Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

Preoperative dipstick albuminuria is associated with acute kidney injury in high-risk patients following non-cardiac surgery: a single-center prospective cohort study.

PURPOSE: This study aimed to investigate the association between preoperative dipstick albuminuria (DA) and acute kidney injury (AKI) in high-risk patients following non-cardiac surgery. METHODS: This was a single-center prospective cohort study. Adult patients with high risk of AKI undergoing non-cardiac surgery were enrolled. The primary outcome was AKI, defined according to KDIGO criteria within 7 days following non-cardiac surgery. DA status was determined by urinalysis performed within 24 h of hospital admission. Multivariate logistic regression model was used to analyze the association between preoperative DA and postoperative AKI. RESULTS: During the study period, 552 patients were enrolled and 8.5% of them developed postoperative AKI. The overall rate of preoperative positive DA was 26.4% with 30 and ≥ 100 mg/dL DA accounting for 19.2% and 7.2%, respectively. Patients with more severe preoperative DA had much higher rate of postoperative AKI (5.2% in patients with negative or trace DA, 13.2% in patients with 30 mg/dL DA and 30.0% in patients with ≥ 100 mg/dL DA, P < 0.001). After adjusting for several perioperative variables, preoperative 30 mg/dL DA (OR 2.575; 95% CI 1.049-6.322; P = 0.039) and ≥ 100 mg/dL DA (OR 3.868; 95% CI 1.246-12.010; P = 0.019) showed an independent association with postoperative AKI. In addition, patients with higher DA status demonstrated significantly increased level of postoperative urine biomarkers and their ratio to urine creatinine. CONCLUSIONS: Preoperative DA was independently associated with AKI in high-risk patients following non-cardiac surgery. Preoperative routine urinalysis for determination of DA status was suggested in early risk stratification.

Effect of clinical decision support systems on clinical outcome for acute kidney injury: a systematic review and meta-analysis.

BACKGROUND: Clinical decision support systems including both electronic alerts and care bundles have been developed for hospitalized patients with acute kidney injury. METHODS: Electronic databases were searched for randomized, before-after and cohort studies that implemented a clinical decision support system for hospitalized patients with acute kidney injury between 1990 and 2019. The studies must describe their impact on care processes, patient-related outcomes, or hospital length of stay. The clinical decision support system included both electronic alerts and care bundles. RESULTS: We identified seven studies involving 32,846 participants. Clinical decision support system implementation significantly reduced mortality (OR 0.86; 95 % CI, 0.75-0.99; p = 0.040, I2 = 65.3 %; n = 5 studies; N = 30,791 participants) and increased the proportion of acute kidney injury recognition (OR 3.12; 95 % CI, 2.37-4.10; p < 0.001, I2 = 77.1 %; n = 2 studies; N = 25,121 participants), and investigations (OR 3.07; 95 % CI, 2.91-3.24; p < 0.001, I2 = 0.0 %; n = 2 studies; N = 25,121 participants). CONCLUSIONS: Nonrandomized controlled trials of clinical decision support systems for acute kidney injury have yielded evidence of improved patient-centered outcomes and care processes. This review is limited by the low number of randomized trials and the relatively short follow-up period.

Deglycosylated Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis via the TGF-ß1 Signaling Pathway.

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening lung disease characterized by the proliferation of myofibroblasts and deposition of extracellular matrix that results in irreversible distortion of the lung structure and the formation of focal fibrosis. The molecular mechanism of IPF is not fully understood, and there is no satisfactory treatment. However, most studies suggest that abnormal activation of transforming growth factor-ß1 (TGF-ß1) can promote fibroblast activation and epithelial to mesenchymal transition (EMT) to induce pulmonary fibrosis. Deglycosylated azithromycin (Deg-AZM) is a compound we previously obtained by removing glycosyls from azithromycin; it was demonstrated to exert little or no antibacterial effects. Here, we discovered a new function of Deg-AZM in pulmonary fibrosis. In vivo experiments showed that Deg-AZM could significantly reduce bleomycin-induced pulmonary fibrosis and restore respiratory function. Further study revealed the anti-inflammatory and antioxidant effects of Deg-AZM in vivo. In vitro experiments showed that Deg-AZM inhibited TGF-ß1 signaling, weakened the activation and differentiation of lung fibroblasts, and inhibited TGF-ß1-induced EMT in alveolar epithelial cells. In conclusion, our findings show that Deg-AZM exerts antifibrotic effects by inhibiting TGF-ß1-induced myofibroblast activation and EMT.

Fedratinib Attenuates Bleomycin-Induced Pulmonary Fibrosis via the JAK2/STAT3 and TGF-ß1 Signaling Pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with multiple causes, characterized by excessive myofibrocyte aggregation and extracellular matrix deposition. Related studies have shown that transforming growth factor-ß1 (TGF-ß1) is a key cytokine causing fibrosis, promoting abnormal epithelial-mesenchymal communication and fibroblast-to-myofibroblast transition. Fedratinib (Fed) is a marketed drug for the treatment of primary and secondary myelofibrosis, targeting selective JAK2 tyrosine kinase inhibitors. However, its role in pulmonary fibrosis remains unclear. In this study, we investigated the potential effects and mechanisms of Fed on pulmonary fibrosis in vitro and in vivo. In vitro studies have shown that Fed attenuates TGF-ß1- and IL-6-induced myofibroblast activation and inflammatory response by regulating the JAK2/STAT3 signaling pathway. In vivo studies have shown that Fed can reduce bleomycin-induced inflammation and collagen deposition and improve lung function. In conclusion, Fed inhibited inflammation and fibrosis processes induced by TGF-ß1 and IL-6 by targeting the JAK2 receptor.

Mouse strain-specific responses of mitochondrial respiratory function and cardiac hypertrophy to isoproterenol treatment.

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases and eventually develops into heart failure. This paper was aimed to study the different pathological characteristics exhibited by different mouse strains after hypertrophy stimulation. Two mouse strains, A/J and FVB/nJ, were treated with isoproterenol (ISO) by osmotic pump to induce cardiac hypertrophy. Echocardiography was performed to monitor heart morphology and function. Mitochondria were isolated from hearts in each group, and oxidative phosphorylation function was assayed in vitro. The results showed that both strains showed a compensatory enhancement of heart contractile function after 1-week ISO treatment. The A/J mice, but not the FVB/nJ mice, developed significant cardiac hypertrophy after 3-week ISO treatment as evidenced by increases in left ventricular posterior wall thickness, heart weight/body weight ratio, cross sectional area of cardiomyocytes and cardiac hypertrophic markers. Interestingly, the heart from A/J mice contained higher mitochondrial DNA copy number compared with that from FVB/nJ mice. Functionally, the mitochondria from A/J mice displayed faster O2 consumption at state III with either complex I substrates or complex II substrate, compared with those from FVB/nJ mice. ISO treatment did not affect mitochondrial respiratory control rate (RCR), but significantly suppressed the ADP/O ratio generated from the complex II substrate in both strains. The ADP/O ratio generated from the complex I substrates in A/J mice declined by 50% after ISO treatment, whereas FVB/nJ mice were not affected. These results suggest that, compared with FVB/nJ mice, A/J mice possesses a poor integrity of mitochondrial respiratory chain that might contribute to its vulnerability to ISO-induced cardiac hypertrophy.

Appropriate Source Control and Antifungal Therapy are Associated with Improved Survival in Critically Ill Surgical Patients with Intra-abdominal Candidiasis.

BACKGROUND: Intra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in surgical intensive care patients. The purpose of this study was to investigate the impact of appropriate source control and antifungal therapy on the outcomes of critically ill surgical patients with IAC. METHODS: This was a retrospective single-center cohort study. Adult surgical patients who were admitted to the intensive care unit and diagnosed with IAC from January 1, 2003, to December 31, 2016, were enrolled. The patients' data including risk factors of IAC, infection-related information, antifungal treatment and 30-day outcomes were collected. The primary endpoint was 30-day mortality. A COX proportional hazards model was used to analyze the association between appropriate treatment and 30-day survival. RESULTS: A total of 82 patients were included in the analysis. Of these, 45 (54.9%) were complicated with septic shock at IAC diagnosis. Types of IAC included peritonitis (61.0%), intra-abdominal abscesses (23.2%) and biliary tract infections (15.9%). Of the included patients, 53 (64.6%) received appropriate source control and 44 (53.7%) appropriate antifungal therapy. Compared with patients with neither of these treatments, appropriate source control (HR 0.08, 95% CI 0.02-0.30; P < 0.001), appropriate antifungal therapy (HR 0.14, 95% CI 0.04-0.55; P = 0.005), and a combination of these treatments (HR 0.02, 95% CI 0.00-0.08; P < 0.001) were associated with reduced risk of death within 30 days after IAC diagnosis. CONCLUSION: For critically ill surgical patients with IAC, both appropriate source control and appropriate antifungal therapy were associated with reduced risk of 30-day mortality, and the protective effects of the two appropriate treatments were additive.

Thymidine phosphorylase promotes angiogenesis and tumour growth in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer, and thymidine phosphorylase (TP) is a regulator of angiogenesis. To investigate the biological activities of TP in ICC, we established human cholangiocarcinoma RBE cell lines overexpressing TP or silencing TP. Overexpression of TP enhanced viability, suppressed apoptosis and increased tube formation in human umbilical vein endothelial cells, while downregulation of TP reversed these effects. Moreover, an orthotopic xenograft mouse model of ICC was built to further explore TP's function in ICC in vivo. Histological analysis using H&E, TUNEL and Ki67 staining showed that TP promoted tumour growth and inhibited cell apoptosis. Immunostaining for CD31 revealed an elevation in microvessel density in the presence of TP. Besides, upregulation of TP increased the expression of vascular endothelial growth factor, basic fibroblast growth factor, interleukin-8 and tumour necrosis factor alpha. In contrast, TP knockdown inhibited tumour growth, suppressed microvessel formation and decreased the expression of angiogenesis-related proteins. Therefore, we suggest that TP promotes angiogenesis and tumour growth in ICC, which can be a potent therapeutic target for ICC treatment.

Intraoperative hypotension is associated with increased postoperative complications in patients undergoing surgery for pheochromocytoma-paraganglioma: a retrospective cohort study.

BACKGROUND: Dramatic hemodynamic fluctuation occurs frequently during surgery for pheochromocytoma or paraganglioma. However, the criteria of intraoperative hemodynamic instability vary widely, and most of them were defined arbitrarily but not according to patients' prognosis. The objective was to analyze the relationship between different thresholds and durations of intraoperative hyper-/hypotension and the risk of postoperative complications in patients undergoing surgery for pheochromocytoma or paraganglioma. METHODS: This was a retrospective single-center cohort study performed in a tertiary care hospital from January 1, 2005 to December 31, 2017. Three hundred twenty-seven patients who underwent surgery for pheochromocytoma or paraganglioma, of which the diagnoses were confirmed by postoperative pathologic examination, were enrolled. Those who were less than 18 years, underwent surgery involving non-tumor organs, or had incomplete data were excluded. The primary endpoint was a composite of the occurrence of AKI or other complications during hospital stay after surgery. Multivariate Logistic regression models were used to analyze the association between different thresholds and durations of intraoperative hyper-/hypotension and the development of postoperative complications. RESULTS: Forty three (13.1%) patients developed complications during hospital stay after surgery. After adjusting for confounding factors, intraoperative hypotension, defined as systolic blood pressure (SBP) of ≤95 mmHg for ≥20 min (OR 3.211; 99% CI 1.081-9.536; P = 0.006), SBP of ≤90 mmHg for ≥20 min (OR 3.680; 98.8% CI 1.107-12.240; P = 0.006), SBP of ≤85 mmHg for ≥10 min (OR 3.975; 98.3% CI 1.321-11.961; P = 0.003), and SBP of ≤80 mmHg for ≥1 min (OR 3.465; 95% CI 1.484-8.093; P = 0.004), were associated with an increased risk of postoperative complications. On the other hand, intraoperative hypertension was not significantly associated with the development of postoperative complications. CONCLUSIONS: For patients undergoing surgery for pheochromocytoma or paraganglioma, intraoperative hypotension is associated with increased postoperative complications; and the harmful effects are level- and duration-dependent. The effects of intraoperative hypertension need to be studied further.

Predictors of 1-year mortality in patients on prolonged mechanical ventilation after surgery in intensive care unit: a multicenter, retrospective cohort study.

OBJECTIVES: The requirement of prolonged mechanical ventilation (PMV) is associated with increased medical care demand and expenses, high early and long-term mortality, and worse life quality. However, no study has assessed the prognostic factors associated with 1-year mortality among PMV patients, not less than 21 days after surgery. This study analyzed the predictors of 1-year mortality in patients requiring PMV in intensive care units (ICUs) after surgery. METHODS: In this multicenter, respective cohort study, 124 patients who required PMV after surgery in the ICUs of five tertiary hospitals in Beijing between January 2007 and June 2016 were enrolled. The primary outcome was the duration of survival within 1 year. Predictors of 1-year mortality were identified with a multivariable Cox proportional hazard model. The predictive effect of the ProVent score was also validated. RESULTS: Of the 124 patients enrolled, the cumulative 1-year mortality was 74.2% (92/124). From the multivariable Cox proportional hazard analysis, cancer diagnosis (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.37-3.35; P < 0.01), no tracheostomy (HR 2.01, 95% CI 1.22-3.30; P < 0.01), enteral nutrition intolerance (HR 1.88, 95% CI 1.19-2.97; P = 0.01), blood platelet count ≤150 × 109/L (HR 1.77, 95% CI 1.14-2.75; P = 0.01), requirement of vasopressors (HR 1.78, 95% CI 1.13-2.80; P = 0.02), and renal replacement therapy (HR 1.71, 95% CI 1.01-2.91; P = 0.047) on the 21st day of mechanical ventilation (MV) were associated with shortened 1-year survival. CONCLUSIONS: For patients who required PMV after surgery, cancer diagnosis, no tracheostomy, enteral nutrition intolerance, blood platelet count ≤150 × 109/L, vasopressor requirement, and renal replacement therapy on the 21st day of MV were associated with shortened 1-year survival. The prognosis in PMV patients in ICUs can facilitate the decision-making process of physicians and patients' family members on treatment schedule.

Preoperative hypoalbuminemia was associated with acute kidney injury in high-risk patients following non-cardiac surgery: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common complication following non-cardiac surgery with adverse short- and long- term morbidity and mortality. Evidence shows that hypoalbuminemia is associated with increased AKI risk in patients with infectious diseases and cancer and following cardiac surgery and transplant surgery. However, little evidence is available on non-cardiac surgery population. Thus, we investigated the association between preoperative hypoalbuminemia and AKI following non-cardiac surgery. METHODS: We retrospectively assessed perioperative risk factors and preoperative serum albumin concentration in 729 consecutive adult patients who underwent non-cardiac surgery from July 1, 2017, to June 30, 2018. Each patient was categorized according to maximal Kidney Disease Improving Global Outcomes criteria based on creatinine changes and urine output within the first week after surgery. Multivariate Logistic regression models were used to analyze the association between preoperative hypoalbuminemia and postoperative AKI. RESULTS: Of 729 patients, 188 (25.8%) developed AKI. AKI incidence was higher in patients with preoperative serum albumin < 37.5 g/L than in those with preoperative serum albumin ≥37.5 g/L [35.9% (98/273) vs. 19.7% (90/456), P < 0.001]. Multivariate logistic regression analysis showed that preoperative serum albumin < 37.5 g/L (odds ratio 1.892; 95% confidence interval 1.238-2.891; P = 0.003) was independently associated with postoperative AKI. Patients with preoperative serum albumin < 37.5 g/L tended to have a higher but not significant ratio in AKI stage 2 (2.6% vs 1.1%, P = 0.144) and much higher ratio in AKI stage 3 (4.8% vs 0.7%, P < 0.001) than those with preoperative serum albumin ≥37.5 g/L. AKI patients had a higher in-hospital mortality rate [6.9% (13/188) vs. 0.2% (1/541), P < 0.001]. Kaplan-Meier analysis revealed that the cumulative survival rate decreased with increasing AKI severity (P < 0.001). Postoperative AKI was also associated with other worse outcomes, such as prolonged mechanical ventilation [53.4 (33.0, 73.8) vs 14.7 (11.1, 18.3) hours, P < 0.001], intensive care unit stay [4.0 (3.1, 4.9) vs 2.0 (1.8, 2.3) days, P < 0.001], postoperative hospital stay [17.8 (14.8, 20.9) vs 12.3 (11.3, 13.3) days, P < 0.001], and higher total cost [13,453 (8538, 20,228) vs 11,306 (6277, 16,400) dollars, P < 0.001]. CONCLUSIONS: Preoperative hypoalbuminemia was independently associated with AKI after non-cardiac surgery, and postoperative AKI was associated with poor outcomes.

Perioperative Acute Ischemic Stroke Increases Mortality After Noncardiac, Nonvascular, and Non-Neurologic Surgery: A Retrospective Case Series.

OBJECTIVE: To identify the predictors of in-hospital mortality in patients who develop perioperative acute ischemic stroke (PAIS) associated with noncardiac, nonvascular, and non-neurologic surgery. DESIGN: Retrospective study. SETTING: University-affiliated hospital. PARTICIPANTS: The study comprised 100 patients with PAIS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The data of 351,531 patients who underwent noncardiac, nonvascular, and non-neurologic surgery in the authors' hospital between January 2003 and December 2016 were retrospectively reviewed. PAIS occurred in 100 patients. The incidence of PAIS (overall 2.8/10,000) was significantly lower in patients <45 years old (0.12/10,000) than in patients >75 years old (15.79/10,000; p < 0.001). The in-hospital mortality rate was higher among patients with PAIS (26%) than among patients without PAIS (0.34%; p < 0.01). Multiple logistic regression analysis revealed the following independent risk factors for in-hospital mortality: preoperative atrial fibrillation (odds ratio [OR] 9.013, 95% confidence interval [CI] 1.400-58.016; p = 0.021), disturbance of consciousness as the first PAIS symptom (OR 5.561, 95% CI 1.521-20.332; p = 0.009), no anticoagulant/antiplatelet therapy after PAIS (OR 8.196, 95% CI 1.017-66.065; p= 0.048), diuretic treatment (OR 4.942, 95% CI 1.233-19.818; p = 0.024), and pulmonary infection (OR 6.979, 95% CI 1.853-26.291; p = 0.004). CONCLUSIONS: The risk of PAIS after noncardiac, nonvascular, and non-neurologic surgery significantly increased with age, and development of PAIS increased the mortality rate. Among these patients, the independent predictors of in-hospital mortality were preoperative atrial fibrillation, disturbance of consciousness as the first PAIS symptom, no anticoagulant/antiplatelet therapy after PAIS, diuretic treatment, and pulmonary infection.

Pregnancy-Related ICU Admissions From 2008 to 2016 in China: A First Multicenter Report.

OBJECTIVES: To identify the key points for improving severe maternal morbidity by analyzing pregnancy-related ICU admissions in Beijing. DESIGN: This was a retrospective, multicenter cohort study. SETTING: Three ICUs in tertiary hospitals in Beijing. PATIENTS: A total of 491 severe maternal cases in any trimester of pregnancy or within 42 days of delivery were reviewed between January 1, 2008, and December 31, 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 491 obstetric ICU admissions (median Sequential Organ Failure Assessment score, 2) out of 87,850 hospital deliveries (a frequency of 5.6 admissions per 1,000 deliveries), the leading diagnoses were postpartum hemorrhage (170; 34.62%), hypertensive disorders of pregnancy (156; 31.77%), and cardio-cerebrovascular diseases (78; 15.9%). Comparing 2008-2011 to 2012-2016, the rates of maternal mortality (2.5% vs 1.9%; p = 0.991) and fetal loss (8.5% vs 8.6%; p = 0.977) did not decrease significantly, whereas the rates of ICU admission (3.05% vs 7.85%; p trends < 0.001) and postpartum hemorrhage (23% vs 38.5%; p = 0.002) increased. Hypertensive disorder (150/156; 96.2% transferred to the ICU postpartum, 24/28 women with fetal loss transferred from lower-level hospitals) was an independent maternal factor associated with fetal loss, and infections were the leading cause of maternal death (6/10) in the ICU. CONCLUSIONS: Our study highlights the increasing rate of intensive care admissions for postpartum hemorrhage. Improving prenatal care quality for pregnancy-induced hypertension and sepsis at lower-level hospitals may improve maternal and fetal outcomes. Specifically, providing more effective regional cooperation before transfer and shifting patients who require continuous surveillance but not necessarily intensive care to a transitional ward in a tertiary hospital would provide more ICU beds for more prenatal intensive care for the most complex medical conditions.

Genomic and Transcriptomic Analysis Identified Gene Clusters and Candidate Genes for Oil Content in Peanut (Arachis hypogaea L.).

Peanut (Arachis hypogaea), a major source of vegetable oil in many Asian countries, has become an integral part of human diet globally due to its high nutritional properties and option to consume in different forms. In order to meet the demand of vegetable oil, many peanut breeding programs of China have intensified their efforts in increasing oil content in newly bred varieties for reducing the import of edible oils in China. In this context, transcriptome sequencing data generated on 49 peanut cultivars were analyzed to identify candidate genes and develop molecular markers for seed oil content across multiple environments. Transcriptome analysis identified 5458 differentially expressed genes (DEGs) including 2243 positive DEGs and 3215 negative DEGs involved in oil synthesis process. Genome-wide association study identified 48 significant insertion/deletion (InDel) markers associated with seed oil content across five environments. A comparative genomics and transcriptomics analysis detected a total of 147 common gene clusters located in 17 chromosomes. Interestingly, an InDel cluster associated with seed oil content on A03 chromosome was detected in three different environments. Candidate genes identified on A03 form a haplotype, in which variable alleles were found to be different in oil content in an independent population. This locus is important for understanding the genetic control of peanut oil content and may be useful for marker-assisted selection in peanut breeding programs.

Peptide-Conjugated Quantum Dots Act as the Target Marker for Human Pancreatic Carcinoma Cells.

BACKGROUND/AIMS: In the present study, we describe a novel and straightforward approach to produce a cyclic- arginine-glycine-aspartic (RGD)-peptide-conjugated quantum dot (QD) probe as an ideal target tumor biomarker. Due to its specific structure, the probe can be used for targeted imaging of pancreatic carcinoma cells. METHODS: Pancreatic carcinoma cells were routinely cultured and marked with QD-RGD probe. The QD-RGD probe on the fluorescence-labeled cancer cell was observed by fluorescence microscopy and laser confocal microscopy. Cancer cell viability was detected by MTT assay after culturing with QD-RGD probe. RESULTS: Fluorescence microscopy and laser confocal microscopy displayed that 10nmol/L QD-RGD probe was able to effectively mark pancreatic carcinoma cells. In comparison with organic dyes and fluorescent proteins, the quantum dot-RGD probe had unique optical and electronic properties. CONCLUSION: QD-RGD probe has a low cytotoxicity with an excellent optical property and biocompatibility. These findings support further evaluation of QD-RGD probes for the early detection of pancreatic cancer.

Insulin-like growth factor 1 promotes growth of gastric cancer by inhibiting foxo1 nuclear retention.

Gastric cancer (GC) is the fourth most common malignant human cancer. So far, the molecular mechanisms underlying the tumorigenesis of GC are not completely understood. Here, we reported significantly higher levels of serum insulin-like growth factor (IGF)-1 in GC patients and significantly higher levels of phosphorylated IGF-1 receptor (IGF-1R) in the GC specimen. Moreover, IGF-1 induced phosphorylation of IGF-1R and then phosphorylation of its downstream factor Akt in the GC cells. Further, IGF-1/Akt-induced forkhead box protein O1 (FoxO1) nuclear exclusion, but not IGF-1/Akt-induced mTOR phosphorylation, was essential for the augment in GC cell growth. Together, IGF-1/Akt/FoxO1 regulatory machinery appears to be a previously unappreciated signaling axis involved in the carcinogenesis of GC.

[Is monitoring of anti-factor Xa levels required for low molecular weight heparin prophylaxis of venous thromboembolism in critically ill patients?]

The incidence and mortality of venous thromboembolism (VTE) are high in critically ill patients, and there is still a risk of VTE and bleeding after the use of fixed-dose low molecular weight heparin (LMWH) for prophylaxis. The level of anti-factor Xa is not up to standard after LMWH prophylaxis in patients with surgery or trauma. The condition of critically ill patients is complicated, and the proportion of patients with low antithrombin III is high, which can affect the prophylactic efficacy of LMWH and contribute to VTE occurrence. There is currently no consensus on whether adjusting LMWH dose according to anti-factor Xa levels can reduce VTE occurrence in critically ill patients. High-quality multicenter randomized controlled studies are needed in the future to establish new approaches for precise prevention of VTE in critically ill patients.

Perioperative acute myocardial infarction increases mortality following noncardiac surgery.

OBJECTIVE: To provide insight into diagnosis, treatment, and prevention of perioperative myocardial infarction (PMI). DESIGN: The authors retrospectively analyzed PMI characteristics in patients undergoing noncardiac surgery and identified risk factors for death. SETTING: An affiliated teaching hospital with about 1500 beds. PARTICIPANTS: The authors screened electronic medical records and retrospectively analyzed clinical data from 117,856 patients who underwent noncardiac surgery during the period from August 2003 through June 2011. INTERVENTIONS: Patients were divided into two groups based on survival at 30 days after PMI. MEASUREMENTS AND MAIN RESULTS: PMI was reported in 61 patients, for an overall incidence rate of 5.2 per 10,000. PMI incidence increased significantly with age, with a rate of 0.97 per 10,000 for the 45- to 60-year-old group, and increasing to a rate of 40.4 per 10,000 for the>75-year-old group (p<0.001). The mortality rate of non-PMI patients (n = 117,795) was 0.32%, whereas the mortality rate for the 61 PMI patients was 36.1% (p<0.001). PMI occurred acutely (within 48 to 72 hours of surgery) in the majority of patients (78.7%), and only 18% of these patients complained of chest pain. The majority of patients who suffered PMI had non-ST segment elevation acute myocardial infarction (78.7%). By multiple logistic regression analysis, lack of anticoagulation/antiplatelet therapy and cardiogenic shock were independent risk factors for death in PMI patients (p = 0.001 for both). CONCLUSIONS: PMI incidence increased significantly with advanced age. PMI increased mortality following non-cardiac surgery. The independent risk factors for death in PMI patients following noncardiac surgery were lack of anticoagulation/antiplatelet therapy and cardiogenic shock.

Differences in right hemisphere fNIRS activation associated with executive network during performance of the lateralized attention network tast by elite, expert and novice ice hockey athletes.

OBJECTIVE: We investigated brain activity associated with executive control attention network in elite, expert, and novice female ice hockey athletes during the revised lateralized attention network tast to determine whether the neural correlates of performance differ by skill level. METHODS: We collected and analyzed functional near-infrared spectroscopy data of 38 participants while performing the revised lateralized attention network tast. RESULTS: Elite players were significantly faster than novices (p = .005), and the experts' overall accuracy rate (ACC) was higher than that of novices (p = .001). The effect of the executive network on reaction time was higher in novices than in elite players (p = .008) and experts (p = .004). The effect of the executive network on the ACC was lower in elite players than in experts (p = .009) and novices (p = .010). Finally, elite player had higher flanker conflict effects on RT (p = .005) under the invalid cue condition. the effect of the alertness network and orientation on the ACC was lower in elite players than in novices (p = .000) and experts (p = .022). Changes in the blood oxygen level-dependent signal related to the flanker effect were significantly different in the right dorsolateral prefrontal cortex (F=3.980, p = .028) and right inferior frontal gyrus (F=3.703, p = .035) among the three groups. Elit players showed more efficient executive control (reduced conflict effect on ACC) (p = .006)in the RH.The changes related to the effect of blood oxygen level on orienting were significantly different in the right frontal eye fields (F=3.883, p = .030) among the three groups, Accompanied by significant activation of the right dorsolateral prefrontal cortex(p = .026). CONCLUSION: Our findings provide partial evidence of the superior cognitive performance and high neural efficiency of elite ice hockey players during cognitive tasks. These results demonstrate the right hemisphere superiority for executive control.We also found that specific brain activation in hockey players does not show a clear and linear relationship with skill level.

[Related factors of viral nucleic acid change in critically ill patients with SARS-CoV-2 infection after treatment with Nirmatrelvir/Ritonavir: a single center retrospective cohort study].

OBJECTIVE: To describe negative conversion and rebound of patients with severe and critical acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after treatment with Nirmatrelvir/Ritonavir, and to analyze related factors associating with failure of SARS-CoV-2 negative conversion and relapse and prognosis. METHODS: A single center retrospective cohort study was conducted. Patients aged ≥ 16 years old who were diagnosed with severe or critical SARS-CoV-2 infection and took Nirmatrelvir/Ritonavir for 5 days in Peking University First Hospital from December 7, 2022 to January 27, 2023, were included. General characteristics and clinical data were collected from electronic medical record system. The Kaplan-Meier curve of SARS-CoV-2 negative conversion was drawn. Factors with P < 0.10 were incorporated into multivariate Logistic regression model to analyze the relationship between the factors and persistent nucleic acid positive and rebound. RESULTS: A total of 31 severe and 37 critical SARS-CoV-2 infection patients were included. The median duration from initiation of Nirmatrelvir/Ritonavir to negative conversion of SARS-CoV-2 for both was 6.0 days, and the negative conversion rate on day 15 was 93.5% and 86.5%, respectively. SARS-CoV-2 rebound was observed in 7 patients (11.3%), among whom were 1 severe patient and 6 critical patients. The above 7 patients with SARS-CoV-2 rebound and 6 patients with failure of SARS-CoV-2 negative conversion were compared with 55 patients with persistent negative conversion. Factors with P < 0.10, including the lowest lymphocyte count (LYM), the highest D-dimer, the highest procalcitonin (PCT), the lowest Ct value, cardiovascular diseases other than hypertension and coronary heart disease, were incorporated into multivariate Logistic regression analysis. The decreased LYM [odds ratio (OR) = 0.146, 95% confidence interval (95%CI) was 0.031-0.689, P = 0.015] and the increased PCT (OR = 2.008, 95%CI was 1.042-3.868, P = 0.037) were revealed to be independent risk factors of the failure of SARS-CoV-2 negative conversion or rebound. The proportion of mechanical ventilation and invasive ventilation were significantly higher in patients with persistent SARS-CoV-2 infection or rebound than those in patients with SARS-CoV-2 negative conversion (84.6% vs. 38.2%, 69.2% vs. 25.5%, both P < 0.01), but no significant difference in mechanical ventilation and invasive ventilation duration was observed. Compared with the patients with SARS-CoV-2 negative conversion, more patients with persistent SARS-CoV-2 infection or rebound were admitted to intensive care unit (ICU, 76.9% vs. 50.9%), and length of ICU stay in patients with persistent SARS-CoV-2 infection or rebound tended to be longer [days: 13.0 (10.3, 24.3) vs. 11.0 (5.3, 23.0), P > 0.05]. CONCLUSIONS: The decreased LYM and increased PCT are independent risk factors for the failure of SARS-CoV-2 negative conversion or rebound in patients with severe and critical SARS-CoV-2 infection. Attention should be paid to these patients for their poor prognosis.