The optimal puncture time point of prolonged occlusion flow-mediated dilatation in radial artery catheterization: a prospective observational study.

Previous studies have demonstrated prolonged occlusion flow-mediated dilatation (PO-FMD) could reduce cannulation failure rates and decrease radial artery pulsation loss during trans-radial coronary angiography. However, the time and degree of radial artery dilatation induced after PO-FMD were unclear. This study aimed to evaluate the degree and duration of the radial artery dilation after PO-FMD, and the time point at which the radial artery diameter is expanded to the maximum. This was a prospective observational study. According to the Chinese guideline on the primary prevention of cardiovascular diseases, 142 patients awaking from general anesthesia were divided into two groups: low-risk (LR) group and high-risk (HR) group. Firstly, the baseline radial artery diameter was measured on the left wrist using ultrasound in both groups. Subsequently, the radial artery diameters were obtained continuously at the same location for 5 min after PO-FMD. The baseline radial artery diameter, the maximum radial artery diameter, and the duration of radial artery dilation in the two groups were recorded. The time point at which the radial artery diameter is expanded to the maximum in the LR group and HR group was 26.49 ± 11.69 s and 46.27 ± 12.03 s, respectively (P < 0.01). The time of radial artery dilation and the percentage changes in arterial diameter in HR group were significantly lower than LR group (duration time: mean [mean ± standard]: 136.65 ± 31.55 s vs. 168.98 ± 33.27 s; percentage changes: median [interquartile range] 10.5 [8.6, 12.9] % vs. 15.2 [12.4, 19.0] %). In this study, the optimal puncture time point of PO-FMD in the LR group was 26 s, and in the HR group was 46 s. It would be helpful to guide the time point in radial artery catheterization after PO-FMD.Chinese Clinical Trial Registry identifier: ChiCTR2200066214.

Critical roles of m6A methylation in cardiovascular diseases.

Cardiovascular diseases (CVDs) have been established as a major cause of mortality globally. However, the exact pathogenesis remains obscure. N6-methyladenosine (m6A) methylation is the most common epigenetic modification on mRNAs regulated by methyltransferase complexes (writers), demethylase transferases (erasers) and binding proteins (readers). It is now understood that m6A is a major player in physiological and pathological cardiac processes. m6A methylation are potentially involved in many mechanisms, for instance, regulation of calcium homeostasis, endothelial function, different forms of cell death, autophagy, endoplasmic reticulum stress, macrophage response and inflammation. In this review, we will summarize the molecular functions of m6A enzymes. We mainly focus on m6A-associated mechanisms and functions in CVDs, especially in heart failure and ischemia heart disease. We will also discuss the potential application and clinical transformation of m6A modification.

Prediction of post-Darcy flow based on the spatial non-local distribution of hydraulic gradient: Preliminary assessment of wastewater management.

Understanding high-velocity pollutant transport dependent on the large hydraulic gradient and/or heterogeneity of the aquifer and criteria for the onset of post-Darcy flow have attracted considerable attention in water resources and environmental engineering applications. In this study, a parameterized model is established based on the equivalent hydraulic gradient (EHG) which affected by spatial nonlocality of nonlinear head distribution due to the inhomogeneity at a wide range of scales. Two parameters relevant to the spatially non-local effect were selected to predict the development of post-Darcy flow. Over 510 sets of laboratory one-dimensional (1-D) steady hydraulic experimental data were used to validate the performance of this parameterized EHG model. The results show that (1) the spatial nonlocal effect of the whole upstream is related to the mean grain size of the medium, and the anomalous variation due to the small grain size implies the existence of the particle size threshold. (2) The parameterized EHG model can effectively capture the nonlinear trend that fails to be described by the traditional local form of nonlinear models, even if the specific discharge stabilizes at the later stages. (3) The Sub-Darcy flow distinguished by the parameterized EHG model can be equated to the post-Darcy flow, and then the criteria for the post-Darcy flow will be strictly distinguished under the premise of determining the hydraulic conductivity. The results of this study facilitate the identification and prediction of high-velocity non-Darcian flow in wastewater management and provide insight into mass transport by advection at the fine-scale.

Efficacy of preemptive analgesia treatments for the management of postoperative pain: a network meta-analysis.

BACKGROUND: Preemptive analgesia may improve postoperative pain management, but the optimal regimen is unclear. This study aimed to compare the effects and adverse events of preemptive analgesia on postoperative pain and opioid consumption. METHODS: In this network meta-analysis, 19 preemptive analgesia regimens were compared. Two authors independently searched databases, selected studies, and extracted data. Primary outcomes were the intensity of postoperative pain and opioid consumption. Secondary outcomes included the time to first analgesia rescue and incidence of postoperative nausea or vomiting (PONV). RESULTS: In total, 188 studies were included (13 769 subjects). Ten of 19 regimens reduced postoperative pain intensity compared with placebo, with mean differences 100-point scale ranging from -4.79 (95% confidence interval [CI]: -8.61 to -0.96.) for gabapentin at 48 h to -21.99 (95% CI: -36.97 to -7.02) for lornoxicam at 6 h. Eight regimens reduced opioid consumption compared with placebo, with mean differences ranging from -0.48 mg (95% CI: -0.89 to -0.08) i.v. milligrams of morphine equivalents (IMME) for acetaminophen at 12 h to -2.27 IMME (95% CI: -3.07 to -1.46) for ibuprofen at 24 h. Five regimens delayed rescue analgesia from 1.75 (95% CI: 0.59-2.91) h for gabapentin to 7.35 (95% CI: 3.66-11.04) h for epidural analgesia. Five regimens had a lower incidence of PONV compared with placebo, ranging from an odds ratio of 0.22 (95% CI: 0.11-0.42) for ibuprofen to 0.59 (95% CI: 0.40-0.87) for pregabalin. CONCLUSIONS: Use of preemptive analgesia reduces postoperative pain, opioid consumption, and postoperative nausea or vomiting, and delays rescue analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021232593.

Identification of hub genes and construction of diagnostic nomogram model in schizophrenia.

Schizophrenia (SCZ), which is characterized by debilitating neuropsychiatric disorders with significant cognitive impairment, remains an etiological and therapeutic challenge. Using transcriptomic profile analysis, disease-related biomarkers linked with SCZ have been identified, and clinical outcomes can also be predicted. This study aimed to discover diagnostic hub genes and investigate their possible involvement in SCZ immunopathology. The Gene Expression Omnibus (GEO) database was utilized to get SCZ Gene expression data. Differentially expressed genes (DEGs) were identified and enriched by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and disease ontology (DO) analysis. The related gene modules were then examined using integrated weighted gene co-expression network analysis. Single-sample gene set enrichment (GSEA) was exploited to detect immune infiltration. SVM-REF, random forest, and least absolute shrinkage and selection operator (LASSO) algorithms were used to identify hub genes. A diagnostic model of nomogram was constructed for SCZ prediction based on the hub genes. The clinical utility of nomogram prediction was evaluated, and the diagnostic utility of hub genes was validated. mRNA levels of the candidate genes in SCZ rat model were determined. Finally, 24 DEGs were discovered, the majority of which were enriched in biological pathways and activities. Four hub genes (NEUROD6, NMU, PVALB, and NECAB1) were identified. A difference in immune infiltration was identified between SCZ and normal groups, and immune cells were shown to potentially interact with hub genes. The hub gene model for the two datasets was verified, showing good discrimination of the nomogram. Calibration curves demonstrated valid concordance between predicted and practical probabilities, and the nomogram was verified to be clinically useful. According to our research, NEUROD6, NMU, PVALB, and NECAB1 are prospective biomarkers in SCZ and that a reliable nomogram based on hub genes could be helpful for SCZ risk prediction.

When does hepatitis B virus meet long-stranded noncoding RNAs?

Hepatitis B virus (HBV) infection in humans and its associated diseases are long-standing problems. HBV can produce a large number of non-self-molecules during its life cycle, which acts as targets for innate immune recognition and initiation. Among these, interferon and its large number of downstream interferon-stimulated gene molecules are important early antiviral factors. However, the development of an effective antiviral immune response is not simple and depends not only on the delicate regulation of the immune response but also on the various mechanisms of virus-related immune escape and immune tolerance. Therefore, despite there being a relatively well-established consensus on the major pathways of the antiviral response and their component molecules, the complete clearance of HBV remains a challenge in both basic and clinical research. Long-noncoding RNAs (lncRNAs) are generally >200 bp in length and perform different functions in the RNA strand encoding the protein. As an important part of the IFN-inducible genes, interferon-stimulated lncRNAs are involved in the regulation of several HBV infection-related pathways. This review traces the basic elements of such pathways and characterizes the various recent targets of lncRNAs, which not only complement the regulatory mechanisms of pathways related to chronic HBV infection, fibrosis, and cancer promotion but also present with new potential therapeutic targets for controlling HBV infection and the malignant transformation of hepatocytes.

Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences.

The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease (CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction (CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas: (1) mechanisms underlying age-related cardiac remodeling; (2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women; (3) we select a few polyphenol or polyamine rich compounds as the CR-mimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.

General Transcription Factor IIF Polypeptide 2: A Novel Therapeutic Target for Depression Identified Using an Integrated Bioinformatic Analysis.

Depression currently affects 4% of the world's population; it is associated with disability in 11% of the global population. Moreover, there are limited resources to treat depression effectively. Therefore, we aimed to identify a promising novel therapeutic target for depression using bioinformatic analysis. The GSE54568, GSE54570, GSE87610, and GSE92538 gene expression data profiles were retrieved from the Gene Expression Omnibus (GEO) database. We prepared the four GEO profiles for differential analysis, protein-protein interaction (PPI) network construction, and weighted gene co-expression network analysis (WGCNA). Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes metabolic pathway analyses were conducted to determine the key functions of the corresponding genes. Additionally, we performed correlation analyses of the hub genes with transcription factors, immune genes, and N6-methyladenosine (m6A) genes to reveal the functional landscape of the core genes associated with depression. Compared with the control samples, the depression samples contained 110 differentially expressed genes (DEGs), which comprised 56 downregulated and 54 upregulated DEGs. Moreover, using the WGCNA and PPI clustering analysis, the blue module and cluster 1 were found to be significantly correlated with depression. GTF2F2 was the only common gene identified using the differential analysis and WGCNA; thus, it was used as the hub gene. According to the enrichment analyses, GTF2F2 was predominantly involved in the cell cycle and JAK-STAT, PI3K-Akt, and p53 signaling pathways. Furthermore, differential and correlation analyses revealed that 9 transcription factors, 12 immune genes, and 2 m6A genes were associated with GTF2F2 in depression samples. GTF2F2 may serve as a promising diagnostic biomarker and treatment target of depression, and this study provides a novel perspective and valuable information to explore the molecular mechanism of depression.

Dual-Role of Cholesterol-25-Hydroxylase in Regulating Hepatitis B Virus Infection and Replication.

Hepatitis B virus (HBV)-related diseases are among the major diseases that affect millions of people worldwide. These diseases are difficult to eradicate and thus pose a serious global health challenge. There is an urgent need to understand the cross talk mechanism between HBV and the host. Cholesterol-25-hydroxylase (CH25H) and its enzymatic product, 25-hydroxycholesterol (25HC), were previously shown to exhibit effective broad-spectrum antiviral activity. However, the role of CH25H in the regulation of HBV infection and replication remains unclear. The present study reported increased expression of CH25H in HBV-infected patients compared to healthy subjects. Importantly, higher expression of CH25H expression was found to be associated with low HBV replication. Additionally, the present study aimed to identify CH25H mutants, which would lack hydroxylase activity but retain antiviral activity toward HBV infection and replication. Interestingly, it was observed that both CH25H and its mutants interacted with HBx protein and inhibited nuclear translocation of HBx. In particular, CH25H interacted with the C-terminal region of HBx, while transmembrane region 3 of CH25H was found to be critical for CH25H-HBx interaction and inhibition of HBV replication. The study results suggested that 25HC promoted HBV infection but not HBV replication. Thus, the results of the present study suggested the involvement of a dual mechanism in CH25H-mediated regulation of HBV replication. The study clearly demonstrated cross talk between HBV and the host through CH25H-HBx axis. IMPORTANCE The enzymatic product of CH25H, 25-hydroxycholesterol (25HC), has been previously shown to play a critical role in the blockage of the cell-virus fusion in response to viral infection. However, our study indicates a dual role of CH25H in regulating HBV. We find the CH25H-mediated inhibition of HBV replication is independent on its enzyme activity and CH25H binds to HBx and inhibits HBx nucleus translocation. We are interested to find out 25HC promotes HBV infection.

Efficacy of different analgesia treatments for abdominal surgery: A network meta-analysis.

OBJECTIVE: This study was designed to evaluate the efficacy of analgesia and incidence of postoperative nausea and vomiting (PONV) of several widely used clinical treatments for postoperative analgesia following abdominal surgery through network meta-analysis (NMA) based on published randomized controlled trials (RCTs). METHODS: This NMA was registered on PROSPERO as CRD 42020169606. Primary outcomes were pain scores (visual analog scale) and accumulative opioid consumption, and secondary outcomes assessed the incidence of PONV at 24 h after surgery. RESULTS: A total of 215 RCTs and 15,114 patients were identified in this NMA. In comparison with placebo, use of a preoperative paravertebral block (mean: -12.63, 95% CI: -21.12 to -4.13), continuous wound infiltration (mean: -9.68, 95%CI: -13.15 to -6.22) and postoperative wound infiltration (mean: -6.34, 95%CI: -10.59 to -2.08) had significantly lower pain scores, less opioid consumption (mean: -2.00, 95%CI: -3.52 to -0.48; mean: -1.34, 95%CI: -1.87 to -0.81; mean: -1.41, 95%CI: -2.07 to -0.74, respectively) and lower incidence of PONV (OR: 0.30, 95%CI: 0.13 to 0.67; OR: 0.49, 95%CI: 0.24 to 0.98; OR: 0.55, 95%CI: 0.34 to 0.89, respectively). CONCLUSIONS: The findings from our work provide evidence that preoperative paravertebral block was superior to continuous or postoperative wound infiltration to provide postoperative analgesia, nausea and vomiting after abdominal surgery.

GRK2 promotes activation of lung fibroblast cells and contributes to pathogenesis of pulmonary fibrosis through increasing Smad3 expression.

Pulmonary fibrosis is a chronic, progressive, and irreversible interstitial lung disease. Transforming growth factor-ß1 (TGF-ß1) plays a major role in lung fibroblast cell differentiation to myofibroblast cells and production of extracellular matrix, which are hallmarks of pulmonary fibrosis. G protein-coupled receptor kinase-2 (GRK2) has been shown to play controversial roles in TGF-ß1-induced signal transduction in different cell types; however, the role of GRK2 in TGF-ß1-induced activation of lung fibroblast cells and development of pulmonary fibrosis has not been revealed. In this study, we found that GRK2 levels were increased in lungs and isolated fibroblast cells in a murine model of pulmonary fibrosis, as well as TGF-ß1-treated lung fibroblasts. GRK2 levels were not changed in lungs in the injury phase of pulmonary fibrosis. Posttreatment with GRK2 inhibitor reduced extracellular matrix (ECM) accumulation in lungs in bleomycin-challenged mice, suggesting that GRK2 activation contributes to the progressive phase of pulmonary fibrosis. Inhibition or downregulation of GRK2 attenuates fibronectin, collagen, and α-smooth muscle actin expression in TGF-ß1-induced lung fibroblast cells or myofibroblast cells isolated from patients with pulmonary fibrosis. Furthermore, we showed that GRK2 regulates Smad3 expression, indicating that inhibition of GRK2 attenuates ECM accumulation through downregulation of Smad3 expression. This study reveals that GRK2 is a therapeutic target in treating pulmonary fibrosis and inhibition of GRK2 dampens pulmonary fibrosis by suppression of Smad3 expression, eventually attenuating TGF-ß1 signal pathway and ECM accumulation.

The Facilitatory Effects of Adjuvant Pharmaceutics to Prolong the Duration of Local Anesthetic for Peripheral Nerve Block: A Systematic Review and Network Meta-analysis.

BACKGROUND: Peripheral nerve block (PNB) with perineural local anesthetic is used for anesthesia or analgesia with many benefits. To extend these benefits, various adjuvant drugs have been used to prolong the duration of analgesia. We aimed to evaluate the effectiveness of various adjuvants at prolonging the duration of sensory and motor blockade for PNB. METHODS: A network meta-analysis of placebo-controlled and active randomized controlled trials was performed comparing 10 adjuvants. Embase, PubMed, Web of Science, and Cochrane library were searched, with articles before May 21, 2020 included. Two authors independently selected studies and extracted data. The primary outcomes were sensory block (SB) and motor block (MB) time, and the secondary outcome was time of first analgesia rescue (FAR). Effect size measures were described as mean differences (MD) with 95% confidence intervals (CIs). Confidence in evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The study protocol was preregistered with the prospectively registered systematic reviews in health and social care international database (PROSPERO), as number CRD42020187866. RESULTS: Overall 16,364 citations were identified, of which 53 studies were included with data for 3649 patients. In network meta-analyses, 4 of 7 included treatment strategies were associated with more efficacious analgesia compared with placebo therapy, including dexamethasone (SB time: 5.73 hours, 95% CI, 4.16-7.30; MB time: 4.20 hours, 95% CI, 2.51-5.89; time of FAR: 8.71 hours, 95% CI, 6.63-10.79), dexmedetomidine (SB time: 4.51 hours, 95% CI, 3.52-5.50; MB time: 4.04 hours, 95% CI, 2.98-5.11; time of FAR: 5.25 hours, 95% CI, 4.08-6.43), fentanyl (SB time: 3.59 hours, 95% CI, 0.11-7.06; MB time: 4.42 hours, 95% CI, 0.78-8.06), and clonidine (SB time: 2.75 hours, 95% CI, 1.46-4.04; MB time: 2.93 hours, 95% CI, 1.69-4.16; time of FAR: 3.35 hours, 95% CI, 1.82-4.87). In a subgroup analysis, addition of dexamethasone to ropivacaine significantly increased the time of FAR when compared to dexmedetomidine (time of FAR: 5.23 hours, 95% CI, 2.92-7.54) or clonidine (time of FAR: 6.61 hours, 95% CI, 4.29-8.92) with ropivacaine. CONCLUSIONS: These findings provide evidence for the consideration of dexmedetomidine, dexamethasone, and clonidine as adjuvants to prolong the duration of PNB. The addition of dexamethasone to ropivacaine has a longer time of FAR compared with clonidine or dexmedetomidine.

Cellular communication network factor 1 (CCN1) knockdown exerts a protective effect for hepatic ischemia/reperfusion injury by deactivating the MEK/ERK pathway.

OBJECTIVE: Hepatic ischemia/reperfusion injury (IRI) is an unsettled and intractable conundrum in clinical treatment after liver transplantation and resection. Cellular communication network factor 1 (CCN1) is upregulated in liver IRI and may play a key role in this process. The objective of this study is to investigate the regulatory mechanism of CCN1 in liver IRI, which may provide new insight into liver IRI clinical treatment. METHODS: The hepatic ischemia/reperfusion model was established in male C57BL/6 mice by occlusion of vessels in the liver followed by reperfusion. The mice were transfected with two small interfering RNAs (siRNAs) against CCN1 for CCN1 knockdown. The hypoxia/reoxygenation (HR) model was established in vitro using mouse hepatic cells followed by transfection with a siRNA and treatment with an ERK activator TPA to confirm the effects of CCN1 on the MEK/ERK pathway in liver IRI. RESULTS: In hepatic IRI, CCN1 was upregulated and its knockdown reduced alanine aminotransferase and aspartate transaminase levels, myeloperoxidase activity, and the levels of IL-6 and TNF-α. CCN1 downregulation alleviated inflammatory cell infiltration and apoptosis in the liver. The expressions of cleaved caspase-9, cleaved caspase-3, Bax, and CHOP were decreased with an increased Bcl-2 level after CCN1 knockdown. The phosphorylation and activation of proteins in ER stress and MEK/ERK pathway were inhibited by CCN1 knockdown. In vitro, the levels of proinflammatory cytokines, apoptosis-inducing proteins, and proteins in ER stress and MEK/ERK pathway, which were decreased by CCN1 knockdown in HR, were restored by TPA, confirming that the activation of ERK aggravated cell apoptosis after reoxygenation. CONCLUSION: Overall, CCN1 knockdown may suppress the inflammation, apoptosis during hepatic IRI by reducing the MEK/ERK pathway activation, which may be a breakthrough point in clinical alleviation of hepatic IRI caused by liver transplantation and resection.

Effect of Preemptive Acetaminophen on Opioid Consumption: A Meta-Analysis.

BACKGROUND: Strategies for reducing postoperative opioid consumption have been explored in many recent studies, due in large part to the recent opioid epidemic. Preemptive analgesia has been proposed as a potential method, but its use is still controversial. OBJECTIVES: This review aimed to evaluate the efficacy of a single dose of acetaminophen as preemptive analgesia for patients undergoing general anesthesia. STUDY DESIGN: A meta-analysis of randomized controlled trials (RCTs). SETTING: The electronic databases of PubMed, EMBASE, Cochrane Library, and the Web of Science were searched. The protocol was previously registered in the PROSPERO database under the registration number CRD 42020165634. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. RCTs that compared preemptive acetaminophen with placebo in surgical patients receiving general anesthesia were included. The risk of bias for each included study was independently assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Six studies with 563 patients were included. Overall, the studies showed a reduction in 24-hour opioid consumption (standardized mean difference [SMD], -1.45; 95% confidence interval [CI], -2.36 to -0.55; P = 0.002), pain scores at 12 hours postoperatively (SMD, -0.86; 95% CI, -1.25 to -0.48; P < 0.0001), and a lower incidence of postoperative nausea (risk ratio [RR] 0.45; 95% CI, 0.34-0.58; P < 0.001) and vomiting (RR 0.39; 95% CI, 0.22-0.72; P = 0.002). LIMITATIONS: The major limitation of this meta-analysis relates to the risk of bias in the limited number of included studies. CONCLUSIONS: Preemptive acetaminophen administration significantly reduces opioid consumption within the initial 24 hours following general anesthesia, with lower pain scores at 12 hours after surgery, and less nausea and vomiting. However, well-conducted RCTs are still needed.

Ubiquitin-specific protease 14 is a new therapeutic target for the treatment of diseases.

Ubiquitin-specific protease 14 (USP14) is a ubiquitin-specific protease that is associated with the proteasome and plays important roles in cellular functions, viral infection, inflammatory responses, neurodegenerative diseases, and tumorigenesis. USP14 appears to have a dual function in regulating intracellular proteolytic degradation. USP14 impedes degradation of ubiquitinated proteins by removing ubiquitin chains from its substrates, while it could promote protein degradation via increasing proteasome activation. Increasing evidence has shown that USP14 is also involved in the regulation of autophagy. Thus, USP14 might act as a key regulator in two major intracellular proteolytic pathways: the ubiquitin-proteasome system (UPS) and autophagy. The important roles of USP14 in multiple diseases have encouraged the development of clinically viable USP14 antagonists. This review summarizes the current state of knowledge about the regulation of USP14 expression, activity, and its functions in physiological and pathological processes.

A Patient with COVID-19 Treated with ECMO for 26 Days.

In December 2019, an outbreak of a novel coronavirus disease 2019 (COVID-19) was reported in Wuhan, China, which was subsequently reported in other countries worldwide. COVID-19 is typically an acute self-limited disease that can rarely be fatal with a 5.6% case mortality rate (May, 2020), mainly due to substantial damage to pulmonary alveolar structures, and subsequent respiratory failure. Given the previous experience, extracorporeal membrane oxygenation (ECMO) has been proven to be an effective therapy in the treatment of respiratory failure or acute respiratory distress syndrome (ARDS). On the basis of similar principle, ECMO may also be an effective therapy in the treatment of severe COVID-19. However, due to huge cost, it is not common to apply ECMO continuously for a long time. We, herein, describe a COVID-19 pneumonia patient, a 77-year female，who was treated with ECMO for 26 days. The hospitalisation costs of the patient were highest in Jilin Province. Key Words: COVID-19, ECMO, Pneumonia.

Ultrasonographic Assessment of Anatomic Relationship Between the Internal Jugular Vein and the Common Carotid Artery in Infants and Children After ETT or LMA Insertion: A Prospective Observational Study.

Background: Central venous catheterization is used for fluid management and infusion of drugs, but it is difficult to perform and carries a high incidence of complications in infants and children. In adults, the anatomic relationship and the overlap index between the internal jugular vein (IJV) and the common carotid artery (CCA) changed significantly after laryngeal mask airway (LMA) placement. However, there are conflicting results regarding the anatomic relationship between the IJV and the CCA after endotracheal tube (ETT) or LMA insertion in pediatric populations. Aim: The aim of this study was to compare the overlap index and anatomic relationship between the IJV and the CCA in infants and children after ETT or LMA insertion by ultrasonography. Method: This single-center, prospective, observational study including 92 infants and children, aged 1 month to 6 years, were grouped according to the airway devices placed: Group ETT (n = 44) and Group LMA (n = 48). The overlap index and anatomic relationship between the IJV and the CCA before and after airway device insertion at neutral and 30° head rotation position were evaluated by ultrasonography. Results: Before airway device insertion, as the head was rotated 30° to the contralateral side, the overlap index increased significantly on the right side of the neck compared to the neutral head position. In Group ETT, there was no significant difference in the overlap index after intubation in the neutral head position or 30° head rotated position on either side. In Group LMA, the overlap indexes were increased significantly after LMA insertion in the neutral head position on both sides. Likewise, the overlap indexes were increased significantly after LMA insertion in the 30° head rotated position on both sides. The most common positional relationship between the IJV and the CCA was anterolateral (AL) in both the right side and left side in the neutral head position. In Group ETT, the AL position was still the most common position relationship between the IJV and the CCA before and after intubation in the 30° head rotated position. In Group LMA, the anterior (A) position increased significantly after LMA insertion in the left side. In the 30° head rotated position, there was a significant increase to the A position after LMA insertion in both the right side and left side. The change from AL to A was increased after LMA insertion, especially in the 30° head rotated position. Conclusions: The overlap indexes of the IJV and the CCA increased significantly in both sides of the neck after LMA placement in the neutral head position, especially in 30° head rotated position. The IJVs after LMA placement had a tendency to become anterior to the CCA when the head of the patient rotated to the opposite direction in infants and children.

MiR-181c-5p Promotes Inflammatory Response during Hypoxia/Reoxygenation Injury by Downregulating Protein Tyrosine Phosphatase Nonreceptor Type 4 in H9C2 Cardiomyocytes.

BACKGROUND: Constitutive nuclear factor kappa B (NFκB) activation has been shown to exacerbate during myocardial ischemia/reperfusion (I/R) injury. We recently showed that miR-181c-5p exacerbated cardiomyocytes injury and apoptosis by directly targeting the 3'-untranslated region of protein tyrosine phosphatase nonreceptor type 4 (PTPN4). However, whether miR-181c-5p mediates cardiac I/R injury through NFκB-mediated inflammation is unknown. Thus, the present study aimed to investigate the role of miR-181c-5p during myocardial I/R injury and explore its mechanism in relation to inflammation in H9C2 cardiomyocytes. METHODS AND RESULTS: In hypoxia/reoxygenation (H/R, 6 h hypoxia followed by 6 h reoxygenation)-stimulated H9C2 cardiomyocytes or postischemic myocardium of rat, the expression of miR-181c-5p was significantly upregulated, which was concomitant increased NFκB activity when compared to the nonhypoxic or nonischemic control groups. This is indicative that miR-181c-5p may be involved in NFκB-mediated inflammation during myocardial I/R injury. To investigate the potential role of miR-181c-5p in H/R-induced cell inflammation and injury, H9C2 cardiomyocytes were transfected with the miR-181c-5p agomir. Overexpression of miR-181c-5p significantly aggravated H/R-induced cell injury (increased lactate dehydrogenase (LDH) level) and exacerbated NFκB-mediated inflammation (greater phosphorylation and degradation of IκBα, phosphorylation of p65, and increased levels of proinflammatory cytokines tumor necrosis factor α (TNFα), interleukin (IL)-6, and IL-1ß). In contrast, inhibition of miR-181c-5p by its antagomir transfection in vitro had the opposite effect. Furthermore, overexpression of miR-181c-5p significantly enhanced lipopolysaccharide-induced NFκB signalling. Additionally, knockdown of PTPN4, the direct target of miR-181c-5p, significantly aggravated H/R-induced phosphorylation and degradation of IκBα, phosphorylation of p65, and the levels of proinflammatory cytokines. PTPN4 knockdown also cancelled miR-181c-5p antagomir mediated anti-inflammatory effects in H9C2 cardiomyocytes during H/R injury. CONCLUSIONS: It is concluded that miR-181c-5p may exacerbate myocardial I/R injury and NFκB-mediated inflammation via PTPN4, and that targeting miR-181c-5p/PTPN4/NFκB signalling may represent a novel strategy to combat myocardial I/R injury.

Understanding Diabetic Neuropathy: Focus on Oxidative Stress.

Diabetic neuropathy is one of the clinical syndromes characterized by pain and substantial morbidity primarily due to a lesion of the somatosensory nervous system. The burden of diabetic neuropathy is related not only to the complexity of diabetes but also to the poor outcomes and difficult treatment options. There is no specific treatment for diabetic neuropathy other than glycemic control and diligent foot care. Although various metabolic pathways are impaired in diabetic neuropathy, enhanced cellular oxidative stress is proposed as a common initiator. A mechanism-based treatment of diabetic neuropathy is challenging; a better understanding of the pathophysiology of diabetic neuropathy will help to develop strategies for the new and correct diagnostic procedures and personalized interventions. Thus, we review the current knowledge of the pathophysiology in diabetic neuropathy. We focus on discussing how the defects in metabolic and vascular pathways converge to enhance oxidative stress and how they produce the onset and progression of nerve injury present in diabetic neuropathy. We discuss if the mechanisms underlying neuropathy are similarly operated in type I and type II diabetes and the progression of antioxidants in treating diabetic neuropathy.

Folic acid and RAAS blockers in ischemia/reperfusion-induced hepatic injury: A current mechanistic concept for understanding the incidence, significance & outcome.

Hepatic ischemia-reperfusion injury (IRI) is not only one of the pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. IRI after liver transplant occurs due to in major resections and occlusion of vessels, or during the perioperative period, leads to acute liver failure which shows the dynamic process that involves two interrelated phases of local ischemic insult and inflammation-mediated reperfusion injury and has an impact on morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) is activated locally in the injured cells by the occurrence of I/R, which plays an essential role in the fate of the damaged tissue. However, a preclinical study explores the protective role of RAAS inhibitor in acute liver injury in a model of inflammation caused by ischemia and reperfusion. In-addition to RAAS blockers in monotherapy does not effectively block the complete pathway. Thus, the present study is designed to explore the effect of combined folic acid with RAAS blockers in combination, produce a synergistic effect. Moreover, in this review, we will describe the understanding of the possible incidence of downregulatory molecular mechanisms associated with renin-angiotensin-aldosterone system and the significance & outcome of the combination of folic acid and RAAS blockers in liver injury due to ischemia/reperfusion.