Effect of enalapril maleate-folic acid tablets on inflammatory response and myocardial endoplasmic reticulum stress-related factors in hypertensive rats

Purpose: To determine the effect of enalapril maleate folate on inflammatory reaction and myocardial endoplasmic reticulum stress-related factors in hypertensive rats.Methods: Eighty (80) hypertensive rats with SBP > 140 mmHg were equally assigned to control and study groups. Rats in control group were given normal saline by gavage, while the observation group was given enalapril maleate powder (10 mg/kg/day). After 4 weeks of treatment, 2 mL of inferior vena cava blood was collected from each of the two rat groups. The level of homocysteine (Hcy) was determined with Hcy assay kit, while C-reactive protein (CRP) levels in patients were determined by latex immunoturbidimetry. Serum FBG was assessed using automatic biochemical analyzer. The expression levels of GRP78, CRP94, chop and caspase-12 in aortic smooth muscle cells were assayed immunohistochemically.Results: Central arterial pressure (MAP), aortic media thickness, lvwi, HWI FBG and CRP were significantly higher in the study rats, while Hcy level was lower, than in controls (p < 0.05). There were significantly lower levels of glucose regulatory protein 78 (GRP78), CRP94, CHOP and caspase-12 in study rats than in control rats (p < 0.05).Conclusion: Enalapril maleate-folate slows down inflammatory reaction by reducing the levels of Hcy, CRP and FBG. It inhibits the expressions of GRP78, CRP94, CHOP and caspase-12 in myocardium, reduces damage to myocardial cells, and alleviates or reverses left ventricular hypertrophy in rats with high blood pressure. This provides new insight into the research and development of other drugs

Protective Regulatory T Cell Immune Response Induced by Intranasal Immunization With the Live-Attenuated Pneumococcal Vaccine SPY1 via the Transforming Growth Factor-β1-Smad2/3 Pathway

Vaccine effectiveness is mainly determined by the mechanism mediating protection, emphasizing the importance of unraveling the protective mechanism for novel pneumococcal vaccine development. We previously demonstrated that the regulatory T cell (Treg) immune response has a protective effect against pneumococcal infection elicited by the live-attenuated pneumococcal vaccine SPY1. However, the mechanism underlying this protective effect remains unclear. In this study, a short synthetic peptide (P17) was used to downregulate Tregs during immunization and subsequent challenges in a mouse model. In immunized mice, increase in immune cytokines (IL-12p70, IL-4, IL-5, and IL-17A) induced by SPY1 were further upregulated by P17 treatment, whereas the decrease in the infection-associated inflammatory cytokine TNF-α by SPY1 was reversed. P17 also inhibited the increase in the immunosuppressive cytokine IL-10 and inflammatory mediator IL-6 in immunized mice. More severe pulmonary injuries and more dramatic inflammatory responses with worse survival in P17-treated immunized mice indicated the indispensable role of the Treg immune response in protection against pneumococcal infection by maintaining a balance among acquired immune responses stimulated by SPY1. Further studies revealed that the significant elevation of active transforming growth factor β (TGF-β)1 by SPY1 vaccination activated FOXP3, leading to increased frequencies of CD4+CD25+Foxp3+ T cells. Moreover, SPY1 vaccination elevated the levels of Smad2/3 and phosphor-Smad2/3 and downregulated the negative regulatory factor Smad7 in a time-dependent manner during pneumococcal infection, and these changes were reversed by P17 treatment. These results illustrate that SPY1-stimulated TGF-β1 induced the generation of SPY1-specific Tregs via the Smad2/3 signaling pathway. In addition, SPY1-specific Tregs may participate in protection via the enhanced expression of PD-1 and CTLA-4. The data presented here extend our understanding of how the SPY1-induced acquired Treg immune response contributes to protection elicited by live-attenuated vaccines and may be helpful for the evaluation of live vaccines and other mucosal vaccine candidates

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Cellulose Nanofiber-Assisted Dispersion of Halloysite Nanotubes via Silane Coupling Agent-Reinforced Starch–PVA Biodegradable Composite Membrane

HNTs (halloysite nanotubes) are widely used in reinforcing material, often used in material reinforcement and particle loading. However, their easy agglomeration causes them to have great limitations in application. In this work, two kinds of silane coupling agents (KH560 and KH570) were introduced to graft the CNF/HNT (cellulose nanofiber) nanoparticles used to reinforce the starch-polyvinyl alcohol (PVA) composite membranes. The mechanical properties, water resistance properties and thermal performance of the composite membrane were tested. The results showed that the CNF/HNTs nanoparticle system modified by two silane coupling agents enhanced the tensile strength (TS) of the starch–PVA composite membranes by increments of 60.11% and 68.35%, and, in addition, the water resistance of starch–PVA composite membrane improved. The introduction of chemical bonds formed associations and a compact network structure, which increased the thermal stability and the crystallinity of the starch–PVA composite membrane. In the study, we creatively used CNF to disperse HNTs. CNF and HNTs were combined under the action of the silane coupling agent, and then mixed into the starch–PVA membranes matrix to prepare high-performance degradable biological composite membranes

The Characteristic and Short-Term Prognosis of Tinnitus Associated with Sudden Sensorineural Hearing Loss

Tinnitus is believed to result from the maladaptive plasticity of the auditory nervous system; reports regarding its severity and prognosis are conflicting. We evaluated the characteristic and short-term prognosis of tinnitus associated with sudden sensorineural hearing loss (SSNHL). A total of 230 cases were enrolled. The severity and 1-month prognosis of tinnitus (according to the Tinnitus Handicap Inventory (THI)) were assessed in terms of the patients’ sex, age, level of hearing loss, type of audiogram results, and so on. According to our statistical analysis, the degree of handicap due to tinnitus was not related to sex, age, or level of hearing loss; the Tinnitus Handicap Inventory indicated that the low-frequency-audiogram group had a low tinnitus handicap (F=7.516, P=0.000). Furthermore, we found that the prognosis of tinnitus was not related to the type of audiogram or level of hearing loss. Recovery from a severe level of hearing loss was, however, found to be associated with a poor tinnitus prognosis (F=5.203, P=0.006). In summary, our study indicates that the association between tinnitus and SSNHL is extremely high. Tinnitus can be ameliorated by the successful treatment of hearing loss. The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800014797)

RETRACTED ARTICLE: Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis

Abstract Background There is growing evidence of the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). The objective was to discuss whether exosomal lncRNA HNF1A-AS1 impacted drug resistance in CC via binding to microRNA-34b (miR-34b) and regulating TUFT1 expression. Methods The expression of HNF1A-AS1 in normal cervical epithelial cells, cisplatin (DDP)-sensitive cell line (HeLa/S) and DDP-resistant cell line (HeLa/DDP) cells were detected. HeLa/S and HeLa/DDP cells were interfered with HNF1A-AS1 to determine IC50, proliferation, colony formation and apoptosis of CC cells. The exosomes were isolated and identified. Subcellular localization of HNF1A-AS1, expression of miR-34b and TUFT1 in receptor cells were also verified. The binding site between HNF1A-AS1 and miR-34b, together with miR-34b and TUFT1 were confirmed. Tumorigenic ability of cells in nude mice was also detected. Results HNF1A-AS1 was upregulated in DDP-resistant cell line HeLa/DDP. Silencing HNF1A-AS1 suppressed CC cell proliferation and promoted its apoptosis. HNF1A-AS1 was found to act as a competing endogenous RNA (ceRNA) of miR-34b to promote the expression of TUFT1. Exosomes shuttled HNF1A-AS1 promoted the proliferation and drug resistance of CC cells and inhibited their apoptosis by upregulating the expression of TUFT1 and downregulating miR-34b. Furthermore, suppressed exosomal HNF1A-AS1 in combination with DDP inhibited tumor growth in nude mice. Conclusion Our study provides evidence that CC-secreted exosomes carrying HNF1A-AS1 as a ceRNA of miR-34b to promote the expression of TUFT1, thereby promoting the DDP resistance in CC cells

Hydraulic fracture propagation geometry and acoustic emission interpretation: A case study of Silurian Longmaxi Formation shale in Sichuan Basin, SW China

A series of laboratory fracturing experiments was performed on samples mined from an outcrop of the Silurian Longmaxi Formation shale in the Sichuan Basin, using a true triaxial fracturing simulation system. To reveal the characteristics of acoustic emission (AE) response in hydraulic fracture (HF) propagation, the HF propagation geometry obtained by specimen splitting and CT scanning technology was compared with the interpretation results of AE monitoring. And the difference of hypocenter mechanism between hydraulically connected and unconnected regions was further discussed. Experimental results show that the AE events distribution indicates well the internal fractures geometry of the rock samples. Numerous AE events occur and concentrate around the wellbore where the HF initiated. Sparse AE events were presented nearby bedding planes (BPs) activated by the HF. AE events tended to be denser where HF geometry was more complex. The hydraulically connected region was obviously distinct with the spatial distribution of AE events, which resulted in the overestimation of stimulated reservoir volume (SRV) based on micro-seismic mapping result. Both tensile and shear events occurred in the zone connected by the HFs, while only shear events were observed around BPs which were not hydraulically connected. Thus, the hydraulically connected and unconnected region can be identified in accordance with the hypocenter mechanism, which is beneficial to improve the accuracy of SRV evaluation. Key words: shale, bedding plane, hydraulic fracture, propagation geometry, acoustic emission, CT scannin

The Effects of Co on the Microstructure and Mechanical Properties of Ni-Based Superalloys Prepared via Selective Laser Melting

In this work, two Ni-based superalloys with 13 wt.% and 35 wt.% Co were prepared via selective laser melting (SLM), and the effects of Co on the microstructure and mechanical properties of the additively manufactured superalloys were investigated. As the Co fraction increased from 13 wt.% to 35 wt.%, the average grain size decreased from 25.69 μm to 17.57 μm, and the size of the nano-phases significantly increased from 80.54 nm to 230 nm. Moreover, the morphology of the γ′ phase changed from that of a cuboid to a sphere, since Co decreased the γ/γ′ lattice mismatch from 0.64% to 0.19%. At room temperature, the yield strength and ultimate tensile strength of the 13Co alloy reached 1379 MPa and 1487.34 MPa, and those of the 35Co alloy were reduced to 1231 MPa and 1350 MPa, while the elongation increased by 52%. The theoretical calculation indicated that the precipitation strengthening derived from the γ′ precipitates made the greatest contribution to the strength