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Objectives Most instruments to measure frailty are impractical to operationalize in emergency department (ED), due to the busy work of the staff and the acute presentations of the patients. The current work aimed to develop and validate a clinical model by combining clinical data and biomarkers available in the ED to evaluate the probability of frailty among older emergency patients. Design: A cross-sectional research. Setting and participants: A total of 273 adults aged 65 years and older who visited the ED of a university-affiliated hospital in Beijing, China during the period from January 2021 to September 2021 were included. Measurements: Fried's frailty phenotype was employed for assessing frailty. Clinical data and blood biomarkers were collected within 24 hours of admission. Clinical data included demographic characteristics, chronic diseases, main causes of admission and nutrition risk screening (NRS) 2002 score. Blood biomarkers included hallmarks of inflammation, nutrition and metabolism, coagulation and other biomarkers such as alanine transaminase (ALT), aspartate transaminase (AST), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and creatinine. Results Totally 151 patients were frail. Eight variables were included in the diagnosis model: nutritional risk, prior ischemic heart disease (IHD), age > 77 years, ALT ≤ 9.2 U/L, albumin ≤ 31.9 g/L, homocysteine > 18 umol/L, 25-OH vitamin D ≤ 10.89 ng/mL, and NT-pro-BNP > 2070 ng/L. Through the area under receiver operating characteristics curve (AUC) (0.855), leave-one-out cross-validation (AUC = 0.828), as well as Hosmer-Lemeshow test (P = 0.615), the validity of the diagnosis model was verified. The clinical diagnosis model was converted into a scale score with a total score of 10. The AUC of the diagnostic score for predicting frailty was 0.851 (95% confidence interval: 0.806–0.895, P< 0.001) and the cutoff value was 4.5 points with the Youden index of 0.579. Following adjustment for gender and main causes of admission, the diagnostic score was an independent predictor for 28-day mortality, with a hazard ratio of 1.486 and a 95% confidence interval of 1.224–1.804 (P < 0.001). Conclusion In the current work, a clinical diagnosis model to estimate the probability of frailty in older emergency patients was developed using clinical data and biomarkers generally readily available in the ED. This diagnosis model may facilitate targeted intervention and risk stratification in the EDs.

BACKGROUND Pheochromocytomas are rare endocrine tumors with various clinical manifestations, and few of them might present with profound, life-threatening conditions. CASE SUMMARY We report the case of a 65-year-old man who complained of sudden dyspnea and hemoptysis for half a day. There was no obvious cause for the patient to have dyspnea, coughing, or coughing up to approximately 100 mL of fresh blood. Finally, he was diagnosed with pheochromocytoma crisis (PCC), coexisting with an abdominal aortic aneurysm (AAA). CONCLUSION We report a case of pheochromocytoma presenting with recurrent hemoptysis, dyspnea and hypotension coexisting with an AAA. It not only proved the uncommon manifestations of pheochromocytoma but also directed clinicians to consider PCC among the possible diagnoses when meeting similar cases. Moreover, surgical excision is the most beneficial method for the treatment of pheochromocytoma coexisting with AAA when the situation is stable.

To investigate the tissue factor (TF) expression on different subsets of monocyte and tissue factor secretion of peripheral blood and evaluate their association with the prognosis of sepsis in the Chinese older adult population.Monocyte subsets and TF expression on different subsets of monocyte were measured using flow cytometry in 80 older adult sepsis patients and 40 age and sex matched healthy controls. Plasma level of TF was measured using ELISA (enzyme-linked immunosorbent assay) method.TF expression on CD14++CD16- (MO1) monocyte was lower in death (28-day non-survivor) group compared with survival (28-day survivor) groups [1.01 % (0.58 %, 1.62 %) vs. 3.66 % (1.32 %, 6.93 %), p = 0.001]. The plasma level of TF was increased in death group compared to survival group according to the 28-day mortality [109.2 (67.3, 154.2) vs. 62.1 (44.7, 115.5) pg/mL, p = 0.031]. Logistic regression analysis showed TF expression on MO1 monocyte (β = -0.776, OR = 0.460, CI: 0.251, 0.843, p = 0.012) was independently associated with the 28-day mortality. The ROC (receiver operating characteristic) curve showed that the AUC (area under the curve) of the TF expression on MO1 monocyte for predicting 28-day mortality was 0.846 (p 0.001).The TF expression on CD14++CD16- monocyte is a new marker for the prognosis of older adult sepsis.

The microcirculation is correlated with the prognosis of patients with cardiac arrest and changes after resuscitation. In the present study, the effects of anisodamine hydrobromide (AH) on microcirculation was investigated and its potential mechanisms were explored. A total of 24 pigs were randomly grouped into three groups (n=8): Sham, Saline and AH group. After pigs were anesthetized, intubated and mechanically ventilated, ventricular fibrillation was induced by electrical stimulation. After 8 min, cardiopulmonary resuscitation was given to the restoration of spontaneous circulation (ROSC). Arteriovenous blood was collected at baseline and 0, 1, 2, 4 and 6 h after ROSC to measure blood gas and cytokines. Perfused vessel density (PVD) and microvascular flow index (MFI) were measured to reflect the microcirculation. Continuous cardiac output and global ejection fraction were measured to indicate hemodynamics. Compared with Sham group, PVD and MFI in the intestines and the sublingual regions decreased significantly after resuscitation. The microcirculation recovered faster in the AH group than the SA group. The decrease of intestinal microcirculatory blood flow was closely related to the decrease of sublingual microcirculatory blood flow. The cardiac function was impaired after resuscitation, and a decrease of IFN-γ as well as IL-2 and an increase of IL-4 as well as IL-10 suggested the immune imbalance. The microcirculation changes in sublingual regions were closely related to the changes in intestines. AH could improve the immune imbalance after resuscitation and was beneficial to the recovery of cardiac function.

Atrial fibrillation (AF) is frequently associated with increased inflammatory response characterized by infiltration of monocytes/macrophages. The chemokine receptor CXCR-2 is a critical regulator of monocyte mobilization in hypertension and cardiac remodeling, but it is not known whether CXCR-2 is involved in the development of hypertensive AF. AF was induced by infusion of Ang II (angiotensin II; 2000 ng/kg per minute) for 3 weeks in male C57BL/6 wild-type mice, CXCR-2 knockout mice, bone marrow-reconstituted chimeric mice, and mice treated with the CXCR-2 inhibitor SB225002. Microarray analysis revealed that 4 chemokine ligands of CXCR-2 were significantly upregulated in the atria during 3 weeks of Ang II infusion. CXCR-2 expression and the number of CXCR2 + immune cells markedly increased in Ang II–infused atria in a time-dependent manner. Moreover, Ang II–infused wild-type mice had increased blood pressure, AF inducibility, atrial diameter, fibrosis, infiltration of macrophages, and superoxide production compared with saline-treated wild-type mice, whereas these effects were significantly attenuated in CXCR-2 knockout mice and wild-type mice transplanted with CXCR-2-deficient bone marrow cells or treated with SB225002. Moreover, circulating blood CXCL-1 levels and CXCR2 + monocyte counts were higher and associated with AF in human patients (n=31) compared with sinus rhythm controls (n=31). In summary, this study identified a novel role for CXCR-2 in driving monocyte infiltration of the atria, which accelerates atrial remodeling and AF after hypertension. Blocking CXCR-2 activation may serve as a new therapeutic strategy for AF.

Hypertensive cardiac remodeling is a major cause of heart failure. The immunoproteasome is an inducible form of the proteasome and its catalytic subunit β5i (also named LMP7) is involved in angiotensin II-induced atrial fibrillation; however, its role in deoxycorticosterone-acetate (DOCA)-salt-induced cardiac remodeling remains unclear. C57BL/6 J wild-type (WT) and β5i knockout (β5i KO) mice were subjected to uninephrectomy (sham) and DOCA-salt treatment for three weeks. Cardiac function, fibrosis, and inflammation were evaluated by echocardiography and histological analysis. Protein and gene expression levels were analyzed by quantitative real-time PCR and immunoblotting. Our results showed that after 21 days of DOCA-salt treatment, β5i expression and chymotrypsin-like activity were the most significantly increased factors in the heart compared with the sham control. Moreover, DOCA-salt-induced elevation of blood pressure, adverse cardiac function, chamber and myocyte hypertrophy, interstitial fibrosis, oxidative stress, and inflammation were markedly attenuated in β5i KO mice. These findings were verified in β5i inhibitor PR-957-treated mice. Moreover, blocking of PTEN (the gene of phosphate and tensin homolog deleted on chromosome ten) markedly attenuated the inhibitory effect of β5i knockout on DOCA-salt-induced cardiac remodeling. Mechanistically, DOCA-salt stress upregulated the expression of β5i, which promoted the degradation of PTEN and the activation of downstream signals (AKT/mTOR, TGF-β1/Smad2/3, NOX, and NF-κB), which ultimately led to cardiac hypertrophic remodeling. This study provides new evidence of the critical role of β5i in DOCA-salt-induced cardiac remodeling through the regulation of PTEN stability, and indicates that the inhibition of β5i may be a promising therapeutic target for the treatment of hypertensive heart diseases.

Background Severe influenza is often associated with bacterial coinfection and can trigger sepsis, which increases the severity, complexity and mortality of the disease. To determine an effective method for predicting 28-day mortality of emergency department (ED) patients with influenza, we investigated the Mortality in Emergency Department Sepsis (MEDS) score, procalcitonin (PCT) and other relevant biomarkers. Methods We conducted a retrospective, observational, monocentric study, and the endpoint was 28-day mortality. Independent predictors were identified and a new combination predictive model was created both by logistic regression, and the model was evaluated by a receiver operating characteristic (ROC) curve. Results A total of 364 consecutive ED admitted patients with influenza were enrolled and 45 patients died within 28 days. For predicting 28-day mortality, the MEDS score and PCT were independent predictors with adjusted odds ratio of 1.318 (95% CI 1.206–1.439) and 1.038 (95% CI 1.010–1.065), and with AUCs of 0.817 (95% CI 0.756–0.878) and 0.793 (95% CI 0.725–0.861), respectively. The new combination of the MEDS score with PCT significantly improved the efficacy for predicting 28-day mortality with an AUC of 0.857 (95% CI 0.809–0.905), and was superior to the SOFA score with an AUC of 0.837 (95% CI 0.779–0.894). Conclusion The MEDS score and PCT, especially when combined, perform well for predicting mortality of ED admitted patients with influenza.

ObjectiveThis study aimed to explore whether thyroid-stimulating hormone (TSH) plays an early warning role in detecting progression of bacterial infection to sepsis and can serve as a novel marker for the diagnosis of sepsis.MethodThis was a prospective study of patients treated for ‘bacterial infection’ in the emergency department of Beijing Chaoyang Hospital from 1 January 2021 to 31 August 2021. Subjects were divided into a sepsis group (SG) and a non-SG (NSG), according to whether their condition had progressed to sepsis within 72 hours of admission. Routine blood test results as well as biochemical and thyroid function indices (T4, FT4, T3, FT3) were recorded at the time of admission. TSH, Acute Physiology and Chronic Health Evaluation II scores and Sequential Organ Failure Assessment scores were likewise documented.ResultsA total of 62 patients were enrolled, the SG and the NSG showed significant differences in their levels of TSH. The results indicate that TSH is an early warning marker for sepsis.ConclusionsTSH plays an early warning role in the diagnosis of bacterial infection progressing to sepsis, having a strong predictive value.

This study aimed to examine the effects of microcirculatory dysfunction and 654-1 intervention after cardiopulmonary resuscitation on myocardial injury.Landrace pigs were divided into a sham operation group (S group,After administration of 654-1 at 1.5 h post-ROSC, the hemodynamics in the VF-I group, as compared with the VF-C group, was significantly improved. The visceral microcirculation detected by SDF was also significantly improved in the VF-I group. As observed through electron microscopy, significantly less myocardial tissue injury was present in the VF-I group than the VF-C group.Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.

Background: Sepsis is a dangerous disease with rapid development and high mortality rate, which is an important cause of death for critically ill patients. Therefore, timely and accurate assessment of patients’ condition is beneficial to improve prognosis and reduce mortality. Objective: This study was designed to investigate the potential correlation between red blood cell distribution width and 28-day prognosis of patients with sepsis. Methods: A prospective observational study enrolling 236 patients with sepsis or septic shock was performed at our hospital. All cases were divided into survival versus non-survival group on 28th day after diagnosis. The two groups were compared for general condition, underlying diseases, quick Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II score, C-reactive protein, procalcitonin, and red blood cell distribution width at admission. Results: The red blood cell distribution width level in non-survivors was higher than that in survivors (16.3 ± 2.8 vs 15.2 ± 1.7, p = 0.013). Cox regression analysis indicated that red blood cell distribution width was an independent predictor for 28-day mortality (hazard ratio: 1.311, 95% confidence interval: 1.119–3.011, p = 0.018). The red blood cell distribution width cutoff value of red blood cell distribution width for 28-day mortality was 16.1%, while patients with lower red blood cell distribution width levels had a better prognosis as demonstrated by Kaplan–Meier survival curves (log-rank = 7.398, p = 0.007). Unlike the septic shock group, in the sepsis group, the red blood cell distribution width level was higher in the non-survival group compared to the survival group (15.82% ± 0.93% vs 15.01% ± 0.89%, p Conclusion: Increased red blood cell distribution width may be an important predictor of disease progression and prognosis in patients with sepsis and septic shock. In the sepsis group, higher red blood cell distribution width levels predict poor prognosis.

Influenza is frequently complicated by bacterial co-infection, causing additional hospitalization and mortality. We determined the incidence, risk factors and outcomes of patients with influenza-associated community-acquired bacterial co-infection.This was a retrospective, observational study. Influenza was diagnosed using the polymerase chain reaction. Co-infection had to be confirmed using standard bacteriological tests. The primary endpoint was presence of community-acquired co-infection, and the secondary endpoint was in-hospital mortality.During the 8 influenza seasons from 2010 to 2018, of the 209 influenza-associated pneumonia admitted patients, 41 (19.6%) were identified with community-acquired bacterial co-infections and Staphylococcus aureus was the predominant strain. Compared with patients without co-infection, patients with co-infection had similar demographic characteristics and co-morbidities, obtained a higher APACHE II score and a higher SOFA score, and had higher ratio of sepsis shock, invasive mechanical ventilation, and ICU requirement. In-hospital mortality independently associated with bacterial co-infection (adjusted hazard ratio (aHR) 2.619; 95%CI 1.252-5.480; p = 0.011); in subgroup S. aureus (aHR 6.267; 95%CI 2.679-14.662; p 0.001) and other pathogens (aHR 2.964; 95%CI 1.160-7.577; p = 0.023); and in subgroup positive findings in bloodstream (aHR 7.420; 95%CI 2.712-20.302; p 0.001) and positive findings in other site (aHR 3.427; 95%CI 1.514-7.757; p = 0.003).Community-acquired bacterial co-infection was frequent in influenza-associated pneumonia, without risk factor identified yet. Bacterial co-infection was likely to predict severity, and was an independent risk factor for in-hospital mortality. Co-infection of Staphylococcus aureus with influenza was identified as a lethal synergism, and should be targeted when developing clinical antibiotic strategies.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is a major cause of stroke and heart failure. We and others have found that gallic acid (GA) plays a beneficial role in cardiac hypertrophic remodeling and hypertension. However, the effect of GA on angiotensin II (Ang II)-induced AF and atrial remodeling as well as the underlying mechanisms remain unknown. AF was induced in mice by Ang II infusion (2000 ng/kg/min) for 3 weeks. Blood pressure was measured using the tail-cuff method. Atrial volume was evaluated by echocardiography. Atrial remodeling was studied using hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining. Atrial oxidative stress was assessed by dihydroethidium staining. The gene expression of fibrotic and inflammatory markers and protein levels of signaling mediators were measured by quantitative real-time PCR and western blot analysis. In mice, GA administration significantly attenuated Ang II-induced elevation of blood pressure, AF incidence and duration, atrial dilation, fibrosis, inflammation, and oxidative stress compared with the vehicle control. Furthermore, GA downregulated Ang II-induced activity and expression of immunoproteasome subunits (β2i and β5i), which reduced PTEN degradation and led to the inactivation of AKT1 and downstream signaling mediators. Importantly, blocking PTEN activity by VO-Ohpic markedly reversed the GA-mediated protective effects on Ang II-induced AF and atrial remodeling. Therefore, our results provide novel evidence that GA exerts a cardioprotective role by inhibiting immunoproteasome activity, which attenuates PTEN degradation and activation of downstream signaling, and may represent a promising candidate for treating hypertensive AF.

Hypertension is a major cause of heart attack and stroke. Our recent study revealed that gallic acid (GA) exerts protective effects on pressure overload-induced cardiac hypertrophy and dysfunction. However, the role of GA in angiotensin II (Ang II)-induced hypertension and vascular remodeling remains unknown. C57BL/6J mice were subjected to saline and Ang II infusion. Systolic blood pressure was measured using a tail-cuff system. Vascular remodeling and oxidative stress were examined by histopathological staining. Vasodilatory function was evaluated in the aortic ring. Our findings revealed that GA administration significantly ameliorated Ang II-induced hypertension, vascular inflammation, and fibrosis. GA also abolished vascular endothelial dysfunction and oxidative stress in Ang II-infused aortas. Mechanistically, GA treatment attenuated Ang II-induced upregulation of the immunoproteasome catalytic subunits β2i and β5i leading to reduction of the trypsin-like and chymotrypsin-like activity of the proteasome, which suppressed degradation of endothelial nitric oxide synthase (eNOS) and reduction of nitric oxide (NO) levels. Furthermore, blocking eNOS activity by using a specific inhibitor (L-N G-nitroarginine methyl ester) markedly abolished the GA-mediated beneficial effect. This study identifies GA as a novel immunoproteasome inhibitor that may be a potential therapeutic agent for hypertension and vascular dysfunction.

Atrial fibrillation (AF) is associated with inflammation and oxidative stress. Recently, we demonstrated that the chemokine‐receptor CXCR2 plays a critical role in the recruitment of monocytes/macrophages and the development of hypertension and cardiac remodelling. However, the role of CXCR2 in the pathogenesis of hypertensive AF remains unclear. AF was induced in Wistar‐Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) administered with the CXCR2 inhibitor SB225002. Atrial remodelling, pathological changes and electrophysiology were examined. Our results showed that the chemokine CXCL1 and its receptor CXCR2 were markedly increased in atrial tissue of SHRs compared with WKYs. The administration of SB225002 to SHRs significantly reduced the elevation of blood pressure, AF inducibility and duration, atrial remodelling, recruitment of macrophages, superoxide production and conduction abnormalities compared with vehicle treatment. The administration of SB225002 to SHRs also reversed pre‐existing AF development, atrial remodelling, inflammation and oxidative stress. These effects were associated with the inhibition of multiple signalling pathways, including TGF‐β1/Smad2/3, NF‐κB‐P65, NOX1, NOX2, Kir2.1, Kv1.5 and Cx43. In conclusion, this study provides new evidence that blocking CXCR2 prevents and reverses the development of AF in SHRs, and suggests that CXCR2 may be a potential therapeutic target for hypertensive AF.

Background: Influenza-associated lower respiratory tract infection (I-LRTI) brings a heavy clinical burden, and clinicians lack an effective prognostic evaluation system to control disease progression. Methods: This was a prospective, observational study, and the endpoint was 28-day mortality. Plasma microarrays were used for quantitative analysis of immunoglobulin (Ig) and its subclasses. Prognostic factors from Ig and clinical variables in the patients with I-LRTI were identified to create a prediction model. Results: To address this issue, we prospectively and observationally studied the difference of immunoglobulin proteome and clinical variables between survivors and non-survivals in 107 patients with influenza-associated lower respiratory tract infection (I-LRTI) selected from four hospitals affiliated to Capital Medical University. The results identified 17 variables with significant or marginally statistical differences by univariate analysis, including lymphocyte count (LY), monocytes count (MO), CD3 + CD4 + T-cell count, CD3 + CD8 + T-cell count, IgA, IgA1, IgG2, IgG4, CRP, PCT, D-dimer, oxygenation index, glycosylated hemoglobin, lactic acid (LAC), base excess of blood, lactic dehydrogenase, and α-hydroxybutyrate dehydrogenase. Furthermore, we analyzed the correlations of all the variables by hierarchical clustering analysis in which different functional modules were formed between survival and non-survival groups that are associated with the immunity and severe infection. At last, we built a prediction model with nine variables (D-dimer, days from onset to ED, IgA, IgG2, LAC, LY, MO, Staphylococcus aureus co-infection and age), with which the AUC value of 0.810 (95% CI 0.755-0.839) was achieved with the evaluation of LOO cross validation. The predictive model was further validated by disease severity evaluation. Conclusion: Lethal bacterial (especially S. aureus ) co-infection was associated with cellular immunity, oxygenation index, HbA1C and age. The combined prediction model with D-dimer, Days from onset to ED, IgA, IgG2, LAC, LY, MO, S.aureus co-infection and age demonstrate the predictive mortality powerfully in patients with I-LRTI.

Background: Preoperative anatomical scoring system is conducive to comparison between treatment options and evaluation of postoperative outcomes in patients with small renal tumors. This study aimed to evaluate the clinical application efficacy of the R.E.N.A.L. nephrometry score (RNS) in predicting perioperative outcomes in patients with renal tumor who underwent laparoscopic partial nephrectomy (LPN). Methods: The clinical data of 139 patients with renal tumors who underwent LPN between 2009 and 2015 were collected and analyzed. Patients were divided into three groups according to their RNS (low, moderate, and high). Clinical characteristics including perioperative variables, complications, and RNS were compared to evaluate the differences between the three groups. Multivariable logistic regression analysis was used to analyze the risk factors of postoperative complications. Results: According to the RNS, there were 74, 50, and 15 patients in the low, moderate, and high RNS groups, respectively. There were significant differences in estimated blood loss (EBL; χ2 = 7.285, P = 0.026), warm ischemia time (WIT; χ2 = 13.718, P = 0.001), operation time (OT; χ2 = 6.882, P = 0.032), perioperative creatinine clearance change (PCCC; χ2 = 6.206, P = 0.045), and number of patients with complications (NPC; P = 0.002) among the three groups. The values for EBL, WIT, OT, PCCC, and NPC for patients in the high RNS group were higher than those for patients in the low RNS group. After adjustment for OT, WIT, and EBL, RNS was statistically significantly associated with the risk of postoperative complications in a multivariable logistic regression model (odds ratio = 1.541, 95% confidence interval: 1.059–2.242, P = 0.024). Conclusions: The RNS is a valuable tool for evaluating the complexity of renal tumor anatomy. It can aid surgeons in preoperative decision-making concerning management therapy. Future multicenter, large sample size studies are warranted for evaluating its predicting performance of perioperative outcomes. Key words: Laparoscopic Partial Nephrectomy; R.E.N.A.L. Nephrometry Score; Renal Cell Carcinoma

Background: Shock is a life-threatening condition in emergency departments (EDs) and is associated with a high mortality; however, its clinical characteristics and current interventions in China are seldom reported. This study investigated the clinical characteristics and current interventions of shock patients in Chinese EDs. Methods: This multicenter prospective cohort study was conducted in the EDs of 33 academic hospitals in 16 Chinese provinces. Adult shock patients were enrolled from December 2013 to April 2014. Age, sex, comorbidities, shock subtype, and vital signs were recorded on ED arrival; details of subsequent interventions and treatments were added. We compared those data between survivors and nonsurvivors. All patients were followed up for 3 days. The primary outcome was 3-day mortality. Binary logistic regression analysis identified the independent predictors of that mortality. Results: We enrolled 1095 shock patients. The 3-day mortality was 27.5%, 36.3%, and 29.0%, respectively, in the whole cohort and for cardiogenic and septic shock. Within the first 24 h, 1039 patients (94.9%) were admitted to the Intensive Care Unit. Use of bicarbonate, epinephrine, and dopamine is an independent predictor for mortality. Hemorrhage and trauma (39.1%), along with sepsis (40.4%) were the most commonly observed causes of shock in the ED. In nondiabetic patients with cardiogenic shock, 3-day mortality was 69.2% for patients needing glucose control — much higher than in those not needing glucose control (30.0%, P = 0.01). Hydroxyethyl starch (HES) was applied in 29.6% of septic shock patients, and the mortality of septic patients who received HES was much higher than those who did not (38.2% vs. 25.1%, P = 0.006). Conclusions: In China, short-term mortality of shock patients in EDs is still high, especially among those with cardiogenic and septic shock. HES application needs to be restricted — particularly in septic shock patients. Key words: Emergencies; Mortality; Sepsis; Shock; Therapeutics

Scope Cardiac fibrosis is a key feature of cardiac remodeling. Recently, a protective role for resveratrol (RES) in pressure-overload-induced cardiac hypertrophy and contractile dysfunction has been demonstrated. However, the effect of RES on cardiac fibrosis and diastolic function in this model remains unclear. Methods and results Cardiac remodeling is induced in mice by transverse aortic constriction (TAC) for 2-4 weeks. RES is administered at dose of 5 or 50 mg kg-1 d-1 for 2 weeks. It is found that RES administration at 50 mg kg-1 d-1 significantly attenuates TAC-induced adverse cardiac systolic and diastolic function, fibrosis, inflammation, and oxidative stress via inhibiting PTEN degradation and the downstream mediators. However, RES at 5 mg kg-1 d-1 has no significant effects. RES at 50 mg kg-1 d-1 also ameliorates pre-established adverse cardiac function and remodeling induced by TAC. Treatment with PTEN inhibitor VO-OHpic (10 mg kg-1 d-1 ) for 2 weeks abolishes RES-mediated protective effects. Additionally, the effect of RES (100 µm) on inhibition of Ang II-induced fibroblast proliferation and activation in vitro is verified. Conclusions The findings provide new evidence that RES plays a critical role in the progression of cardiac fibrosis and diastolic dysfunction, and suggest that RES may be a promising therapeutic agent for cardiac fibrosis.

Heart failure is a serious condition with high prevalence and mortality. The application of the novel big data analysis in heart failure can improve the management of this condition,especially in terms of diagnosis,classification,and prognostic prediction. This articles reviews relevant literature and validates the role of big data analysis for heart failure patients.

Inflammation is associated with retinal diseases. Our recent data demonstrate that immunoproteasome catalytic subunit β2i contributes to angiotensin II (Ang II)-induced retinopathy in mice. Here, we investigated the role of another catalytic subunit β5i in regulating retinopathy and its underlying mechanisms. We induced a murine model of retinopathy by infusing Ang II (3,000 ng/kg/min) for 3 weeks into wild-type (WT) mice, β5i-knockout (KO) mice, or WT mice injected with either adenovirus-expressing β5i (Ad-β5i) or angiotensin II type 1 receptor (AT1R)-associated protein (Ad-ATRAP), which inhibits AT1R. The β5i expression and chymotrypsin-like activity were most significantly elevated in Ang II-infused retinas and serum from patients with hypertensive retinopathy. Moreover, Ang II infusion-induced retinopathy was markedly attenuated in β5i-KO mice but aggravated in Ad-β5i-injected mice. Accordingly, β5i KO markedly restored Ang II-induced downregulation of ATRAP and activation of AT1R downstream mediators, which was further enhanced in Ad-β5i-injected mice. Interestingly, overexpression of ATRAP significantly abrogated Ang II-induced retinopathy in Ad-β5i-injected mice. This study found that β5i promoted Ang II-induced retinopathy by promoting ATRAP degradation and activation of AT1R-mediated signals.

System hypertension is a major risk factor for cardiac hypertrophy and heart failure. Our recent findings reveal that the ablation or inhibition of C-X-C chemokine receptor (CXCR) 2 blocks this process in mice; however, it is not clear whether the pharmacological inhibition of CXCR2 attenuates hypertension and subsequent cardiac remodeling in spontaneously hypertensive rats (SHRs). In the present study, we showed that chemokines (CXCL1 and CXCL2) and CXCR2 were significantly upregulated in SHR hearts compared with Wistar–Kyoto rat (WKY) hearts. Moreover, the administration of CXCR2-specific inhibitor N-(2-hydroxy-4-nitrophenyl)-N′-(2-bromophenyl)-urea (SB225002) in SHRs (at 2 months of age) for an additional 4 months significantly suppressed the elevation of blood pressure, cardiac myocyte hypertrophy, fibrosis, inflammation, and superoxide production and improved heart dysfunction in SHRs compared with vehicle-treated SHRs. SB225002 treatment also reduced established hypertension, cardiac remodeling and contractile dysfunction. Moreover, CXCR2-mediated increases in the recruitment of Mac-2-positive macrophages, proinflammatory cytokines, vascular permeability and ROS production in SHR hearts were markedly attenuated by SB225002. Accordingly, the inhibition of CXCR2 by SB225002 deactivates multiple signaling pathways (AKT/mTOR, ERK1/2, STAT3, calcineurin A, TGF-β/Smad2/3, NF-κB-p65, and NOX). Our results provide new evidence that the chronic blocking of CXCR2 activation attenuates progression of cardiac hypertrophic remodeling and dysfunction in SHRs. These findings may be of value in understanding the benefits of CXCR2 inhibition for hypertensive cardiac hypertrophy and provide further support for the clinical application of CXCR2 inhibitors for the prevention and treatment of heart failure.

Objective: Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. In this article, we reviewed the correlation between neutrophil dysfunction and sepsis. Data Sources: Articles published up to May 31, 2016, were selected from the PubMed databases, with the keywords of "neutrophil function", "neutrophil dysfunction", and "sepsis". Study Selection: Articles were obtained and reviewed to analyze the neutrophil function in infection and neutrophil dysfunction in sepsis. Results: We emphasized the diagnosis of sepsis and its limitations. Pathophysiological mechanisms involve a generalized circulatory, immune, coagulopathic, and/or neuroendocrine response to infection. Many studies focused on neutrophil burst or cytokines. Complement activation, impairment of neutrophil migration, and endothelial lesions are involved in this progress. Alterations of cytokines, chemokines, and other mediators contribute to neutrophil dysfunction in sepsis. Conclusions: Sepsis represents a severe derangement of the immune response to infection, resulting in neutrophil dysfunction. Neutrophil dysfunction promotes sepsis and even leads to organ failure. Mechanism studies, clinical practice, and strategies to interrupt dysregulated neutrophil function in sepsis are desperately needed. Key words: Migration; Neutrophil Dysfunction; Neutrophil Function; Sepsis

In order to adapt the use of workover rig for offshore completion and workover operations, it generally uses two different drive mode of milling, downhole motor and surface turntable, in dealing with deep inclined well permanent packer issues. In this thesis, the material property of pipe strings is analyzed and the axial forces, torques and frictions and other mechanical calculation models of the pipe string are established under two kinds of drive modes. Through the results of analysis of pipe string force, it analyzes the material property of permanent packer, optimizes the parameters of downhole tools and operation methods in milling operation.

Objective To determine whether the onset of acute lung injury (ALI) induces the up-regulation of pentraxin 3 (PTX3) expression in mice and whether PTX3 concentration in the biofluid can help recognizing sepsis-induced ALI. Methods Wild-type C57BL/6 mice (12-14 weeks old) were randomly divided into 3 groups. Mice in the group 1 (n=12) and group 2 (n=12) were instilled with lipopolysaccharide via intratracheal or intraperitoneal routes, respectively. Mice in the group 3 (n=8) were taken as blank controls. Pulmonary morphological and functional alterations were measured to determine the presence of experimental ALI. PTX3 expression in the lung was quantified at both protein and mRNA levels. PTX3 protein concentration in blood and bronchoalveolar lavage fluid was measured to evaluate its ability to diagnose sepsis-induced ALI by computing area under receiver operator characteristic curve (AUROCC). Results ALI was commonly confirmed in the group 1 but never in the other groups. PTX3 expression was up-regulated indiscriminately among lipopolysaccharide-challenged mice. PTX3 protein concentration in the biofluid was unable to diagnose sepsis-induced ALI evidenced by its small AUROCC. PTX3 concentration in bronchoalveolar lavage fluid did not correlate with that in serum. Conclusions Lipopolysaccharide challenges induced PTX3 expression in mice regardless of the presence of ALI. PTX3 may act as an indicator of inflammatory response instead of organ injury per se.

To explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury (ALI) in mice.Lipopolysaccharide (LPS, 10 mg/kg) injection or cecal ligation and puncture (CLP) was performed to induce severe sepsis and ALI in C57 BL/6 male mice randomly divided into 5 groups (n=10 in each group): group A (intraperitoneal LPS injection), group B (intravenous LPS injection via tail vein), group C (CLP with 25% of the cecum ligated), group D (CLP with 75% of the cecum ligated), and the control group (6 sham-operation controls plus 4 saline controls). All the mice received volume resuscitation. Measurements of pulmonary morphological and functional alterations were used to identify the presence of experimental ALI. The expressions of lipocalin-2 and interleukin (IL)-6 in serum, bronchoalveolar lavage fluid (BALF), and lung tissue were quantified at both protein and mRNA levels. The overall abilities of lipocalin-2 and IL-6 tests to diagnose sepsis-induced ALI were evaluated by generating receiver operator characteristic curves (ROC) and computing area under curve (AUC).In both group B and group D, most of the main features of experimental ALI were reproduced in mice, while group A and group C showed septic syndrome without definite evidence for the presence of ALI. Compared with septic mice without ALI (group A+group C), lipocalin-2 protein expression in septic mice with ALI (group B+group D) was significantly up-regulated in BALF (P0.01) and in serum (P0.01), and mRNA expression boosted in lung tissues (all P0.05). Lipocalin-2 tests performed better than IL-6 tests in recognizing sepsis-induced ALI cases, evidenced by the larger AUC of the former (BALF tests, 0.8800 versus 0.6625; serum tests, 0.8500 versus 0.7000). Using a dual cutoff system to diagnose sepsis-induced ALI, BALF lipocalin-2 test exhibited the highest positive likelihood ratio (13.000) and the lowest negative likelihood ratio (0.077) among the tests of lipocalin-2 and IL-6 in blood and BALF. A statistically significant correlation was found between lipocalin-2 concentration in BALF and that in serum (Spearman r=0.8803, P0.0001).Lipocalin-2 expression is significantly up-regulated in septic ALI mice compared with those without ALI. Lipocalin-2 tests with a dual cutoff system could be an effective tool in distinguishing experimental ALI cases.

The author list for this article should be updated to include Junjie Li as co-first author for the work. The revised author list should thus read as follows: Yong Zeng*, Junjie Li*, Hong-Xia Wang, Shu-Bin Guo, Hui Yang, Xiang-Jun Zeng, Quan Fang, Chao-Shu Tang, Jie Du, Hui-Hua Li *These authors contributed equally Junjie Li is affiliated at the Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 100005, China. Junjie Li declares no competing interests in relation to this work and contributed to the following aspects of the study: Performed experiments, analyzed the data, wrote the paper, contributed analysis and tools. The correct citation is: Zeng Y, Li J, Wang H-X, Guo S-B, Yang H, Zeng X-J, et al. (2013) Transcriptional Effects of E3 Ligase Atrogin-1/MAFbx on Apoptosis, Hypertrophy and Inflammation in Neonatal Rat Cardiomyocytes. PLoS ONE 8(1): e53831. doi:10.1371/journal.pone.0053831. The correct abbreviation in Contributions is: JL.