role in the development of POCD. This review summarizes the recent findings in the study of the role of postoperative pain in the pathogenesis of POCD in light of nerve injuries, neural remodeling and stress, and the progress in the prevention and treatment of POCD in elderly patients. It is of vital important to assess the postoperative pain and formulate adequate analgesic regimens for effective prevention and management of POCD to protect the brain functions of elderly patients.
This paper researches and validates a predictive modeling method for complex industrial environment. Via combining industrial field data with system mechanism, the paper analyzes the technology of industrial data pretreatment and establishes the impulse response model of cement decomposing furnace temperature, then explores the model adjusting method. The paper compares the modeling performance between the regression method without constraints and the regression method with constraints. The field control results demonstrate the good performance of this modeling method.
Progranulin (PGRN) is a widely expressed, pleiotropic protein that is involved in diverse biological processes, including cellular proliferation, neuron development, and wound healing. However, the role of PGRN in the regulation of pathogen-induced systemic inflammation and the mechanisms involved have not been established. In this study, we show that PGRN-deficient mice display heightened mortality in models of polymicrobial sepsis and endotoxinemia, with increased tissue levels of inflammatory cytokines and reduced IL-10 production. Conversely, administration of rPGRN decreases the susceptibility of PGRN-deficient mice to LPS-induced endotoxemic shock and augments IL-10 production by LPS-activated macrophages in a TNFR-dependent manner. Molecular analysis reveals a direct role of the transcription factor C/EBPα in PGRN-regulated IL-10 expression. C/EBPα-deficient macrophages produce less IL-10 in response to LPS. Furthermore, mice deficient in C/EBPα in hematopoietic cells are highly vulnerable to LPS-induced septic shock. Lastly, the defective IL-10 production by PGRN-deficient cells is primarily due to reduced C/EBPα protein stability via the E3 ubiquitin-conjugating enzyme E6AP and proteasome-mediated degradation. To our knowledge, this study provides the first evidence that PGRN is a nonredundant regulator of systemic inflammation via modulating the levels and activity of C/EBPα, IL-10, and the ubiquitin-proteasome proteolysis pathway. The results bear strong and profound implications for PGRN insufficiency and its mutation-associated systemic and organ-specific inflammatory human diseases.
Objective:The effectiveness and safety of high frequency ventilation system in laryngopharyngeal and tracheal surgery is discussed. Methods:According to The American Society of Anesthesiologists Ⅰ-Ⅱ level, 60 cases of selective throat and tracheal surgery undering general anesthesia were randomly divided into high frequency jet ventilation group （group HFJV） and intermittent positive pressure ventilation group （IPPV group）, with 30 cases in each group. Group HFJV was treated with HFJV and group IPPV with a small caliber endotracheal tube connected to an anesthesia machine was treated with IPPV.Before anesthesia （T0）, after the success of the laryngoscope placed （T1）, 5 minites after ventilation （T2） and 5 minites after the laryngoscope removed （T3）, hemodynamic parameters were recorded at each time point , in T0, T2 and T3 record , arterial blood gas index, the patient's airway pressure, end-expiratory carbon dioxide concentration, surgical field quality and total blood loss, operating time and awakening time were recorded and compared between the two groups. Results:The average airway pressure and intraoperative average total blood loss of group HFJV were significantly lower than that of group IPPV（P<0.01）, and the average operative field quality of group HFJV was significantly better（P<0.01）, but there was no statistical significance in the effects on hemodynamics, arterial blood gas and other indicators compared with group IPPV（P>0.05）. No serious adverse events occurred in 2 groups. Conclusion:HFJV system can be used effectively in laryngopharyngeal and tracheal surgery, reducing intraoperative blood loss and improving surgical field of vision without obvious adverse reactions.目的：探讨高频通气手术系统在咽喉气管手术中应用的有效性及安全性。 方法：将符合美国麻醉医师协会分级标准Ⅰ~Ⅱ级，且拟在全身麻醉下行择期咽喉气管手术的60例患者随机分为高频喷射通气（HFJV）组和间歇正压通气（IPPV）组各30例。HFJV组借助高频喷射呼吸机行HFJV，IPPV组通过小口径气管导管接麻醉机行IPPV。在麻醉前（T0）、支撑喉镜放置成功后（T1）、通气5 min后（T2）及支撑喉镜取出5 min后（T3）各时间点记录血流动力学指标，在T0、T2和T3各时间点测量动脉血气指标，同时记录平均气道压、呼气末二氧化碳浓度、手术视野质量、总出血量、手术时间和苏醒时间，对比2组方案对上述指标的影响并记录不良事件发生情况。 结果：HFJV组的平均气道压、平均总出血量明显低于IPPV组（P<0.01），而且HFJV组的平均手术视野质量明显更好（P<0.01），但对血流动力学、动脉血气等指标的影响与IPPV组相比差异均无统计学意义（P>0.05）。2组均未发生严重不良事件。 结论：高频通气手术系统可有效地应用于咽喉气管手术，减少术中出血量，改善手术视野质量，且无明显不良反应。.
Tumor suppressor p53, known as 'the guardian of the genome', has the ability to prevent the emergence of transformed cells by the induction of cell cycle arrest and apoptosis. Otherwise, there were researches about the function of p53, such as NDA repair, regulating metabolism and maternal reproduction in recent years. Furthermore, there was a new function for p53 in antiviral apoptosis mentioned in the research, Integration of interferon-alpha/beta signaling to p53 responses in tumour suppression and antiviral defense. In order to define the antiviral function of p53, many target genes has been defined, such as IRF9, IRF5, ISG15 and TLR3. All of these implied there must be a complex mechanism for role of p53 in antiviral innate immunity, adaptive immunity and inflammation.
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