Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model.

Posttraumatic stress disorder (PTSD) is a complex mental disorder notable for traumatic experience memory. Although current first-line treatments are linked with clinically important symptom reduction, a large proportion of patients retained to experience considerable residual symptoms, indicating pathogenic mechanism should be illustrated further. Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation. However, its role in PTSD remains to be elucidated. In this study, we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus. Fluoxetine, but not risperidone or sertraline, has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities. Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling. Our data demonstrated the correlation between PTSD and abnormal myelination, suggesting that the oligodendroglial lineage could be a target for PTSD treatment.

T-Wave Alternans Measured by 24-Hour Ambulatory Recordings Rather Than Exercise Stress Tests as a Risk Stratification Marker in Patients With Long QT Syndrome.

BACKGROUND: Few small-sample studies have quantified the T-wave alternans (TWA) value by 24-hour ambulatory recordings or exercise stress tests in patients with long QT syndrome (LQTS). The cutoff point of TWA ≥47 µV was based on patients with myocardial infarction. In our study, we aimed to (1) evaluate the association of TWA with life-threatening arrhythmic events (LAEs); (2) compare the predictive model of LAEs according to the TWA value measured by 24-hour ambulatory recordings and exercise stress tests; and (3) propose a cutoff point for the high risk of LAEs in patients with LQTS. METHODS AND RESULTS: The study cohort included 110 patients with LQTS referred to our hospital, and the primary outcome was LAEs. Thirty-one patients with LQTS (31/110 [28.2%]) developed LAEs during the following 24 (12-47) months. Peak TWA value quantified from 12 leads by 24-hour ambulatory recordings in patients with LQTS with LAEs (LQTS-LAEs group) was significantly higher than LQTS without LAEs (LQTS-non-LAEs group) (64.0 [42.0-86.0] µV versus 43.0 [36.0-53.0] µV; P<0.01). There was no statistical difference in TWA value measured by exercise stress tests between the 2 groups (69.0 [54.5-127.5] µV versus 68.5 [53.3-99.8] µV; P=0.871). The new cutoff point of the peak TWA value measured by 24-hour ambulatory recordings was 55.5 µV, with a sensitivity of 75.0% and a specificity of 78.6%. A univariate Cox regression analysis revealed that TWA value ≥55.5 µV was a strong predictor of LAEs (hazard ratio [HR], 4.5 [2.1-9.6]; P<0.001]. A multivariate Cox regression analysis indicated that TWA value ≥55.5 µV remained significant (HR, 2.7 [1.1-6.8]; P=0.034). CONCLUSIONS: Peak TWA measured by 24-hour ambulatory recordings was a more favorable risk stratification marker than exercise stress tests for patients with LQTS.

Men with nonobstructive coronary disease have higher burden of ischemic heart disease detected by cardiopulmonary exercise test.

BACKGROUND: Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. METHODS: We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO2 , O2 pulse trajectory, and exercise ECG test. RESULTS: Men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O2 pulse trajectory (2% vs. 0%) (p < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O2 pulse trajectory (21% vs. 6%, p < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, p < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO2 (ß -27.4, 95% CI -30.74 to -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (p < .0001). CONCLUSION: Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.

Effects of the Novel Coronavirus Pandemic on the Identification and Care of Critically Ill Emergency Patients Not Infected with COVID-19.

Objective: To clarify variations of diagnosis and treatment in the emergency care of critically ill patients not infected with novel coronavirus (COVID-19) prior to and amidst the COVID-19 pandemic. Methods: A retrospective cohort study was conducted to compare and analyze the diagnosis and treatment data of critically ill patients with non-COVID-19 infection who were admitted to the emergency department of the Fourth Medical Center of Chinese PLA General Hospital from January 2019 to November 2022. The variations in emergency care of the pandemic were summarized, and the influence of the pandemic on emergency care was assessed. Results: A total of 6634 critically ill patients with non-COVID-19 infection were included in this study. These patients were elderly, high incidence of chronic diseases, and extended emergency duration during the pandemic. Notably, the proportion of patients requiring intensive care was twofold higher compared to the period before the pandemic. Throughout the pandemic, patients experienced prolonged emergency durations, increased overall costs and daily expenses per patient. Further investigation revealed that elderly patients exhibited worse medical conditions, requiring lengthier emergency treatment and incurring escalated healthcare expenses. However, the presence of pre-existing chronic diseases did not appear to influence disease severity, nor extended emergency durations or heightened healthcare expenditures. Irrespective of the pandemic phase-be it short-term, medium-term, or long-term emergency care-greater healthcare spending was necessary. Conclusion: There was no difference in the disease spectrum of emergency critical ill patients with non-COVID-19 infection prior to and amidst the COVID-19 pandemic, nor the duration and expenditure in prior chronic illness patients. However, the disease severity and emergency duration have led to an increase in the total cost and economic intensity of emergency care for all patients during the epidemic. Especially, elderly patients required longer emergency duration, greater healthcare spending, and more inpatient medical resources than usual.

IL-8 is a novel prometastatic chemokine in intrahepatic cholangiocarcinoma that induces CXCR2-PI3K/AKT signaling upon CD97 activation.

Intrahepatic cholangiocarcinoma (ICC) is a rare but highly aggressive malignant tumor arising within the liver, with a 5-year survival rate of only 20-40% after surgery. The role of interleukin-8 (IL-8) in ICC progression remains elusive. A transcriptomic approach based on IL-8 stimulation first revealed significant upregulation of the prometastatic gene CD97 and key epithelial-mesenchymal transition (EMT) factors E-cadherin and vimentin. Immunohistochemistry of 125 ICC tissues confirmed the positive correlation between IL-8 and CD97. Multivariable Cox regression indicated that they are both independent predictors of ICC prognosis. Mechanistically, IL-8 treatment induced CD97 expression at 50 and 100 ng/ml in QBC-939 and QBE cells, respectively. Moreover, the induction of cell migration and invasion upon IL-8 treatment was attenuated by CD97 RNA interference, and the expression of EMT-associated genes was dramatically inhibited. To determine whether CXCR1 or CXCR2 are downstream effectors of IL-8, siCXCR2 was applied and shown to significantly attenuate the oncogenic effects of IL-8 by inhibiting the phosphorylation of PI3K/AKT. Finally, the induction of CD97 expression by the PI3K pathway was verified by treatment with the inhibitor LY294002. In vivo, the significant tumor growth and lung metastasis effects induced by intraperitoneal injection of IL-8 were greatly inhibited by silencing CD97 in nude mice. Collectively, the study presents a novel mechanism of the IL-8-CXCR2-PI3K/AKT axis in regulating CD97 expression, which leads to ICC metastasis mainly through EMT. The study may provide alternatives for targeting the tumor microenvironment in metastatic ICC.

The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis.

INTRODUCTION: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). OBJECTIVES: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. METHODOLOGY: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. RESULTS: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. CONCLUSIONS: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.

Cold Roll Forming Process Design for Complex Stainless-Steel Section Based on COPRA and Orthogonal Experiment.

Cold roll forming can fabricate products with complex profiles, and its parameter optimization can achieve high quality and improved precision of products. In this paper, taking the side shield as a typical product, the cold roll forming of a complex section of stainless steel SUS301L-ST is analyzed, establishing a 3D finite element model by using the professional roll forming software COPRA. We propose a floating roll device for complex sections with asymmetry and large depth. We use an orthogonal experiment to obtain the inter-distance between rolls, friction coefficients, the diameter increments, and line velocities to investigate the effects on the maximum longitudinal strain of the edge. Results show that the diameter increment has the greatest influence on the maximum strain, and its increases can reduce the strain. The inter-distance value needs a suitable range. A small value is not conducive to the release of elastic deformation, while a large value will cause unexpected displacement and increase the cost. The friction coefficient increases; although it helps to reduce the strain, it will cause scratches and other defects on the stainless steel. The increase in velocity increases the strain. We derive the optimal parameters for the complex section, providing a theoretical basis for practical production.

Coronary stenosis is a risk marker for impaired cardiac function on cardiopulmonary exercise test.

BACKGROUND: Cardiac function varies in different ways in ischemic heart disease (IHD). We aimed to evaluate the characteristics of cardiac function on cardiopulmonary exercise test (CPET) in IHD with different coronary stenoses. METHODS: Totally 614 patients with IHD were divided into non-obstructive coronary artery disease (NOCAD) (stenosis < 50%), obstructive coronary artery disease (OCAD) (stenosis 50-90%) and severe OCAD ( stenosis > 90%) according to the coronary angiography. And 101 healthy volunteers as controls. All participants performed CPET to assess cardiac function by oxygen uptake (VO2), estimated cardiac output (CO), and heart rate (HR). RESULTS: Generally, the values of VO2, CO, and HR in IHD were significantly lower than in healthy volunteers. Among 289 NOCAD, 132 OCAD, and 193 severe OCAD, significantly decreased values of VO2, CO, HR were observed (VO2 peak: 16.01 ± 4.11 vs. 15.66 ± 4.14 vs. 13.33 ± 3.4 mL/min/kg; CO: 6.96 ± 2.34 vs. 6.87 ± 2.37 vs. 6.05 ± 1.79 L/min; HR: 126.44 ± 20.53 vs. 115.15 ± 18.78 vs. 109.07 ± 16.23 bpm, P < 0.05). NOCAD had significantly lower VO2 at anaerobic threshold (-1.35, 95%CI -2.16 - -0.54) and VO2 peak (-2.05, 95%CI -3.18 - -0.93) compared with healthy volunteers after adjustment. All IHD patients were associated with low stroke volume and inefficient gas exchange (P < 0.05). CONCLUSION: IHD with increasing atherosclerotic burdens were associated with impaired cardiac output and chronotropic response on CPET. NOCAD should be given more early prevention and rigorous follow-up.

Analysis of Factors Influencing the Course of Rabies Vaccinations: One Year Study on Compliance of Rabies Vaccination Regimens in Haidian District of Beijing.

Objective: To identify the factors influencing the completion rate of the course of rabies vaccinations without considering the economic factors or the drug supplies. Methods: Rabies vaccination data from the Fourth Medical Center of the PLA General Hospital from January 1 to December 31, 2020, were collected. This includes demographics, information on injury-causing animals, vaccination schemes, and injury assessments. Data on completed the course of rabies vaccinations were compared with data on uncompleted. Internal analysis of Zagreb regimen and Essen regimen was performed. The key factor affecting the completion of the course of rabies vaccinations was analyzed. Results: A total of 1633 patients completed the course of rabies vaccinations, while 462 patients did not. There were differences between the two groups in terms of the vaccination scheme, age, and previous history of rabies vaccinations. The results of a multivariate analysis of variance showed that only the vaccination scheme was significantly correlated with the completion rate of the course of rabies vaccinations. The internal analysis of the vaccination schemes showed that the duration of the vaccination scheme directly affected the completion rate of the course of rabies vaccinations, and the vaccination duration was negatively correlated with the completion rate of rabies vaccinations. Conclusion: The completion rate of the course of rabies vaccinations with Zagreb regimen was higher than Essen regimen. The completion rate was closely correlated with the vaccination scheme, but the duration of the vaccination scheme was the key factor. There was a linear relationship between the vaccination duration and the completion rate of the course of vaccinations, which can be represented by the following linear equation: the completion rate of the course of rabies vaccinations (%) = 98.342-0.999 × vaccination duration (d). Duration is the critical factor affecting the completion rate. To improve the completion rate of vaccination, it is recommended to use a shorter vaccination duration regimen.

The Mediating Effects of Resilience on Perceived Social Support and Fear of Cancer Recurrence in Glioma Patients.

Objective: To investigate the mediating effect of resilience on perceived social support and fear of cancer recurrence (FCR) in glioma patients. Methods: A total of 128 glioma patients were enrolled for the survey by Connor-Davidson resilience scale (CD-RISC), perceived social support scale (PSSS) and Chinese version of fear of progression questionnaire-short form (FoP-Q-SF). Structural equation model was used to analyze the effects of resilience. Results: The score of FCR in glioma patients was 29.52±8.30. A total of 47 patients had FCR (total score ≥34), with an incidence of 36.7%. There was a correlation between FCR, resilience and social support (P<0.01). The resilience between perceived social support and FCR in glioma patients had good fitting with the structural equation model. Resilience played a mediating role between perceived social support and FCR, with a mediating effect of 48.4%. Conclusion: The level of resilience can be improved by improving the perceived social support in patients with glioma to reduce the FCR of patients.

Mass Spectrometry-Based Quantitative Proteomics Analysis for Better Understanding of Telomeric Zinc Finger-Associated Protein-Induced Pathogenesis in Cardiomyocytes.

Telomere length is highly related to cardiovascular diseases. Telomeric zinc finger-associated protein (TZAP) directly binds to telomeric TTAGGG repeats via zinc finger domains and triggers the initiation of the telomere trimming process. However, proteomics analysis of TZAP in cardiomyocytes is slightly unknown. In our study, TZAP was overexpressed by adenovirus transfection in cultured H9c2 cardiomyocytes, and then mass spectrometry-based quantitative proteomics research strategies, including Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, subcellular localizations, predicted functional domains, and protein-protein interaction (PPI) analysis, were performed to explore TZAP-induced potential pathogenesis in cardiomyocytes. A total of 184 upregulated and 228 downregulated differentially expressed proteins (DEPs) were identified among identified 5693 quantifiable proteins in TZAP-overexpressed cardiomyocytes. These DEPs were mainly distributed in the nucleus, cytoplasm, and plasma membrane. DEPs were enriched in biological processes including cardiac muscle cell contraction, acute inflammatory response, cell-cell junction assembly, and macromolecule biosynthetic process. They were enriched in 9 KEGG pathways, including Hippo signaling pathway, protein digestion and absorption, and cytokine receptor interaction, and enriched in 17 protein domains, including translation initiation factor 1A/IF-1, class I histocompatibility antigen, and zinc finger. PPI analysis indicated that TZAP interacted with NDUFC2, Gja1, and HDAC2. Further, as proteins closely related to cardiovascular function, the mRNA levels of BRD4, Gja1, HDAC2, MAP2K3, Plakophilin 4, and Syndecan 1 significantly decreased, while Trpm7, clusterin, and NDUFC2 remarkably increased in TZAP-overexpressed cardiomyocytes by RT-PCR assay, which were consistent with the proteomics analysis. Collectively, we provided candidate proteins and enrichment pathways in TZAP-overexpressed cardiomyocytes, which need further investigation.

Andrographolide in atherosclerosis: integrating network pharmacology and in vitro pharmacological evaluation.

OBJECTIVE: Andrographis paniculata (Burm.f.) Nees is a medicinal plant that has been traditionally used as an anti-inflammatory and antibacterial remedy for several conditions. Andrographolide (AG), the active constituent of A. paniculata (Burm.f.) Nees, has anti-lipidic and anti-inflammatory properties as well as cardiovascular protective effects. The present study aimed to explore the effects of AG on the progression of atherosclerosis and to investigate related mechanisms via network pharmacology. MATERIALS AND METHODS: Compound-related information was obtained from the PubChem database. Potential target genes were identified using STITCH, SwissTargetPrediction, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Comparative Toxicogenomics Database. Genes involved in atherosclerosis were obtained from DisGeNet and compared with AG target genes to obtain an overlapping set. Protein-protein interactions were determined by STRING. Gene ontology (GO) analysis was performed at WebGestalt, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was analyzed using Metascape. The final network showing the relationship between compounds, targets, and pathways was constructed using Cytoscape. After that, oxLDL-induced RAW264.7 cells were used to further validate a part of the network pharmacology results. RESULT: Eighty-one potential AG target genes were identified. PPI, GO, and KEGG enrichment revealed genes closely related to tumor progression, lipid transport, inflammation, and related pathways. AG improves the reverse cholesterol transport (RCT) through NF-κB/CEBPB/PPARG signaling in oxLDL-induced RAW264.7 cells. CONCLUSION: We successfully predict AG's potential targets and pathways in atherosclerosis and illustrate the mechanism of action. AG may regulate NF-κB/CEBPB/PPARG signaling to alleviate atherosclerosis.

Report of a patient with refractory atrial tachycardia whose heart rate was controlled using ivabradine.

Ivabradine is an effective treatment for focal atrial tachycardia. However, it may also be effective for re-entrant atrial arrhythmia. An 85-year-old woman with a history of underlying ischaemic cardiomyopathy complained of worsening symptoms of heart failure because of rapid atrial tachycardia that was resistant to several rate-controlling drugs, but responded well to ivabradine. An electrophysiology study demonstrated a roof-dependent macro-re-entrant tachycardia of the left atrium. Linear ablation of the left atrial roof resulted in termination of the tachycardia. Thus, ivabradine can be an effective treatment for re-entrant atrial tachycardia.

Time of the low-level cardiopulmonary exercise test does not affect the evaluation of acute myocardial infarction in stable status.

Introduction: Cardiopulmonary exercise test (CPET) provides the means to evaluate the cardiopulmonary function and guide cardiac rehabilitation. The performance of acute myocardial infarction (AMI) patients at different times is different on CPET. Materials and methods: This was a cross-sectional study. Patients diagnosed as AMI in stable status were included and performed the low- level CPET (RAMP 10W). CPET variables at different times were compared among four groups. Results: Sixty and one patients with AMI conducted the low-level CPET from 3 to 15 days after AMI. Patients were stratified according to quartiles of CPET's time: 5 in 3-6 days group, 34 in 7-9 days group, 14 in 10-12 days group, 8 in 13-15 days group. Only VO2/HR at rest showed statistically different among the four groups.VO2/HR at rest in 3-6 days group and 10-12 days group were higher than in 13-15 days group (3.4 ± 0.85, 3.18 ± 0.78 vs. 2.50 ± 0.49 ml/beat, p < 0.05). Patients with complete revascularization had higher peak heart rate and blood pressure product and peak breathing reserve (BR), and lower Borg score compared with incomplete revascularization. And patients with LVEF >50% had higher peak BR compared with LVEF 40-50%. Conclusion: It was safe and efficient to conduct the low-level CPET in stable AMI patients 3 days after onset. Time was not an effector on cardiopulmonary function and exercise capacity and prognosis in AMI during CPET. Complete revascularization and normal LVEF should be good for exercise test in AMI.

Effects of Neutrophil-to-Lymphocyte Ratio Combined With Interleukin-6 in Predicting 28-Day Mortality in Patients With Sepsis.

Background: The current study aimed to evaluate the relationship between the neutrophil-to-lymphocyte ratio (NLR) combined with interleukin (IL)-6 on admission day and the 28-day mortality of septic patients. Material and Methods: We conducted an observational retrospective study. Patients with presumed sepsis were included. We observed the correlation of studied biomarkers (NLR, IL-6, PCT, and CRP) and the severity scores (APACHE II and SOFA scores) by plotting scatter plots. The relationships of the studied biomarkers and 28-day mortality were evaluated by using Cox regression model, receiver-operating characteristic (ROC) curve, and reclassification analysis. Results: A total of 264 patients diagnosed with sepsis were enrolled. It was revealed that IL-6 had the strongest correlation with both APACHE II and SOFA scores, followed by the NLR and PCT, and there was no obvious correlation between CRP and the illness severity. NLR and IL-6 were independent predictors of the 28-day mortality in septic patients in the Cox regression model [NLR, odds ratio 1.281 (95% CI 1.159-1.414), P < 0.001; IL-6, odds ratio 1.017 (95% CI 1.005-1.028), P=0.004]. The area under the ROC curve (AUC) of NLR, IL-6 and NLR plus IL-6 (NLR_IL-6) was 0.776, 0.849, and 0.904, respectively. Conclusion: Our study showed that the levels of NLR and IL-6 were significantly higher in the deceased patients with sepsis. NLR and IL-6 appeared to be independent predictors of 28-day mortality in septic patients. Moreover, NLR combined with IL-6 could dramatically enhance the prediction value of 28-day mortality.

The prognostic role of high-sensitivity cardiac troponin T over time in ischemic and non-ischemic heart failure.

INTRODUCTION: High-sensitivity cardiac troponin T (hs-cTnT) as a prognostic biomarker can be detected in patients with heart failure (HF). AIM: This study focuses on hs-cTnT to evaluate its prognostic role in ischemic heart failure (IHF) and non-ischemic heart failure (NIHF). MATERIAL AND METHODS: One hundred and sixty patients with HF were divided into IHF and NIHF groups. Hs-cTnT measured at baseline, 2-5 h, 6-24 h and 24 h-7 d after admission was analyzed by generalized estimating equations. Patients were followed up for 1 year at the endpoint events of re-hospitalization for HF and all-cause death that was tested by the Kaplan-Meier method and the Cox regression method. RESULTS: Hs-cTnT varied significantly over time, first increasing and then decreasing in IHF while showing a continuously elevated trend in NIHF. Patients with hs-cTnT levels > 0.014 ng/ml had a significantly higher re-hospitalization rate compared with those with hs-cTnT levels ≤ 0.014 ng/ml (23.7% vs. 7.0%, p < 0.05). Adjusted for age, New York Heart Association class, N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction, baseline hs-cTnT was independently associated with re-hospitalization and all-cause death in HF (p < 0.05). Optimal hs-cTnT cut-off of 0.0275 ng/ml was derived to predict the re-hospitalization and death in IHF (AUC = 0.709, 95% CI: 0.561-0.856, sensitivity: 76.9%, specificity: 63.5%, p < 0.05). CONCLUSIONS: Hs-cTnT varying over time is an important risk factor for the prognosis of patients with IHF and NIHF.

Predictive value of immune cell counts and neutrophil-to-lymphocyte ratio for 28-day mortality in patients with sepsis caused by intra-abdominal infection.

BACKGROUND: The current study aimed to evaluate the value of immune cell counts and neutrophil-to-lymphocyte ratio (NLR) when attempting to predict 28-day mortality. METHODS: We conducted an observational retrospective study that included consecutive septic patients. Severity scores on the first day and peripheral circulating immune cell counts (at day 1, day 3, day 5 and day 7 of admission) were collected during each patient's emergency intensive care unit stay. We assessed the associations of peripheral circulating immune cell counts and NLR with the severity of illness. The relationships between 28-day mortality and peripheral circulating immune cell counts and NLR with were evaluated using Cox proportional cause-specific hazards models. RESULTS: A total of 216 patients diagnosed with sepsis caused by IAI were enrolled. The lymphocyte counts (days 1, 3, 5 and 7) and monocyte counts (days 3, 5 and 7) were significantly lower in non-survivors (n = 72) than survivors (n = 144). The NLR values at each time point were significantly higher in non-survivors. The day 1 lymphocyte counts, as well as the monocyte counts, were significantly lower in the highest-scoring group, when stratified by the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, than in the other groups (p < 0.05). The day 1 NLR was significantly higher in the highest-scoring group than in the other groups (p < 0.05). The day 5 and day 7 lymphocyte counts, day 3 and day 7 monocyte counts and day 7 NLR were significant predictors of 28-day mortality in the Cox proportional hazards models (day 5 lymphocyte count: hazard ratio, 0.123 (95% CI, 0.055-0.279), p < 0.001; day 7 lymphocyte count: hazard ratio, 0.115 (95% CI, 0.052-0.254), p < 0.001; day 3 monocyte count: hazard ratio, 0.067 (95% CI, 0.005-0.861), p = 0.038; day 7 monocyte count: hazard ratio, 0.015 (95% CI, 0.001-0.158), p < 0.001; day 7 NLR: hazard ratio, 0.773 (95% CI, 0.659-0.905), p = 0.001). CONCLUSIONS: The results showed that circulating lymphocytes and monocytes were dramatically decreased within 7 days in non-survivors following sepsis from an IAI. Lymphocyte counts, monocyte counts and NLR appeared to be associated with the severity of illness, and they may serve as independent predictors of 28-day mortality in septic patients with IAIs.

Mexiletine Shortened QT Interval and Reduced Ventricular Arrhythmias in a Pedigree of Type 2 Long QT Syndrome Combined with Left Ventricular Non-Compaction.

In this study, we present a case of a 22-year-old female with a family history of syncope, suffering from recurrent syncope since childhood. She had an obvious prolonged QTc interval of up to 651 ms, a bifid T wave pattern on electrocardiogram, and torsade de pointes, corresponding to a syncope episode. Additionally, her echocardiogram showed left ventricular non-compaction in the apex. After treatment with mexiletine, the QTc interval has been observed to shorten immediately, and the T wave morphology recovered. A similar effect was also observed in her mother and young sister. Administration of propranolol prolonged her QTc interval. Target sequencing of candidate genes revealed a missense mutation in the pore area of the hERG protein, coded by KCNH2. We diagnosed this as a case of type 2 long QT syndrome in which mexiletine could be effective in shortening the QTc interval.

Tryptophan decreases the intensity of lipopolysaccharide-induced acute lung injury in a rat model.

Sepsis is a severe clinical condition that is a result of the cellular and biochemical response to infection. The present study evaluated the therapeutic potential of tryptophan against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. Rats were grouped into sham, control (ALI), and ALI + 1, 25, and 50 mg/kg body weight L-tryptophan. Supplementation with 1, 25, and 50 mg/kg L-tryptophan reduced the total protein content by 4.9%, 33.4%, and 64.5%; the levels of neutrophils (12.5%, 31.8%, and 65.1%), lymphocytes (15.1%, 41.7%, and 63.3%), total cells (12.6%, 42.4%, and 65.7%); lipid peroxidation (9.4%, 28.4%, and 68.7%); myeloperoxidase levels (12.1%, 33.4%, and 68.2%); migration inhibitory factor (12.7%, 39.5%, and 68.2%), interleukin (IL)-8 (5.5%, 46.8%, and 78.5%), tumor necrosis factor (TNF)-α (10.8%, 39.8%, and 72.2%), respectively. Supplementation with 1, 25, and 50 mg/kg L-tryptophan reduced mRNA expression of TNF-α (4.5%, 21.8%, and 41.8%), IL-1ß (5.2%, 17.9%, and 46.2%); and the protein expression of TNF-α (2.8%, 15.2%, and 35.7%) and IL-1ß (5.2%, 15.6%, and 28.6%), respectively. It also reduced glutathione (to near normal levels), neutrophilic infiltration and edema, and the wet/dry ratio of lung tissue. It significantly increased catalase, superoxide dismutase, glutathione peroxidase levels, as well as the partial pressure of oxygen (PaO2) by 21.9%, 52.8%, and 87.4%, respectively. Altogether, our results suggest that supplementation with L-tryptophan has a strong protective effect against LPS-induced ALI.