Machine Learning-Based Screening of Risk Factors and Prediction of Deep Vein Thrombosis and Pulmonary Embolism After Hip Arthroplasty.

Prophylactic anticoagulation is a standard strategy for patients undergoing total hip arthroplasty (THA) to prevent deep venous thromboembolism (DVT) and pulmonary embolism (PE). Nevertheless, some patients still experience these complications during their hospital stay. Current risk assessment methods like the Caprini and Geneva scores are not specifically designed for THA and may not accurately predict DVT or PE postoperatively. This study used machine learning techniques to establish models for early diagnosis of DVT and PE in patients undergoing THA. Data were collected from 1481 patients who received perioperative prophylactic anticoagulation. Model establishment and parameter tuning were performed using a training set and evaluated using a test set. Among the models, extreme gradient boosting (XGBoost) performed the best, with an area under the receiver operating characteristic curve (AUC) of 0.982, sensitivity of 0.913, and specificity of 0.998. The main features used in the XGBoost model were direct and indirect bilirubin, partial activation prothrombin time, prealbumin, creatinine, D-dimer, and C-reactive protein. Shapley Additive Explanations analysis was conducted to further analyze these features. This study presents a model for early diagnosis DVT or PE after THA and demonstrates bilirubin could be a potential predictor in the assessment of DVT or PE. Compared to traditional risk assessment, XGBoost has a high sensitivity and specificity to predict DVT and PE in the clinical setting. Furthermore, the results of this study were converted into a web calculator that can be used in clinical practice.

Fibroblast growth factor 21 attenuates ventilator-induced lung injury by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

BACKGROUND: Ventilator-induced lung injury (VILI) is caused by overdistension of the alveoli by the repetitive recruitment and derecruitment of alveolar units. This study aims to investigate the potential role and mechanism of fibroblast growth factor 21 (FGF21), a metabolic regulator secreted by the liver, in VILI development. METHODS: Serum FGF21 concentrations were determined in patients undergoing mechanical ventilation during general anesthesia and in a mouse VILI model. Lung injury was compared between FGF21-knockout (KO) mice and wild-type (WT) mice. Recombinant FGF21 was administrated in vivo and in vitro to determine its therapeutic effect. RESULTS: Serum FGF21 levels in patients and mice with VILI were significantly higher than in those without VILI. Additionally, the increment of serum FGF21 in anesthesia patients was positively correlated with the duration of ventilation. VILI was aggravated in FGF21-KO mice compared with WT mice. Conversely, the administration of FGF21 alleviated VILI in both mouse and cell models. FGF21 reduced Caspase-1 activity, suppressed the mRNA levels of Nlrp3, Asc, Il-1ß, Il-18, Hmgb1 and Nf-κb, and decreased the protein levels of NLRP3, ASC, IL-1ß, IL-18, HMGB1 and the cleaved form of GSDMD. CONCLUSIONS: Our findings reveal that endogenous FGF21 signaling is triggered in response to VILI, which protects against VILI by inhibiting the NLRP3/Caspase-1/GSDMD pyroptosis pathway. These results suggest that boosting endogenous FGF21 or the administration of recombinant FGF21 could be promising therapeutic strategies for the treatment of VILI during anesthesia or critical care.

Attenuation of hepatic ischemia­reperfusion injury by adipose stem cell­derived exosome treatment via ERK1/2 and GSK­3ß signaling pathways.

Exosomes are an emerging therapeutic tool for the treatment of tissue injuries. In the present study, the protective effect of isolated exosomes from adipose­derived stem cells (ADSCs­exo) against hepatic ischemia­reperfusion (I/R) injury was explored. Hepatic I/R injury was achieved by inducing ischemia for 60 min followed by reperfusion for 2 and 6 h. Pre­treatment with ADSCs­exo revealed a significant reduction in necrosis and apoptosis in liver tissue induced by I/R injury. Hypoxic oxidative stress was managed by exosome­mediated reduced reactive oxygen species and increased superoxide dismutase that in turn protected mitochondrial damage and apoptosis. Reduction in inflammatory mediators such as IL­1ß and TNF­α was also observed and protection of hepatocytes from I/R injury was evidenced by a significant decrease in biochemical markers of liver damage (alanine transaminase, aspartate transaminase and lactate dehydrogenase). Exosomal prostaglandin E2 (PGE2)­mediated ERK1/2 and GSK­3ß phosphorylation were revealed to increase Bcl­2 and decrease Bax expression with mitochondrial permeability transition pore­inhibition which may be considered a prime mechanism of exosome­mediated hepatoprotection. In conclusion, our results indicated that ADSCs­exo pre­treatment is effective in protecting liver I/R injury.

Characterization of Human Origin Salmonella Serovar 1,4,[5],12:i:- in Eastern China, 2014 to 2018.

The prevalence of Salmonella serovar 1,4,[5],12:i:- among diarrhea patients has increased considerably in many countries around the world, including China. However, the characterization of this serovar of human origin has been less reported from China. We characterized 76 isolates of Salmonella 1,4,[5],12:i:- gained from diarrhea patients from 2014 to 2018 in the Jiangsu Province of eastern China. These isolates fell into a single-sequence type (ST34) determined by multilocus sequence typing (MLST), and into 44 pulsed-field gel electrophoresis band patterns, with 1 pattern (JSSMM015) comprising 12 isolates (15.9%). By means of PCR-based assays, the seven prophage located virulence genes were detected in our Salmonella 1,4,[5],12:i:- isolates with a high rate of gipA, gtgB, sspH1, sspH2, sodC1, and gtgE (93.4-97.4%), and with a moderate rate of sopE (42.1%). In contrast, none of the five plasmid-borne virulence genes (spvC, pefA, mig5, rck, and srgA) was identified. We tested the isolates' susceptibility to 18 antibiotics of 9 categories using the VITEK 2 system. A high proportion (89.5%) of the isolates were multidrug resistant (MDR) strains with full resistance to cefazolin, cefotetan, amikacin, gentamycin, and tobramycin, followed by resistance to ampicillin (88.2%) and ampicillin/sulbactam (80.3%). The resistance to piperacillin/tazobactam, ceftazidime, cefepime, and levofloxacin was scarce (2.6-9.2%). Notably, an isolate from 2018 was resistant to carbapenems. blaTEM-1B and aac(6')-Ib-cr were the most common drug resistance genes presented in cephalosporin- and fluoroquinolone-resistant strains. All Salmonella 1,4,[5],12:i:- isolates were capable of forming biofilm, with 13.2% of them having strong ability. However, no association was indicated between the scale of biofilm formation ability and MDR. Our results indicate that the combination of these characteristics may together provide a selective and competitive advantage to those Salmonella 1,4,[5],12:i:- isolates, contributing to their increasing prevalence observed worldwide.

Detection of antibiotics in the urine of children and pregnant women in Jiangsu, China.

Exposure to low concentrations of antibiotics links to multiple health hazards, such as drug resistance of bacteria, and childhood obesity. In this study, seven antibiotics were measured in the urine of 107 children and 126 pregnant women in Jiangsu Province by ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). The overall urinary antibiotics detection rate was 38.6%. Most (98.3%) of the participants' antibiotics concentrations were no more than 10 ng/mL. Children had a significantly higher detection rate than pregnant women (47.7% vs. 31.0%, P = 0.009), as well as the concentration (95th percentile: 6.49 vs. 4.08 ng/mL, P = 0.002). The detection rates of individual antibiotics ranged from 0.4% to 15.0%, and the concentrations ranged from lower than the limit of detection (LOD) through up to 31.96 ng/mL individually. Two or more antibiotics were detected in 11.2% of the urines. Tetracyclines were more frequently detected than phenicols (30.9% vs.12.4%). Oxytetracycline was the most frequently detected (15.0%). Multivariate logistic regression showed that consuming puffed food every day was associated with a significantly increased likelihood of detection, and higher concentration of overall antibiotics, and of doxycycline. Children were more likely to be detected of doxycycline and florfenicol, and to have elevated concentration of doxycycline, compared with pregnant women. This study highlights the relatively heavier antibiotics exposure in children, and a possible impact of puffed food on it, which needs to be warranted in future studies.

EP4 activation ameliorates liver ischemia/reperfusion injury via ERK1/2­GSK3ß­dependent MPTP inhibition.

Prostaglandin E receptor subtype 4 (EP4) is widely distributed in the heart, but its role in hepatic ischemia/reperfusion (I/R), particularly in mitochondrial permeability transition pore (MPTP) modulation, is yet to be elucidated. In the present study, an EP4 agonist (CAY10598) was used in a rat model to evaluate the effects of EP4 activation on liver I/R and the mechanisms underlying this. I/R insult upregulated hepatic EP4 expression during early reperfusion. In addition, subcutaneous CAY10598 injection prior to the onset of reperfusion significantly increased hepatocyte cAMP concentrations and decreased serum ALT and AST levels and necrotic and apoptotic cell percentages, after 6 h of reperfusion. Moreover, CAY10598 protected mitochondrial morphology, markedly inhibited mitochondrial permeability transition pore (MPTP) opening and decreased liver reactive oxygen species levels. This occurred via activation of the ERK1/2­GSK3ß pathway rather than the janus kinase (JAK)2­signal transducers and activators of transcription (STAT)3 pathway, and resulted in prevention of mitochondria­associated cell injury. The MPTP opener carboxyatractyloside (CATR) and the ERK1/2 inhibitor PD98059 also partially reversed the protective effects of CAY10598 on the liver and mitochondria. The current findings indicate that EP4 activation induces ERK1/2­GSK3ß signaling and subsequent MPTP inhibition to provide hepatoprotection, and these observations are informative for developing new molecular targets and preventative therapies for I/R in a clinical setting.

Electroacupuncture pretreatment attenuates brain injury in a mouse model of cardiac arrest and cardiopulmonary resuscitation via the AKT/eNOS pathway.

AIMS: This study aims to examine the effects of electroacupuncture (EA) pretreatment on brain injury after cardiac arrest and cardiopulmonary resuscitation (CA/CPR) and its underlying mechanisms. MATERIALS AND METHODS: Adult male C57BL/6 mice were subjected to 6 min of cardiac arrest induced with a potassium chloride infusion and resuscitated by chest compressions and an epinephrine infusion. During the 3 days prior to CA/CRP, mice received EA pretreatment (1 mA, 2 Hz; daily session of 30 min) at the Baihui acupoint (GV20) once daily. Stimulation at a nonacupoint served as a control. In mechanistic studies, mice received the AKT inhibitor LY294002 or endothelial nitric oxide synthase (eNOS) inhibitor L-NIO 30 min before EA pretreatment. A neurological assessment was conducted 24 h after CA/CRP, followed by animal sacrifice and evaluation of physiological brain damage. KEY FINDINGS: CA/CPR resulted in severe brain injury as evidenced by neurological deficits and increased neuronal apoptosis, oxidative stress and the proinflammatory cytokines TNF-α and IL-6. EA pretreatment at the GV20 acupoint but not at a nonacupoint attenuated the neurological deficits and the pathological changes induced by CA/CPR. LY294002 or L-NIO eliminated the neuroprotective effects of the EA pretreatment. SIGNIFICANCE: This study showed that EA pretreatment at the GV20 acupoint can protect the brain from damage associated with globalized ischemia followed by reperfusion and that these protective effects occur via the AKT/eNOS signaling pathway.

Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia.

This study aimed to investigate the influence of dexmedetomidine (DEX) on the tourniquet related responses in hypertension patients receiving unilateral knee arthroplasty (UKA) under general anesthesia. Results showed that the incidence of tourniquet induced hypertension (TIH), hemodynamics, MAC and EtSEV in DEX group were significantly lower than those in control group, regardless of hypertension. However, significant differences in TIH, hemodynamics, minimum alveolar concentration (MAC) and end-tidal sevoflurane (EtSEV) were not observed between hypertension patients and non-hypertension patients in both control group and DEX group. Moreover, oxygen index (OI) and respiratory index (RI) remained unchanged after deflation and DEX failed to affect OI and RI within 30 min after deflation, regardless of hypertension. Taken together, DEX may significantly improve the hemodynamics, which is independent of pre-existing hypertension.

Occurrence of nosocomial methicillin-resistant Staphylococcus aureus as a marker for transmission in a surgical intensive care unit in China.

In 2008, an intensive care unit (ICU) in a large Chinese hospital was moved from a 6-bed old ward to a 20-bed new ward. After the move, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in patients and environmental sites decreased significantly, but the number of ICU-acquired cases per imported MRSA case increased from 1.4 to 4.1. This study suggests that the nurse cohorting level and hand hygiene compliance are strong predicators of MRSA transmission in ICUs.

Gliotoxin promotes Aspergillus fumigatus internalization into type II human pneumocyte A549 cells by inducing host phospholipase D activation.

The internalization of Aspergillus fumigatus into lung epithelial cells is critical for the infection process in the host. Gliotoxin is the most potent toxin produced by A. fumigatus. However, its role in A. fumigatus internalization into the lung epithelial cells is still largely unknown. In the present study, the deletion of the gliP gene regulating the production of gliotoxin in A. fumigatus suppressed the internalization of conidia into the A549 lung epithelial cells, and this suppression could be rescued by the exogenous addition of gliotoxin. At lower concentrations, gliotoxin enhanced the internalization of the conidia of A. fumigatus into A549 cells; in contrast, it inhibited the phagocytosis of J774 macrophages in a dose-dependent manner. Under a concentration of 100 ng/ml, gliotoxin had no effect on A549 cell viability but attenuated ROS production in a dose-dependent manner. Gliotoxin significantly stimulated the phospholipase D activity in the A549 cells at a concentration of 50 ng/ml. This stimulation was blocked by the pretreatment of host cells with PLD1- but not PLD2-specific inhibitor. Morphological cell changes induced by gliotoxin were observed in the A549 cells accompanying with obvious actin cytoskeleton rearrangement and a moderate alteration of phospholipase D distribution. Our data indicated that gliotoxin might be responsible for modulating the A. fumigatus internalization into epithelial cells through phospholipase D1 activation and actin cytoskeleton rearrangement.

Disruption of the phospholipase D gene attenuates the virulence of Aspergillus fumigatus.

Aspergillus fumigatus is the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases on A. fumigatus virulence is rather limited. In this study, disruption of the pld gene encoding phospholipase D (PLD), an important member of the phospholipase protein family in A. fumigatus, was confirmed to significantly decrease both intracellular and extracellular PLD activity of A. fumigatus. The pld gene disruption did not alter conidial morphological characteristics, germination, growth, and biofilm formation but significantly suppressed the internalization of A. fumigatus into A549 epithelial cells without affecting conidial adhesion to epithelial cells. Importantly, the suppressed internalization was fully rescued in the presence of 100 µM phosphatidic acid, the PLD product. Indeed, complementation of pld restored the PLD activity and internalization capacity of A. fumigatus. Phagocytosis of A. fumigatus conidia by J774 macrophages was not affected by the absence of the pld gene. Pretreatment of conidia with 1-butanol and a specific PLD inhibitor decreased the internalization of A. fumigatus into A549 epithelial cells but had no effect on phagocytosis by J774 macrophages. Finally, loss of the pld gene attenuated the virulence of A. fumigatus in mice immunosuppressed with hydrocortisone acetate but not with cyclophosphamide. These data suggest that PLD of A. fumigatus regulates its internalization into lung epithelial cells and may represent an important virulence factor for A. fumigatus infection.