PTX3 mediates PI3K/AKT/mTOR signaling to downregulate apoptosis and autophagy to attenuate myocardial injury in sepsis.

Background: This study aimed to investigate the effect and mechanism of Pentraxin 3 (PTX3) on myocardial injury in sepsis. Methods: Thirty male C57BL/6 mice were randomly assigned to Groups A, B, or C. Mice in Groups A and B were injected with unloaded lentivirus, while mice in Group C were injected with lentivirus encoding PTX3 overexpression. Seven days after injection, septic myocardial injury mouse models were constructed following intraperitoneal injection with LPS in Groups B and C, and mice in Group A were intraperitoneally injected with normal saline. Cardiac function was examined using echocardiography; pathological variation of myocardial cells was measured through HE staining, transmission electron microscopy, and TUNEL staining; and Western blot was used to measure the expression of PI3K/AKT/mTOR pathway-related, autophagy-related, and apoptosis-related proteins in mice myocardial cells. Results: PTX3 significantly improved cardiac function and structure in sepsis-stricken mice, and PTX3 alleviated cardiac damage caused by sepsis. PTX3 reduced the relative protein expression of p-PI3K, p-AKT, mTOR, LC3I/II, Beclin, ATG5, Bax, Caspase-3, and Caspase-9 in septic mouse cardiomyocytes and increased the relative protein expression of Bcl-2. Conclusion: PTX3 can attenuate myocardial injury in sepsis due to the down-regulation of apoptosis and autophagy induced by the PI3K/AKT/mTOR pathway.

EFFECTS OF LEVOSIMENDAN ON DIAPHRAGMATIC DYSFUNCTION IN PATIENTS WITH SEPSIS.

ABSTRACT: Objective: In this study, our aim was to examine the effects of levosimendan on diaphragmatic dysfunction in patients with sepsis, as well as assess its impact on respiratory muscle contractility and the outcome of weaning. Methods: This was a single-blind, randomized, controlled trial. Patients with diaphragmatic dysfunction and failure of spontaneous breathing trials (SBTs) were randomly and equally assigned to the experimental and control groups. The experimental group received levosimendan at a loading dose of 6 µg/kg for 10 min, followed by a continuous infusion at 0.2 µg/kg/min. The control group received an equivalent dose of a placebo. The preadministration and postadministration respiratory mechanics parameters of the patients were recorded. Evaluation of the effect of levosimendan on patients with sepsis-induced diaphragm dysfunction comprised arterial blood gas analysis as well as ultrasound measurements of diaphragm excursion (DE), diaphragm thickness (DT), diaphragm thickening fraction (TFdi), and diaphragm-rapid shallow breathing index (D-RSBI). Results: Forty-four patients were enrolled in the study. We found that postadministration of levosimendan, the patients' tidal volume (GCSMV) increased, whereas the D-RSBI decreased, and the partial pressure of carbon dioxide (PACO 2 ) decreased when compared to the preadministration levels. Additionally, following levosimendan administration, patients showed increased DE and pressure support (PS) when compared to before administration (1.14 ± 0.177 vs. 1.22 ± 0.170 cm and 0.248 ± 0.03 vs. 0.284 ± 0.06, respectively) and decreased D-RSBI (22.76 ± 6.14 vs. 20.06 ± 6.04, respectively), all of which were statistically significant ( P < 0.05). In contrast, in the control group of patients, there were no statistically significant differences in the postadministration levels of DE, TFdi, and D-RSBI as compared to the preadministration period ( P > 0.05). Furthermore, in terms of weaning outcomes, we did not find any statistically significant difference in the number of patients in the two groups who eventually underwent weaning ( P = 0.545). Conclusion: In this study, we found that levosimendan enhanced diaphragm contractile function. However, further investigations are required to explore its effect on weaning outcomes in patients undergoing mechanical ventilation.

Prediction of fluid responsiveness for patients in shock using a ventilator disconnection test combined with the pulse contour-derived cardiac index.

BACKGROUND: Finding a simple and reliable method to predict and assess fluid responsiveness has long been of clinical interest. OBJECTIVE: To investigate the predictive value of a ventilator disconnection (DV) test combined with the pulse contour-derived cardiac output (PiCCO) index on fluid responsiveness for patients in shock. METHODS: Thirty-two patients were chosen for the study. Patients who were in shock, received mechanical ventilation, and met the inclusion criteria were selected. Patients were divided into a fluid-responsive group (14 patients) and fluid-unresponsive group (18 patients) based on whether the increase in cardiac index (Δ CI) was > 10% or not, respectively, following the fluid challenge test. Changes in heart rate, pulse oximeter-measured oxygen saturation, mean arterial pressure (MAP), and CI before and after passive leg raising (PLR), DV, and fluid challenge tests were observed. We used Pearson's correlation coefficient to analyze an increase in the MAP (Δ MAP) and Δ CI before and after the PLR, DV, and fluid challenge tests; the sensitivity and specificity of the Δ MAP and Δ CI in the PLR and DV tests for predicting fluid response were also analyzed by plotting the receiver operating characteristic (ROC) curves. RESULTS: CI results in the PLR and DV tests, as well as the fluid challenge test, were significantly higher in the fluid-responsive group compared with before the test (P< 0.05). The Δ CI before and after the PLR, DV, and fluid challenge tests were positively correlated among patients in the fluid-responsive group. The area under the ROC curve for the post-PLR test CI and the post-DV CI for predicting fluid responsiveness was 0.869 (95% confidence interval (CI) [0.735-1.000, P= 0.000]) and 0.937 (95% CI [0.829-1.000, P= 0.000]), respectively, in patients in the fluid-responsive group. The sensitivity and specificity of the post-DV CI for predicting fluid responsiveness in all patients was 100.0% and 88.9%, respectively, using a 5% increase as the cut-off value. CONCLUSION: Application of DV, combined with PiCCO, has a high predictive value for fluid responsiveness among patients in shock.

Efficacy of Levosimendan in the Treatment of Patients With Severe Septic Cardiomyopathy.

OBJECTIVE: This study was designed to compare the effects of levosimendan and dobutamine on hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤35%). DESIGN: A prospective, single-blind, randomized controlled study. SETTING: In Baoding, China. PARTICIPANTS: Thirty patients with severe septic cardiomyopathy treated in the authors' hospital's Department of Critical Medicine from September 2018 to September 2021 were enrolled in this study. INTERVENTIONS: These patients were divided randomly into the levosimendan group and dobutamine group. The LVEF, cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index, heart rate, norepinephrine dose, and lactate at the time of enrollment and the 24th hour were compared, along with myocardial injury markers on the third day, C-reactive protein, mechanical ventilation time, length of intensive care unit (ICU) stay, cost, and 28-day mortality. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: At the 24th hour after treatment, CI, LVEF, SVI, and fluid volume were found to be higher in the levosimendan group than in the dobutamine group, whereas the dose of norepinephrine was lower in the former rather than the latter group. On the third day of treatment, cardiac troponin I in the levosimendan group was lower than that in the dobutamine group. Although the differences in 28-day mortality, ICU stay, and ICU treatment cost between the groups were not statistically significant, the ventilator application time of the levosimendan group was significantly shorter than that of the dobutamine group. CONCLUSIONS: Compared with dobutamine, levosimendan was more effective at improving cardiac function, reducing myocardial injury, and reducing mechanical ventilation time in patients with severe septic cardiomyopathy.

miR-100-5p in human umbilical cord mesenchymal stem cell-derived exosomes mediates eosinophilic inflammation to alleviate atherosclerosis via the FZD5/Wnt/ß-catenin pathway.

Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-Ex) play important roles in immune and inflammation diseases. However, the role of hUCMSC-Ex in atherosclerosis has not been elucidated. In this study, the isolated exosomes were identified by transmission electron microscopy and nanoparticle tracking analysis. Exosome marker protein levels were increased in the hUCMSC-Ex compared with those in hUCMSC suspension, indicating that exosomes were successfully isolated from hUCMSCs. Furthermore, eosinophils were treated with oxidized low-density lipoprotein (ox-LDL) to construct inflammation model and then incubated with hUCMSC-Ex derived from hUCMSCs which were transfected with miR-100-5p mimic or miR-100-5p inhibitor. We found that hUCMSC-Ex increased miR-100-5p expression, inhibited cell migration, promoted cell apoptosis, and reduced inflammatory cytokine levels in ox-LDL-treated eosinophils, and miR-100-5p overexpression in hUCMSCs enhanced these effects, while miR-100-5p inhibition reversed these effects. Moreover, frizzled 5 (FZD5) was a target gene of miR-100-5p. FZD5 overexpression reversed the inhibitory effects of hUCMSC-Ex-miR-100-5p on cell progression and inflammation in eosinophils. Additionally, hUCMSC-Ex-miR-100-5p decreased the expression of cyclin D1 and ß-catenin proteins. Wnt/ß-catenin pathway activator BML-284 effectively reversed the effects of hUCMSC-Ex-miR-100-5p on cell progression and inflammation in eosinophils. ApoE-/- mice were fed with high-fat diet to construct an atherosclerosis mice model, and hUCMSC-Ex was injected into mice. hUCMSC-Ex reduced atherosclerotic plaque area and inflammation response in atherosclerosis mice. This study demonstrates that hUCMSC-Ex-miR-100-5p inhibits cell progression and inflammatory response in eosinophils via the FZD5/Wnt/ß-catenin pathway, thereby alleviating atherosclerosis progression.

Galactose protects pancreatic acinar cells from cerulein induced damage by regulating FGF21 and Klotho.

To investigate the effect and mechanism of galactose on cerulean-induced pancreatic acinar cell injury. Acute pancreatitis cell injury model was established by arbusin-induced pancreatic acinar cell AR42J injury; galactose (25, 50, 100 mmol / L) was used to treat the injured cells, and the optimal concentration was 50 mmol / L; cell counting kit (CCK-8), enzyme linked immunosorbent assay (ELISA) to detect cell survival rate and necrosis rate; flow cytometry and Western blotting (Western blot) to detect cell apoptosis and autologous phage-related gene (Beclin1) and microtubule-associated protein 1 light chain 3 (LC3), apoptosis-related protein B-cell lymphoma / leukemia-2 (Bcl-2), Bcl-2-related X gene (Bax), and fibroblasts Expression of growth factor 21 antibody (FGF21) and anti-aging gene Klotho. A pancreatic acinar cell injury model was successfully established with cerana (100 nmol / L); galactose (25, 50, 100 mmol/L) In a concentration-dependent manner, the inhibitory effect of ceriferin on AR42J injury was inhibited at an optimal concentration of 50 mmol / L. Compared with the ceriferin group, the apoptosis rate of AR42J cells in the galactose group was significantly reduced. table Significantly increased, Bcl-2, FGF21 and Klotho protein expression was significantly increased, Bax protein was significantly decreased; the FGF21 inhibitor can be significantly reduced on galactose these caerulein-induced AR42J cells. Galactose can inhibit the apoptosis and autophagy of pancreatic acinar cells induced by cerana, and its potential mechanism is to up-regulate FGF21 and Klotho, providing a new potential drug for the treatment of acute pancreatitis.

Research on the Correlation of Serum PCT and Plasma GSN Levels with the Prognosis of Urosepsis Patients.

OBJECTIVE: To explore the correlation of procalcitonin (PCT) and gelsolin (GSN) with the prognosis of urosepsis patients. METHOD: The data of 71 urosepsis patients from March 2015 to April 2019 who were admitted to and treated in Affiliated Hospital of Hebei University were analyzed and compared with those of 92 healthy persons. Serum PCT and plasma GSN levels at different times after treatment were detected. According to prognosis, patients were classified into the good prognosis group or the poor prognosis group. The serum PCT and plasma GSN levels of both groups were compared. RESULT: The serum PCT level of the urosepsis group on the 1st, 3rd, 5th and 7th days was obviously higher than that of the control group (P<0.05). The plasma GSN levels of the urosepsis group on the 1st, 3rd, 5th and 7th days were obviously lower than those of the control group (P<0.05). The serum PCT level of the poor prognosis group on the 1st, 3rd, 5th and 7th days was obviously higher than that of the good prognosis group (P<0.05). The plasma GSN level of the poor prognosis group on the 1st, 3rd, 5th and 7th days was obviously lower than that of the good prognosis group (P<0.05). PCT was an independent risk factor influencing the prognosis of urosepsis patients and that GSN was a protective factor (P<0.05). CONCLUSION: The serum PCT and plasma GSN levels can accurately predict the severity and prognosis of urosepsis patients and reflect the disease state of early urosepsis patients. High PCT levels and low GSN levels indicate poor prognosis, and clinicians should consider these values.

A cross-sectional study on factors associated with hypertension and genetic polymorphisms of renin-angiotensin-aldosterone system in Chinese hui pilgrims to hajj.

BACKGROUND: Hypertension is the leading risk factor for cardiovascular disease (CVD), however, the studies on lifestyle and genetic risks in Chinese pilgrims to Hajj was limited. The aim of this study is to examine the prevalence and associated lifestyle and genetic risks for hypertension among Hui Hajj pilgrims in China. METHODS: We performed a cross-sectional analysis of data in 1,465 participants aged 30-70 years who participated in a medical examination for Hui Hajj pilgrims from Gansu province, China in 2017. Multiple logistic regression was used to evaluate the association of potential risk factors with hypertension. Deoxyribonucleic acid (DNA) polymorphism was examined at sites in the renin-angiotensin-aldosterone system (RAAS). RESULTS: The prevalence of hypertension was 47% among this population. Lifestyle factors such as fried food preference (like vs. dislike: odds ratio [OR]: =1.53, 95% confidence interval [CI]: 1.13-2.09) and barbecued food preference (like vs. dislike: OR = 1.45, 95% CI: 1.06-1.97) were associated with elevated risk of hypertension among Hui pilgrims. Comparing with Angiotensin converting enzyme (ACE) rs4425 AA genotype, TT genotype was associated with hypertension risk (OR = 2.16, 95% CI: 1.17-4.00). Similar results were also observed for ACE rs4437 CC genotype (OR = 1.95, 95% CI: 1.07-3.55), Angiotensin II receptor (ATR) rs129876 AA genotype (OR = 4.10, 95% CI: 2.30-7.32) and Aldosterone synthase (CYP11B2) rs1912 TT genotype (OR = 2.82, 95% CI: 1.57-5.06) genotypes. CONCLUSIONS: Unhealthy lifestyle and genetic factors were associated with the prevalence of hypertension in Chinese Hui pilgrims and their interactions were also observed.

Prognostic significance of PCT and CRP evaluation for adult ICU patients with sepsis and septic shock: retrospective analysis of 59 cases.

OBJECTIVE: To investigate the prognostic significance of serum procalcitonin (PCT) and C-reactive protein (CRP) in patients with sepsis and those with septic shock. METHODS: Fifty-nine patients were divided into sepsis and septic shock groups, as well as survivor and non-survivor groups, according to the severity of the disease and patient survival. Serum PCT and CRP measurements at the time of hospitalization in the intensive care unit were examined. RESULTS: On the 2nd, 3rd, and 5th days, the CRP level was higher in the non-survivor group than in the survivor group, and the serum CRP level was higher in patients in the septic shock group than in patients in the sepsis group. Regarding changes in serum PCT level in each group, the levels of PCT were significantly different between non-survivor and survivor groups, whereas they did not differ between patients in the sepsis and septic shock groups. Serum PCT kinetics (ΔPCT) were similar between groups. CONCLUSIONS: Serum PCT and CRP have good clinical diagnostic and prognostic value for patients with sepsis and septic shock. Kinetic studies of PCT and CRP can improve sensitivity and accuracy when evaluating the prognosis of patients with sepsis and those with septic shock.

[Effect of diallyl trisulfide on tumor necrosis factor-alpha expression and nuclear factor-KappaB activity in mice with acute lung injury induced by lipopolysaccharide].

OBJECTIVE: To investigate the effect of diallyl trisulfide (DATS) on tumor necrosis factor-alpha (TNF-alpha) expression and nuclear factor-KappaB (NF-KappaB) activity in mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: ALI murine model was reproduced by injection of LPS intraperitoneally. Mice were randomly divided into normal saline control group, ALI group, DATS prevention group, DATS treatment group, and DATS control group. The TNF-alpha levels in the serum and in the supernatant of lung homogenates were measured with enzyme linked immunoadsorbent assay (ELISA). The expression of TNF-alpha mRNA in the lung tissues was detected by reverse transcription polymerase chain reaction (RT-PCR). NF-KappaB activity in the lung tissues was detected by electrophoresis mobility shift assay (EMSA). RESULTS: The levels of TNF-alpha induced by LPS in the serum and the supernatant of lung homogenates were increased markedly at 2 hours in ALI group (both P<0.01), and decreased at 6 hours, but they were still higher than those of the control groups (all P<0.01). They were reduced in DATS prevention group at 2 and 6 hours compared with those of ALI group (P<0.05 or P<0.01), but no change was noted in DATS treatment group (all P>0.05). The expression of TNF-alpha mRNA in the lung tissues of ALI group increased markedly at 2 hours compared with those of control groups (both P<0.01), and it could be down-regulated by pretreatment with DATS (P<0.05). No change in DATS was found in treatment group. NF-KappaB activity in the lung tissue increased in ALI group compared with that of control groups (both P<0.05), and it was markedly reduced in DATS prevention group (P<0.05), but no change was found in DATS treatment group. CONCLUSION: Pretreatment of DATS for ALI in mice could inhibit NF-KappaB activity, TNF-alpha mRNA expression in lung tissues, and decrease the release of TNF-alpha in the serum and the lung homogenates, and they might be the underlying mechanisms of prevention of the occurrence of ALI by DATS.