Electrochemical Methods for Water Purification, Ion Separations, and Energy Conversion.

Agricultural development, extensive industrialization, and rapid growth of the global population have inadvertently been accompanied by environmental pollution. Water pollution is exacerbated by the decreasing ability of traditional treatment methods to comply with tightening environmental standards. This review provides a comprehensive description of the principles and applications of electrochemical methods for water purification, ion separations, and energy conversion. Electrochemical methods have attractive features such as compact size, chemical selectivity, broad applicability, and reduced generation of secondary waste. Perhaps the greatest advantage of electrochemical methods, however, is that they remove contaminants directly from the water, while other technologies extract the water from the contaminants, which enables efficient removal of trace pollutants. The review begins with an overview of conventional electrochemical methods, which drive chemical or physical transformations via Faradaic reactions at electrodes, and proceeds to a detailed examination of the two primary mechanisms by which contaminants are separated in nondestructive electrochemical processes, namely electrokinetics and electrosorption. In these sections, special attention is given to emerging methods, such as shock electrodialysis and Faradaic electrosorption. Given the importance of generating clean, renewable energy, which may sometimes be combined with water purification, the review also discusses inverse methods of electrochemical energy conversion based on reverse electrosorption, electrowetting, and electrokinetic phenomena. The review concludes with a discussion of technology comparisons, remaining challenges, and potential innovations for the field such as process intensification and technoeconomic optimization.

Two Putative Pheromone Receptors, but Not Their Cognate Pheromones, Regulate Female Fertility in the Atypical Mating Fungus Colletotrichum fructicola.

Colletotrichum fungi are a group of damaging phytopathogens with atypical mating type loci (harboring only MAT1-2-1 but not MAT1-1-1) and complex sexual behaviors. Sex pheromones and their cognate G-protein-coupled receptors are conserved regulators of fungal mating. These genes, however, lose function frequently among Colletotrichum species, indicating a possibility that pheromone signaling is dispensable for Colletotrichum sexual reproduction. We have identified two putative pheromone-receptor pairs (PPG1:PRE2, PPG2:PRE1) in C. fructicola, a species that exhibits plus-to-minus mating type switching and plus-minus-mediated mating line development. Here, we report the generation and characterization of gene-deletion mutants for all four genes in both plus and minus strain backgrounds. Single-gene deletion of pre1 or pre2 had no effect on sexual development, whereas their double deletion caused self-sterility in both the plus and minus strains. Moreover, double deletion of pre1 and pre2 caused female sterility in plus-minus outcrossing. Double deletion of pre1 and pre2, however, did not inhibit perithecial differentiation or plus-minus-mediated enhancement of perithecial differentiation. Contrary to the results with pre1 and pre2, double deletion of ppg1 and ppg2 had no effect on sexual compatibility, development, or fecundity. We concluded that pre1 and pre2 coordinately regulate C. fructicola mating by recognizing novel signal molecule(s) distinct from canonical Ascomycota pheromones. The contrasting importance between pheromone receptors and their cognate pheromones highlights the complicated nature of sex regulation in Colletotrichum fungi.

Interfacial Resistive Switching by Multiphase Polarization in Ion-Intercalation Nanofilms.

Nonvolatile resistive-switching (RS) memories promise to revolutionize hardware architectures with in-memory computing. Recently, ion-interclation materials have attracted increasing attention as potential RS materials for their ion-modulated electronic conductivity. In this Letter, we propose RS by multiphase polarization (MP) of ion-intercalated thin films between ion-blocking electrodes, in which interfacial phase separation triggered by an applied voltage switches the electron-transfer resistance. We develop an electrochemical phase-field model for simulations of coupled ion-electron transport and ion-modulated electron-transfer rates and use it to analyze the MP switching current and time, resistance ratio, and current-voltage response. The model is able to reproduce the complex cyclic voltammograms of lithium titanate (LTO) memristors, which cannot be explained by existing models based on bulk dielectric breakdown. The theory predicts the achievable switching speeds for multiphase ion-intercalation materials and could be used to guide the design of high-performance MP-based RS memories.

[A Brief Analysis of Equivalence Demonstration Techniques for Clinical Evaluation of Medical Devices].

This study overviewed equivalence demonstration, the principles for the selection of comparative devices, the difficulties in equivalence demonstration, and the equivalence demonstration of special medical devices. In addition, the concept of equivalence demonstration was adopted for the products exempted from clinical evaluation, and there were many confusion in actual use. The operation points and difficult points of equivalence demonstration for the products exempted from clinical evaluation were introduced in order to provide reference for medical device colleagues.

GPS2 promotes erythroid differentiation by control of the stability of EKLF protein.

Erythropoiesis is a complex multistage process that involves differentiation of early erythroid progenitors to enucleated mature red blood cells, in which lineage-specific transcription factors play essential roles. Erythroid Krüppel-like factor (EKLF/KLF1) is a pleiotropic erythroid transcription factor that is required for the proper maturation of the erythroid cells, whose expression and activation are tightly controlled in a temporal and differentiation stage-specific manner. Here, we uncover a novel role of G-protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor/silencing mediator of retinoic acid and thyroid hormone receptor corepressor complex, in erythrocyte differentiation. Our study demonstrates that knockdown of GPS2 significantly suppresses erythroid differentiation of human CD34+ cells cultured in vitro and xenotransplanted in nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor γ-chain null mice. Moreover, global deletion of GPS2 in mice causes impaired erythropoiesis in the fetal liver and leads to severe anemia. Flow cytometric analysis and Wright-Giemsa staining show a defective differentiation at late stages of erythropoiesis in Gps2-/- embryos. Mechanistically, GPS2 interacts with EKLF and prevents proteasome-mediated degradation of EKLF, thereby increasing EKLF stability and transcriptional activity. Moreover, we identify the amino acids 191-230 region in EKLF protein, responsible for GPS2 binding, that is highly conserved in mammals and essential for EKLF protein stability. Collectively, our study uncovers a previously unknown role of GPS2 as a posttranslational regulator that enhances the stability of EKLF protein and thereby promotes erythroid differentiation.

Selective and Chemical-Free Removal of Toxic Heavy Metal Cations from Water Using Shock Ion Extraction.

Electrochemical methods are known to have attractive features and capabilities when used for ion separations and water purification. In this study, we developed a new process called shock ion extraction (shock IX) for selective and chemical-free removal of toxic heavy metals from water. Shock IX is a hybrid process that combines shock electrodialysis (shock ED) and ion exchange using an ion exchange resin wafer (IERW), and this method can be thought of functionally as an electrochemically assisted variation of traditional ion exchange. In particular, shock IX exhibits greater ion removal and selectivity for longer periods of time, compared to the use of ion exchange alone. The use of an IERW in shock ED also increases multivalent ion selectivity, reduces energy consumption, and improves the hydrodynamics and scalability of the system.

Plasma Endothelial Glycocalyx Components as a Potential Biomarker for Predicting the Development of Disseminated Intravascular Coagulation in Patients With Sepsis.

BACKGROUND: Sepsis coagulopathy or disseminated intravascular coagulation (DIC) mainly due to progressive endothelial disruption and damage. The glycocalyx is expressed on the endothelial cell surface and contributes to anti-thrombogenicity, anti-inflammatory, and regulates vascular permeability. We aimed to evaluate the clinical utility of plasma glycocalyx components as biomarkers in predicting the onset of DIC in sepsis. MATERIALS AND METHODS: This was a prospective observational study of 45 patients with sepsis (June to December 2018). Demographic, clinical (Acute Physiology, Age, Chronic Health Evaluation II [APACHE II], Sequential Organ Failure Assessment [SOFA]), and laboratory data from medical records were analyzed. Endothelial glycocalyx components (syndecan-1, heparan sulfate, hyaluronan) were measured using an ELISA kit. RESULTS: Among the 45 patients (23, sepsis; 22, septic shock), plasma syndecan-1, heparan sulfate, and hyaluronan levels were higher in those with septic shock and were positively correlated with disease severity as determined by the APACHE II and SOFA scores and lactate levels. Receiver operating characteristic curve analysis revealed high sensitivity and specificity of syndecan-1 for predicting septic shock. Further, these levels were compared between patients with or without the development of DIC. Plasma syndecan-1 and hyaluronan levels were significantly elevated in patients with DIC compared to those in patients without DIC and were strongly associated with activated partial thromboplastin time, prothrombin time, and platelet counts. Area under the curve values for predicting DIC based on syndecan-1 and hyaluronan levels measurements were 0.774 and 0.740, respectively. CONCLUSIONS: Increased plasma syndecan-1 and hyaluronan levels may be indicators of disease severity and useful predictors for DIC development in sepsis.

Continuous Separation of Radionuclides from Contaminated Water by Shock Electrodialysis.

The increasing popularity of nuclear energy necessitates development of new methods to treat water that becomes contaminated with radioactive substances. Because this polluted water comprises several dissolved species (not all of which are radioactive), selective accumulation of the radionuclides is desirable to minimize the volume of nuclear waste and to facilitate its containment or disposal. In this article, we use shock electrodialysis to selectively, continuously, and efficiently remove cobalt and cesium from a feed of dissolved lithium, cobalt, cesium, and boric acid. This formulation models the contaminated water commonly found in light-water reactors and in other nuclear processes. In a three-pass process, a consistent trade-off is observed between the recovery of decontaminated water and the percentage of cobalt removed, which offers flexibility in operating the system. For example, 99.5% of cobalt can be removed with a water recovery of 43%, but up to 66% of the water can be recovered if deionization of cobalt is allowed to drop to 98.3%. In general, the energy consumed during this process (ranging between 1.76 and 4.8 kW h m-3) is low because only charged species are targeted and virtually no energy is expended removing boric acid, the most abundant species in solution.

Comparison of high flow nasal cannula with noninvasive ventilation in chronic obstructive pulmonary disease patients with hypercapnia in preventing postextubation respiratory failure: A pilot randomized controlled trial.

High flow nasal cannula (HFNC) has been shown to improve extubation outcomes in patients with hypoxemia, but the role of HFNC in weaning patients with chronic obstructive pulmonary disease (COPD) with hypercapnia from invasive ventilation is unclear. We compared the effects of HFNC to noninvasive ventilation (NIV) on postextubation vital signs and arterial blood gases (ABGs) among patients with COPD. Other outcomes included comfort scores, need for bronchoscopy, use of pulmonary medications, and chest physiotherapy. Forty-two COPD patients who had persistent hypercapnia at extubation were assigned randomly to receive HFNC (22) or NIV (20). Twenty patients in each group were enrolled for per-protocol analysis with regard to primary outcomes. Vital signs and ABGs before extubation were similar between groups. At 3 hr after extubation, pH in the NIV group was lower than HFNC group (7.42 ± 0.06 vs. 7.45 ± 0.05, p = 0.01). At 24 hr after extubation, patients' mean arterial pressure (82.97 ± 9.04 vs. 92.06 ± 11.11 mmHg, p = 0.05) and pH (7.42 ± 0.05 vs. 7.46 ± 0.03, p = 0.05) in the NIV group were lower than in the HFNC group. No significant differences were found at 48 hr after extubation. In the HFNC group, comfort scores were better (3.55 ± 2.01 vs. 5.15 ± 2.28, p = 0.02) and fewer patients needed bronchoscopy for secretion management within 48 hr after extubation (2/22 vs. 9/20, p = 0.03). HFNC is a potential alternative to NIV to wean hypercapnic COPD patients with regard to vital signs and ABGs, HFNC improved patients' comfort and secretion clearance.

Attitude Angle Compensation for a Synchronous Acquisition Method Based on an MEMS Sensor.

As a new type of micro-electro-mechanical systems (MEMS) inertial sensor, the Quartz Vibrating Beam Accelerometer (QVBA) is widely used in intelligent sweeping robots, small aircraft, navigation systems, etc. For these applications, correcting and compensating the attitude angle with the result of acceleration plays an important role to improve the measurement accuracy. The synchronization error between the measurement of the accelerometer and gyroscope attitude angle has an adverse impact on the accuracy of the attitude angle. In this paper, a synchronous acquisition scheme of the accelerometer and gyroscope attitude angle in a strapdown inertial navigation system (SINS) is proposed. At the same time, to improve the sampling accuracy and the conversion speed of QVBA, an improved equal-precision frequency measuring method is also implemented in this paper. The hardware float point unit (FPU) is used to accelerate the calculation of the frequency measurement value. The long-term cumulative error of the frequency measurement value is less than 10 - 4 . The calculation process time from sampling to attitude angle compensation calculation is reduced by 40.8%. This work has played a very good role in improving the measurement accuracy and speed of the SINS.

Propagation of partially coherent Laguerre Gaussian beams through inhomogeneous turbulent atmosphere.

Analytical formulas for the root-mean-square (rms) spatial width, the rms angular width, and the M2-factor of partially coherent standard Laguerre Gaussian beams (PC-SLGBs) and partially coherent elegant Laguerre Gaussian beams (PC-ELGBs) in inhomogeneous turbulent atmosphere have been derived. The propagation properties of PC-SLGBs and PC-ELGBs in inhomogeneous atmospheric turbulence are studied numerically and comparatively. It can be found that the propagation of laser beams in inhomogeneous turbulence is different from that in homogeneous turbulence. It is also shown that relative rms spatial widths and M2-factors of PC-ELGBs are more affected by inhomogeneous turbulence than those of PC-SLGBs. Moreover, the relative rms spatial widths and M2-factors of PC-SLGBs and PC-ELGBs in inhomogeneous turbulent atmosphere are closely related with waist widths, coherence widths, zenith angles, inner scales, and beam orders. Furthermore, the saturation propagation distance of the relative M2-factor and rms angular width with zenith angles of π/6 are 20 km and 0.5 km, respectively.

Propagation characteristics of partially coherent flat-topped beams propagating through inhomogeneous atmospheric turbulence.

M2-factor and root-mean-square (rms) angular width of partially coherent flat-topped (PCFT) beams propagating through inhomogeneous atmospheric turbulence are studied based on the extended Huygens-Fresnel principle and the Wigner distribution function (WDF). It is shown that the effect of turbulence on the PCFT beams can be neglected as the vertical height increases, which is different from the homogeneous turbulence. Analytical formulae of the M2-factor and rms angular width of PCFT beams have been given. The saturation propagation distances (SPDs) increase with increasing zenith angle. It can be seen that the SPDs of the M2-factor and rms angular width of PCFT beams propagating through inhomogeneous atmospheric turbulence are about 30 km and 0.5 km, respectively, when the zenith angle is π/4. It can be found that the M2-factor increases with increasing beam order and zenith angle, and with decreasing waist width, inner scale, wavelength, and transverse coherence length. The rms angular width increases with increasing beam order, wavelength, and zenith angle, and decreasing waist width, inner scale, and transverse coherence length.

Effect on glycemia in rats with type 2 diabetes induced by streptozotocin: low-frequency electro-pulse needling stimulated Weiwanxiashu (EX-B 3) and Zusanli (ST 36).

OBJECTIVE: To investigate the effect of low frequency electro-pulse acupuncture (EA) on blood glucose in rats with streptozotocin-induced type 2 diabetes, and the possible mechanism underlying the action. METHODS: Rat models were established with high fat feeding and intraperitoneal injection of streptozotocin (STZ) (30 mg/kg). Rats with a random blood glucose > 16.7 mmol/L and blood glucose at 2 h-point of oral glucose tolerance test (OGTT) > 11.1 mmol/L were included as diabetic rats, and randomly divided into model group, EA Weiwanxiashu (EX-B 3) group, EA Zusanli (ST 36) group, glimepiride group, and EA non-acupoint group (n = 12). EA (2 Hz continuous wave, 2 mA, 20 min/day, 6 days/week, 4 weeks) and intra-gastric administration of glimepiride were applied as interventions. With fasting blood glucose and OGTT tested at the end of the intervention, the study observed the patterns of hypoglycemic effects. For mechanism study, it observes hematoxylin and eosin staining and Masson staining of pancreas paraffin sections, protein expression of glucagon- like peptide 1 receptor (GLP-1R) in the pancreas and skeletal muscle, glucose transporter 4 (GLUT4) protein expression in skeletal muscle membrane, to detect whether EA controls blood glucose via regulation of GLP-1R. RESULTS: EA Weiwanxiashu (EX-B 3) significantly increased model rats' pancreas GLP-1R, and GLUT4 of skeletal muscle membrane; the therapy significantly decreased model rats' skeletal muscle GLP-1R, restored pancreas morphology, and reduced fasting blood glucose and insulin resistance indices. CONCLUSION: EA Weiwanxiashu (EX-B 3) alone has significant effect on glycemia. EA Weiwanxiashu (EX-B 3) plus glimepiride further strengthen the effect. The regulation of the GLP-1R in pancreas and skeletal muscle might be mechanism underpinning the effect.

Genome comparisons reveal accessory genes crucial for the evolution of apple Glomerella leaf spot pathogenicity in Colletotrichum fungi.

Apple Glomerella leaf spot (GLS) is an emerging fungal disease caused by Colletotrichum fructicola and other Colletotrichum species. These species are polyphyletic and it is currently unknown how these pathogens convergently evolved to infect apple. We generated chromosome-level genome assemblies of a GLS-adapted isolate and a non-adapted isolate in C. fructicola using long-read sequencing. Additionally, we resequenced 17 C. fructicola and C. aenigma isolates varying in GLS pathogenicity using short-read sequencing. Genome comparisons revealed a conserved bipartite genome architecture involving minichromosomes (accessory chromosomes) shared by C. fructicola and other closely related species within the C. gloeosporioides species complex. Moreover, two repeat-rich genomic regions (1.61 Mb in total) were specifically conserved among GLS-pathogenic isolates in C. fructicola and C. aenigma. Single-gene deletion of 10 accessory genes within the GLS-specific regions of C. fructicola identified three that were essential for GLS pathogenicity. These genes encoded a putative non-ribosomal peptide synthetase, a flavin-binding monooxygenase and a small protein with unknown function. These results highlight the crucial role accessory genes play in the evolution of Colletotrichum pathogenicity and imply the significance of an unidentified secondary metabolite in GLS pathogenesis.

[Effect of continuous blood purification on immunity and endothelial cell function in patients with sepsis].

OBJECTIVE: To explore the effect of continuous blood purification (CBP) on the immunity and endothelial cell function of patients with sepsis. METHODS: A prospective study was conducted. The patients aged ≥ 18 years old and meeting the diagnostic criteria of sepsis admitted to the department of critical care medicine of Binzhou Medical University Hospital from March 2019 to October 2020 were selected as the research subjects, and the patients were divided into standard treatment group and CBP treatment group according to random number table method. Both groups were given standard treatment including initial fluid resuscitation, infection source control and antibiotics according to the 2016 international guidelines for the management of sepsis and septic shock. CBP treatment group was additionally given continuous veno-venous hemofiltration (CVVH) at a dose of 25-30 mL×kg-1×h-1 and blood flow rate of 150-200 mL/min for more than 20 hours a day for 3 days. The clinical data of patients including blood lactic acid (Lac), procalcitonin (PCT), lymphocyte count (LYM), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score were recorded before treatment and 1 day and 3 days after treatment. At the same time, the venous blood was collected, and the immune function related indexes [interleukins (IL-4, IL-7), programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), interferon-γ (IFN-γ)] and endothelial cell injury related markers [soluble thrombomodulin (sTM), angiopoietin-2 (Ang-2), von Willebrand factor (vWF), heparan sulfate (HS), syndecan-1 (SDC-1)] levels in serum were determined by enzyme-linked immunosorbent assay (ELISA). The length of intensive care unit (ICU) stay of patients in the two groups was recorded, and the outcomes of patients in the two groups were followed up for 28 days. RESULTS: Finally, 20 patients were enrolled in the standard treatment group, and 19 patients were enrolled in the CBP treatment group. There were no significant differences in gender, age and infection site between the two groups. The length of ICU stay in the standard treatment group was (10±5) days, and 5 patients died and 15 patients survived after 28 days. The length of ICU stay in the CBP treatment group was (9±4) days, and 8 patients died and 11 patients survived after 28 days. There were no significant differences in the length of ICU stay and number of patients who died within 28 days between the two groups (both P > 0.05). There were no significant differences in the Lac, PCT, LYM, APACHE II score, SOFA score and immune function and endothelial cell injury related indexes before treatment and 1 day after treatment between the two groups. After 3 days of treatment, the Lac, PCT, APACHE II score and SOFA score of the CBP treatment group were significantly lower than those before treatment, and pro-inflammatory and anti-inflammatory cytokines such as IFN-γ and IL-4, apoptosis-related indicators such as PD-1 and IL-7, and endothelial injury related factors such as sTM, SDC-1 and HS were significantly improved compared with the pre-treatment, the improvement degree of the above indicators was more obvious than that of the standard treatment group, and LYM was significantly higher than that of the standard treatment group (×109/L: 1.3±0.3 vs. 0.9±0.4, P < 0.05), IL-4, IFN-γ, IFN-γ/IL-4 ratio, IL-7, PD-1, sTM, SDC-1, HS, and Ang-2 were significantly lower than those of the standard treatment group [IL-4 (ng/L): 2.8 (1.5, 3.2) vs. 3.3 (2.7, 5.2), IFN-γ (ng/L): 6.3 (5.4, 106.5) vs. 217.9 (71.4, 517.1), IFN-γ/IL-4 ratio: 3.7 (1.8, 70.3) vs. 59.1 (18.3, 124.9), IL-7 (ng/L): 4.6 (3.2, 5.1) vs. 6.3 (5.2, 8.0), PD-1 (µg/L): 0.04 (0.03, 0.06) vs. 0.08 (0.05, 0.12), sTM (µg/L): 4.9 (4.3, 7.4) vs. 8.7 (6.0, 10.8), SDC-1 (µg/L): 0.6 (0.3, 1.1) vs. 0.9 (0.8, 2.5), HS (ng/L): 434.8 (256.2, 805.0) vs. 887.9 (620.1, 957.3), Ang-2 (ng/L): 934.0 (673.3, 1 502.1) vs. 2 233.9 (1 472.5, 3 808.4)], the differences were statistically significant (all P < 0.05). CONCLUSIONS: CBP treatment can eliminate the patient's immunosuppressive state, reduce a variety of endothelial injury markers and the degradation of glycocalyx, but cannot decrease the 28-day death risk or shorten the length of ICU stay.

Artificial intelligence-assisted ultrasound image analysis to discriminate early breast cancer in Chinese population: a retrospective, multicentre, cohort study.

Background: Early diagnosis of breast cancer has always been a difficult clinical challenge. We developed a deep-learning model EDL-BC to discriminate early breast cancer with ultrasound (US) benign findings. This study aimed to investigate how the EDL-BC model could help radiologists improve the detection rate of early breast cancer while reducing misdiagnosis. Methods: In this retrospective, multicentre cohort study, we developed an ensemble deep learning model called EDL-BC based on deep convolutional neural networks. The EDL-BC model was trained and internally validated on B-mode and color Doppler US image of 7955 lesions from 6795 patients between January 1, 2015 and December 31, 2021 in the First Affiliated Hospital of Army Medical University (SW), Chongqing, China. The model was assessed by internal and external validations, and outperformed radiologists. The model performance was validated in two independent external validation cohorts included 448 lesions from 391 patients between January 1 to December 31, 2021 in the Tangshan People's Hospital (TS), Chongqing, China, and 245 lesions from 235 patients between January 1 to December 31, 2021 in the Dazu People's Hospital (DZ), Chongqing, China. All lesions in the training and total validation cohort were US benign findings during screening and biopsy-confirmed malignant, benign, and benign with 3-year follow-up records. Six radiologists performed the clinical diagnostic performance of EDL-BC, and six radiologists independently reviewed the retrospective datasets on a web-based rating platform. Findings: The area under the receiver operating characteristic curve (AUC) of the internal validation cohort and two independent external validation cohorts for EDL-BC was 0.950 (95% confidence interval [CI]: 0.909-0.969), 0.956 (95% [CI]: 0.939-0.971), and 0.907 (95% [CI]: 0.877-0.938), respectively. The sensitivity values were 94.4% (95% [CI]: 72.7%-99.9%), 100% (95% [CI]: 69.2%-100%), and 80% (95% [CI]: 28.4%-99.5%), respectively, at 0.76. The AUC for accurate diagnosis of EDL-BC (0.945 [95% [CI]: 0.933-0.965]) and radiologists with artificial intelligence (AI) assistance (0.899 [95% [CI]: 0.883-0.913]) was significantly higher than that of the radiologists without AI assistance (0.716 [95% [CI]: 0.693-0.738]; p < 0.0001). Furthermore, there were no significant differences between the EDL-BC model and radiologists with AI assistance (p = 0.099). Interpretation: EDL-BC can identify subtle but informative elements on US images of breast lesions and can significantly improve radiologists' diagnostic performance for identifying patients with early breast cancer and benefiting the clinical practice. Funding: The National Key R&D Program of China.

[The effect of early goal lactate clearance rate on the outcome of septic shock patients with severe pneumonia].

OBJECTIVE: To observe the clinical effects of 10%, 30% lactate clearance rate and early goal-directed therapy (EGDT) as 6-hour resuscitation goals directing treatment in septic shock patients with severe pneumonia. METHODS: In this randomized, perspective study, septic shock patients with severe pneumonia were divided into control group and experimental group, which included 10% lactate clearance rate group and 30% lactate clearance rate group, adopting random number method. The control group was treated with 6-hour EGDT strategy, and the experimental groups were treated with 10% lactate clearance rate protocol and 30% lactate clearance rate protocol respectively, beside the EGDT. RESULTS: There were 19 patients in control group, and 43 patients in experimental group, which included 22 patients in 10% lactate clearance rate group and 21 patients in 30% lactate clearance rate group. Patients were well matched by basic features. After 48 hours, the acute physiology and chronic health evaluation II (APACHE II ) score of both 10% lactate clearance rate group (13.76 ± 6.00, P < 0.05) and 30% lactate clearance rate group (13.60 ± 6.18, P < 0.05) were lower than that of control group (18.15 ± 6.62). There were no differences in time of mechanical ventilation (hours) between control group and experimental group (10% group 136.90 ± 100.02, 30% group 97.00 ± 75.20, control group 152.32 ± 96.51, P > 0.05). The length in intensive care unit (ICU, days) of 10% and 30% lactate clearance rate groups were significantly shorter than control group (10% group 7.94 ± 6.00, 30% group 7.51 ± 3.99, control group 11.31 ± 5.97, both P < 0.05). The three groups had no differences in 7-day mortality rate (10% group 18.18%, 30% group 14.29%, control group 21.05%, all P > 0.05), but the 28-day mortality of 10% and 30% lactate clearance rate groups were significantly lower than control group (10% group 36.36%, 30% group 28.57%, control group 63.16%), especially in 30% lactate clearance rate group (P < 0.05). CONCLUSION: For the septic shock patients with severe pneumonia, prompt archiving EGDT strategy and 6-hour lactate clearance more than 30% were associated with an optimal outcome.

Association between plasma glycocalyx component levels and poor prognosis in severe influenza type A (H1N1).

Influenza A virus infection causes a series of diseases, but the factors associated with disease severity are not fully understood. Disruption of the endothelial glycocalyx contributes to acute lung injury in sepsis, but has not been well studied in H1N1 influenza. We aim to determine whether the plasma glycocalyx components levels are predictive of disease severity in H1N1 influenza. This prospective observational study included 53 patients with influenza A (H1N1) during the influenza season, and 30 healthy controls in our hospital. Patients were grouped by severity and survival. We collected clinical data and blood samples at admission. Inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-10) and endothelial glycocalyx components (syndecan-1, hyaluronan, heparan sulfate) were measured. The plasma levels of syndecan-1, hyaluronan, and heparan sulfate were significantly higher in patients with severe influenza A (H1N1) than in mild cases. Syndecan-1 and hyaluronan were positively correlated with disease severity, which was indicated by the APACHE II and SOFA scores and lactate levels, and negatively correlated with albumin levels. At a cutoff point ≥ 173.9 ng/mL, syndecan-1 had a 81.3% sensitivity and 70.3% specificity for predicting of 28-day mortality. Kaplan-Meier analysis demonstrated a strong association between syndecan-1 levels and 28-day mortality (log-rank 11.04, P = 0.001). Elevated plasma levels of syndecan-1 has a potential role in systemic organ dysfunction and may be indicative of disease severity in patients with influenza A (H1N1).

CD155 Cooperates with PD-1/PD-L1 to Promote Proliferation of Esophageal Squamous Cancer Cells via PI3K/Akt and MAPK Signaling Pathways.

BACKGROUND: Esophageal cancer is still a leading cause of death among all tumors in males, with unsatisfactory responses to novel immunotherapies such as anti-PD-1 agents. Herein, we explored the role of CD155 in esophageal squamous cell cancer (ESCA) and its underlying molecular mechanisms. METHODS: Publicly available datasets were used for differential gene expression and immune infiltration analyses, and their correlation with patient survival. A total of 322 ESCA and 161 paracancer samples were collected and evaluated by performing immunohistochemistry and the H score was obtained by performing semiquantitative analysis. In vitro transfection of ESCA cell lines with lentivirus vectors targeting CD155 was performed to knockdown the protein. These cells were analyzed by conducting RNA sequencing, and the effects of CD155 knockdown on cell cycle and apoptosis were verified with flow cytometry and Western blotting. In addition, in vivo experiments using these engineered cell lines were performed to determine the role of CD155 in tumor formation. A small interfering RNA-mediated knockdown of Nectin3 was used to determine whether it phenocopied the profile of CD155 knockdown. RESULTS: CD155 is highly expressed in ESCA tissues and is positively associated with PD1, PDL1, CD4, IL2RA, and S100A9 expression. Furthermore, CD155 knockdown inhibited ESCA cells' proliferation by impairing the cell cycle and inducing cell apoptosis. Bioinformatics analysis of the gene expression profile of these engineered cells showed that CD155 mainly contributed to the regulation of PI3K/Akt and MAPK signals. The downregulation of Nectin3 expression phenocopied the profile of CD155 knockdown. DISCUSSION: CD155 may cooperate with PD-1/PD-L1 to support ESCA proliferation in ways other than regulating its underlying immune mechanisms. Indeed, CD155 downregulation can impair ESCA cell pro-cancerous behavior via the inhibition of the PI3K/Akt and MAPK signaling pathways. Moreover, Nectin3 may be a ligand of CD155 and participate in the regulation of ESCA cells' proliferation. Hence, the inhibition of CD155 may enhance the therapeutic effect of anti-PD-1 immunotherapies in ESCA.

[Prognostic value of PCSK9 and blood lipid in patients with sepsis].

OBJECTIVE: To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis. METHODS: Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn. RESULTS: There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [µg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [µg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95%CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (ß value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 µg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly. CONCLUSIONS: PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 µg/L, the 28-day survival rate decreased significantly.