Programmable DNA hydrogel provides suitable microenvironment for enhancing autophagy-based therapies in intervertebral disc degeneration treatment.

The pathogenesis of intervertebral disc degeneration (IVDD) is attributed to metabolic dysregulation within the extracellular matrix and heightened apoptosis of nucleus pulposus cells (NPC). Therefore, a potential therapeutic strategy for managing IVDD involves the reestablishment of metabolic equilibrium within the extracellular matrix and the suppression of excessive myeloid cell apoptosis. The microRNA, miR-5590, displays marked differential expression in degenerative nucleus pulposus (NP) tissues and exerts a direct influence on the regulation of DDX5 expression. This, in turn, modulates mammalian target of rapamycin (mTOR) phosphorylation, thereby impacting autophagy and apoptosis. However, ensuring the smooth delivery of miRNA to a specific injury site poses a significant challenge. To address this issue, a multifunctional DNA hydrogel was developed and subsequently loaded with miR-5590 via spherical nucleic acids (SNAs) for the treatment of IVDD. The hydrogel, which exhibits versatility, has the potential to be administered through injection at the site of injury, resulting in a consistent and prolonged release of miR-5590. This leads to the creation of a genetic microenvironment within the NP, which triggers the onset of autophagy in NPCs and subsequently suppresses apoptosis. As a result, this process regulates the metabolic equilibrium within the extracellular matrix, thereby impeding the in vitro and in vivo progression of IVDD. The amalgamation of miRNAs and biomaterials offers a promising therapeutic strategy for the management of IVDD in clinical settings.

Hydrogen sulfide plays a potential alternative for the treatment of metabolic disorders of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication that tends to occur in patients with diabetes, obesity, or insulin resistance, with a higher late mortality rate. Sustained hyperglycemia, increased free fatty acids, or insulin resistance induces metabolic disorders in cardiac tissues and cells, leading to myocardial fibrosis, left ventricular hypertrophy, diastolic and/or systolic dysfunction, and finally develop into congestive heart failure. The close connection between all signaling pathways and the complex pathogenesis of DCM cause difficulties in finding effective targets for the treatment of DCM. It reported that hydrogen sulfide (H2S) could regulate cell energy substrate metabolism, reduce insulin resistance, protect cardiomyocytes, and improve myocardial function by acting on related key proteins such as differentiation cluster 36 (CD36) and glucose transporter 4 (GLUT4). In this article, the relative mechanisms of H2S in alleviating metabolic disorders of DCM were reviewed, and how H2S can better prevent and treat DCM in clinical practice will be discussed.

A Standardized Step-by-Step Approach for the Diagnosis and Treatment of Sepsis.

Sepsis is the major culprit of death among critically ill patients who are hospitalized in intensive care units (ICUs). Although sepsis-related mortality is steadily declining year-by-year due to the continuous understanding of the pathophysiological mechanism on sepsis and improvement of the bundle treatment, sepsis-associated hospitalization is rising worldwide. Surviving Sepsis Campaign (SSC) guidelines are continuously updating, while their content is extremely complex and comprehensive for a precisely implementation in clinical practice. As a consequence, a standardized step-by-step approach for the diagnosis and treatment of sepsis is particularly important. In the present study, we proposed a standardized step-by-step approach for the diagnosis and treatment of sepsis using our daily clinical experience and the latest researches, which is close to clinical practice and is easy to implement. The proposed approach may assist clinicians to more effectively diagnose and treat septic patients and avoid the emergence of adverse clinical outcomes.

Histone lysine demethylase KDM4B regulates the alternative splicing of the androgen receptor in response to androgen deprivation.

Alternative splicing is emerging as an oncogenic mechanism. In prostate cancer, generation of constitutively active forms of androgen receptor (AR) variants including AR-V7 plays an important role in progression of castration-resistant prostate cancer (CRPC). AR-V7 is generated by alternative splicing that results in inclusion of cryptic exon CE3 and translation of truncated AR protein that lacks the ligand binding domain. Whether AR-V7 can be a driver for CRPC remains controversial as the oncogenic mechanism of AR-V7 activation remains elusive. Here, we found that KDM4B promotes AR-V7 and identified a novel regulatory mechanism. KDM4B is phosphorylated by protein kinase A under conditions that promote castration-resistance, eliciting its binding to the splicing factor SF3B3. KDM4B binds RNA specifically near the 5'-CE3, upregulates the chromatin accessibility, and couples the spliceosome to the chromatin. Our data suggest that KDM4B can function as a signal responsive trans-acting splicing factor and scaffold that recruits and stabilizes the spliceosome near the alternative exon, thus promoting its inclusion. Genome-wide profiling of KDM4B-regulated genes also identified additional alternative splicing events implicated in tumorigenesis. Our study defines KDM4B-regulated alternative splicing as a pivotal mechanism for generating AR-V7 and a contributing factor for CRPC, providing insight for mechanistic targeting of CRPC.

Acute right ventricular dysfunction in severe COVID-19 pneumonia.

To investigate the right heart function in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS), a retrospective analysis of 49 COVID-19 patients with ARDS was performed. Patients were divided into severe group and critically-severe group according to the severity of illness. Age-matched healthy volunteers were recruited as a control group. The cardiac cavity diameters, tricuspid annular plane systolic excursion (TAPSE), tricuspid valve regurgitation pressure gradient biggest (TRPG), pulmonary arterial systolic pressure (PASP), maximum inferior vena cava diameter (IVCmax) and minimum diameter (IVCmin), and inferior vena cava collapse index (ICV-CI) were measured using echocardiography. We found that the TAPSE was significantly decreased in pneumonia patients compared to healthy subjects (P < 0.0001), and it was significantly lower in critically-severe patients (P = 0.0068). The TAPSE was less than 17 mm in three (8.6%) severe and five (35.7%) critically-severe patients. In addition, the TAPSE was significantly decreased in severe ARDS patients than in mild ARDS patients. The IVCmax and IVCmin were significantly increased in critically-severe patients compared to healthy subjects and severe patients (P < 0.01), whereas the ICV-CI was significantly decreased (P < 0.05). COVID-19 patients had significantly larger right atrium and ventricle than healthy controls (P < 0.01). The left ventricular ejection fraction (LVEF) in critically-severe patients was significantly lower than that in severe patients and healthy controls (P < 0.05). Right ventricular function was impaired in critically-severe COVID-19 patients. The assessment and protection of the right heart function in COVID-19 patients should be strengthened.

Sectioning protocol determines accuracy of intraoperative pathological examination of sentinel lymph node in cervical cancer: A systematic review and meta-analysis.

OBJECTIVES: To determine the diagnostic performance and optimal protocol of frozen section examination (FSE) in SLNB for cervical cancer. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure were searched from inception to July 30, 2019, for studies concerning SLNB with FSE in cervical cancer. Sensitivity of FSE in detecting SLN metastasis was the primary diagnostic indicator for evaluation. RESULTS: The pooled sensitivity of FSE among 31 eligible studies (1887 patients) was 0.77 (95% CI 0.66-0.85) with high heterogeneity (I2 = 69.73%). Two representative sectioning protocols for FSE were identified from 26 studies, described as equatorial (E-protocol, SLN was bisected) and latitudinal (L-protocol, SLN was cut at intervals). Meta-regression showed that FSE protocol was the only source of heterogeneity (p < 0.001). The pooled sensitivity was 0.86 (95% CI 0.79-0.91, I2 = 0%) and 0.59 (0.46-0.72, I2 = 58.47%) for FSE using L- (13 studies, 650 patients) and E- (13 studies, 1047 patients) protocol, respectively. Among the available data, marcometastases (>2 mm) were missed in 4 and 20 patients; small-volume metastases (≤2 mm) were detected in 13 and 2 patients, respectively, under L- and E-protocol. The pooled sensitivity of FSE using L-protocol would reach 0.97 (95% CI 0.89-0.99) if only marcometastases were considered. These findings were robust to sensitivity analyses. CONCLUSION: The sectioning protocol determines the accuracy of FSE in SLNB. With L-protocol, FSE can provide precise intraoperative pathology for SLNB, which enables immediate decision-making for individualized managements.

MicroRNA-223-5p and -3p Cooperatively Suppress Necroptosis in Ischemic/Reperfused Hearts.

Recent studies have shown that myocardial ischemia/reperfusion (I/R)-induced necrosis can be controlled by multiple genes. In this study, we observed that both strands (5p and 3p) of miR-223 were remarkably dysregulated in mouse hearts upon I/R. Precursor miR-223 (pre-miR-223) transgenic mouse hearts exhibited better recovery of contractile performance over reperfusion period and lesser degree of myocardial necrosis than wild type hearts upon ex vivo and in vivo myocardial ischemia. Conversely, pre-miR-223 knock-out (KO) mouse hearts displayed opposite effects. Furthermore, we found that the RIP1/RIP3/MLKL necroptotic pathway and inflammatory response were suppressed in transgenic hearts, whereas they were activated in pre-miR-223 KO hearts upon I/R compared with wild type controls. Accordingly, treatment of pre-miR-223 KO mice with necrostatin-1s, a potent necroptosis inhibitor, significantly decreased I/R-triggered cardiac necroptosis, infarction size, and dysfunction. Mechanistically, we identified two critical cell death receptors, TNFR1 and DR6, as direct targets of miR-223-5p, whereas miR-223-3p directly suppressed the expression of NLRP3 and IκB kinase α, two important mediators known to be involved in I/R-induced inflammation and cell necroptosis. Our findings indicate that miR-223-5p/-3p duplex works together and cooperatively inhibits I/R-induced cardiac necroptosis at multiple layers. Thus, pre-miR-223 may constitute a new therapeutic agent for the treatment of ischemic heart disease.

Suppression of Ghrelin Exacerbates HFCS-Induced Adiposity and Insulin Resistance.

High fructose corn syrup (HFCS) is widely used as sweetener in processed foods and soft drinks in the United States, largely substituting sucrose (SUC). The orexigenic hormone ghrelin promotes obesity and insulin resistance; ghrelin responds differently to HFCS and SUC ingestion. Here we investigated the roles of ghrelin in HFCS- and SUC-induced adiposity and insulin resistance. To mimic soft drinks, 10-week-old male wild-type (WT) and ghrelin knockout (Ghrelin-/-) mice were subjected to ad lib. regular chow diet supplemented with either water (RD), 8% HFCS (HFCS), or 10% sucrose (SUC). We found that SUC-feeding induced more robust increases in body weight and body fat than HFCS-feeding. Comparing to SUC-fed mice, HFCS-fed mice showed lower body weight but higher circulating glucose and insulin levels. Interestingly, we also found that ghrelin deletion exacerbates HFCS-induced adiposity and inflammation in adipose tissues, as well as whole-body insulin resistance. Our findings suggest that HFCS and SUC have differential effects on lipid metabolism: while sucrose promotes obesogenesis, HFCS primarily enhances inflammation and insulin resistance, and ghrelin confers protective effects for these metabolic dysfunctions.

Budesonide ameliorates lung injury induced by large volume ventilation.

BACKGROUND: Ventilation-induced lung injury (VILI) is a health problem for patients with acute respiratory dysfunction syndrome. The aim of this study was to investigate the effectiveness of budesonide in treating VILI. METHODS: Twenty-four rats were randomized to three groups: a ventilation group, ventilation/budesonide group, and sham group were ventilated with 30 ml/kg tidal volume or only anesthesia for 4 hor saline or budesonide airway instillation immediately after ventilation. The PaO2/FiO2and wet-to-dry weight ratios, protein concentration, neutrophil count, and neutrophil elastase levels in bronchoalveolar lavage fluid (BALF) and the levels of inflammation-related factors were examined. Histological evaluation of and apoptosis measurement inthe lung were conducted. RESULTS: Compared with that in the ventilation group, the PaO2/FiO2 ratio was significantly increased by treatment with budesonide. The lung wet-to-dry weight ratio, total protein, neutrophil elastase level, and neutrophilcount in BALF were decreased in the budesonide group. The BALF and plasma tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, intercellular adhesion molecule (ICAM)-1, and macrophage inflammatory protein (MIP)-2 levels were decreased, whereas the IL-10 level was increased in the budesonide group. The phosphorylated nuclear factor (NF)-kBlevels in lung tissue were inhibited by budesonide. The histological changes in the lung and apoptosis were reduced by budesonide treatment. Bax, caspase-3, and cleaved caspase-3 were down-regulated, and Bcl-2 was up-regulated by budesonide. CONCLUSIONS: Budesonide ameliorated lung injury induced by large volume ventilation, likely by improving epithelial permeability, decreasing edema, inhibiting local and systemic inflammation, and reducing apoptosis in VILI.

MicroRNA-373 functions as an oncogene and targets YOD1 gene in cervical cancer.

miR-373 was reported to be elevated in several tumors; however, the role of miR-373 in cervical cancer has not been investigated. In this study we aimed to investigate the role of miR-373 in tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-373 was investigated using real-time reverse transcription-polymerase chain reaction assay in 45 cervical specimens and cervical cancer cell lines. The role of miR-373 in tumorigenicity of cervical cancer cells was assessed by cell proliferation, colony formation in vitro as well as tumor growth assays in vivo with the overexpression of miR-373 or gene silencing. The functional target gene of miR-373 in cervical cancer cells was identified using integrated bioinformatics analysis, gene expression arrays, and luciferase assay. We founded that the expression of miR-373 is upregulated in human cervical cancer tissues and cervical carcinoma cell lines when compared to the corresponding noncancerous tissues. Ectopic overexpression of miR-373 in human cervical cancer cells promoted cell growth in vitro and tumorigenicity in vivo, whereas silencing the expression of miR-373 decreased the rate of cell growth. YOD1 was identified as a direct and functional target of miR-373 in cervical cancer cells. Expression levels of miR-373 were inversely correlated with YOD1 levels in human cervical cancer tissues. RNAi-mediated knockdown of YOD1 phenocopied the proliferation-promoting effect of miR-373. Moreover, overexpression of YOD1 abrogated miR-373-induced proliferation of cervical cancer cells. These results demonstrate that miR-373 increases proliferation by directly targeting YOD1, a new potential therapeutic target in cervical cancer.

Prediction of metallic nano-optical trapping forces by finite element-boundary integral method.

The hybrid of finite element and boundary integral (FE-BI) method is employed to predict nano-optical trapping forces of arbitrarily shaped metallic nanostructures. A preconditioning strategy is proposed to improve the convergence of the iterative solution. Skeletonization is employed to speed up the design and optimization where iteration has to be repeated for each beam configuration. The radiation pressure force (RPF) is computed by vector flux of the Maxwell's stress tensor. Numerical simulations are performed to validate the developed method in analyzing the plasmonic effects as well as the optical trapping forces. It is shown that the proposed method is capable of predicting the trapping forces of complex metallic nanostructures accurately and efficiently.

Increased whole blood viscosity associated with arterial stiffness in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for increased cardiovascular disease. The brachial-ankle pulse wave velocity (baPWV) is a marker for early atherosclerotic changes. Recently, the effect of changed blood rheology on atherosclerosis has received attention. A study confirmed that whole blood viscosity (WBV) is a predictor of cardiovascular events. Therefore, this study aimed to investigate the association of WBV with baPWV in patients with NAFLD. METHODS: In this cross-sectional study, the relationship between WBV and baPWV was investigated in 2032 participants (1035 men and 997 women) with NAFLD in a general health examination. RESULTS: Different metabolic parameters were compared across WBV (3/s) quartiles. The mean values of baPWV gradually increased with WBV (3/s) quartiles. Stepwise multiple linear regression analysis revealed that WBV (3/s) is a significant determinant for increased baPWV both in men and in women (for male, ß = 0.229; P < 0.001; for female, ß = 0.672; P < 0.001). CONCLUSIONS: The findings showed that baPWV elevated as WBV (3/s) increased in NAFLD. Moreover, WBV (3/s) is independently associated with baPWV even after adjusting other cardiovascular risk factors. Early detection of abnormal WBV levels at low shear rate should warrant for early search of undetected arterial stiffness in patients with NAFLD.

Impact of KRAS mutation on outcome of patients with metastatic colorectal cancer.

BACKGROUND/AIMS: KRAS mutation is present in 30%-50% of colorectal cancers and is associated with the inefficacy of anti-epidermal growth factor receptor therapy, while the impact of KRAS on survival is seldom discussed. The aim of this study was to elucidate the impact of KRAS status on the survival of patients with metastatic colorectal cancer. METHODOLOGY: Two hundred and one patients with metastatic colorectal cancer were enrolled. Amplification and sequencing of the KRAS gene were performed, with the overall survival according to KRAS status analyzed. RESULTS: KRAS mutations were present in 72 (35.8%) of patients, including 55 (27.3%) codon 12 mutations and 17 (8.5%) codon 13 mutations. Lymphovascular invasion (hazard ratio 1.841, 95% confidence interval 1.043-3.247, p = 0.035) and KRAS mutation (hazard ratio 1.919, 95% confidence interval 1.104-3.333, p = 0.021) were independent prognostic factors for overall survival. The median overall survival for patients with KRAS mutation at codon 12 was 27.3 months, and was similar to those with KRAS mutation at codon 13 (20.4 months, p = 0.628). CONCLUSIONS: KRAS mutation is a poor prognostic factor in patients with metastatic colorectal cancer. In KRAS mutation metastatic colorectal cancer, mutation at codon 12 or at codon 13 had no relationship with prognosis.

Functional characterization of MiFTs implicated in early flowering and stress resistances of mango.

Phosphatidylethanolamine binding protein (PEBP) family plays important roles in multiple developmental processes in plants. In this study, a total of 11 PEBP gene family members were identified from the mango (Mangifera indica L.) genome, and these proteins were divided into three subfamilies based on their phylogenetic relationships: TERMINAL FLOWER 1 (TFL1)-like, MOTHER OF FT AND TFL (MFT)-like, and FLOWERING LOCUS T (FT)-like. Expression analysis revealed that MiFT1a, MiFT1b and MiFT2 were expressed mainly in leaves, whereas MiFT3 and MiFT4 were expressed mainly in embryos. The overexpression of MiFTs significantly promoted early flowering under both long- and short-day conditions. Interestingly, it still significantly promoted early flowering at 16 °C and 28 °C, with MiFT1a exhibiting the most significant, followed by MiFT1b and MiFT2. Additionally, the expression level of MiFT3 is related to the embryonic development of mango. Further studies revealed that overexpression of MiFT3 inhibited seed germination in transgenic Arabidopsis lines. In addition, the MiFT1a and MiFT1b transgenic lines did not respond to abiotic stress, while MiFT2, MiFT3 and MiFT4 enhanced resistance to salt or drought stress in Arabidopsis. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays revealed that MiFTs can interact with flower related and multiple stress proteins, such as bZIP protein (MiFD), 14-3-3 protein, zinc finger protein (MiZFP4), RING zinc-finger protein (MiRZFP34), and phosphatase 2C (MiPP2C25A and MiPP2C25B). These results indicate that FT subfamily not only regulates flowering but also participates in stress response, but there are differences in the function among these genes.

LncRNA-mediated Modulation of Endothelial Cells: Novel Progress in the Pathogenesis of Coronary Atherosclerotic Disease.

Coronary atherosclerotic disease (CAD) is a common cardiovascular disease and an important cause of death. Moreover, endothelial cells (ECs) injury is an early pathophysiological feature of CAD, and long noncoding RNAs (lncRNAs) can modulate gene expression. Recent studies have shown that lncRNAs are involved in the pathogenesis of CAD, especially by regulating ECs. In this review, we summarize the novel progress of lncRNA-modulated ECs in the pathogenesis of CAD, including ECs proliferation, migration, adhesion, angiogenesis, inflammation, apoptosis, autophagy, and pyroptosis. Thus, as lncRNAs regulate ECs in CAD, lncRNAs will provide ideal and novel targets for the diagnosis and drug therapy of CAD.

Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

[Application of carbon nanoparticles in the laparoscopic sentinel lymph node detection in patients with cervical cancer].

OBJECTIVE: To explore the role of laparoscopic sentinel lymph node(SLN) detection with carbon nanoparticles tracer in cervical carcinoma. METHODS: Totally 21 patients with confirmed early cervical cancer were enrolled in this study.Before laparoscopic extended hysterectomy and pelvic lymphadenoetomy(and para-aortic lymphadenoectomy) , they were injected with carbon nanoparticles suspension injection tracer from cervical neck before surgery. The black-staining lymph nodes were cut as SLN under the laparoscope for routine pathological examination. RESULTS: Of these 21 patients, at least one SLN was successfully detected in 20 patients(95.24%) , and a total of 158 SLNs were detected.The conventional pathology results suggested that 5 patients(23.81%) had positive lymph nodes(n=16, including 14 in 4 patients) . The new approach showed a sensitivity of 80.0%(4/5) , accuracy of 100.0%(20/20) , and negative predictive value of 100.0%(16/16) for SLN detection. CONCLUSION: Laparoscopic SLN detection with carbon nanoparticles tracer is a relative safe and sensitive method for in cervical carcinoma.

Up-regulation of Myocardial Klotho Expression to Promote Cardiac Functional Recovery in Old Mice following Endotoxemia.

Objective: Endotoxemic cardiac dysfunction contributes to greater morbidity and mortality in elderly patients with sepsis. This study tested the hypothesis that Klotho insufficiency in aging heart exaggerates and prolongs myocardial inflammation to hinder cardiac function recovery following endotoxemia. Methods: Endotoxin (0.5 mg/kg, iv) was administered to young adult (3-4 months) and old (18-22 months) mice with or without subsequent treatment with recombinant interleukin-37 (IL-37, 50 µg/kg, iv) or recombinant Klotho (10 µg/kg, iv). Cardiac function was analyzed using a microcatheter 24, 48 and 96 h later. Myocardial levels of Klotho, ICAM-1, VCAM-1 and IL-6 were determined by immunoblotting and ELISA. Results: In comparison to young adult mice, old mice had worse cardiac dysfunction accompanied by greater myocardial levels of ICAM-1, VCAM-1 and IL-6 at each time point following endotoxemia and failed to fully recover cardiac function by 96 h. The exacerbated myocardial inflammation and cardiac dysfunction were associated with endotoxemia-caused further reduction of lower myocardial Klotho level in old mice. Recombinant IL-37 promoted inflammation resolution and cardiac functional recovery in old mice. Interestingly, recombinant IL-37 markedly up-regulated myocardial Klotho levels in old mice with or without endotoxemia. Similarly, recombinant Klotho suppressed myocardial inflammatory response and promoted inflammation resolution in old endotoxemic mice, leading to complete recovery of cardiac function by 96 h. Conclusion: Myocardial Klotho insufficiency in old endotoxemic mice exacerbates myocardial inflammatory response, impairs inflammation resolution and thereby hinders cardiac functional recovery. IL-37 is capable of up-regulating myocardial Klotho expression to improve cardiac functional recovery in old endotoxemic mice.

Successful treatment of near-fatal pulmonary embolism and cardiac arrest in an adult patient with fulminant psittacosis-induced severe acute respiratory distress syndrome after veno-venous extracorporeal membrane oxygenation rescue: A case report and follow-up.

Background: Veno-venous extracorporeal membrane oxygenation (ECMO) was successfully performed for the rescue of an adult patient with severe acute respiratory distress syndrome (ARDS) induced by fulminant psittacosis, and then a near-fatal pulmonary embolism (PE) and cardiac arrest (CA) of the same patient was cured through catheter-directed thrombolysis. Case presentation: A 51-year-old female patient was admitted to the hospital on September 10, 2021 due to slurred speech, weakness in lower limbs, dizziness, and nausea. Subsequently, she developed confusion and was transferred to the intensive care unit (ICU), where she received anti-shock, antibiotics, invasive mechanical ventilation (IMV), and veno-venous ECMO due to the diagnosis of severe pneumonia, severe ARDS, and septic shock based on comprehensive physical examination, laboratory tests, and imaging findings. The metagenomic next-gengeration sequencing (m-NGS) in the bronchoalveolar lavage fluid (BALF) suggested that the pathogen was chlamydia psittaci, so the antibiotics were adjusted to doxycycline combined with azithromycin. After withdrawal from ECMO, ultrasound (US) re-examination of the left lower limb revealed inter-muscular vein thrombosis, following which heparin was replaced by subcutaneous injection of 0.4ml enoxaparin sodium twice daily for anti-coagulation therapy. After withdrawal from IMV, the patient suffered sudden CA and successful cardiopulmonary resuscitation (CPR), and emergency pulmonary angiography (PA) was performed to show bilateral main pulmonary artery embolism. After immediate catheter-directed thrombolysis and placement of an inferior vena cava filter, the patient's condition gradually stabilized. Conclusions: Veno-venous ECMO can be successfully performed as an emergency life-saving treatment for patients with severe ARDS induced by fulminant psittacosis, and during ECMO regular examinations should be conducted to detect and manage thrombosis in time, thereby avoiding the occurrence of near-fatal PE and CA.

[Effects of extracorporeal membrane oxygenation on hemodynamics in acute right heart failure in dogs].

OBJECTIVE: To investigate the effects of extracorporeal membrane oxygenation (ECMO) on the hemodynamics in dogs with acute right heart failure. METHODS: Ten healthy adult male dogs (weighted 20-25 kg) were randomly divided into two groups: acute right heart failure group (n = 5) and ECMO group (n = 5). Under anesthesia, dogs were underwent thoracotomy, then the catheters were placed in the right atrium, right ventricle, and pulmonary artery, for measuring the relevant pressures, including right arterial pressure (RAP), right ventricular pressure (RVP), and pulmonary artery pressure (PAP). The vascular ultrasound probe were placed on the aorta and pulmonary artery for measuring the cardiac output (CO) and pulmonary artery flow rate (QPA). Then, a baseline measurement was acquired. The femoral artery and femoral vein were cannulated and used for the venoarterial extracorporeal membrane oxygenation (VA-ECMO), and then connected to extracorporeal circuit, which was initially primed. The pulmonary artery was progressively ligated to decrease blood flow until QPA was 60%, 40%, and 0% of baseline in both groups. The above flow conditions were respectively maintained for 30 minutes, after which hemodynamic data were collected. RESULTS: The baseline hemodynamic measurements were not different between acute right heart failure group and ECMO group. After ligating the pulmonary artery, compared with baseline, CO (L/min) decreased significantly at 60% and 40% QPA in acute right heart failure group (1.80 ± 0.19, 1.48 ± 0.22 vs. 3.24 ± 0.23, both P < 0.05), and significantly lower than that of ECMO group (60%QPA: 1.80 ± 0.19 vs. 3.24 ± 0.35; 40%QPA: 1.48 ± 0.22 vs. 3.20 ± 0.37, both P < 0.05). CO was not significantly different from baseline in ECMO group at 60%, 40% and 0% QPA (3.24 ± 0.35, 3.20 ± 0.37, 3.12 ± 0.28 vs. 3.44 ± 0.32, all P>0.05). PAP, RAP and RVP (all mm Hg, 1 mm Hg = 0.133 kPa) were significantly elevated in acute right heart failure group at 60% and 40% QPA compared with baseline (PAP: 36.2 ± 5.3, 39.8 ± 5.4 vs. 17.4 ± 2.7; RAP: 11.2 ± 2.8, 12.8 ± 2.6 vs. 4.4 ± 1.7; RVP: 25.6 ± 4.9, 27.8 ± 4.5 vs. 11.6 ± 1.8, all P < 0.05), and significantly higher than those of ECMO group (60%QPA: PAP 36.2 ± 5.3 vs. 23.2 ± 5.2, RAP 11.2 ± 2.8 vs. 6.2 ± 2.3, RVP 25.6 ± 4.9 vs. 15.2 ± 3.5; 40%QPA: PAP 39.8 ± 5.4 vs. 24.4 ± 4.8, RAP 12.8 ± 2.6 vs. 7.0 ± 2.4, RVP 27.8 ± 4.5 vs. 16.8 ± 4.2, all P < 0.05), whereas mean artery pressure (MAP, mm Hg) was significantly lowered compared with that of baseline (81.2 ± 15.8, 62.2 ± 14.4 vs. 128.6 ± 16.4, both P < 0.05), and it was lower than that of ECMO group (60%QPA: 81.2 ± 15.8 vs. 128.0 ± 26.5; 40%QPA: 62.2 ± 14.4 vs. 124.6 ± 25.4, both P < 0.05). At 60%, 40% and 0% QPA in ECMO group, whereas heart rate (HR, beats/min), PAP, RAP and RVP were slightly increased compared with those of baseline (HR: 161.4 ± 14.8, 160.6 ± 13.1, 157.6 ± 11.9 vs. 152.6 ± 14.5; PAP: 23.2 ± 5.2, 24.4 ± 4.8, 25.2 ± 6.2 vs. 18.8 ± 3.4; RAP: 6.2 ± 2.3, 7.0 ± 2.4, 7.6 ± 4.2 vs. 4.6 ± 1.5; RVP: 15.2 ± 3.5, 16.8 ± 4.2, 16.2 ± 3.3 vs. 12.2 ± 2.3), but MAP was slightly decreased (128.0 ± 26.5, 124.6 ± 25.4, 121.2 ± 21.4 vs. 135.8 ± 22.2), however, all differences were not statistically significant (all P>0.05). CONCLUSION: These findings demonstrate that VA-ECMO could be helpful in improving cardiac function, and maintaining stability of hemodynamics in dogs with acute right heart failure.