Usp9x contributes to the development of sepsis-induced acute kidney injury by promoting inflammation and apoptosis in renal tubular epithelial cells via activation of the TLR4/nf-κb pathway.

As a pattern recognition receptor, Toll-like receptor 4 (TLR4) is crucial for the development and progression of acute kidney injury (AKI). This study aims to explore whether the deubiquitinase Usp9x influences the TLR4/NF-B pathway to cause sepsis-induced acute kidney injury (S-AKI). The model of AKI was established in Sprague-Dawley rats using the cecal ligation and puncture (CLP) method, while renal tubular epithelial cell NRK-52E was stimulated with lipopolysaccharide (LPS) in vitro. All plasmids were transfected into NRK-52E cells according to the indicated group. The deubiquitinase of TLR4 was predicted by the online prediction software Ubibrowser. Subsequently, Western blot and Pearson correlation analysis identified Usp9x protein as a potential candidate. Co-IP analysis verified the interaction between TLR4 and Usp9x. Further research revealed that overexpression of Usp9x inhibited degradation of TLR4 protein by downregulating its ubiquitination modification levels. Both in vivo and in vitro experiments observed that interference with Usp9x effectively alleviated the inflammatory response and apoptosis of renal tubular epithelial cells (RTECs) induced by CLP or LPS, whereas overexpression of TLR4 reversed this situation. Transfection with sh-Usp9x in NRK-52E cells suppressed the expression of proteins associated with the TLR4/NF-κB pathway induced by LPS. Moreover, the overexpression of TLR4 reversed the effect of sh-Usp9x transfection. Therefore, the deubiquitinase Usp9x interacts with TLR4, leading to the upregulation of its expression through deubiquitination modification, and the activation of the TLR4/NF-κB signaling pathway, thereby promoting inflammation and apoptosis in renal tubular epithelial cells and contributing to sepsis-induced acute kidney injury.

Predicting the prognosis in patients with sepsis by an endoplasmic reticulum stress gene signature.

BACKGROUND: Prognostic stratification of patients with sepsis is important for the development of individualized treatment strategies. Endoplasmic reticulum stress (ERS) plays a key role in sepsis. This study aimed to identify a set of genes related to ER stress to construct a predictive model for the prognosis of sepsis. METHODS: The transcriptomic and clinical data of 479 sepsis patients were obtained from GSE65682 and divided into a training set (n=288) and a validation set (n=191) at a ratio of 3:2. The external test set was GSE95233 (n=51). LASSO and Cox regression analyses were performed to establish a signature to predict the prognosis of patients with sepsis. Moreover, we developed a nomogram that included the risk signature and clinical features to predict survival probability. RESULTS: A prognostic signature was constructed with ten endoplasmic reticulum related genes (ADRB2, DHCR7, GABARAPL2, MAOA, MPO, PDZD8, QDPR, SCAP, TFRC, and TLR4) in the training set, which significantly divided patients with sepsis into high- and low-risk groups in terms of survival. This signature was validated using validation and external test sets. A nomogram based on the risk signature was constructed to quantitatively predict the prognosis of patients with sepsis. CONCLUSIONS: We constructed an ERS signature as a novel prognostic marker for predicting survival in sepsis patients, which could be used to develop novel biomarkers for the diagnosis, treatment, and prognosis of sepsis and to provide new ideas and prospects for future clinical research.

Defined, low threshold for caesarean section and multidisciplinary team management improves fetal outcome from acute pancreatitis in pregnancy.

BACKGROUND: Acute pancreatitis in pregnancy (APIP) is associated with increased maternal and fetal mortality. OBJECTIVES: We sought to determine whether a low threshold for cesarean section (C-section) in severe acute pancreatitis (SAP) or Predict SAP improves maternal and fetal outcomes in patients with APIP. METHODS: We identified patients with APIP at a single institution from a prospective database and studied fetal and maternal health in APIP before (2005-2014) and after (2015-2019) introduction of multidisciplinary team management with a defined, lowered threshold for C-section. The primary end point was fetal mortality comprising abortion and perinatal death. Risk factors associated with fetal mortality were analyzed by univariable and multivariable logistic regression analysis. RESULTS: A total of 165 patients with APIP were eligible for analysis. There was a highly significant increase in patients undergoing C-section from 37 (30.8%) of 120 during 2005-2014 to 27 (60%) of 45 in 2015-2019 (P = 0.001), with a highly significant fall in fetal mortality from 37 (30.8%) of 120 to 3 (6.7%) of 45 between the same periods (P = 0.001), when maternal mortality fell from 6 to zero (P = 0.19). Maternal early systemic inflammatory response syndrome (SIRS) (odds ratio [OR] 6.98, 95% confidence interval [CI] 1.53, 30.80, P = 0.01) and SAP (OR 3.64, 95%CI 1.25, 10.60, P = 0.02) were two independent risk factors associated with fetal mortality. CONCLUSIONS: Multidisciplinary collaboration and a defined, low threshold for C-section improve fetal outcomes in patients with APIP.

Gait Quality Aware Network: Toward the Interpretability of Silhouette-Based Gait Recognition.

Gait recognition receives increasing attention since it can be conducted at a long distance in a nonintrusive way and applied to the condition of changing clothes. Most existing methods take the silhouettes of gait sequences as the input and learn a unified representation from multiple silhouettes to match probe and gallery. However, these models are all faced with the lack of interpretability, e.g., it is not clear which silhouette in a gait sequence and which part in the human body are relatively more important for recognition. In this work, we propose a gait quality aware network (GQAN) for gait recognition which explicitly assesses the quality of each silhouette and each part via two blocks: frame quality block (FQBlock) and part quality block (PQBlock). Specifically, FQBlock works in a squeeze-and-excitation style to recalibrate the features for each silhouette, and the scores of all the channels are added as frame quality indicator. PQBlock predicts a score for each part which is used to compute the weighted distance between the probe and gallery. Particularly, we propose a part quality loss (PQLoss) which enables GQAN to be trained in an end-to-end manner with only sequence-level identity annotations. This work is meaningful by moving toward the interpretability of silhouette-based gait recognition, and our method also achieves very competitive performance on CASIA-B and OUMVLP.

Successful treatment of severe myocardial injury complicated with refractory cardiogenic shock caused by AOPP using extracorporeal membrane oxygenation: A case report.

RATIONALE: Acute organophosphorus pesticide poisoning (AOPP) is a common critical illness observed in clinical practice, and severe AOPP can cause serious cardiac toxicity. PATIENT CONCERNS: This patient was a 43-year-old woman who was admitted to the emergency department with acute respiratory failure and hypotension 13 hours after oral consumption of 300 mL of phoxim pesticide. DIAGNOSES: Acute organophosphorus pesticide poisoning, cardiogenic shock. INTERVENTIONS: We conducted veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy as the patient did not respond to conventional measures. OUTCOMES: This patient was successfully rescued with VA-ECMO therapy and discharged. LESSONS: We suggest that for patients with severe myocardial injury complicated with cardiogenic shock caused by AOPP, the use of VA-ECMO therapy can improve the prognosis.

Extracorporeal membrane oxygenation combined with sequential blood purification in the treatment of myocardial damage and cardiac arrest caused by mushroom poisoning.

Mushroom poisoning is a common clinical problem. Severe mushroom poisoning often causes liver and kidney failure. Although severe myocardial damage is rare, the fatality rate is extremely high. This case report describes a 56-year-old male suffered severe myocardial damage, multiple organ dysfunction, circulatory failure, recurrent malignant arrhythmia, and cardiac arrest after the ingestion of wild mushrooms. He was administered venoarterial extracorporeal membrane oxygenation (VA-ECMO) combined with hemoperfusion, plasma exchange and continuous renal replacement therapy. The heart rhythm gradually stabilized 3 hours after ECMO surgery. On the 6th day after ECMO, heart function recovered. The patient was then weaned from ECMO, and he ultimately recovered and was discharged. In patients with fatal mushroom poisoning leading to refractory arrhythmia and cardiac arrest, early implementation of VA-ECMO combined with sequential blood purification treatment can improve the prognosis and increase the survival rate.

"Awake" Extracorporeal Membrane Oxygenation Combined With Continuous Renal Replacement Therapy For the Treatment of Severe Chemical Gas Inhalation Lung Injury.

Lung injury caused by chemical gas inhalation is a common clinically severe disease that very easily progresses to acute respiratory distress syndrome (ARDS). Traditional respiratory support consists mainly of mechanical ventilation, but the prognosis of this condition is still poor. "Awake" extracorporeal membrane oxygenation (ECMO) maintains oxygenation, improves ventilation, adequately allows the injured lungs to rest, and avoids complications associated with sedation, intubation, and mechanical ventilation. Continuous renal replacement therapy (CRRT) can provide better fluid management and reduce pulmonary edema. Herein, we describe the case of a patient with severe chemical gas inhalation lung injury who failed to respond to traditional mechanical ventilation and was subsequently treated with awake ECMO combined with CRRT.

Feedback Convolutional Neural Network for Visual Localization and Segmentation.

Feedback is a fundamental mechanism existing in the human visual system, but has not been explored deeply in designing computer vision algorithms. In this paper, we claim that feedback plays a critical role in understanding convolutional neural networks (CNNs), e.g., how a neuron in CNNs describes an object's pattern, and how a collection of neurons form comprehensive perception to an object. To model the feedback in CNNs, we propose a novel model named Feedback CNN and develop two new processing algorithms, i.e., neural pathway pruning and pattern recovering. We mathematically prove that the proposed method can reach local optimum. Note that Feedback CNN belongs to weakly supervised methods and can be trained only using category-level labels. But it possesses a powerful capability to accurately localize and segment category-specific objects. We conduct extensive visualization analysis, and the results reveal the close relationship between neurons and object parts in Feedback CNN. Finally, we evaluate the proposed Feedback CNN over the tasks of weakly supervised object localization and segmentation, and the experimental results on ImageNet and Pascal VOC show that our method remarkably outperforms the state-of-the-art ones.

Inhibition of AMP-activated protein kinase alleviates focal cerebral ischemia injury in mice: Interference with mTOR and autophagy.

Ischemic stroke is one of the most frequent acute cerebrovascular events worldwide. This study evaluated the variability of AMPK and mTOR and their relevance on LC3 and Beclin-1 expression, and further expounded the possible protective mechanism of inhibiting AMPK activity in the cerebral cortex after permanent focal cerebral ischemia injury in mice. Western blot and immunohistochemistry showed that p-AMPK expression was low in the cerebral cortex of the sham group; whereas it was significantly increased at 3h and 6h and peaked at 3h after pMCAO in the cerebral ischemic cortex, and was decreased at 12h and 24h. The expression patterns of LC3 and Beclin-1 were the same as that of p-AMPK after occlusion, and the variability pattern between p-AMPK and p-mTOR levels was completely inverted. After treatment with the AMPK inhibitor Compound C, p-AMPK/LC3/Beclin-1 expression was decreased significantly, whereas p-mTOR level was increased significantly. Deficiency of Nissl bodies was reduced compared with that in the vehicle group at all times points after occlusion. Neurological deficits, infarct areas, and brain water content were also significantly reduced 24h after occlusion with compound C treatment. The results suggested that the AMPK-autophagy pathway was activated, concomitant with mTOR inhibition in cerebral cortex after ischemic injury in mice. Moreover, inhibition of AMPK activity by Compound C inhibited autophagy and conferred protection against brain damage by restoring mTOR activity.

[Effect of angiotensin II on the expression of aquaporin 1 in lung of rats following acute lung injury].

OBJECTIVE: To investigate the effect of angiotensin II (Ang II) on the expression of aquaporin 1 (AQP1) in lung of rats with acute lung injury (ALI) and the role of Ang II in the formation of lung edema. METHODS: Forty healthy Sprague-Dawley (SD) rats were randomly divided into sham-operated group, model group, Ang II receptor blocker pretreatment group, and Ang II receptor blocker treatment group according to random digits table, with 10 rats in each group. ALI model of rats was reproduced with administration of endotoxin after hemorrhagic shock. In rats of pretreatment group Ang II receptor blocker 30 microg/kg was given 30 minutes before lipopolysaccharide (LPS) injection; rats in treatment group Ang II receptor blocker 30 microg/kg was given 30 minutes after LPS injection; rats in model group received 30 microg/kg normal saline 30 minutes before and after LPS injection. Rats were sacrificed 6 hours after model establishment, samples of venous blood and lung tissue were collected, radioimmunoassay was used to measure the level of tumor necrosis factor-alpha (TNF-alpha) in serum and the expression of Ang II in lung tissue, ratio of wet to dry (W/D) weight of lung tissue was calculated, reverse transcription-polymerase chain reaction was used to measure the expression of AQP1 mRNA in lung tissue. RESULTS: Compared with rats of sham-operated group, the level of TNF-alpha in venous blood, W/D ratio and the expression of Ang II in lung tissue increased significantly, the expression of AQP1 mRNA in lung tissue decreased significantly in rats of ALI. Compared with rats of model group, the level of TNF-alpha in venous blood (microg/L) decreased significantly (4.79+/-0.24, 5.55+/-0.36 vs. 6.34+/-0.31, both P<0.05), W/D ratio decreased significantly (4.34+/-0.23, 4.85+/-0.20 vs. 5.41+/-0.26, both P<0.05), the expression of AQP1 mRNA in lung tissue increased significantly (0.854+/-0.067, 0.727+/-0.081 vs. 0.358+/-0.071, both P<0.05), and the expression of Ang II in lung tissue (ng/g) decreased to some extent (172.19+/-15.82, 202.82+/-20.47 vs. 245.88+/-26.31), but without statistical significance (both P>0.05) in rats of pretreatment group and treatment group. The expression of AQP1 mRNA was negatively correlated with both the level of Ang II and W/D ratio (r1=-0.782, r2=-0.726, both P<0.05). CONCLUSION: During ALI, Ang II may downregulate the expression of AQP1 mRNA in lung tissue directly or through inflammatory mediators, Ang II may play a role in the formation of lung edema.