Prognostic value of serum cystatin C in patients with sepsis.

Background: Early identification and diagnosis of sepsis are very important because timely and appropriate treatment can improve the survival outcomes. Aim: The aim of this study was to explore the clinical significance of serum cystatin C level in sepsis. Materials and Methods: The levels of serum cystatin C, C-reactive protein (CRP), and procalcitonin (PCT) were measured via enzyme-linked immunosorbent assay (ELISA). The patients with sepsis were followed up for 30 days to record their survival conditions. Results: The expression level of cystatin C was remarkably elevated in patients with sepsis compared with that in healthy controls. The serum cystatin C level was significantly correlated with the SOFA score and CRP, PCT, and creatinine levels in patients with sepsis. The patients in death group had a markedly higher level of serum cystatin C than those in survival group. The area under curve (AUC) of cystatin C for assessing the 30-day mortality rate of sepsis patients was 0.765. Conclusion: The serum cystatin C level is elevated in patients with sepsis and it may serve as a biomarker for early diagnosis of sepsis and possess promising effects in assessing the severity of sepsis and the prognosis of patients.

Handgrip strength and the prognosis of patients with heart failure: A meta-analysis.

BACKGROUND: Reduced muscular strength is common in patients with heart failure (HF). The aim of the systematic review and meta-analysis was to evaluate the association between handgrip strength (HGS) and prognosis of patients with HF. HYPOTHESIS: Reduced HGS may be a risk factor of poor prognosis of patients with HF. METHODS: Relevant observational studies with longitudinal follow-up were obtained by a comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases. A random-effects model was used to pool the results. RESULTS: Fifteen studies involving 7350 patients with HF were included in the meta-analysis. Pooled results showed that HF patients with lower HGS were associated with a higher risk of mortality during follow-up (risk ratio [RR]: 2.00, 95% confidence interval [CI]: 1.55-2.58, p < .001; I2 = 0%). Subgroup analysis showed that the association was not significantly affected by characteristics such as study country, design, mean age of the patients, HF status (stable or advanced/acute), HF type (reduced or preserved ejection fraction), follow-up duration, and quality score (p for subgroup difference all > 0.05). Further analysis showed that per 1 kgf decrease of HGS was associated with an 8% increased risk of mortality during follow-up (RR: 1.08, 95% CI: 1.05-1.11, p < .001; I2 = 12%). Moreover, HF patients with lower HGS were also related to a higher risk of composite outcome of HF rehospitalization or mortality (RR: 1.67, 95% CI: 1.19-2.35, p = .003; I2 = 53%). CONCLUSION: A low HGS may be associated with poor clinical outcomes of patients with HF.

Evaluation of efficacy and safety of esmolol in treating patients with septic shock: A protocol for systematic review and meta-analysis.

BACKGROUND: In septic shock cases, tachycardia and a hyperdynamic hemodynamic profile are characteristics of the condition. It has been reported that using beta antagonist esmolol constitutes a form of treatment to reduce heart rate to improve diastolic filling time and elevate cardiac output, which reduces vasopressor support. Still, there are controversial results. Therefore, in this study, the primary objective is to perform a meta-analysis by systematically evaluating the efficiency and security of using esmolol to treat septic shocks. METHODS: A systematic literature search for relevant randomized controlled trials that report evaluations on the efficiency and safety of using esmolol to treat septic shock patients from their inception to February 2022 will be conducted in three databases containing publications in Chinese language (WanFang, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure) and four databases containing English language publications (Cochrane Library, PubMed, Web of Science, and EMBASE). The screening of the relevant studies will be performed by a pair of authors independently, and the screening involves examining the title, abstract and full-text stages, data extraction, and bias risk assessment. The results are summarized through the fixed-effects and random-effects models, the respective models will be utilized for data pooling according to the heterogeneity of studies that will be included. Moreover, publication bias is assessed if more than ten studies are considered. RESULTS: The results are a high-quality synthesis of the most recent evidence for esmolol usage in septic shock treatment. CONCLUSION: Up-to-date evidence will be provided through the results of this systematic review related to assessing the efficacy and safeness of esmolol usage in treating septic shock. ETHICS AND DISSEMINATION: Ethical permissions are not required as prepublished data are used. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/SKEZ7.

Silencing of circular RNA ANRIL attenuates oxygen-glucose deprivation and reoxygenation-induced injury in human brain microvascular endothelial cells by sponging miR-622.

BACKGROUND: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury. RESULTS: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-κB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. CONCLUSIONS: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.

Silencing of circular RNA ANRIL attenuates oxygen-glucose deprivation and reoxygenation-induced injury in human brain microvascular endothelial cells by sponging miR-622

BACKGROUND: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury. RESULTS: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1ß, IL-6, tumor necrosis factor-a, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-kB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. CONCLUSIONS: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.

The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms.

BACKGROUND The aim of the present study was to investigate the protective effects of protease inhibitor MG-132 on sepsis-induced acute lung injury rats. MATERIAL AND METHODS Sprague Dawley rats were employed to induce sepsis by cecal ligation and puncture (CLP) method. Rats were divided into 4 groups: control, sham, model (CLP), and MG-132. Histopathology observation was detected by hematoxylin and eosin staining. The ratio of wet lung to dry lung (W/D) was calculated. In addition, the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Also, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were evaluated. Western blotting was performed to measure the expression of hypoxia-inducible factor-1 alpha (HIF-1alpha). In order to assess the role of HIF-1alpha, YC-1, the inhibitor of HIF-1alpha, was used to treat the rats. The expression of phosphor-mTOR (p-mTOR), p-4EBP1, and p-EIF4E were evaluated by western blotting. RESULTS Obvious pathological injury and increasing ratio of W/D in the model group were observed. Both pathological injury and W/D were improved in the MG-132 group, and the greatest improvement could be seen in the YC-1+MG-132 group. Furthermore, the MDA levels in the MG-132 group was decreased, accompanied by an increase in SOD levels. The level of HIF-1alpha was increased in the model group while a decreased was detected in the MG-132 group. The levels of inflammatory factors were high in the model group, whereas the opposite result was found in the MG-132 group, and the lowest in were in the YC-1+MG-132 group. Furthermore, the expression levels of p-mTOR, p-4EBP1, and p-EIF4E proteins were downregulated in the MG-132 group compared to the model group, and the lowest was in the YC-1+MG-132 group. CONCLUSIONS Our study suggested that MG-132 was able to protect against acute lung injury via inhibition of HIF-1alpha mediated mTOR/4EBP1/EIF4E pathway.

MicroRNA-340-5p relieved chronic constriction injury-induced neuropathic pain by targeting Rap1A in rat model.

OBJECTIVES: Neuropathic pain (NP) is one of the main challenges towards NP syndrome treatment. miR-340-5p exhibit different expression levels in NP models. Its effects on NP remained unclear. The objective of this study was to explore the potential regulation mechanisms of miR-340-5p in NP. METHODS: Rat model of chronic constriction injury (CCI) was established to induce NP in vivo. NP levels were assessed using mechanical withdrawal threshold (MWT). The inflammation response in CCI rats were determined by HE staining and ELISA assay. The target genes of miR-340-5p were verified by luciferase report assays. RESULTS: In CCI rats, level of miR-340-5p was down-regulated both in spinal cord tissues and isolated microglial cells. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were decreased in CCI rats, which were restored upon miR-340-5p overexpression. miR-340-5p overexpression also decreased inflammation as well as expression levels of COX-2, IL-1ß, TNF-α and IL-6 in CCI rats. Luciferase report assays revealed Rap1A was a target gene of miR-340-5p in the experimental model. Elevated miR-340-5p decreased Rap1A expression level in vitro and in vivo. Overexpression of Rap1A protein restored expression levels of COX-2, IL-1ß, TNF-α and IL-6, reduced the PWT and PWL and increased inflammation response in CCI rats. CONCLUSION: miR-340-5p alleviated CCI-induced NP by targeting Rap1A. miR-340-5p and Rap1A may be the potential treatment targets for NP therapeutics.

Pentraxin 3, a Predicator for 28-Day Mortality in Patients With Septic Shock.

BACKGROUND: Useful biomarkers that can serve as prognostic predictors are of great value in clinical practice because of the complex individual response to sepsis. Pentraxin 3 (PTX3), as a multifunctional pattern-recognition molecule, has been reported to be closely associated with the severity of infectious diseases in intensive care units (ICU). The aim of this study was to investigate whether PTX3 could serve as a potential prognostic biomarker in patients with septic shock. MATERIALS AND METHODS: This single-center prospective observational study was conducted during May 2012-May 2015 in the ICU of Taizhou People׳s Hospital. We compared the clinical data and laboratory tests in surviving and deceased patients with septic shock within 28 days from admission. Potential independent prognostic factors for septic shock were analyzed by using univariate and multiple Cox proportional hazards regression analyses. RESULTS: A total of 112 patients admitted to the ICU with septic shock were enrolled in our study with an overall 28-day mortality of 25.9% (29 of 112 patients). PTX3 level was the only independent risk factor for the 28-day mortality by univariate and multivariate Cox analysis (hazard ratio = 3.87; 95% CI: 1.66-8.81, P = 0.004). The deceased patients had significant higher levels of PTX3 at the 4 different points (baseline, day 1, day 2 and day 3) versus the survivors (P < 0.001). Results from Kaplan-Meier curves and log-rank test revealed that high PTX3 level (above the median value) was statistically associated with a lower 28-day survival rate (P = 0.014). CONCLUSIONS: The baseline PTX3 level was an independent predictor for 28-day mortality in patients with septic shock.

[Evaluation of high volume hemofiltration according to pulse-indicated continuous cardiac output on patients with acute respiratory distress syndrome].

OBJECTIVE: To study the effects of high volume hemofiltration (HVHF) according to pulse-indicated continuous cardiac output (PiCCO) on patients with acute respiratory distress syndrome (ARDS). METHODS: A prospective randomly controlled trial was conducted. 163 patients with ARDS admitted to Taizhou People's Hospital, Medical College, Nantong University, between February 2011 and January 2014, were enrolled. The patients were randomly divided into conventional therapy group (n=50), HVHF group (n=55), and PiCCO + HVHF group (n=58) by random number table. The patients in conventional therapy group received routine treatment including mechanical ventilation and drug treatment according to ARDS treatment guideline. The patients in the HVHF group received HVHF treatment of 18 hours per day on 1, 3, 5, 7 days on the basis of conventional therapy. Patients in the PiCCO + HVHF group received HVHF treatment according to PiCCO. The indexes of lung function and PiCCO monitoring were recorded at intensive care unit (ICU) admission (before) and 4 days and 7 days after treatment. The serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were determined by enzyme linked immunosorbent assay (ELISA), and the prognosis of patients was recorded. RESULTS: In three groups, oxygenation index (PaO2/FiO2), static lung compliance (Cs) were gradually increased, and respiratory rate (RR), lactic acid (Lac) were gradually decreased. The indicators in HVHF and PiCCO + HVHF groups were significantly improved compared with conventional therapy group. The indexes in PiCCO + HVHF group were significantly increased or decreased compared with those in HVHF group, and the statistical differences were found on the 7th day after treatment [PaO2/FiO2(mmHg, 1 mmHg=0.133 kPa): 189.3 ± 36.8 vs. 166.3 ± 36.1, Cs (mL/cmH2O): 76.7 ± 18.9 vs. 67.0 ± 18.2, RR (times/min): 16.4 ± 5.2 vs. 19.2 ± 5.4, Lac (mmol/L): 1.20 ± 0.41 vs. 1.41 ± 0.43, all P<0.01]. In PiCCO + HVHF group, cardiac index (CI) was gradually increased, and extra vascular lung water index (EVLWI) and intra thoracic blood volume index (ITBVI) were gradually decreased. There were significant differences in the indexes 4 days and 7 days after treatment compared with those before treatment [CI (L × min⁻¹ m⁻²): 4.62 ± 1.13, 4.83 ± 1.10 vs. 4.01 ± 1.02, EVLWI (mL/kg): 7.6 ± 2.7, 6.5 ± 2.6 vs. 12.4 ± 2.9, ITBVI (mL/m²): 801.3 ± 120.9, 785.4 ± 118.7 vs. 980.1 ± 168.6, all P<0.01]. After treatment, the serum levels of TNF-α and IL-1ß in three groups were gradually decreased. Compared with the conventional therapy group, the serum levels of TNF-α and IL-1ß on 4 days and 7 days in the HVHF and PiCCO + HVHF groups were significantly decreased, and the statistical differences were found on 7 days [TNF-α (ng/L): 68.35 ± 12.63, 67.54 ± 12.90 vs. 85.35 ± 13.70; IL-1ß (ng/L): 424.6 ± 142.9, 412.2 ± 140.2 vs. 895.2 ± 187.7, all P<0.01]. Compared with the HVHF group, the serum levels of TNF-α and IL-1ß in the PiCCO + HVHF group were slightly decreased without statistical differences. Compared with the conventional therapy group, the number of organ failure, duration of mechanical ventilation, the length of stay in ICU and hospital mortality in HVHF group and PiCCO + HVHF group were lowered, and the statistical differences were found in PiCCO + HVHF group compared with HVHF group [number of organ failure: 2.41 ± 0.79 vs. 2.72 ± 0.80, duration of mechanical ventilation (days): 4.8 ± 2.0 vs. 5.7 ± 2.1, the length of stay in ICU (days): 11.5 ± 3.4 vs. 13.1 ± 3.6, hospital mortality: 31.0% (18/58) vs. 41.8% (23/55), all P<0.05]. CONCLUSIONS: Levels of inflammatory factors in patients with ARDS could be reduced by HVHF. The oxygenation and compliance of lung can be improved, the number of organ failure can be lowered, the duration of mechanical ventilation and the length of stay in ICU can be shortened, and the hospital mortality could be declined by PiCCO guided HVHF.