Guanxin V alleviates ventricular remodeling after acute myocardial infarction with circadian disruption by regulating mitochondrial dynamics.

PURPOSE: Circadian disruption has been a common issue due to modern lifestyles. Ventricular remodeling (VR) is a pivotal progressive pathologic change after acute myocardial infarction (AMI) and circadian disruption may have a negative influence on VR according to the latest research. Whether or not Guanxin V (GXV) has a positive effect on VR after AMI with circadian disruption drew our interest. METHODS: Rats were randomly divided into a sham group, an AMI group, an AMI with circadian disruption group, and an AMI with circadian disruption treated with the GXV group according to a random number table. RNA sequencing (RNA-Seq) was utilized to confirm the different expressed genes regulated by circadian disruption. Cardiac function, inflammation factors, pathological evaluation, and mitochondrial dynamics after the intervention were conducted to reveal the mechanism by which GXV regulated VR after AMI with circadian disruption. RESULTS: RNA-Seq demonstrated that NF-κB was up-regulated by circadian disruption in rats with AMI. Functional and pathological evaluation indicated that compared with the AMI group, circadian disruption was associcataed with deteriorated cardiac function, expanded infarcted size, and exacerbated fibrosis and cardiomyocyte apoptosis. Further investigation demonstrated that mitochondrial dynamics imbalance was induced by circadian disruption. GXV intervention reversed the inflammatory status including down-regulation of NF-κB. Reserved cardiac function, limited infarct size, and ameliorated fibrosis and apoptosis were also observed in the GXV treated group. GXV maintained mitochondrial fission/fusion imbalance through suppressed expression of mitochondrial fission-associated proteins. CONCLUSION: The study findings suggest that identified mitochondrial dysfunctions may underlie the link between circadian disruption and VR. GXV may exert cardioprotection after AMI with circadian disruption through regulating mitochondrial dynamics.

Ziqi Dihuang decoction ameliorates thrombosis in septic rats by inhitbiting plasminogen activator inhibitor-1.

Introduction: Sepsis is now a global medical burden with high morbility and mortality. The focus of this study was to evaluate the effects of Ziqi Dihuang (ZQDH) decoction on inflammatory and thrombosis-related parameters in septic rats. Mothods: A rat model of sepsis was established by cecal ligation and puncture (CLP). Male Sprague-Dawley rats were randomly divided into Sham group, CLP group, ZQDH-1ow group (0.735 g/kg) and ZQDH-high group (1.47 g/kg). Rats in ZQDH groups were given ZQDH decoction by gavage for 7 days before CLP. White blood cells (WBC), inflammatory cell infiltration of liver, kidney and lung, as well as serum levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and reactive oxygen species (ROS) were used to assess systemic inflammatory response. Coagulation and fibrinolytic indexes included platelet count, coagulation function, fibrin deposition, and levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in serum, liver, kidney and lung. Results: LPS rats showed significant changes in inflammatory and thrombosis-related parameters such as increased WBC and inflammatory factors, decreased platelet counts, and increased tPA and PAI-1 concentrations in serum and organs. ZQDH decoction pretreatment can significantly inhibit the infiltration of inflammatory cells in the lung, and inhibit the production of TNF-α, IL-6 and ROS in a dose-dependent manner. ZQDH decoction also ameliorated thrombocytopenia, renal fibrin deposition, and tPA and PAI-1 levels in serum and organs. Conclusion: These results suggest that ZQDH decoction can dose-dependently relieve systemic inflammatory injury and regulate fibrinolysis system in septic rats, which may be mediated by PAI-1.

Understanding clinical characteristics influencing adverse outcomes of Omicron infection: a retrospective study with propensity score matching from a Fangcang hospital.

Objectives: The epidemic of coronavirus disease 2019 (COVID-19) is causing global health concerns. The aim of this study was to evaluate influence of clinical characteristics on outcomes during the Omicron outbreak. Methods: A total of 25182 hospitalized patients were enrolled, including 39 severe patients and 25143 non-severe patients. Propensity score matching (PSM) was applied to balance the baseline characteristics. Logistic regression analysis was used to assess the risk of severe disease, as well as the risk of prolonged viral shedding time (VST) and increased length of hospital stay (LOS). Results: Before PSM, patients in the severe group were older, had higher symptom scores, and had a higher proportion of comorbidities (p<0.001). After PSM, there were no significant differences in age, gender, symptom score and comorbidities between severe (n=39) and non-severe (n=156) patients. Symptoms of fever (OR=6.358, 95%CI 1.748-23.119, p=0.005) and diarrhea (OR=6.523, 95%CI 1.061-40.110, p=0.043) were independent risk factors for development of severe disease. In non-severe patients, higher symptom score was associated with prolonged VST (OR=1.056, 95% CI 1.000-1.115, p=0.049) and LOS (OR=1.128, 95% CI 1.039-1.225, p=0.004); older age was associated with longer LOS (OR=1.045, 95% CI 1.007-1.084, p=0.020). Conclusion: The overall condition of the Shanghai Omicron epidemic was relatively mild. Potential risk factors for fever, diarrhea, and higher symptom score can help clinicians to predict clinical outcomes in COVID-19 patients.

LPS-aggravated Ferroptosis via Disrupting Circadian Rhythm by Bmal1/AKT/p53 in Sepsis-Induced Myocardial Injury.

Circadian disruption is involved in the progress of sepsis-induced cardiomyopathy (SICM), one of the leading causes of death in sepsis. The molecular mechanism remains ambiguous. In this study, LPS was used to build SICM model in H9c2 cell. The results suggested that LPS induced cytotoxicity via increasing ferroptosis over the time of course. After screening the expressions of six circadian genes, the circadian swing of Bmal1 was dramatically restrained by LPS in H9c2 cell of SIMC vitro model. PcDNA and siRNA were used to upregulate and downregulate Bmal1 and confirmed that Bmal1 inhibited LPS-triggered ferroptosis in H9c2 cells. Then, the results suggested that AKT/p53 pathway was restrained by LPS in H9c2 cell. Rescue test indicated that Bmal1 inhibited LPS-triggered ferroptosis via AKT/p53 pathway in H9c2 cells. In summary, our findings demonstrated that LPS induced cytotoxicity via increasing ferroptosis over the time of course in H9c2 cells and Bmal1 inhibited this toxicity of LPS via AKT/p53 pathway. Although further studies are needed, our findings may contribute to a new insight to mechanism of SICM.

ECG criteria to distinguish hypertrophic cardiomyopathy featured with "Pseudo-STEMI" from acute ST-elevation myocardial infarction.

BACKGROUD: The ECG profile of Hypertrophic Cardiomyopathy (HCM) includes ST-segment elevation (STE) that may lead to misdiagnosis of acute ST-segment elevation myocardial infarction (STEMI). This pseudo-STEMI may bring non-essential treatment. We aimed to confirm the ECG differences between HCM featured with pseudo-STEMI and acute STEMI. MATERIAL AND METHODS: We retrospectively enrolled 59 HCM cases (Group A) and 56 acute STEMI cases (Group B). Based on the locations of STE, all the patients were divided into four subgroups, including HCM with STE in anterior leads (Group A1), anterior STEMI (Group B1), HCM with STE in inferior leads (Group A2) and inferior STEMI (Group B2). Several ECG parameters were compared between these subgroups. RESULTS: ECG parameters significantly differed between these groups, especially the number of leads with TWI. We evaluated the diagnostic value of ECG profiles for those groups. ROC analysis showed that for Group A vs. Group B, number of leads with TWI showed the highest AUC value of 0.805 and its cutoff of 2.5, with 76.3% sensitivity and 76.8% specificity. For Group A1 vs. Group B1, it showed the highest AUC value of 0.801 and its cut-off point was 2.5, with 77.1% sensitivity and 79.1% specificity. For Group A2 vs. Group B2, it showed the highest AUC value of 0.822 and the cut-off value was 4.5, with 54.5% sensitivity and 92.3% specificity. CONCLUSION: ECG plays a valid tool to distinguish "Pseudo-STEMI" HCM from acute STEMI, especially number of leads with TWI.

Association between short-term exposure to ambient air pollution and heart failure: An updated systematic review and meta-analysis of more than 7 million participants.

Introduction: Exposure to air pollution has been linked to the mortality of heart failure. In this study, we sought to update the existing systematic review and meta-analysis, published in 2013, to further assess the association between air pollution and acute decompensated heart failure, including hospitalization and heart failure mortality. Methods: PubMed, Web of Science, EMBASE, and OVID databases were systematically searched till April 2022. We enrolled the studies regarding air pollution exposure and heart failure and extracted the original data to combine and obtain an overall risk estimate for each pollutant. Results: We analyzed 51 studies and 7,555,442 patients. Our results indicated that heart failure hospitalization or death was associated with increases in carbon monoxide (3.46% per 1 part per million; 95% CI 1.0233-1.046, P < 0.001), sulfur dioxide (2.20% per 10 parts per billion; 95% CI 1.0106-1.0335, P < 0.001), nitrogen dioxide (2.07% per 10 parts per billion; 95% CI 1.0106-1.0335, P < 0.001), and ozone (0.95% per 10 parts per billion; 95% CI 1.0024-1.0166, P < 0.001) concentrations. Increases in particulate matter concentration were related to heart failure hospitalization or death (PM2.5 1.29% per 10 µg/m3, 95% CI 1.0093-1.0165, P < 0.001; PM10 1.30% per 10 µg/m3, 95% CI 1.0102-1.0157, P < 0.001). Conclusion: The increase in the concentration of all pollutants, including gases (carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone) and particulate matter [(PM2.5), (PM10)], is positively correlated with hospitalization rates and mortality of heart failure. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021256241.

Quercetin Antagonizes Glucose Fluctuation Induced Renal Injury by Inhibiting Aerobic Glycolysis via HIF-1α/miR-210/ISCU/FeS Pathway.

Background and Objective: Glucose fluctuation (GF) has been reported to induce renal injury and diabetic nephropathy (DN). However, the mechanism still remains ambiguous. Mitochondrial energy metabolism, especially aerobic glycolysis, has been a hotspot of DN research for decades. The activation of HIF-1α/miR210/ISCU/FeS axis has provided a new explanation for aerobic glycolysis. Our previous studies indicated quercetin as a potential therapeutic drug for DN. This study aims to evaluate levels of aerobic glycolysis and repressive effect of quercetin via HIF-1α/miR210/ISCU/FeS axis in a cell model of GF. Methods: The mouse glomerular mesangial cells (MCs) were exposed in high or oscillating glucose with or without quercetin treatment. Cell viability was measured by CCK8 assay. Aerobic glycolysis flux was evaluated by lactate acid, pH activity of PFK. Apoptosis level was confirmed by Annexin V-APC/7-AAD double staining and activity of caspase-3. TNF-α and IL-1ß were used to evaluate inflammation levels. Results: GF deteriorated inflammation damage and apoptosis injury in MCs, while quercetin could alleviate this GF-triggered cytotoxicity. GF intensified aerobic glycolysis in MCs and quercetin could inhibit this intensification in a dose-dependent manner. Quercetin prevented activities of two FeS-dependent metabolic enzymes, aconitase, and complex I, under GF injury in MCs. The mRNA expression and protein contents of HIF-1α were increased after GF exposure, and these could be alleviated by quercetin treatment. Knockdown of ISCU by siRNA and Up-regulating of miR-210 by mimic could weaken the effects of quercetin that maintained protein levels of ISCU1/2, improved cell viability, relieved inflammation injury, decreased apoptosis, and reduced aerobic glycolysis switch in MCs. Conclusion: Quercetin antagonizes GF-induced renal injury by suppressing aerobic glycolysis via HIF-1α/miR-210/ISCU/FeS pathway in MCs cell model. Our findings contribute to a new insight into understanding the mechanism of GF-induced renal injury and protective effects of quercetin.

[A systematic review and Meta-analysis of Tongfu Xiefei method in the treatment of acute respiratory distress syndrome].

OBJECTIVE: To systematically review the effect of Tongfu Xiefei method on prognosis and respiratory mechanics parameters in patients with acute respiratory distress syndrome (ARDS). METHODS: The randomized controlled trials (RCT) of Tongfu Xiefei method for ARDS published on PubMed, Web of Science, Embase, CNKI and Wanfang database from January 1st 2001 to June 30th 2019 were searched. Conventional treatment for ARDS that included mechanical ventilation, prone ventilation, anti-infection, organ function maintenance and nutritional therapy were used in the control group. While the Tongfu Xiefei method was applied in the experimental group based on the conventional treatment. The main outcome was in-hospital mortality, and the secondary outcomes included mechanic ventilation time, length of intensive care unit (ICU) stay and respiratory mechanics parameters. Two researchers independently searched the literature, collected data and assessed the risk of bias. The bias risk assessment was completed by RevMan 5.3 software. The Meta-analysis was completed by R software. The potential publication bias of main outcome was evaluation. RESULTS: A total of 27 RCTs were included. There were 1 763 patients, including 899 in the experimental group and 864 in the control group. Meta-analysis showed that, compared with the control group, the in-hospital mortality of the experimental group significantly decreased [relative risk (RR) = 0.46, 95% confidence interval (95%CI) was 0.36 to 0.59, P < 0.000 1], the mechanic ventilation time and the length of ICU stay were significantly shortened [mechanical ventilation time: standard mean difference (SMD) = -1.92, 95%CI was -2.56 to -1.29, P < 0.000 1; length of ICU stay: SMD = -1.84, 95%CI was -2.49 to -1.18, P < 0.000 1], oxygenation index was significantly improved (SMD = 2.26, 95%CI was 1.56 to 2.96, P < 0.000 1), airway peak pressure, airway platform pressure, mean airway pressure and airway resistance significantly decreased (airway peak pressure: SMD = -1.26, 95%CI was -2.35 to -0.18, P = 0.021 8; airway platform pressure: SMD = -0.61, 95%CI was -1.08 to -0.14, P = 0.010 7; mean airway pressure: SMD = - 1.67, 95%CI was - 2.93 to -0.42, P = 0.009 1; airway resistance: SMD = -0.88, 95%CI was -1.09 to -0.67, P < 0.000 1), while lung compliance increased (SMD = 1.57, 95%CI was 0.78 to 2.36, P < 0.000 1). The results of publication bias assessment showed that there was no potential publication bias (P = 0.499). CONCLUSIONS: Tongfu Xiefei method is capable of reducing the in-hospital mortality, shortening the mechanical ventilation time and the length of ICU stay, and improving respiratory mechanics parameters for patients with ARDS.

miR-34b-3p protects against acute kidney injury in sepsis mice via targeting ubiquitin-like protein 4A.

MicroRNAs (miRNAs) have been reported as a diagnostic markers for sepsis, and miRNAs have also been found to play a regulatory role in sepsis-induced acute kidney injury (AKI). However, the regulatory effect and mechanism of miR-34b-3p on AKI remains elusive. First, sepsis mice with AKI was established via cecal ligation puncture (CLP), and verified through hematoxylin-eosin staining, determination of tumor necrosis factor-α (TNF-α), interleukin (IL)-6/1ß and serum levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). Data showed that CLP-induced mice demonstrated increased ALT, BUN, TNF-α, IL-1ß, and IL-6 with injured pathological morphology of kidney tissues. Second, lipopolysaccharide (LPS) treatment elevated TNF-α, IL-1ß, and IL-6 contents in rat mesangial cells (RMCs). MiR-34b-3p was downregulated in both CLP-induced mice and LPS-induced RMCs. Third, target gene of miR-34b-3p was verified as ubiquitin-like protein 4A (UBL4A), and UBL4A was upregulated in LPS-induced RMCs. MiR-34b-3p could inhibit UBL4A expression and decreased TNF-α, IL-1ß and IL-6 contents in LPS-induced RMCs, while overexpression of UBL4A counteract with the suppressive effects of miR-34b-3p on the protein expression. Moreover, transcriptional activity of UBL4A-induced NF-κB was decreased by miR-34b-3p. Lastly, in vivo injection of miR-34b-3p agomir improved CLP-induced kidney tissues injury with declined ALT, BUN, TNF-α, IL-1ß, IL-6, and UBL4A. In general, miR-34b-3p overexpression could alleviate AKI in sepsis mice through downregulation of UBL4A/NF-κB, providing potential therapeutic strategy for AKI.

Effect of a short-term vitamin E supplementation on oxidative stress in infertile PCOS women under ovulation induction: a retrospective cohort study.

BACKGROUND: Vitamin E, which is critically important in the whole process of reproduction, can antagonize the oxidative stress caused by the oxygen free radicals and antioxidant imbalance and regulate normal physiological function of the reproductive system. The effect of short-term supplementation of vitamin E on outcomes of infertile women with polycystic ovary syndrome (PCOS) when they underwent ovulation induction with clomiphene citrate (CC) and human menopausal gonadotropin (HMG) remains unknown. METHODS: This was a retrospective cohort clinical trial from October 2015 to April 2017. A total of 321 PCOS cases underwent ovulation induction with CC and HMG. Patients in group A (n = 110) did not receive vitamin E while patients in group B (n = 105) and group C (n = 106) received oral treatment of vitamin E at 100 mg/day during follicular phase and luteal phase, respectively. RESULTS: It was observed no significant differences of ovulation rate, clinical pregnancy rate, and ongoing pregnancy rate among the three groups. It was interesting that dosage of HMG were significant lower in group B compared with those in group A and group C (P<0.05). CONCLUSIONS: A short-term supplementation of vitamin E can improve oxidative stress, and reduce exogenous HMG dosage to lower the economic cost with a similar pregnancy rate in the ovulation induction cycle. However, the supplementation does not alter the pregnancy rate in the ovulation induction cycle. TRIAL REGISTRATION: ChiCTR-OOC-14005389, 2014.

[Diagnostic accuracy of artery peak velocity variation measured by bedside real-time ultrasound for prediction of fluid responsiveness: a Meta-analysis].

OBJECTIVE: To evaluate the diagnostic value of ultrasonic measurement of artery peak velocity variation (ΔVpeak) on predicting fluid responsiveness in critically ill patients. METHODS: Databases of PubMed, Embase, Cochrane Library, SinoMed, Wanfang, CNKI and VIP were retrieved from the establishment of the database to November 2019. The retrieval literatures were about the research of ΔVpeak used to judge fluid responsiveness. According to the inclusion and exclusion criteria, the relevant literatures were screened by two researchers, and the data of the included literatures were extracted. The quality of literatures was evaluated by quality assessment of diagnostic accuracy studies (QUADAS). Meta Dics 1.4 software was used to analyze the literatures that met the quality standard by Meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curve was drawn and the area under SROC curve (AUC) was calculated. The χ2 test and Spearman correlation coefficient were used to analyze heterogeneity, and Deek test was used to analyze publication bias. RESULTS: A total of 1 854 patients were enrolled in 31 studies, including 11 domestic studies and 20 foreign studies. Using 14 items of QUADAS to evaluate the quality of literatures, it was found that the enrolled literatures were all in Grade A, indicating that the overall quality of literatures was high. The scattered distribution of SROC curve was not "shoulder arm shape", and Spearman correlation coefficient was 0.062 (P = 0.710), so there was no threshold effect. The heterogeneity test showed that I2 = 57.2% (P = 0.001), indicating that there was a certain degree of heterogeneity among the studies, and the source of heterogeneity was non threshold effect. Meta regression analysis showed that the reason for heterogeneity was the method of volume load test [DOR = 3.87, 95% confidence interval (95%CI) was 1.56-9.57, P = 0.004 8]. According to the results of heterogeneity analysis, there was no significant heterogeneity (I2 = 10.6, P = 0.288 5) among the studies after removing the samples of the passive leg raising (PLR) instead of the volume expansion. A meta-analysis was done with random effects model. The results showed that the pooled DOR was 23.85 (95%CI was 17.57 to 32.37), pooled sensitivity was 0.82 (95%CI was 0.80 to 0.85), pooled specificity was 0.83 (95%CI was 0.80 to 0.85), pooled PLR was 4.17 (95%CI was 3.58 to 4.86), and pooled NLR was 0.22 (95%CI was 0.18 to 0.28). The AUC was 0.901 2 (95%CI was 0.88 to 0.93), and Q index was 0.832 5. The results of Deek funnel plot showed that there was no published bias in all the studies (P = 0.19). CONCLUSIONS: Ultrasonic measurement of ΔVpeak has a high value in predicting fluid responsiveness. It is a reliable parameter for the evaluation of shock, critical illness and surgical operation population who need to monitor the fluid responsiveness.

LncRNA PEAMIR inhibits apoptosis and inflammatory response in PM2.5 exposure aggravated myocardial ischemia/reperfusion injury as a competing endogenous RNA of miR-29b-3p.

The sensitivity of myocardium is enhanced to ischemia/reperfusion (I/R) injury under PM2.5 exposure. It is still under prelude for lncRNA-miRNA pair in the study of aggravated myocardial I/R injury under PM2.5 exposure. In this study, we first built a rat model of 30 min ischemia and 24 h reperfusion followed PM2.5 (6.0 mg/kg) exposure. We found PM2.5 exposure could obviously aggravate I/R injury in the fields of myocardium damage, apoptosis levels and cardiac function which were evaluated by TTC staining, TUNEL and echocardiography, respectively. Then, based on results of sequencing and RT-qPCR, we selected NONRATT003473.2 in the follow-up experiments and named this lncRNA as PM2.5 exposure aggravated myocardial I/R injury lncRNA (PEAMIR). Consistent with the results rat model, we confirmed PEAMIR to be a protective lncRNA against PM + HR triggered damages in H9c2 cells. Next, according to the bioinformatics analysis from miRanda database and a series of gain- and loss-of-function experiments, we proved PEAMIR to be a ceRNA for miR-29b-3p to inhibit cardiac inflammation and apoptosis. Finally, using Target-Scan database, the conserved binding sites for miR-29b-3p was identified in the 3'UTR of PI3K (p85a), a key protein of apoptosis. Our subsequent experiments validated the regulatory relationship between PEAMIR-miR-29b-3p ceRNA pair and PI3K (p85a)/Akt/GSK3b/p53 cascade pathway. In conclusion, our study demonstrated the role and mechanism of PEAMIR in the augment of I/R injury under PM2.5 exposure, suggesting a promising strategy for the prevention and treatment of I/R injury under PM2.5 exposure.

[Inferior vena cava diameter combined with lung ultrasound B-line score to guide fluid resuscitation in patients with septic shock].

OBJECTIVE: To compare the effect of goal-directed fluid resuscitation and bedside ultrasound-guided fluid resuscitation in patients with septic shock, and to evaluate the application value of bedside ultrasound in fluid resuscitation of patients with septic shock. METHODS: Forty patients with septic shock admitted to department of critical care medicine of Affiliated Hospital of Nanjing University of Chinese Medicine from June 2018 to October 2019 were enrolled, and they were divided into early goal-directed therapy (EGDT) group and ultrasound group according to random number table, with 20 patients in each group. Bacterial cultures were routinely performed, and all patients received conventional treatments, such as anti-infection, nutritional support and organ support. All patients were given initial fluid resuscitation (30 mL/kg). The patients in the EGDT group continued to be given fluid resuscitation according to the guidelines (EGDT 6-hour target) after the initial fluid resuscitation. The patients in the ultrasound group were given follow-up fluid resuscitation based on bedside ultrasound inferior vena cava diameter and lung ultrasound B-line score after initial fluid resuscitation. The general data, main laboratory indexes and efficacy indexes of the two groups were compared, including 6-hour blood pressure achieved rate [mean arterial pressure (MAP) ≥ 65 mmHg (1 mmHg = 0.133 kPa) was defined as blood pressure reaching standard], 24-hour resuscitation fluid volume, 24-hour norepinephrine (NE) consumption, 24-hour oxygenation index (PaO2/FiO2) and 24-hour clearance of lactic acid (LCR) were compared between the two groups. The survival curve of intensive care unit (ICU) was drawn by Kaplan-Meier analysis. RESULTS: There was no significant difference in the gender, age, heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), underlying diseases, sequential organ failure assessment (SOFA) score, PaO2/FiO2, blood lactic acid (Lac), D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), total bilirubin (TBil) and serum creatinine (SCr) baselines at admission between the two groups. There was also no significant difference in the 6-hour target blood pressure achieved rate [65.0% (13/20) vs. 70.0% (14/20)], 24-hour total NE dosage [mg: 20.0 (10.0, 66.5) vs. 30.0 (10.5, 85.0)], 24-hour PaO2/FiO2 (mmHg: 274.6±123.8 vs. 243.1±124.0) or 24-hour LCR [9.1% (-34.5%, 58.0%) vs. 44.0% (-24.1%, 81.3%)] between the EGDT group and ultrasound group (all P > 0.05), but the 24-hour total fluid infusion in the ultrasound group was significantly less than that in the EGDT group (mL: 2 783.1±704.2 vs. 3 692.0±1 433.1, P < 0.05). The Kaplan-Meier survival curve showed that the cumulative survival rate of ICU between the two groups was not statistically significant (Log-Rank test: χ2 = 0.088, P = 0.767). CONCLUSIONS: Bedside ultrasound protocol combined inferior vena cava diameter with lung ultrasound B-line score can be used to guide fluid resuscitation in patients with septic shock, the total fluid infusion is decreased and the risk of oxygenation deterioration is reduced.

[Clinical Trial of Electroacupuncture Treatment for Relieving Stress Responses in Patients Undergoing Gastrointestinal Surgery].

OBJECTIVE: To observe the therapeutic effect of electroacupuncture (EA) at Zusanli (ST 36) and Neiguan (PC 6) on stress responses of patients undergoing gastrointestinal surgery. METHODS: A total of 40 patients undergoing gastrointestinal surgery were randomized into conventional treatment group (control) and EA group (n＝20 in each group). Patients of the EA group received conventional treatment (pre- and post-surgical fasting, measures for gastrointestinal decompression, parenteral nutrition support, and patient controlled analgesia pump, etc.) and EA stimulation (2 Hz, 30 min) of bilateral ST 36 and PC 6 (twice after surgery, at an interval of 6 h), and patients of the control group received conventional treatment only. The visual analogue scale (VAS) score was used to assess the patients' pain severity and the blood glucose levels were detected once every 4－6 h within 24 h after operation. Serum cortisol (Cort) and adrenocorticotropic hormone (ACTH) levels were detected by chemiluminescence method, and serum D-lactic acid level (for assessing gastrointestinal mucosal injury) was assayed by ELISA. RESULTS: After the treatment, the levels of serum Cort, ACTH, D-lactate acid and the highest blood glucose were significantly lower in the EA group than those in the control group (P<0.05, P<0.01), suggesting a reduction of stress reactions after EA. But no significant difference was found between the control and EA groups in the VAS score (P>0.05). CONCLUSION: EA at ST 36 and PC 6 can alleviate stress responses and reduce intestinal mucosal damage in patients undergoing gastrointestinal surgery.

Hydroxytyrosol Protects against Myocardial Ischemia/Reperfusion Injury through a PI3K/Akt-Dependent Mechanism.

OBJECTIVE: To investigate the effects and mechanisms of hydroxytyrosol (HT) during the pathogenesis of myocardial ischemia reperfusion (I/R) in rat hearts. METHODS: The rats were randomized into five groups: sham group, I/R group, HT+I/R group, HT+LY294002+I/R group, and LY+I/R group. Myocardial infarct size, markers of oxidative stress, extent of myocardial apoptosis, echocardiographically assessed cardiac function, and expression of Akt and GSK 3ß were measured in each group. RESULTS: Prereperfusion administration of HT was associated with a significantly smaller area of myocardial infarction and remarkably decreased level of myocardial apoptosis and necrosis, as evidenced by a lower apoptotic index, reduced cleaved caspase-3, and the serum activities of lactate dehydrogenase and creatinine kinase MB. Moreover, HT also attenuated the impairment of cardiac systolic function. However, cotreatment with LY294002 and HT completely abolished the above cardioprotective effects of HT. A subsequent mechanistic study revealed that the cardioprotective effects of HT during the process of I/R of the myocardium were dependent on the activation of the Akt/GSK3ß pathway. CONCLUSION: Pretreatment with HT may have antiapoptotic and cardioprotective effects against myocardial I/R injury, and these effects seem to be related to the activation of the Akt/GSK3ß pathway in the myocardium.

Concentration depth distribution of grain boundary segregation measured by wavelength dispersive X-ray spectroscopy.

A method using wavelength dispersive X-ray spectroscopy (WDS) is applied to the measurement of grain boundary segregation of Sn in silicon steel. The quantification of monolayer concentration of Sn is acquired, which demonstrates an obvious segregation of Sn at grain boundaries. In consideration of the fact that segregated impurities (Sn or other species) distribute in multilayer and not just monolayer segregation can be characterized by WDS, the Gaussian distribution is applied to formulate the multilayer concentration depth distribution according to the measured total concentration. A correction factor is then put forward to improve the quantification. Based on the measured segregation of Sn and the derived formula of multilayer concentration depth distribution, the grain boundary concentrations of Sn are calculated for different thicknesses of segregated layer. From the experimental measurement, theoretical analyses and calculated results, an effective approach for the research of grain boundary segregation is provided.

The role of p38 MAPK in acute paraquat-induced lung injury in rats.

CONTEXT: Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium dichloride) is highly toxic and accounts for a large proportion of the herbicide poisonings seen in clinic. The major cause of mortality is respiratory failure. The p38 mitogen-activated protein kinase (MAPK) signal transduction pathway coordinates various cellular stress responses that have been shown to participate in the pathogenesis of PQ-induced lung injury. OBJECTIVE: To evaluate the effect of the specific p38 MAPK inhibitor SB203580 on PQ-induced lung injury and cytokine secretion. METHODS: In groups of 24, rats were treated with PQ, PQ and SB203580 (SB + PQ), SB203580 alone (SB) or normal saline (control group). Six rats from each group were euthanized at 1, 3, 5 or 7 d. Pathology of lung specimens was scored through hematoxylin and eosin staining. Edema in the lung was quantified from wet-to-dry weight ratios. p38 and p-p38MAPK proteins were measured via electrochemiluminescent Western blots. tumor necrosis factor (TNF)-alpha and interleukin-1 beta (IL-1ß) concentrations in lung specimens and bronchoalveolar lavage fluid (BALF) were quantified via enzyme-linked immunosorbent assay. RESULTS: The mortality rate of the SB + PQ group (16.7%) was significantly lower than that of the PQ group (33.3%; p < 0.05). The PQ group had significantly higher pulmonary histology scores, wet-to-dry weight ratios and phosphorylated p-p38 MAPK levels, as well as higher IL-1ß and TNF-alpha levels in BALF and lung tissues, that did the SB + PQ and control groups (p < 0.05, all). CONCLUSION: The data suggest that the p38 MAPK signaling pathway has an important role in regulating the production of IL-1ß and TNF-alpha in PQ-induced lung injury in rats.

Altered serum microRNAs as novel diagnostic biomarkers for atypical coronary artery disease.

BACKGROUND AND AIM: Atypical coronary artery disease (ACAD) is characterized by atypical angina pectoris or silent myocardial ischemia. However, conventional diagnostic techniques are insufficient to identify this subtype of coronary atherosclerotic pathology, and specific and sensitive markers for diagnosing ACAD are still currently lacking. The aim of the present study is to identify a novel serum microRNA (miRNA) expression profile of ACAD patients and evaluate its clinical diagnostic value. PATIENTS AND METHODS: 127 patients who were diagnosed with ACAD and 54 age-matched controls were enrolled in this study. An initial screen of miRNA expression was performed in serum samples from 35 patients and 20 controls using TaqMan Low Density Array. A stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and validation sets to confirm the levels of the altered miRNAs in 122 patients with ACAD and 68 controls. In addition, the potential target genes of the altered miRNAs were predicted using bioinformatics methods. RESULTS: The TaqMan low density array and RT-qPCR analysis identified four serum miRNAs including miR-487a, miR-502, miR-208 and miR-215 that were significantly increased, while one miRNA, miR-29b, that was significantly decreased in ACAD patients compared with normal controls (P<0.05). The area under the receiver-operating-characteristic (ROC) curve (AUC) for the combined 5 serum miRNAs were 0.850 (95% CI, 0.734-0.966, P<0.001) and 0.909 (95% CI, 0.858-0.960, P<0.001) for the training set and validation set, respectively. In addition, target gene prediction showed that these five altered miRNAs are involved in affecting various aspects of cardiac or vascular remodeling, especially in the pathway involving inflammation and fibrosis. CONCLUSION: Our findings indicate that the five altered serum miRNAs could be novel non-invasive biomarkers for ACAD and may also represent potential therapeutic targets for atherosclerosis and myocardial ischemia.

Oscillating high glucose enhances oxidative stress and apoptosis in human coronary artery endothelial cells.

PURPOSE: To investigate the toxic effect of oscillating high glucose (OHG) versus persistent high glucose (PHG) in inducing oxidative stress and cellular apoptosis in human coronary artery endothelial cells (HCAECs) in vitro. METHODS: HCAECs were incubated for 72 h continuously in normal glucose (5.5 mmol/L glucose), PHG (25 mmol/L glucose), OHG (5.5 mmol and 25 glucose mmol/L alternating every 6 h) and mannitol, respectively. Cellular viability, concentration of oxidative stress biomarkers (MDA and GSH) in the supernatants of cell culture, and intracellular ROS level were quantitated after exposure to different concentrations of glucose for a total 72 h. Apoptosis of HCAECs cultured with various glucose levels was evaluated by annexin V-FITC and PI staining followed by analysis with flow cytometry. The expressions of HO-1 and Nrf2 were measured by RT-qPCR and Western blotting at the end of the experiment. RESULTS: HCAECs cultured with PHG showed decreased cellular viability compared to those with normal level of glucose (p < 0.05). The decrease was more pronounced under OHG condition (p < 0.05). Cellular oxidative stress was provoked in HCAECs exposed to PHG with marked increased MDA level, reduced GSH concentration and elevated ROS production (p < 0.05). The stress was further amplified in the setting of OHG (p < 0.05). The cellular apoptosis was enhanced by culturing with PHG, and to a greater extent when incubated with OHG. Both expressions of HO-1 and Nrf2 were suppressed in HCAECs in persistent hyperglycemia condition, while the inhibition was more intense in the fluctuating hyperglycemia condition (p < 0.05). CONCLUSIONS: These findings indicate that OHG could be more detrimental to HCAECs than PHG. This is probably due to the enhancement of oxidative stress and cellular apoptosis induced by frequent glucose swings through the inhibition of Nrf2/HO-1 pathway.