Heparin-free after 3000 IU heparin loaded in veno-venous ECMO supported acute respiratory failure patients with hemorrhage risk: a novel anti-coagulation strategy.

BACKGROUND: The anti-coagulation protocol of patients with hemorrhage risk primary disease who need extracorporeal membrane oxygenation (ECMO) supported is controversial. This study evaluated the feasibility of a new anti-coagulation strategy, that is heparin-free after 3000 IU heparin loaded in veno-venous ECMO (VV ECMO) supported acute respiratory failure patients with hemorrhage risk. METHODS: A retrospective study was performed in a series of hemorrhage risk patients supported with VV ECMO at the First Affiliated Hospital of Zhengzhou University, between June 2012 to Sept 2020. A total of 70 patients received a low heparin bolus of 3000 units for cannulation but without subsequent, ongoing heparin administration. Patients were divided into survival (n = 25) and non-survival group (n = 45). Data of coagulation, hemolysis and membrane lung function were calculated and analyzed. The complications of patients were recorded. Finally, the binary Logistic regression was conducted. RESULTS: The longest heparin-free time was 216 h, and the mean heparin-free time was 102 h. Compared with survivors, the non-survivors were showed higher baseline SOFA score and lower platelet counts in 0.5 h, 24 h, 48 h and 96 h after ECMO applied. However, there was no significant differences between survivors and non-survivors in ACT, APTT, INR, D-dimer, fibrinogen, LDH, blood flow rate, Δp and Ppost-MLO2 (all p < 0.05) of all different time point. Moreover, only the baseline SOFA score was significantly associated with mortality (p < 0.001, OR(95%CI): 2.754 (1.486-5.103)) while the baseline levels of ACT, APTT, INR, platelet, D-dimer, fibrinogen and LDH have no association with mortality. The percentage of thrombosis complications was 54.3% (38/70) including 3 oxygenator changed but there was no significant difference of complications in survival and non-survival groups (p > 0.05). CONCLUSIONS: The anticoagulation protocol that no heparin after a 3000 units heparin bolus in VV ECMO supported acute respiratory failure patients with hemorrhage risk is feasible.

Beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating GSK-3ß expression in rats.

OBJECTIVE: The aim of this study was to elucidate the mechanism of beraprost sodium (BPS) in the intervention of myocardial fibrosis after myocardial infarction (MI) through glycogen synthase kinase-3ß (GSK-3ß) and to provide new ideas for intervention in myocardial fibrosis. MATERIALS AND METHODS: MI model rats given BPS and cardiac fibroblasts (CFs) treated with BPS and TGF-ß. HE staining and Masson staining were used to detect the pathological changes of myocardial tissue. Fibrotic markers were detected by immunohistochemical staining. The expressions of GSK-3ß, cAMP response element binding protein (CREB), and p-CREB were analyzed by qPCR and western blot analysis. EDU staining was used to detect the proliferation of CFs. The promoter activity of GSK-3ß was detected by luciferase assay. Chromatin immunoprecipitation assay was used to detect the binding levels of GSK-3ß promoter and Y-box binding protein 1 (YBX1). The levels of intracellular cyclic adenosine monophosphate (cAMP) were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: After operation, BPS improved myocardial fibrosis and upregulated GSK-3ß protein expression in male SD rats. BPS can down-regulate α-smooth muscle actin (α-SMA) level and up-regulate GSK-3ß protein expression in CFs after TGF-ß stimulation. Furthermore, GSK-3ß knockdown can reverse the effect of BPS on TGF-ß-activated CFs, enhance α-SMA expression, and promote the proliferation of CFs. BPS could regulate GSK-3ß expression by promoting the binding of GSK-3ß promoter to YBX1. BPS induced upregulation of p-CREB and cAMP, resulting in reduced fibrosis, which was reversed by the knockdown of GSK-3ß or prostaglandin receptor (IPR) antagonists. CONCLUSION: BPS treatment increased the binding of YBX1 to the GSK-3ß promoter, and GSK-3ß protein expression was upregulated, which further caused the upregulation of p-CREB and cAMP, and finally inhibited myocardial fibrosis.

[Distribution, Source, and Ecological Risk Assessment of Persistent Organic Pollutants in Surface Sediments of Boao Coastal Waters].

Persistent organic pollutants (POPs) in the environment have the characteristics of persistence, bioaccumulation, teratogenicity, carcinogenicity, and mutagenicity. Long-term exposure of low-content POPs will also have a certain impact on marine ecosystems and human beings. The contents of three typical persistent organic pollutants[polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), and polycyclic biphenyls (PCBs)] of surface sediments were analyzed using gas chromatography and mass spectrometry (GC-MS) to assess the pollution characteristics of persistent organic pollutants in Boao coastal waters. The distribution and source of persistent organic pollutants were analyzed in this study, and the ecological risk was assessed using three different methods:the effect interval low/median method (ERL/ERM), mean effect interval median quotient method (M-ERM-Q), and mean potential impact concentration quotient method (M-PEC-Q). The results indicated that the contents (measured by dry weight) of ΣPAHs, ΣOCPs, and ΣPCBs in the study area were 4.5-367.50, 3.99-175.30, and ND-2.89 ng·g-1, respectively, which were at a low level, and the overall distribution showed a trend of gradually increasing toward the sea. The results of POPs source analysis showed that the PAHs in the study area were mainly from the combustion of wood and coal. Among OCPs, the HCH was mainly from lindane, the historical land-based input had been completely degraded, and the DDT was mainly the traditional DDTs pesticides, with additional continuous DDT input. The PCBs were primarily pentachlorobiphenyls, which might have come from the release of paint on the bottom of the hull in the early stage of shipping and the peeling off of paint from old ships. The ecological risk assessment results showed that there was little difference among the assessment results of the three methods, which showed that only phenanthrene monomer of PAHs in the study area had a slight negative impact, and the DDT and the γ-HCH among PAHs would cause great ecological risk, whereas PCBs and other pollutants would not cause ecological risk. On the whole, the possibility of comprehensive ecological risk caused by the three pollutants was very small.

Clinical application of metagenomic next-generation sequencing in non-immunocompromised patients with severe pneumonia supported by veno-venous extracorporeal membrane oxygenation.

Objectives: This study aims to explore the pathogen-detected effect of mNGS technology and its clinical application in non-immunocompromised patients with severe pneumonia supported by vv-ECMO. Methods: A retrospective analysis was conducted on a cohort of 50 non-immunocompromised patients who received vv-ECMO support for severe pneumonia between January 2016 and December 2022. These patients were divided into two groups based on their discharge outcomes: the deterioration group (Group D), which included 31 cases, and the improvement group (Group I), consisting of 19 cases. Baseline characteristics and clinical data were collected and analyzed. Results: Among the 50 patients enrolled, Group D exhibited a higher prevalence of male patients (80.6% vs. 52.6%, p < 0.05), more smokers (54.8% vs. 21.1%, p < 0.05), and were older than those in Group I (55.16 ± 16.34 years vs. 42.32 ± 19.65 years, p < 0.05). Out of the 64 samples subjected to mNGS detection, 55 (85.9%) yielded positive results, with a positivity rate of 83.7% (36/43) in Group D and 90.5% (19/21) in Group I. By contrast, the positive rate through traditional culture stood at 64.9% (74/114). Among the 54 samples that underwent both culture and mNGS testing, 23 (42.6%) displayed consistent pathogen identification, 13 (24.1%) exhibited partial consistency, and 18 (33.3%) showed complete inconsistency. Among the last cases with complete inconsistency, 14 (77.8%) were culture-negative, while two (11.1%) were mNGS-negative, and the remaining two (11.1%) presented mismatches. Remarkably, mNGS surpassed traditional culture in pathogen identification (65 strains vs. 23 strains). Within these 65 strains, 56 were found in Group D, 26 in Group I, and 17 were overlapping strains. Interestingly, a diverse array of G+ bacteria, fungi, viruses, and special pathogens were exclusive to Group D. Furthermore, Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were more prevalent in Group D compared to Group I. Importantly, mNGS prompted antibiotic treatment adjustments in 26 patients (52.0%). Conclusions: Compared with the conventional culture, mNGS demonstrated a higher positive rate, and emerges as a promising method for identifying mixed pathogens in non-immunodeficient patients with severe pneumonia supported by vv-ECMO. However, it is crucial to combine the interpretation of mNGS data with clinical information and traditional culture results for a comprehensive assessment.

Outcomes of Transferred Adult Venovenous and Venoarterial Extracorporeal Membrane Oxygenation Patients: A Single Center Experience.

Objectives: Extracorporeal membrane oxygenation (ECMO) patients with or without transport both have high hospital mortality rate and there are few data on adult VA-ECMO transport patients. Hence, this study was designed to analyze factors that affect the outcomes of patients with ECMO transport. Methods: This study retrospectively enrolled 126 ECMO patients transferred from regional hospital to the First Affiliated Hospital of Zhengzhou University by our ECMO team during June 2012 to Sept 2020. Data were calculated and analyzed. Results: The median distance of transportation was 141 (76-228) km, the median transport time consuming was 3 (1.3-4) h, the percentage of complications during transport was 40.5% (except for bleeding on cannula site, and no one death during transport), and the survival rate in hospital was 38.9%. Compared with survivors, the non-survivors were older and showed higher SOFA score, longer time with ECMO assisted, longer time in ICU and in hospital. However, after divided into VA-ECMO and VV-ECMO groups, the older age showed no significant difference between survivors and non-survivors groups of VA-ECMO patients. Moreover, the Cox regression survival analysis showed that higher SOFA score and lactate level indicated higher ICU mortality of VA-ECMO patients while higher SOFA score, higher lactate level, older age and lower MAP after transportation (<70mmHg) indicated higher ICU mortality of VV-ECMO patients. However, there was no significant difference of comorbidities and complications in survivors and non-survivors groups of ECMO patients. Conclusions: The transportation for ECMO patients can be feasible performed although life-threatening complications might occur. The SOFA score and the lactate level could be used to evaluate the risk of ICU mortality of transportation ECMO patients. Besides, lower MAP after transportation (<70mmHg) had potential predictive value for short-term outcome of VV-ECMO patients.

Role and Clinical Application of Metagenomic Next-Generation Sequencing in Immunocompromised Patients With Acute Respiratory Failure During Veno-Venous Extracorporeal Membrane Oxygenation.

Objectives: There are few studies of metagenomic next-generation sequencing (mNGS) in immunocompromised patients assisted by veno-venous extracorporeal membrane oxygenation (vv-ECMO). The present study is aimed to investigate the pathogen-detected effect and clinical therapy value of mNGS technologies in immunocompromised patients assisted by vv-ECMO. Methods: Our study retrospectively enrolled 46 immunocompromised patients supported by vv-ECMO from Jan 2017 to June 2021 at the First Affiliated Hospital of Zhengzhou University, respectively. Patients were divided into the deterioration group (Group D) (n = 31) and improvement group (Group I) (n = 15) according to their outcomes. Baseline characteristics and etiological data of patients during hospitalization of 2 groups were compared. The pathogens detected by mNGS and antibiotic regimens guided by mNGS in immunocompromised patients assisted by vv-ECMO were analyzed. Results: Compared with Group I, the deterioration patients showed a higher percentage of chronic obstructive pulmonary disease (COPD) (32.3% vs. 6.7%, p < 0.01) and were significantly older (47.77 ± 16.72 years vs. 32 ± 15.05 years, p < 0.01). Within 48 h of being ECMO assisted, the consistency of the samples detected by traditional culture and mNGS at the same time was good (traditional culture vs. mNGS detection, the positive rate of bronchoalveolar lavage fluid (BALF) culture: 26.1% vs. 30.4%; the positive rate of blood sample culture: 12.2% vs. 12.2%, p > 0.05). However, mNGS detected far more pathogen species and strains than conventional culture (30 strains vs. 78 strains, p < 0.01); the most popular pathogen was Klebsiella pneumoniae. Parts of patients had their antibiotic treatment adjustments, and the improvement patients showed less usage of broad-spectrum antibiotics. Conclusions: mNGS may play a relatively important role in detecting mixed pathogens and personalized antibiotic treatment in immunocompromised patients assisted by vv-ECMO.

[Countermeasures for strict water quality management of drinking water sources: some thoughts and suggestions on implementing strict water resources management].

Suggestions on Carrying Out Strict Management Regulations of Water Resources were promulgated by the State Council in January, 2012. This is an important issue which has drawn public attention. I strongly support the principle and spirit of the regulations, as well as the request that governments above the county level bear the overall management responsibility. However, as to the technical route of and countermeasures for achieving strict management, several problems exist in reality. Relevant opinions and suggestions are given in this paper (the paper focuses exclusively on drinking water sources which are most in need of strict protection and management). Main opinions are as follows. (1) The sources of drinking water meeting the Class II standard in Surface Water Environment Quality Standards (GB 3838-2002) may not necessarily be unpolluted; (2) A necessary condition for protecting drinking water sources is that the effluents of enterprises' workshops discharged into the conservation zone should meet the regulation on the permitted maximum concentration of priority-I pollutants defined in the Integrated Wastewater Discharge Standard (GB 8978-1996); (3) There is a strong doubt about whether Class II standard in GB 3838-2002 for priority I pollutants reflects environmental background values in water.

[Effect analysis on the two total load control methods for poisonous heavy metals].

Firstly it should be made clear that implementation of source total load control for the first type of pollutants is necessary for environmental pollution control legislation and economic structure regulation. This kind of surveillance method has been more practical to be implemented since the Manual of the Industry Discharge Coefficient of First National Pollution Sources Investigation was published. The source total load control and water environment total load control are independent of each other and none of them is redundant, on the other side they can be complementary to each other. In the present, some local planning managers are blurring and confusing the contents and styles of the two surveillance methods. They just use the water total load control to manage all the pollutants, and source total load control is discarded, which results in the loss of control for the first type of pollutants especially for the drinking water source surveillance. There is a big difference between the water quality standards and the water environmental background concentration values for the first type of pollutants in the Environmental quality standard for surface water (GB 3838-88), which means that there are problems such as "relaxing the pollutant discharge permit" and "risk induced by valence state change". Taking an enterprise with 10t electrolytic lead production capacity as an example, there is a big difference between the allowable lead discharged loads by the two total load surveillance methods. In summary, it will bring a lot of harmful effects if the water total load control is implemented for the two types of pollutants, so the source total load control and water environmental total load control should be implemented strictly at the same time.