Skin mottling score assesses peripheral tissue hypoperfusion in critically ill patients following cardiac surgery.

BACKGROUND: Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. METHODS: Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. RESULTS: Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p < 0.001). The occurrences of skin mottling were higher in hypotension population and shock population, reaching 5.6% and 15.7%, respectively. The AUROC for SMS to identify peripheral hypoperfusion was 0.64, 0.68, and 0.81 in the overall, hypotension, and shock populations, respectively. The optimal SMS threshold was 1, which corresponded to specificities of 98, 97 and 91 and sensitivities of 29, 38 and 67 in the three populations (overall, hypotension and shock). The correlation of UO, lactate, CRT and vasopressor dose with SMS was significant, among them, UO and CRT were identified as two major factors associated with the presence of skin mottling. CONCLUSION: In critically ill patients following cardiac surgery, SMS is a very specific yet less sensitive parameter for detecting peripheral tissue hypoperfusion.

Risk and prediction of job burnout in responding nurses to public health emergencies.

BACKGROUND: In public health emergencies, nurses are vulnerable to adverse reactions, especially job burnout. It is critical to identify nurses at risk of burnout early and implement interventions as early as possible. METHODS: A cross-sectional survey of the hospitals in Xiangyang City was conducted in January, 2023 using stratified cluster sampling. Anonymized data were collected from 1584 working nurses. The Impact of Events Scale-Revised (IES-R) and the Chinese version of the Maslach Burnout Inventory-General Survey (MBI-GS) were used to evaluate the post-traumatic stress disorder (PTSD) and burnout of nurses in public health emergencies. Logistic regression analysis was established to screen for risk factors of burnout, and a nomogram was developed to predict the risk of burnout. A calibration curve and the area under the receiver operating characteristic (ROC) curve were used to validate the nomogram internally. RESULTS: This study showed that only 3.7% of nurses were completely free of PTSD during a public health emergency. We found that PTSD varied by age, marital status, procreation status, length of service, employee status, and whether working in the ICU. The nurses aged 30 ~ 40 years old, single, married without children, non-regular employees, worked for less than three years or worked in the ICU had higher levels of PTSD. Regarding the prevalence of burnout, 27.4%, 48.5%, and 18.6% of nurses had a high level of emotional exhaustion (EE), depersonalization (DP), and diminished personal accomplishment (PA), respectively. There, 31.1% of nurses had more than two types of job burnout. The number of night shifts, the type of hospital, marital status, and the severity of PTSD were all associated with higher rates of exhaustion among nurses. As a graphical representation of the model, a nomogram was created and demonstrated excellent calibration and discrimination in both sets (AUC = 0.787). CONCLUSIONS: This study confirmed the PTSD and burnout are common problems for in-service nurses during public health emergencies and screened out the high-risk groups of job burnout. It is necessary to pay more attention nurses who are single and working in general hospitals with many night shifts, especially nurses with severe PTSD. Hospitals can set up nurses' personal health records to give timely warnings to nurses with health problems, and carry out support interventions to relieve occupational stress.

Extracellular vesicles derived from CD4+ T cells carry DGKK to promote sepsis-induced lung injury by regulating oxidative stress and inflammation.

BACKGROUND: Sepsis is an abnormal immune response after infection, wherein the lung is the most susceptible organ to fail, leading to acute lung injury. To overcome the limitations of current therapeutic strategies and develop more specific treatment, the inflammatory process, in which T cell-derived extracellular vesicles (EVs) play a central role, should be explored deeply. METHODS: Liquid chromatography-tandem mass spectrometry was performed for serum EV protein profiling. The serum diacylglycerol kinase kappa (DGKK) and endotoxin contents of patients with sepsis-induced lung injury were measured. Apoptosis, oxidative stress, and inflammation in A549 cells, bronchoalveolar lavage fluid, and lung tissues of mice were measured by flow cytometry, biochemical analysis, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and western blot. RESULTS: DGKK, the key regulator of the diacylglycerol (DAG)/protein kinase C (PKC) pathway, exhibited elevated expression in serum EVs of patients with sepsis-induced lung injury and showed strong correlation with sepsis severity and disease progression. DGKK was expressed in CD4+ T cells under regulation of the NF-κB pathway and delivered by EVs to target cells, including alveolar epithelial cells. EVs produced by CD4+ T lymphocytes exerted toxic effects on A549 cells to induce apoptotic cell death, oxidative cell damage, and inflammation. In mice with sepsis induced by cecal ligation and puncture, EVs derived from CD4+ T cells also promoted tissue damage, oxidative stress, and inflammation in the lungs. These toxic effects of T cell-derived EVs were attenuated by the inhibition of PKC and NOX4, the downstream effectors of DGKK and DAG. CONCLUSIONS: This approach established the mechanism that T-cell-derived EVs carrying DGKK triggered alveolar epithelial cell apoptosis, oxidative stress, inflammation, and tissue damage in sepsis-induced lung injury through the DAG/PKC/NOX4 pathway. Thus, T-cell-derived EVs and the elevated distribution of DGKK should be further investigated to develop therapeutic strategies for sepsis-induced lung injury.

Postoperative glucocorticoids in patients with acute type A aortic dissection (GLAD): study protocol for a prospective, single-center, randomized controlled trial.

BACKGROUND: Patients receiving surgical treatment of acute type A Aortic Dissection (aTAAD) are common to suffer organ dysfunction in the intensive care unit due to overwhelming inflammation. Previous studies have revealed that glucocorticoids may reduce complications in certain patient groups, but evidence between postoperative glucocorticoids administration and improvement in organ dysfunction after aTAAD surgery are lacking. METHODS: This study will be an investigator-initiated, prospective, single-blind, randomized, single-center study. Subjects with confirmed diagnosis of aTAAD undergoing surgical treatment will be enrolled and 1:1 randomly assigned to receive either glucocorticoids or normal treatment. All patients in the glucocorticoids group will be given methylprednisolone intravenously for 3 days after enrollment. The primary endpoint will be the amplitude of variation of Sequential Organ Failure Assessment score on post-operative day 4 compared to baseline. DISCUSSION: The trial will explore the rationale for postoperative application of glucocorticoids in patients after aTAAD surgery. TRIAL REGISTRATION: This study has been registered on ClinicalTrials.gov (NCT04734418).

The dynamic alteration of transcriptional regulation by crucial TFs during tumorigenesis of gastric cancer.

BACKGROUND: The mechanisms of Gastric cancer (GC) initiation and progression are complicated, at least partly owing to the dynamic changes of gene regulation during carcinogenesis. Thus, investigations on the changes in regulatory networks can improve the understanding of cancer development and provide novel insights into the molecular mechanisms of cancer. METHODS: Differential co-expression analysis (DCEA), differential gene regulation network (GRN) modeling and differential regulation analysis (DRA) were integrated to detect differential transcriptional regulation events between gastric normal mucosa and cancer samples based on GSE54129 dataset. Cytological experiments and IHC staining assays were used to validate the dynamic changes of CREB1 regulated targets in different stages. RESULTS: A total of 1955 differentially regulated genes (DRGs) were identified and prioritized in a quantitative way. Among the top 1% DRGs, 14 out of 19 genes have been reported to be GC relevant. The four transcription factors (TFs) among the top 1% DRGs, including CREB1, BPTF, GATA6 and CEBPA, were regarded as crucial TFs relevant to GC progression. The differentially regulated links (DRLs) around the four crucial TFs were then prioritized to generate testable hypotheses on the differential regulation mechanisms of gastric carcinogenesis. To validate the dynamic alterations of gene regulation patterns of crucial TFs during GC progression, we took CREB1 as an example to screen its differentially regulated targets by using cytological and IHC staining assays. Eventually, TCEAL2 and MBNL1 were proved to be differentially regulated by CREB1 during tumorigenesis of gastric cancer. CONCLUSIONS: By combining differential networking information and molecular cell experiments verification, testable hypotheses on the regulation mechanisms of GC around the core TFs and their top ranked DRLs were generated. Since TCEAL2 and MBNL1 have been reported to be potential therapeutic targets in SCLC and breast cancer respectively, their translation values in GC are worthy of further investigation.

ATP5B promotes the metastasis and growth of gastric cancer by activating the FAK/AKT/MMP2 pathway.

Adenosine triphosphate (ATP) in the tumor microenvironment serves a vital role during tumor progression. ATP synthase F1 ß subunit (ATP5B) is one of the most important subunits of ATP synthase and increases cellular ATP levels. ATP5B reportedly participates in carcinogenesis in several tumors. However, the regulatory mechanisms of ATP5B remain poorly understood in gastric cancer (GC). Here, we determined that high ATP5B expression in tumor tissues of GC is positively correlated with age, the tumor size, the TNM stage, lymph node metastasis, and patients' poor prognosis. The overexpression of ATP5B in GC cells elevated the cellular ATP content and promoted migration, invasion and proliferation. The levels of MMP2 expression, phosphorylated FAK, and phosphorylated AKT were increased after ATP5B overexpression in GC cells. Additionally, ATP5B overexpression increased the extracellular ATP level through the secretion of intracellular ATP and activated the FAK/AKT/MMP2 signaling pathway. ATP5B-induced downstream pathway activation was induced through the plasma membrane P2X7 receptor. Inhibitors of P2X7, FAK, AKT, and MMP2 suppressed the proliferative, migratory, and invasive capabilities of GC cells. In conclusion, our experiments indicate that ATP5B contributes to tumor progression of GC via FAK/AKT/MMP2 pathway. ATP5B, therefore, may be a biomarker of poor prognosis and a potential therapeutic target for GC.

The effect of enhanced recovery after minimally invasive esophagectomy: a randomized controlled trial.

BACKGROUND: The purpose of this randomized controlled trial was to determine if enhanced recovery after surgery (ERAS) would improve outcomes for three-stage minimally invasive esophagectomy (MIE). METHODS: Patients with esophageal cancer undergoing MIE between March 2016 and August 2018 were consecutively enrolled, and were randomly divided into 2 groups: ERAS+group that received a guideline-based ERAS protocol, and ERAS- group that received standard care. The primary endpoint was morbidity after MIE. The secondary endpoints were the length of stay (LOS) and time to ambulation after the surgery. The perioperative results including the Surgical Apgar Score (SAS) and Visualized Analgesia Score (VAS) were also collected and compared. RESULTS: A total of 60 patients in the ERAS+ group and 58 patients in the ERAS- group were included. Postoperatively, lower morbidity and pulmonary complication rate were recorded in the ERAS+ group (33.3% vs. 51.7%; p = 0.04, 16.7% vs. 32.8%; p = 0.04), while the incidence of anastomotic leakage remained comparable (11.7% vs. 15.5%; p = 0.54). There was an earlier ambulation (3 [2-3] days vs. 3 [3-4] days, p = 0.001), but comparable LOS (10 [9-11.25] days vs. 10 [9-13] days; p = 0.165) recorded in ERAS+ group. The ERAS protocol led to close scores in both SAS (7.80 ± 1.03 vs. 8.07 ± 0.89, p = 0.21) and VAS (1.74 ± 0.85 vs. 1.78 ± 1.06, p = 0.84). CONCLUSIONS: Implementation of an ERAS protocol for patients undergoing MIE resulted in earlier ambulation and lower pulmonary complications, without a change in anastomotic leakage or length of hospital stay. Further studies on minimizing leakage should be addressed in ERAS for MIE.

Crocetin suppresses angiogenesis and metastasis through inhibiting sonic hedgehog signaling pathway in gastric cancer.

Gastric cancer (GC) is one of the major causes of cancer-related deaths and chemoresistance is a key obstacle to the treatment of GC, particularly in advanced GC. As an active component of saffron stigma, crocetin has important therapeutic effects on various diseases including tumors. However, the therapeutic potential of crocetin targeting GC is still unclear and the underlying mechanisms are remained to be further explored. In this study, crocetin significantly inhibited angiogenesis in GC, including tubes of HUVECs and vasculogenic mimicry (VM) formation of GC cells. Crocetin also suppressed cell proliferation, migration and invasion. To explore which signaling pathway involving in crocetin, HIF-1α, Notch1, Sonic hedgehog (SHH) and VEGF were examined with crocetin treatment and we found that SHH significantly decreased. Crocetin suppressed SHH signaling with SHH, PTCH2, Sufu and Gli1 protein level decreased in western blot assay. In addition, crocetin suppressed SHH secretion in GC and HUVEC cells. The promoted effects on cell migration induced by secreted SHH were also inhibited by crocetin in GC and HUVEC cell co-culture system. Furthermore, recombinant SHH promoted angiogenesis as well as cell migration and proliferation. However, these promoted effects were reversed by crocetin treatment. These results revealed that crocetin suppressed GC angiogenesis and metastasis through SHH signaling pathway, indicating that crocetin may function as an effective therapeutic drug against GC.

Inhaled nitric oxide reduces the intrapulmonary shunt to ameliorate severe hypoxemia after acute type A aortic dissection surgery.

BACKGROUND: To assess the relationship between the intrapulmonary shunt and PaO2/FiO2 in severe hypoxemic patients after acute type A aortic dissection (ATAAD) surgery and to evaluate the effect of inhaled nitric oxide (iNO) on intrapulmonary shunt. METHODS: Postoperative ATAAD patients with PaO2/FiO2 ≤ 150 mmHg were enrolled. Intrapulmonary shunt was calculated from oxygen content of different sites (artery [CaO2], mixed venous [CvO2], and alveolar capillary [CcO2]) using the Fick equation, where intrapulmonary shunt = (CcO2-CaO2)/(CcO2-CvO2). Related variables were measured at baseline (positive end expiratory pressure [PEEP] 5 cm H2O), 30 min after increasing PEEP (PEEP 10 cm H2O), 30 min after 5 ppm iNO therapy (PEEP 10 cm H2O + iNO), and 30 min after decreasing PEEP (PEEP 5 cm H2O + iNO). RESULTS: A total of 20 patients were enrolled between April 2019 and December 2019. Intrapulmonary shunt and PaO2/FiO2 were correlated in severe hypoxemic, postoperative ATAAD patients (adjusted R2 = 0.467, p < 0.001). A mixed model for repeated measures revealed that iNO, rather than increasing PEEP, significantly decreased the intrapulmonary shunt (by 15% at a PEEP of 5 cm H2O and 16% at a PEEP of 10 cm H2O, p < 0.001 each) and increased PaO2/FiO2 (by 63% at a PEEP of 5 cm H2O and 65% at a PEEP of 10 cm H2O, p < 0.001 each). After iNO therapy, the decrement of intrapulmonary shunt and the increment of PaO2/FiO2 were also correlated (adjusted R2 = 0.375, p < 0.001). CONCLUSIONS: This study showed that intrapulmonary shunt and PaO2/FiO2 were correlated in severe hypoxemic, postoperative ATAAD patients. Furthermore, iNO, rather than increasing PEEP, significantly decreased the intrapulmonary shunt to improve severe hypoxemic conditions.

Changes in Stroke Volume Variation Induced by Passive Leg Raising to Predict Fluid Responsiveness in Cardiac Surgical Patients With Protective Ventilation.

OBJECTIVES: Stroke volume variation (SVV) has been used to predict fluid responsiveness. The authors hypothesized the changes in SVV induced by passive leg raising (PLR) might be an indicator of fluid responsiveness in patients with protective ventilation after cardiac surgery. DESIGN: A prospective single-center observational study. SETTING: A single cardiac surgery intensive care unit at a tertiary hospital. PARTICIPANTS: A total of 123 patients undergoing cardiac surgery with hemodynamic instability. Tidal volume was set between 6 and 8 mL/kg of ideal body weight. INTERVENTIONS: PLR maneuver, fluid challenge. MEASUREMENTS AND MAIN RESULTS: SVV was continuously recorded using pulse contour analysis before and immediately after a PLR test and after fluid challenge (500 mL of colloid given over 30 min). Sixty-three (51.22%) patients responded to fluid challenge, in which PLR and fluid challenge significantly increased the SV and decreased the SVV. The decrease in SVV induced by PLR was correlated with the SV changes induced by fluid challenge. A 4% decrease in the SVV induced by PLR-discriminated responders to fluid challenge with an area under the curve of 0.90. The gray zone identified a range of SVV changes induced by PLR (between -3.94% and -2.91%) for which fluid responsiveness could not be predicted reliably. The gray zone included 15.45% of the patients. The SVV at baseline predicted fluid responsiveness with an area under the curve of 0.72. CONCLUSIONS: Changes in the SVV induced by PLR predicted fluid responsiveness in cardiac surgical patients with protective ventilation.

CXCL16/CXCR6 is involved in LPS-induced acute lung injury via P38 signalling.

Although several chemokines play key roles in the pathogenesis of acute lung injury (ALI), the roles of chemokine (C-X-C motif) ligand 16 (CXCL16) and its receptor C-X-C chemokine receptor type 6 (CXCR6) in ALI pathogenesis remain to be elucidated. The mRNA and protein expression of CXCL16 and CXCR6 was detected after lipopolysaccharide (LPS) stimulation with or without treatment with the nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC). Lung injury induced by LPS was evaluated in CXCR6 knockout mice. CXCL16 level was elevated in the serum of ALI patients (n = 20) compared with healthy controls (n = 30). CXCL16 treatment (50, 100, and 200 ng/mL) in 16HBE cells significantly decreased the epithelial barrier integrity and E-cadherin expression, and increased CXCR6 expression, reactive oxygen species (ROS) production, and p38 phosphorylation. Knockdown of CXCR6 or treatment with the p38 inhibitor SB203580 abolished the effects of CXCL16. Moreover, treatment of 16HBE cells with LPS (5, 10, 20 and 50 µg/mL) significantly increased CXCL16 release as well as the mRNA and protein levels of CXCL16 and CXCR6. The effects of LPS treatment (20 µg/mL) were abolished by treatment with PDTC. The results of the luciferase assay further demonstrated that PDTC treatment markedly inhibited the activity of the CXCL16 promoter. In conclusion, CXCL16, whose transcription was enhanced by LPS, may be involved in ROS production, epithelial barrier dysfunction and E-cadherin down-regulation via p38 signalling, thus contributing to the pathogenesis of ALI. Importantly, CXCR6 knockout or inhibition of p38 signalling may protect mice from LPS-induced lung injury by decreasing E-cadherin expression.

Circ_ZNF124 promotes non-small cell lung cancer progression by abolishing miR-337-3p mediated downregulation of JAK2/STAT3 signaling pathway.

BACKGROUND: Previous genome-wide transcriptome profiling found circ_ZNF124 was highly expressed in lung adenocarcinoma, however, the role of circ_ZNF124 in non-small cell lung cancer (NSCLC) is still unknown. The purpose of this study was to investigate the role and molecular mechanism of circ_ZNF124 in NSCLC development. METHODS: The expression of circ_ZNF124, miR-337-3p and JAK2 (Janus Kinase 2) in lung cancer cell lines and normal epithelial cells were detected by qRT-PCR (quantitative real-time PCR). siRNA was used to knockdown circ_ZNF124 expression in cells. The effects of circ_ZNF124 in NSCLC cells were determined by cell growth, cell migration, cell cycle analysis and colony formation. Bioinformatics analysis, RNA immunoprecipitation, luciferase assay and western blots were used to study the molecular mechanism of circ_ZNF124 in NSCLC. RESULTS: The results showed that circ_ZNF124 expression was highly upregulated in NSCLC cells than in normal epithelial cells. Knockdown of circ_ZNF124 by using siRNA significantly decreased cell growth, promoted cell cycle arrested in sub-G1 phase, impaired cell migration and colony formation. Bioinformatic analysis discovered that miR-337-3p was a direct target of circ_ZNF124. In contrast to circ_ZNF124, miR-337-3p expression was significantly downregulated in NSCLC cells. Biotin labeled circ_ZNF124 immunoprecipitation and luciferase assay showed that miR-337-3p could directly bind to and affect circ_ZNF124 activity. The regulation of circ_ZNF124 on miR-337-3p was also investigated. Further analysis showed that despite STAT3 (signal transducer and activator of transcription 3), JAK2 was also a target of miR-337-3p, overexpression of miR-337-3p greatly downregulated JAK2, STAT3 and JAK2/STAT3 downstream regulated oncogenes HIF1a (Hypoxia-inducible factor 1-alpha), BCL2 (B cell lymphoma 2) and c-FOS expression, however, the roles of miR-337-3p in JAK2/STAT3 signaling pathway were greatly inhibited in the presence of circ_ZNF124. CONCLUSION: In NSCLC, highly expressed circ_ZNF124 promoted the activation of JAK2/STAT3 signaling pathway by acting as a sponge of miR-337-3p, thus promoting the occurrence and development of NSCLC. Circ_ZNF124 could be a potential biomarker or target for the treatment of NSCLC patients in the future.

Reliability of three-dimensional color flow Doppler and two-dimensional pulse wave Doppler transthoracic echocardiography for estimating cardiac output after cardiac surgery.

BACKGROUND: Three-dimensional color flow Doppler (3DCF) is a new convenient technique for cardiac output (CO) measurement. However, to date, no one has evaluated the accuracy of 3DCF echocardiography for CO measurement after cardiac surgery. Therefore, this single-center, prospective study was designed to evaluate the reliability of three-dimensional color flow and two-dimensional pulse wave Doppler (2D-PWD) transthoracic echocardiography for estimating cardiac output after cardiac surgery. METHODS: Post-cardiac surgical patients with a good acoustic window and a low dose or no dose of vasoactive drugs (norepinephrine < 0.05 µg/kg/min) were enrolled for CO estimation. Three different methods (third generation FloTrac/Vigileo™ [FT/V] system as the reference method, 3DCF, and 2D-PWD) were used to estimate CO before and after interventions (baseline, after volume expansion, and after a dobutamine test). RESULTS: A total of 20 patients were enrolled in this study, and 59 pairs of CO measurements were collected (one pair was not included because of increasing drainage after the dobutamine test). Pearson's coefficients were 0.260 between the CO-FT/V and CO-PWD measurements and 0.729 between the CO-FT/V and CO-3DCF measurements. Bland-Altman analysis showed the bias between the absolute values of CO-FT/V and CO-PWD measurements was - 0.6 L/min with limits of agreement between - 3.3 L/min and 2.2 L/min, with a percentage error (PE) of 61.3%. The bias between CO-FT/V and CO-3DCF was - 0.14 L/min with limits of agreement between - 1.42 L /min and 1.14 L/min, with a PE of 29.9%. Four-quadrant plot analysis showed the concordance rate between ΔCO-PWD and ΔCO-3FT/V was 93.3%. CONCLUSIONS: In a comparison with the FT/V system, 3DCF transthoracic echocardiography could accurately estimate CO in post-cardiac surgical patients, and the two methods could be considered interchangeable. Although 2D-PWD echocardiography was not as accurate as the 3D technique, its ability to track directional changes was reliable.

Dual Balanced Class-Incremental Learning With im-Softmax and Angular Rectification.

Owing to the superior performances, exemplar-based methods with knowledge distillation (KD) are widely applied in class incremental learning (CIL). However, it suffers from two drawbacks: 1) data imbalance between the old/learned and new classes causes the bias of the new classifier toward the head/new classes and 2) deep neural networks (DNNs) suffer from distribution drift when learning sequence tasks, which results in narrowed feature space and deficient representation of old tasks. For the first problem, we analyze the insufficiency of softmax loss when dealing with the problem of data imbalance in theory and then propose the imbalance softmax (im-softmax) loss to relieve the imbalanced data learning, where we re-scale the output logits to underfit the head/new classes. For another problem, we calibrate the feature space by incremental-adaptive angular margin (IAAM) loss. The new classes form a complete distribution in feature space yet the old are squeezed. To recover the old feature space, we first compute the included angle of normalized features and normalized anchor prototypes, and use the angle distribution to represent the class distribution, then we replenish the old distribution with the deviation from the new. Each anchor prototype is predefined as a learnable vector for a designated class. The proposed im-softmax reduces the bias in the linear classification layer. IAAM rectifies the representation learning, reduces the intra-class distance, and enlarges the inter-class margin. Finally, we seamlessly combine the im-softmax and IAAM in an end-to-end training framework, called the dual balanced class incremental learning (DBL), for further improvements. Experiments demonstrate the proposed method achieves state-of-the-art (SOTA) performances on several benchmarks, such as CIFAR10, CIFAR100, Tiny-ImageNet, and ImageNet-100.

Furosemide Responsiveness Predicts Acute Kidney Injury Progression After Cardiac Surgery.

BACKGROUND: As patients with acute kidney injury (AKI) progress to a higher stage, the risk for poor outcomes dramatically rises. Early identification of patients at high risk for AKI progression remains a major challenge. This study aimed to evaluate the value of furosemide responsiveness (FR) for predicting AKI progression in patients with initial mild and moderate AKI after cardiac surgery. METHODS: We performed 2 separate exploratory analyses. The Zhongshan cohort was a single-center, prospective, observational cohort, whereas the Beth Israel Deaconess Medical Center cohort was a single-center, retrospective cohort. We calculated 2 FR parameters for each patient, namely the FR index and modified FR index, defined as 2-hour urine output divided by furosemide dose (FR index, mL/mg/2 h) and by furosemide dose and body weight (modified FR index, mL/[mg·kg]/2 h), respectively. The primary outcome was AKI progression within 7 days. RESULTS: AKI progression occurred in 80 (16.0%) and 359 (11.3%) patients in the Zhongshan and Beth Israel Deaconess Medical Center cohorts, respectively. All FR parameters (considered continuously or in quartiles) were inversely associated with risk of AKI progression in both cohorts (all adjusted P < .01). The addition of FR parameters significantly improved prediction for AKI progression based on baseline clinical models involving C-index, net reclassification improvement, and integrated discrimination improvement index in both cohorts (all P < .01). CONCLUSIONS: FR parameters were inversely associated with risk of AKI progression in patients with mild and moderate AKI after cardiac surgery. The addition of FR parameters significantly improved prediction for AKI progression based on baseline clinical models.

Plane-wave medical image reconstruction based on dynamic Criss-Cross attention and multi-scale convolution.

BACKGROUND: Plane-wave imaging is widely employed in medical imaging due to its ultra-fast imaging speed. However, the image quality is compromised. Existing techniques to enhance image quality tend to sacrifice the imaging frame rate. OBJECTIVE: The study aims to reconstruct high-quality plane-wave images while maintaining the imaging frame rate. METHODS: The proposed method utilizes a U-Net-based generator incorporating a multi-scale convolution module in the encoder to extract information at different levels. Additionally, a Dynamic Criss-Cross Attention (DCCA) mechanism is proposed in the decoder of the U-Net-based generator to extract both local and global features of plane-wave images while avoiding interference caused by irrelevant regions. RESULTS: In the reconstruction of point targets, the experimental images achieved a reduction in Full Width at Half Maximum (FWHM) of 0.0499 mm, compared to the Coherent Plane-Wave Compounding (CPWC) method using 75-beam plane waves. For the reconstruction of cyst targets, the simulated image achieved a 3.78% improvement in Contrast Ratio (CR) compared to CPWC. CONCLUSIONS: The proposed model effectively addresses the issue of unclear lesion sites in plane-wave images.

TAGLN2 targeted control of ARPC5-mediated activation of the MEK/ERK signaling pathway influences the proliferation, invasion, and metastasis of pancreatic cancer cells.

PURPOSE: Pcancreatic cancer (PC) is a common tumor of the digestive tract with an insidious onset and high malignancy potential. Currently, surgery is the only effective treatment modality. Therefore, it is crucial to discover new targeted therapeutic modalities. We studied whether transgelin 2 (TAGLN2) targeted control of actin-related protein 2/3 complex subunit 5 (ARPC5)-mediated activation of the MEK/ERK signaling pathway to Influences the proliferation, invasion, and metastasis of pancreatic cancer cells. METHODS: The effects of TAGLN2 overexpression and knockdown on the proliferative viability and invasive metastatic ability of pancreatic cancer cells were verified through in vitro and in vivo assays via constructing a stable lentiviral transfection of human pancreatic cancer cell lines PANC-1 and SW1990. Bioinformatics analysis was used to predict the relationship between TAGLN2 and ARPC5. These findings were subsequently verified through protein profiling, immunofluorescence (IF), and coimmunoprecipitation (CO-IP) assays. In vitro experiments were also conducted to confirm the effect of TAGLN2 modulation on ARPC5 expression, which subsequently affects the proliferation and invasive metastatic ability of pancreatic cancer cells. The study analyzed the relationship between TAGLN2 and the MEK/ERK signaling pathway through bioinformatics and in vitro experiments with the MEK signaling pathway inhibitor U0126. RESULTS: TAGLN2 is expressed at high levels in pancreatic cancer cell lines, and its expression is positively correlated with poor prognosis of pancreatic cancer. ARPC5 is a direct target of TAGLN2 and is associated with the MEK/ERK signaling pathway. In vivo and ex vivo experiments confirmed that overexpression of TAGLN2 promoted the proliferation, invasion, and metastasis of pancreatic cancer cells, and silencing ARPC5 reversed these effect. CONCLUSION: Our research revealed that TAGLN2 protein binds to ARPC5 protein and contributes to increased ARPC5 expression and activation of the MEK/ERK signaling pathway. This activation promotes pancreatic cancer cell growth, infiltration, and spread. Hence, TAGLN2 is a potential viable therapeutic target in pancreatic cancer and represents a novel therapeutic approach.

PELI1: key players in the oncogenic characteristics of pancreatic Cancer.

BACKGROUND: Pancreatic cancer (PC) is a highly malignant gastrointestinal tumor, which is characterized by difficulties in early diagnosis, early metastasis, limited therapeutic response and a grim prognosis. Therefore, it is imperative to explore potential therapeutic targets for PC. Currently, although the involvement of the Pellino E3 Ubiquitin Protein Ligase 1 (PELI1) in the human growth of some malignant tumors has been demonstrated, its association with PC remains uncertain. METHODS: Bioinformatics, qRT-PCR, Western blot and IHC were used to detect the expression of PELI1 in pancreas or PC tissues and cells at mRNA and protein levels. The effects of PELI1 on the proliferation and metastatic ability of pancreatic cancer in vitro and in vivo were investigated using CCK8, cloning formation, EdU, flow cytometry, IHC, Transwell assay, wound healing, nude mice subcutaneous tumorigenesis and intrasplenic injection to construct a liver metastasis model. The interactions of PELI1 with proteins as well as the main functions and pathways were investigated by protein profiling, Co-IP, GST-pull down, Immunofluorescence techniques, immunohistochemical co-localization and enrichment analysis. The rescue experiment verified the above experimental results. RESULTS: The mRNA and protein expression levels of PELI1 in PC tissues were upregulated and were associated with poor prognosis of patients, in vitro and in vivo experiments confirmed that PELI1 can affect the proliferation and metastatic ability of PC cells. Co-IP, GST-pull down, and other experiments found that PELI1 interacted with Ribosomal Protein S3 (RPS3) through the FHA structural domain and promoted the polyubiquitination of RPS3 in the K48 chain, thereby activates the PI3K/Akt/GSK3ß signaling pathway. Moreover, ubiquitinated degradation of RPS3 further reduces Tumor Protein P53 (p53) protein stability and increases p53 degradation by MDM2 Proto-Oncogene (MDM2). CONCLUSION: PELI1 is overexpressed in PC, which increased ubiquitination of RPS3 proteins and activates the PI3K/Akt/GSK3ß signaling pathway, as well as reduces the protective effect of RPS3 on p53 and promotes the degradation of the p53 protein, which facilitates the progression of PC and leads to a poor prognosis for patients. Therefore, PELI1 is a potential target for the treatment of PC.

Biodegradation of the neonicotinoid insecticide thiamethoxam by the nitrogen-fixing and plant-growth-promoting rhizobacterium Ensifer adhaerens strain TMX-23.

Thiamethoxam (THIA), a second generation neonicotinoid insecticide in the thianicotinyl subclass, is used worldwide. Environmental studies revealed that microbial degradation is the major mode of removal of this pesticide from soil. However, microbial transformation of THIA is poorly understood. In the present study, we isolated a bacterium able to degrade THIA from rhizosphere soil. The bacterium was identified as Ensifer adhaerens by its morphology and 16S ribosomal DNA sequence analysis. High-performance liquid chromatography and mass spectrometry analysis suggested that the major metabolic pathway of THIA in E. adhaerens TMX-23 involves the transformation of its N-nitroimino group (=N-NO2) to N-nitrosoimino (=N-NO) and urea (=O) metabolites. E. adhaerens TMX-23 is a nitrogen-fixing bacterium harboring two types of nifH genes in its genome, one of which is 98 % identical to the nifH gene in the cyanobacterium Calothrix sp. MCC-3A. E. adhaerens TMX-23 released various plant-growth-promoting substances including indole-3-acetic acid, exopolysaccharides, ammonia, HCN, and siderophores. Inoculation of E. adhaerens TMX-23 onto soybean seeds (Glycine max L.) with NaCl at 50, 100, or 154 mmol/L increased the seed germination rate by 14, 21, and 30 %, respectively. THIA at 10 mg/L had beneficial effects on E. adhaerens TMX-23, enhancing growth of the bacterium and its production of salicylic acid, an important plant phytohormone associated with plant defense responses against abiotic stress. The nitrogen-fixing and plant-growth-promoting rhizobacterium E. adhaerens TMX-23, which is able to degrade THIA, has the potential for bioaugmentation as well as to promote growth of field crops in THIA-contaminated soil.

Acrylamide biodegradation ability and plant growth-promoting properties of Variovorax boronicumulans CGMCC 4969.

Species of the genus Variovorax are often isolated from nitrile or amide-containing organic compound-contaminated soil. However, there have been few biological characterizations of Variovorax and their contaminant-degrading enzymes. Previously, we reported a new soil isolate, Variovorax boronicumulans CGMCC 4969, and its nitrile hydratase that transforms the neonicotinoid insecticide thiacloprid into an amide metabolite. In this study, we showed that CGMCC 4969 is able to degrade acrylamide, a neurotoxicant and carcinogen in animals, during cell growth in a mineral salt medium as well as in its resting state. Resting cells rapidly hydrolyzed 600 mg/L acrylamide to acrylic acid with a half-life of 2.5 min. In in vitro tests, CGMCC 4969 showed plant growth-promoting properties; it produced a siderophore, ammonia, hydrogen cyanide, and the phytohormone salicylic acid. Interestingly, in soil inoculated with this strain, 200 mg/L acrylamide was completely degraded in 4 days. Gene cloning and overexpression in the Escherichia coli strain Rosetta (DE3) pLysS resulted in the production of an aliphatic amidase of 345 amino acids that hydrolyzed acrylamide into acrylic acid. The amidase contained a conserved catalytic triad, Glu59, Lys 134, and Cys166, and an "MRHGDISSS" amino acid sequence at the N-terminal region. Variovorax boronicumulans CGMCC 4969, which is able to use acrylamide for cell growth and rapidly degrade acrylamide in soil, shows promising plant growth-promoting properties. As such, it has the potential to be developed into an effective Bioaugmentation strategy to promote growth of field crops in acrylamide-contaminated soil.