Bone and joint infection complicated with sepsis in neonates and infants under three months of age

Abstract Objective: Studies focusing on bone and joint infections (BJIs) in young infants are rare. Some cases of BJI are accompanied by sepsis. This study aimed to identify the clinical and bacteriological features of sepsis in neonates and young infants with BJIs. Methods: Neonates and infants younger than 3 months diagnosed with BJI in the present institution from 2014 to 2021 were retrospectively reviewed. Patient characteristics, clinical data, and outcomes were documented and compared between those with and without sepsis. Results: Twenty-five patients with a mean age of 34.8 days were included. Nine BJI cases had concomitant sepsis (group A), and 16 had BJI without sepsis (group B). Within group A, staphylococcus aureus was the major pathogenic germ (5 cases, of which 4 were of the methicillin-resistant staphylococcus aureus (MRSA) type). There was no statistical difference in male-to-female ratio, age, history of hospitalization, anemia, birth asphyxia, peripheral leukocyte counts, C-reactive protein on admission, and sequelae between groups. Univariate analyses indicated a significant difference in the incidence of septic arthritis (SA) combined with osteomyelitis (OM) (88.9% vs 37.5%), congenital deformities (44.4% vs 0%), and mean duration of symptoms (2.83 days vs 9.21 days) in comparisons between groups A and B. Conclusion: Staphylococcus aureus is the main pathogenic bacteria in BJI cases complicated with sepsis in neonates and young infants. Among infants younger than 3 months diagnosed with BJI, those with concurrent SA and OM, MRSA infection, or congenital deformities are more likely to develop sepsis.

N6-methyladenosine mRNA methylation positively regulated the response of poplar to salt stress.

As the most abundant form of methylation modification in messenger RNA (mRNA), the distribution of N6-methyladenosine (m6A) has been preliminarily revealed in herbaceous plants under salt stress, but its function and mechanism in woody plants were still unknown. Here, we showed that global m6A levels increased during poplar response to salt stress. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that m6A significantly enriched in the coding sequence region and 3'-untranslated regions in poplar, by recognising the conserved motifs, AGACU, GGACA and UGUAG. A large number of differential m6A transcripts have been identified, and some have been proved involving in salt response and plant growth and development. Further combined analysis of MeRIP-seq and RNA-seq revealed that the m6A hypermethylated and enrich in the CDS region preferred to positively regulate expression abundance. Writer inhibitor, 3-deazaneplanocin A treatment increased the sensitivity of poplar to salt stress by reducing mRNA stability to regulate the expression of salt-responsive transcripts PagMYB48, PagGT2, PagNAC2, PagGPX8 and PagARF2. Furthermore, we verified that the methyltransferase PagFIP37 plays a positively role in the response of poplar to salt stress, overexpressed lines have stronger salt tolerance, while RNAi lines were more sensitive to salt, which relied on regulating mRNA stability in an m6A manner of salt-responsive transcripts PagMYB48, PagGT2, PagNAC2, PagGPX8 and PagARF2. Collectively, these results revealed the regulatory role of m6A methylation in poplar response to salt stress, and revealed the importance and mechanism of m6A methylation in the response of woody plants to salt stress for the first time.

Association of quantitative computed tomography-based right atrial appendage and right atrium parameters with postradiofrequency ablation recurrence of atrial fibrillation.

Background: The significance of the right atrial appendage (RAA) and right atrium (RA) in the recurrence of atrial fibrillation (AF) after radiofrequency ablation (RFA) remains uncertain. This retrospective case-control study aimed to quantitatively evaluate the role of morphological parameters of the RAA and RA in the recurrence of AF after RFA based on 256-slice spiral computed tomography (CT). Methods: A total of 297 patients with AF who underwent RFA for the first time between January 1 and October 31, 2020, were enrolled in the study, and they were divided into a nonrecurrence group (n=214) and a recurrence group (n=83). The volume of the RA, RAA and left atrium (LA); height of the RAA; long and short diameter, perimeter, and area of the RAA base; right atrial anteroposterior diameter; tricuspid annulus diameter; crista terminalis thickness; and cavotricuspid isthmus (CVTI) were measured, and the clinical data of patients were collected. Results: (I) Multivariable logistic regression analysis followed by univariable logistic regression analysis showed that the height of the RAA [odds ratio (OR) =1.124; 95% confidence interval (CI): 1.024-1.233; P=0.014], short diameter of the RAA base (OR =1.247; 95% CI: 1.118-1.391; P=0.001), crista terminalis thickness (OR =1.594; 95% CI: 1.052-2.415; P=0.028) and duration of AF (OR =1.009; 95% CI: 1.003-1.016; P=0.006) were independent predictors of postradiofrequency ablation AF recurrence. (II) Receiver operating characteristic (ROC) curve analysis showed that the prediction model constructed according to the multivariate logistic regression analysis presented good accuracy [area under the curve (AUC) =0.840; P=0.001]. A short diameter of the RAA base >26.95 mm had the highest predictive value for AF recurrence, with a sensitivity of 0.614 and a specificity of 0.822 (AUC =0.786, P=0.001). Pearson correlation analysis showed that there was a significant correlation between right atrial volume and left atrial volume (r=0.720, P<0.001). Conclusions: A significant increase in diameter and volume of the RAA and RA and tricuspid annulus diameter may correlate with postradiofrequency ablation AF recurrence. The height of the RAA, short diameter of the RAA base, crista terminalis thickness, and AF duration were independent predictors of recurrence. Among them, the short diameter of the RAA base had the highest predictive value for recurrence.

Monocytes Undergo Functional Reprogramming to Generate Immunosuppression through HIF-1α Signaling Pathway in the Late Phase of Sepsis.

Severe pneumonia with sepsis is characterized by a dysregulated inflammatory response of endotoxin. In our study, we attempted to investigate the roles of the immune guardian cells (monocytes) in the immune-inflammatory response of severe pneumonia-induced sepsis. We performed analysis in the blood samples of human and animals with ELISA, western blot, flow cytometry (FCM) methods, etc. Results showed that the proinflammatory status shifted to hypoinflammatory phases during the sepsis process. In a clinical study, the levels of IL-1ß, IL-6, TNF-α, etc., except for IL-10, were inhibited in the late phase of sepsis, while, in an animal study, the immune suppression status was attenuated with administration of the adenovirus Ade-HIF-1α. Conversely, the amount of IL-10 was lower in the adenovirus Ade-HIF-1α group compared with the sepsis model group and the Ade-control group. Moreover, in the clinical study, the programmed cell death-ligand 1 (PD-L1) was overexpressed in monocytes in the late phase of sepsis, while the expression of proteins HIF-1α and STAT3 was decreased in the late phase of sepsis. However, in the animal study, we found that the HIF-1α factor facilitated the inflammatory response. The expression of the proteins HIF-1α and STAT3 was increased, and the PD-L1 protein was decreased with the adenovirus Ade-HIF-1α administration compared with the rats without Ade-HIF-1α injection and with the Ade-control injection. Additionally, the proteins HIF-1α and STAT3 were coregulated at transcriptional levels during the inflammatory responses of sepsis. Taken together, monocytes undergo reprogramming to generate immunosuppression through the HIF-1α signaling pathway in the late phase of sepsis.

Factors affecting FiO2 and PEEP during high-flow nasal cannula oxygen therapy: A bench study.

INTRODUCTION: It is unknown if set-flow, peak inspiratory flow (PIF), tidal volume and set fraction of inspired O2 (FiO2 ) affect actual-FiO2 and positive end-expiratory pressure (PEEP) during high-flow nasal cannula (HFNC) oxygen therapy. In addition, the extent of their influence is also unknown. OBJECTIVES: To investigate the effects of set-FiO2 , set-flow, PIF and tidal volume on the actual-FiO2 and PEEP during HFNC oxygen therapy. METHODS: A lung simulation model was used to study the factors that might affect FiO2 and PEEP during HFNC therapy in vitro. These factors included set-flow (20, 40, 60, 80 and 120 L/min), PIF (40, 80 and 120 L/min), tidal volume (400 and 600 mL), and set-FiO2 (30%, 50% and 70%). Actual-FiO2 and PEEP were recorded for 10 consecutive breaths. Actual-FiO2 and PEEP were compared under different conditions. Multivariate linear regressions were performed to investigate the effects of these factors on actual-FiO2 and PEEP. RESULTS AND CONCLUSION: Regression formula were: (a) actual-FiO2 as the dependent variable: actual FiO2  = 2.71 + 0.78 × set-FiO2  + 0.17 × set-flow - 0.09 × PIF (F test, F = 3866.62, P < 0.001, R2  = 0.94), (b) PEEP as the dependent variable: PEEP = 1.35 + 0.15 × set-flow - 0.02 × PIF + 0.01 × tidal volume (F test, F = 4082.39, P < 0.001, R2  = 0.95). The following factors were found to affect actual-FiO2 (in descending order): set-FiO2 , set-flow and PIF. Tidal volume had little effect on actual-FiO2 . Factors which affected PEEP were (in descending order): set-flow, peak inspiratory flow and tidal volume.

Inhibition of lncRNA TUG1 upregulates miR-142-3p to ameliorate myocardial injury during ischemia and reperfusion via targeting HMGB1- and Rac1-induced autophagy.

BACKGROUND: Long non-coding RNAs (lncRNAs) play a central role in regulating heart diseases. In the present study, we examined the effects of lncRNA taurine up-regulated gene 1 (TUG1) in ischemia/reperfusion (I/R)- or hydrogen peroxide-challenged cardiomyocytes, with specific focus on autophagy-induced cell apoptosis. METHODS: The expressions of miR-142-3p and TUG1 in H2O2-challenged cardiomyocytes and I/R-injured heart tissue were measured by RT-qPCR. Cell death was measured by trypan blue staining assay. Cell apoptosis was determined by Annexin V/PI staining and TUNEL assay. Autophagy was examined by quantifying cells or tissues containing LC3+ autophagic vacuoles by immunofluorescence, or by measuring the expressions of autophagy-related biomarkers by Western blot. The direct interaction between miR-142-3p and TUG1, high mobility group box 1 protein (HMGB1), or Ras-related C3 botulinum toxin substrate 1 (Rac1) was examined using luciferase reporter assay. The significance of miR-142-3p and TUG1 on cell apoptosis or autophagy was examined using both gain-of-function and loss-of-function approaches. The importance of HMGB1 or Rac1 was assessed using siRNA-mediated gene silencing. RESULTS: miR-142-3p was down-regulated, while TUG1 up-regulated in H2O2-challenged cardiomyocytes in vitro and I/R-injured heart tissues in vivo. Functionally, inhibition of TUG1 and overexpression of miR-142-3p inhibited cell apoptosis and autophagy in cardiomyocytes. The function of TUG1 were achieved by sponging miR-142-3p and releasing the suppression of the putative targets of miR-142-3p, HMGB1 and Rac1. Both HMGB1 and Rac1 essentially mediated cell apoptosis and autophagy induced by TUG1. CONCLUSIONS: TUG1, by targeting miR-142-3p and up-regulating HMGB1 and Rac1, plays a central role in stimulating autophagic cell apoptosis in ischemia/hypoxia-challenged cardiomyocytes. Down-regulating TUG1 or up-regulating miR-142-3p may ameliorate myocardial injury and protect against acute myocardial infarction.

MicroRNA-486-5p targeting PTEN Protects Against Coronary Microembolization-Induced Cardiomyocyte Apoptosis in Rats by activating the PI3K/AKT pathway.

Coronary microembolization (CME) is responsible for a substantial fraction of microvascular obstruction (MVO), which are strongly associated with mortality and hospitalization for heart failure within 1 year after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI). However, the effect of miRNA on cardiomyocyte apoptosis in a CME model has been less well-studied. miRNA sequencing analysis was performed to examine differentially expressed miRNAs induced by CME in rats. Phosphatase and tensin homologue (PTEN) 3 'RACE and dual-luciferase reporter assays were performed to confirm that PTEN is a direct target gene of miR-486-5p. miRNA-486-5p overexpression was established by injecting AAV into rats via the tail vein. The CME model was established by injecting microspheres into the left ventricle of rats. 6h after surgery, cardiac function, microinfarct area, and the apoptotic index were determined. RT-PCR was used to evaluate mRNA level and Western blotting was used to evaluate protein expression. miRNA sequencing data showed that there were 5 upregulated and 8 downregulated miRNAs, and the relative expression of miRNA-486-5p was significantly downregulated. PTEN 3'RACE and dual-luciferase reporter assays confirmed that miR-486-5p directly targets the rat PTEN gene. The expression of miR-486-5p gradually declined, however, the expression of PTEN mRNA rapidly increased at early time points after CME. Overexpression of miR-486-5p reduced cardiomyocyte apoptosis and improved cardiac function through inhibition of PTEN and activation of the PI3K/Akt pathway in rat CME models. Overexpression of miR-486-5p, which targets PTEN, protects against CME-induced cardiomyocyte apoptosis and improves cardiac function in rats by activating the PI3K/Akt pathway.

Pim1 Overexpression Prevents Apoptosis in Cardiomyocytes After Exposure to Hypoxia and Oxidative Stress via Upregulating Cell Autophagy.

BACKGROUND/AIMS: Microvascular obstruction (MVO), an undesirable complication of percutaneous coronary intervention, is independently associated with adverse left ventricle remodeling and poor prognosis after acute myocardial infarction. Hypoxia and oxidative stress major roles in the pathophysiology of MVO. Pim1 serves an important protective role in the ischemic myocardium, but the underlying mechanisms remain poorly defined. Autophagy in early hypoxia or during moderate oxidative stress has been demonstrated to protect the myocardium. In this study, we investigated the association between the protective effect of Pim1 and autophagy after hypoxia and oxidative stress. METHODS: Ventricular myocytes from neonatal rat heart (NRVMs) were isolated. NRVMs were exposed to hypoxia and H2O2. Rapamycin and 3-methyladenine (3-MA) were used as an activator and inhibitor of autophagy, respectively. pHBAd-Pim1 was transfected into NRVMs. We assessed cardiomyocyte apoptosis by Annexin V-FITC/PI flow cytometry. Autophagy was evaluated by mRFP-GFP-LC3 adenovirus infection by confocal microscopy. Western blotting was used to quantify apoptosis or autophagy protein (caspase-3, LC3, P62, AMPK, mTOR, ATG5) concentrations. RESULTS: Autophagy and apoptosis in NRVMs significantly increased and peaked at 3 h and 6 h, respectively, after exposure to hypoxia and H2O2. The mTOR inhibitor rapamycin induced autophagy and decreased cardiomyocyte apoptosis, but the autophagy inhibitor 3-MA decreased autophagy and increased apoptosis at 3 h after exposure to hypoxia and H2O2. Pim1 levels in NRVMs increased at 3 h and decreased gradually after exposure to hypoxia and H2O2. Pim1 overexpression enhanced autophagy and decreased apoptosis. Pim1-induced promotion of autophagy is partly the result of activation of the AMPK/mTOR/ATG5 pathway after exposure to hypoxia and H2O2. CONCLUSION: Our results revealed that Pim1 overexpression prevented NRVMs from apoptosis via upregulating autophagy after exposure to hypoxia and oxidative stress, partly through activation of the AMPK/mTOR/ATG5 autophagy pathway.

Protective effects of heme oxygenase-1 against severe acute pancreatitis via inhibition of tumor necrosis factor-α and augmentation of interleukin-10.

BACKGROUND: Heme oxygenase-1 (HO-1) is an inducible defense gene which plays a significant role in inflammation. HO-1 protects cells and tissues through the mechanism of anti-oxidation, maintaining microcirculation and anti-inflammation. The aim of the current study is to investigate the role of HO-1 on systemic inflammatory response in severe acute pancreatitis (SAP). METHODS: Forty male Sprague-Dawley (SD) rats were randomly assigned into four groups: control group (n = 10); SAP group (n = 10), SAP model was induced by retrograde injection of 3% sodium taurocholate through pancreatic duct; HO-1 stimulation group (n = 10), SD rats were injected 75 µg/kg hemin intraperitoneally 30 min after induction of SAP; HO-1 inhibition group (n = 10), SD rats were injected 20 µg/kg Zinc porphyrin (Zn-PP) intraperitoneally 30 min after induction of SAP. After 24 h of SAP establishment, tissues were collected for HO-1, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) mRNA expression, and blood samples were collected for cytokines and biochemical measurements. Meanwhile, the histopathological changes of pancreas and liver tissues were observed. RESULTS: The expression of HO-1 mRNA and protein were significantly induced by SAP in rat pancreas and liver. Hemin treatment significantly decreased oxidative stress and TNF-α in plasma and tissues, while the IL-10 was significantly increased. Pancreas and liver injury induced by SAP was markedly attenuated by Hemin treatment. Moreover, inhibition of HO-1 expression by Zn-PP administration aggravated the injury caused by SAP. CONCLUSIONS: Induction of HO-1 in early SAP may modulate systemic inflammatory response and prevent pancreas and nearby organs such as liver injury through inhibition of TNF-α and augmentation of IL-10.

TAK-242 Protects Against Apoptosis in Coronary Microembolization-Induced Myocardial Injury in Rats by Suppressing TLR4/NF-κB Signaling Pathway.

BACKGROUND/AIMS: Myocardial apoptosis is heavily implicated in the myocardial injury caused by coronary microembolization (CME), and toll-like receptor 4 (TLR4) is considered to be involved in this apoptotic cascade. Therefore, the present study was designed to investigate the role of TLR4/NF-κB signaling pathway regulated by TAK-242, a selective TLR4 signal transduction inhibitor, in the myocardial apoptosis after CME in rats. METHODS: Forty-five rats were randomized (random number) into three groups: sham, CME and CME + TAK-242 (n = 15 per group).CME was induced by injecting polyethylene microspheres (42µm) into the left ventricular except the sham group. CME + TAK-242 group was treated with TAK-242 (2mg/kg) via the tail vein 30 minutes before CME modeling. Cardiac function was evaluated 6 hours after operation. Tissue biopsy was stained with HBFP to measure the size of micro-infarction area. TUNEL staining was used to detect myocardial apoptosis. Western blot and qPCR were used to evaluate the expression of TLR4, MyD88, NF-κB p65, p-IκBα and Cleaved caspase-3. RESULTS: Cardiac function in the CME group and CME + TAK-242 group were significantly decreased compared with the sham group (P < 0.05) and the micro-infarction area, the apoptotic index, the expression of TLR4, NF-κB p65, p-IκBα and Cleaved caspase-3 were increased significantly (P < 0.05). Cardiac function in the CME + TAK-242 group was significantly improved compared with the CME group (P < 0.05) and the micro-infarction area, the apoptotic index, the expression of TLR4, MyD88, NF-κB p65, p-IκBα and Cleaved caspase-3 were decreased significantly (P < 0.05). CONCLUSIONS: TAK-242 can effectively improve CME-induced cardiac dysfunction by regulating TLR4/NF-κB signaling pathway and then reducing the myocardial apoptosis.

Features and variations of a radial artery approach in southern Chinese populations and their clinical significance in percutaneous coronary intervention.

BACKGROUND: More and more percutaneous coronary intervention were done from radial artery approach. But the great limitation of radial artery approach and main failure cause of transradial coronary intervention is smaller size and more variations of a radial artery approach. The aim of the study is to explore the features and variations of a radial artery approach in southern Chinese populations and their clinical significance in percutaneous coronary intervention. METHODS: A total of 1400 patients who underwent scheduled first time transradial coronary angiography between July 2007 and September 2010 were enrolled. Radial arteriography was performed in all patients to detect the anatomical variations of this vessel. All patients' radial and ulnar artery inner diameters were measured using a computer assisted quantification method. A detailed patient history was recorded. Multivariate Logistic regression analysis was performed to evaluate the predictive value of variables (including age, gender, ethnicity, height, weight, body mass index, smoking, diabetes, hypertension and dyslipidemia) in arterial tortuosities and variations of this vessel. RESULTS: In southern Chinese populations, there were no significant differences in the diameters of the forearm arteries: the mean radial artery inner diameter was (3.04 ± 0.43) mm in ethnic Han Chinese and (3.05 ± 0.42) mm in ethnic Zhuang Chinese, P > 0.05), the mean ulnar artery inner diameter was (3.03 ± 0.38) mm in Han Chinese and (3.05 ± 0.36) mm in Zhuang Chinese, P > 0.05). It was estimated that the inner diameter of the radial artery was not smaller than a 6F Cordis sheath in 86.1% of male patients and in 57.0% of female patients, and not smaller than a 7F Cordis sheath in 59.3% of male patients and 24.9% of female patients. The factors found to positively affect the size of the radial artery were sex (bj = 0.309, P < 0.01), weight (bj = 0.103, P < 0.01), and diabetes mellitus (bj = -0.088, P < 0.01) was found to negatively affect radial artery size. Arterial tortuosities occurred in 12.1% of patients and arterial variations in 4.1%. The incidence of tortuosities and variations included radial artery tortuosity (3.6%), high origin of radial artery (1.7%), radial artery loop (0.6%), double radial artery (0.1%), brachial artery tortuosity (0.4%), double brachial artery (0.1%), subclavian artery tortuosity (5.4%), small subclavian artery (0.4%), right retro-esophageal subclavian artery (0.6%), brachiocephalic trunk tortuosity (2.8%), small brachiocephalic artery (0.1%), and brachiocephalic artery anomaly (0.4%). For people in Guangxi province, tortuosities of the subclavian artery and radial artery are the most common among the vascular tortuosities of the radial artery approach. The overall rate of transradial procedural success was 96.1%. Procedural failure was more common in patients with anomalous radial artery approach than in patients with normal radial artery approach (22.8% vs. 1.8%, P = 0.000). According to multivariate Logistic regression analysis, age (OR = 2.695, 95%CI 2.232 - 3.253, P = 0.000), female gender (OR = 5.127, 95%CI 3.000 - 8.762, P = 0.000), height (OR = 0.612, 95%CI 0.465 - 0.807, P = 0.000), body mass index (OR = 2.377, 95%CI 1.834 - 3.082, P = 0.000), hypertension (OR = 1.668, 95%CI 1.132 - 2.458, P = 0.010), hyperlipidemia (OR = 1.273, 95%CI 1.425 - 2.049, P = 0.034) and smoking (OR = 5.750, 95%CI 3.636 - 9.093, P = 0.000), were independently associated with arterial tortuosities of the radial artery approach. Female gender was independently associated with arterial variations of the radial artery approach (OR = 3.613, 95%CI 3.208 - 7.826, P = 0.000). CONCLUSIONS: The diameters of the radial and ulnar arteries between the Han people and the Zhuang people in southern Chinese populations are similar. In a transradial operation, the most southern Chinese populations, the use of a 6F sheath and guiding catheter is safe, and using a 7F sheath and guiding catheter is feasible in some selected patients. Radial arterial tortuosities and variations in southern Chinese populations are relatively common and are a significant cause of the failure of transradial coronary procedure. Old age, female gender, short stature, high body mass index, hypertension, hyperlipidemia and smoking, were independently associated with an increased risk of arterial tortuosity. In addition, female gender was an independent predictor of arterial variations.