Robust and high-efficiency dynamical method of enantio-specific state transfer.

We propose a simple dynamical method to realize fast enantio-specific state transfer (ESST) of chiral molecules. Driven by three external electromagenetic fields, the chiral molecules are modeled as cyclic three-level systems, where the overall phase differs by π for the left- and right-handed chiral molecules. We unveil that the ESST is allowed when the amplitudes of three Rabi frequencies in the cyclic three-level systems are equal. Our method is robust and highly efficient in the sense that the external fields can have arbitrary waveforms. This thus provides the opportunity of simplifying the experimental implementations of ESST through pulse design.

Efficient spatial separation for chiral molecules via optically induced forces.

We investigate an efficient spatial enantioseparation method of chiral molecules in cyclic three-level systems coupled with three optical fields using optically induced forces. When the overall phase differs by π between two enantiomers, significant variations in the magnitude and direction of the optically induced forces are observed. The manipulation of the center of mass of chiral molecules in optical fields can be achieved through the induced gauge force, primarily generated from the variations in the chirality-dependent scalar potentials created by the three inhomogeneous laser fields. By appropriately configuring the system, we can completely separate the slow spatial and fast inner dynamics, making instantaneous eigenstates of the inner Hamiltonian independent of the transverse profiles of the laser beams. Compared to previous methods, which required adiabatic conditions to be satisfied, the proposed method overcomes the limitations of the adiabatic approximation by utilizing a specific system configuration. This allows for increased flexibility in the transverse profiles of the laser beams and relaxes the constraints on the velocity of chiral molecules, leading to significantly greater spatial separations achievable across a broader range of parameters.

Enantio-specific state transfer of chiral molecules through enantio-selective shortcut-to-adiabaticity paths.

An interesting method of fast enantio-specific state transfer (ESST) is proposed for cyclic three-level systems of chiral molecules. We show that the fast population transfer via shortcut to adiabaticity can be accomplished for the cyclic three-level system of a general (chiral) molecule with invariant-based inverse engineering of the coupling strengths. By choosing appropriate parameters, the two enantiomers, which are initially prepared in their ground states in the three-level systems, will evolve respectively along their enantio-selective shortcut-to-adiabaticity paths to different-energy final states simultaneously, thereby achieving the fast ESST.

Evaluation of Amide Proton Transfer-Weighted Imaging for Lung Cancer Subtype and Epidermal Growth Factor Receptor: A Comparative Study With Diffusion and Metabolic Parameters.

BACKGROUND: Lung cancer is one of the most devastating diseases worldwide, and it is meaningful to assess the subtype and epidermal growth factor receptor (EGFR) status in lung cancer noninvasively by imaging methods. PURPOSE: To differentiate noninvasively small cell lung cancer (SCLC) from nonsmall cell lung cancer (NSCLC), and EGFR mutation-type from wild-type NSCLC by comparing amide proton transfer-weighted imaging (APTWI), diffusion-weighted imaging (DWI), and 2-[18 F]-fluoro-2-deoxy-d-glucose positron emission tomography (18 F-FDG PET). STUDY TYPE: Prospective. POPULATION: A total of 99 patients with lung cancer. FIELD STRENGTH/SEQUENCE: APTWI and DWI at 18 F-FDG PET/MRI 3.0 T. ASSESSMENT: The apparent diffusion coefficient (ADC), magnetization transfer ratio asymmetry (MTRasym [3.5 ppm]), maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated and compared. STATISTICAL TESTS: Individual sample t-test, Mann-Whitney U test, Logistic regression, and P < 0.05 were considered statistically significant. RESULTS: In NSCLC, MTRasym (3.5 ppm), MTV, and TLG were significantly lower and ADC was significantly higher than in SCLC; MTRasym (3.5 ppm) was significantly higher and SUVmax , MTV, and TLG were significantly lower in EGFR mutation-type NSCLC than in EGFR wild-type NSCLC. In the identification of SCLC and NSCLC, MTRasym (3.5 ppm), ADC, and MTV were independent predictors, the AUCs of the combination of independent predictors, MTV, TLG, MTRasym (3.5 ppm), and ADC were 0.942, 0.875, 0.843, 0.814, and 0.687, respectively. In the identification of EGFR mutation-type and wild-type NSCLC, MTRasym (3.5 ppm) and MTV were independent predictors, the AUCs of the combination of independent predictors, TLG, MTV, MTRasym (3.5 ppm), and SUVmax were 0.919, 0.834, 0.813, 0.795, and 0.771, respectively. DATA CONCLUSION: In the noninvasive assessment of lung cancer subtype and EGFR status, APTWI has similar utility to diffusion and metabolic parameters. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Application of the respiratory "critical care-sub-critical care-rehabilitation integrated management model" in severe stroke associated pneumonia.

BACKGROUND: This study aimed to explore the feasibility of applying the respiratory "critical care-sub-critical care-rehabilitation integrated management model" in severe stroke-associated pneumonia and evaluate its effect. METHODS: From January to September 2018, 24 patients with severe stroke-associated pneumonia, who were admitted to the Respiratory Intensive Care Unit of the Respiratory and Critical Care Medicine Department of Henan Provincial People's Hospital, were randomly divided into two groups: integrated management group and control group. According to the admission criteria of the respiratory "critical care-sub-critical care-rehabilitation integrated model" prescribed by the above-mentioned hospital, patients were grouped. The professional respiratory therapy team participated in the whole treatment. The acute physiology and chronic health evaluation II (APACHE II) score, clinical pulmonary infection score (CPIS) and oxygenation index of these two groups were dynamically observed, and the average hospital stay, 28-day mortality and patient satisfaction were investigated. RESULTS: Patients in the integrated management group and control group were similar before treatment (P > 0.05). After treatment, the main indicators, the APACHE II score, CPIS score and oxygenation index, were significantly different between the integration group and control group (P < 0.05). The secondary indicators, the average hospitalization days and patient/family member satisfaction scores, were also significantly different between the integration group and control group (P < 0.05). However, the 28-day mortality wasn't significantly different (P > 0.05). CONCLUSIONS: For patients with severe stroke-associated pneumonia, it was feasible to implement the respiratory "critical care-sub-critical care-rehabilitation integrated management model", which could significantly improve the treatment effect, shorten average hospitalization days and improve patient/family satisfaction.

[Impact of extracorporeal carbon dioxide removal combined with continuous renal replacement therapy on diaphragmatic function in patients with acute respiratory distress syndrome].

OBJECTIVE: To investigate the effects of extracorporeal carbon dioxide removal (ECCO2R) combined with continuous renal replacement therapy (CRRT) on respiratory efficiency and diaphragm function in patients with acute respiratory distress syndrome (ARDS) received mechanical ventilation. METHODS: A prospective randomized controlled study was conducted. Sixty patients with mild to moderate ARDS admitted to the department of respiratory and critical care medicine of Henan Provincial People's Hospital from January 2019 to January 2021 were enrolled, and they were divided into observation group and control group according to the random number table method, with 30 cases in each group. All patients received antibiotics, anti-inflammatory, and mechanical ventilation therapy. On this basis, the observation group received ECCO2R and CRRT, while the control group received bedside CRRT. Baseline data including gender, age, etiology, acute physiology and chronic health evaluation II (APACHE II), etc., were recorded. Arterial blood gas analysis [including arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and oxygenation index (PaO2/FiO2)] was performed at 12 hours and 24 hours during the treatment, and respiratory mechanics parameters [including tidal volume, respiratory rate, maximum expiratory pressure (MEP), and maximum inspiratory pressure (MIP)] were recorded, and rapid shallow breathing index (RSBI) was calculated. The levels of glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Diaphragm thickness and diaphragm activity were measured by ultrasonography at 24 hours during the treatment. RESULTS: There were no significantly differences in age, gender, etiology, and APACHE II score between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the 12 hours after treatment, the PaO2 and PaO2/FiO2 in the observation group significantly increased, PaCO2 significantly decreased, RSBI significantly decreased, MEP and MIP significantly increased, and serum GSH-Px and MDA significantly decreased, while SOD significantly increased at 24 hours during the treatment. In the control group, only PaCO2 significantly decreased. Compared with the control group, the PaCO2 significantly decreased in the observation group at 12 hours and 24 hours [mmHg (1 mmHg≈0.133 kPa): 55.05±7.57 vs. 59.49±6.95, 52.77±7.88 vs. 58.25±6.92, both P < 0.05], but no significantly differences in PaO2 and PaO2/FiO2. Compared with the control group, the observation group showed significant decreases in RSBI at 12 hours and 24 hours (times×min-1×L-1: 85.92±8.83 vs. 90.38±3.78, 75.73±3.86 vs. 90.05±3.66, both P < 0.05), significant increases in MEP and MIP [MEP (mmH2O, 1 mmH2O≈0.01 kPa): 86.64±5.99 vs. 83.88±4.18, 93.70±5.59 vs. 85.04±3.73; MIP (mmH2O): 44.19±6.66 vs. 41.17±3.13, 57.52±5.28 vs. 42.34±5.39, all P < 0.05], and significant decreases in serum GSH-Px and MDA [GSH-Px (mg/L): 78.52±8.72 vs. 82.10±3.37, 57.11±4.67 vs. 81.17±5.13; MDA (µmol/L): 7.84±1.97 vs. 8.71±0.83, 3.67±0.78 vs. 8.41±1.09, all P < 0.05], as well as a significant increase in SOD (U/L: 681.85±49.24 vs. 659.40±26.47, 782.32±40.56 vs. 676.65±51.97, both P < 0.05). Compared with the control group, the observation group showed significant increases in diaphragm thickness and diaphragm activity at 24 hours of treatment [diaphragm thickness (cm): 1.93±0.28 vs. 1.40±0.24, diaphragmatic thickening fraction: (0.22±0.04)% vs. (0.19±0.02)%, quiet breathing diaphragm displacement (cm): 1.42±0.13 vs. 1.36±0.06, deep breathing diaphragm displacement (cm): 5.11±0.75 vs. 2.64±0.59, all P < 0.05]. CONCLUSIONS: ECCO2R combined with CRRT can reduce work of breathing and oxidative stress levels in ARDS patients receiving non-invasive ventilation, and protect diaphragm function.

[Predictive value of HACOR score on the clinical outcome of non-invasive positive pressure ventilation in the treatment of chronic obstructive pulmonary disease with pulmonary encephalopathy].

OBJECTIVE: To explore the predictive value of HACOR score [heart rate (H), acidosis (A), consciousness (C), oxygenation (O), and respiratory rate (R)] on the clinical outcome of non-invasive positive pressure ventilation in patients with pulmonary encephalopathy due to chronic obstructive pulmonary disease (COPD). METHODS: A prospective study was conducted. The patients with COPD combined with pulmonary encephalopathy who were admitted to Henan Provincial People's Hospital from January 1, 2017 to June 1, 2021 and initially received non-invasive positive pressure ventilation were enrolled. Besides non-invasive positive pressure ventilation, standard medical treatments were delivered to these patients according to guidelines. The need for endotracheal intubation was judged as failure of non-invasive ventilation treatment. Early failure was defined as the need for endotracheal intubation within 48 hours of treatment, and late failure was defined as the need for endotracheal intubation 48 hours and later. The HACOR score at different time points after non-invasive ventilation, the length of intensive care unit (ICU) stay, the total length of hospital stay, and the clinical outcome were recorded. The above indexes of patients with non-invasive ventilation were compared between successful and failed groups. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive effect of HACOR score on the failure of non-invasive positive pressure ventilation in the treatment of COPD with pulmonary encephalopathy. RESULTS: A total of 630 patients were evaluated, and 51 patients were enrolled, including 42 males (82.35%) and 9 females (17.65%), with a median age of 70.0 (62.0, 78.0) years old. Among the 51 patients, 36 patients (70.59%) were successfully treated with non-invasive ventilation and discharged from the hospital eventually, and 15 patients (29.41%) failed and switched to invasive ventilation, of which 10 patients (19.61%) were defined early failure, 5 patients (9.80%) were late failure. The length of ICU and the total length of hospital stay of the non-invasive ventilation successful group were significantly longer than those of the non-invasive ventilation failure group [length of ICU stay (days): 13.0 (10.0, 16.0) vs. 5.0 (3.0, 8.0), total length of hospital stay (days): 23.0 (12.0, 28.0) vs. 12.0 (9.0, 15.0), both P < 0.01]. The HACOR score of patients at 1-2 hours in the non-invasive ventilation failure group was significantly higher than that in the successful group [10.47 (6.00, 16.00) vs. 6.00 (3.25, 8.00), P < 0.05]. However, there was no significant difference in HACOR score before non-invasive ventilation and at 3-6 hours between the two groups. The ROC curve showed that the area under the ROC curve (AUC) of 1-2 hour HACOR score after non-invasive ventilation for predicting non-invasive ventilation failure in COPD patients with pulmonary encephalopathy was 0.686, and the 95% confidence interval (95%CI) was 0.504-0.868. When the best cut-off value was 10.50, the sensitivity was 60.03%, the specificity was 86.10%, positive predictive value was 91.23%, and negative predictive value was 47.21%. CONCLUSIONS: Non-invasive positive pressure ventilation could prevent 70.59% of COPD patients with pulmonary encephalopathy from intubation. HACOR score was valuable to predict non-invasive positive pressure ventilation failure in pulmonary encephalopathy patients due to COPD.

Genomic Epidemiology and Characterization of Carbapenem-Resistant Klebsiella pneumoniae in ICU Inpatients in Henan Province, China: a Multicenter Cross-Sectional Study.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated globally and is difficult to treat, causing increased morbidity and mortality rates in critically ill patients. We conducted a multicenter cross-sectional study of intensive care unit (ICU) inpatients in 78 hospitals to investigate the prevalence and molecular characteristics of CRKP in Henan Province, China, a hyperepidemic region. A total of 327 isolates were collected and downsampled to 189 for whole-genome sequencing. Molecular typing revealed that sequence type 11 (ST11) of clonal group 258 (CG258) was predominant (88.9%, n = 168), followed by ST2237 (5.8%, n = 11) and ST15 (2.6%, n = 5). We used core genome multilocus sequence typing (cgMLST) to further classified the population into 13 subtypes. Capsule polysaccharide (K-antigen) and lipopolysaccharide (LPS; O-antigen) typing revealed that K64 (48.1%, n = 91) and O2a (49.2%, n = 93) were the most common. We studied isolates collected from both the airway and the gut of the same patients and showed that intestinal carriage was associated with respiratory colonization (odds ratio = 10.80, P < 0.0001). Most isolates (95.2%, n = 180) showed multiple drug resistance (MDR), while 59.8% (n = 113) exhibited extensive drug resistance (XDR), and all isolates harbored either blaKPC-2 (98.9%, n = 187) or blaCTX-M and blaSHV extended-spectrum beta-lactamases (ESBLs) (75.7%, n = 143). However, most were susceptible to ceftazidime-avibactam (CZA) (94.7%, n = 179) and colistin (97.9%, n = 185). We found mgrB truncations in isolates conferring resistance to colistin and mutations in blaSHV and OmpK35 and OmpK36 osmoporins in CZA-resistant isolates. Using a regularized regression model, we found that the aerobactin sequence type and the salmochelin sequence type, among others, were predictors of the hypermucoviscosity phenotype. IMPORTANCE In this study, we address the ongoing epidemic of carbapenem-resistant Klebsiella pneumoniae, a critical threat to public health. The alarming genotypic and phenotypic convergence of multidrug resistance and virulence highlights the increasingly aggravated threat posed by K. pneumoniae. This calls for a combined effort of physicians and scientists to study the potential mechanisms and establish guidelines for antimicrobial therapies and interventions. To this end, we have conducted a genomic epidemiology and characterization study using isolates collected in a coordinated effort of multiple hospitals. Innovative biological discoveries of clinical importance are made and brought to the attention of clinical researchers and practitioners. This study presents an important advance in the application of genomics and statistics to recognize, understand, and control an infectious disease of concern.

The value of diffusion kurtosis imaging, diffusion weighted imaging and 18F-FDG PET for differentiating benign and malignant solitary pulmonary lesions and predicting pathological grading.

Objective: To explore the value of PET/MRI, including diffusion kurtosis imaging (DKI), diffusion weighted imaging (DWI) and positron emission tomography (PET), for distinguishing between benign and malignant solitary pulmonary lesions (SPLs) and predicting the histopathological grading of malignant SPLs. Material and methods: Chest PET, DKI and DWI scans of 73 patients with SPL were performed by PET/MRI. The apparent diffusion coefficient (ADC), mean diffusivity (MD), mean kurtosis (MK), maximum standard uptake value (SUVmax), metabolic total volume (MTV) and total lesion glycolysis (TLG) were calculated. Student's t test or the Mann-Whitney U test was used to analyze the differences in parameters between groups. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy. Logistic regression analysis was used to evaluate independent predictors. Results: The MK and SUVmax were significantly higher, and the MD and ADC were significantly lower in the malignant group (0.59 ± 0.13, 10.25 ± 4.20, 2.27 ± 0.51[×10-3 mm2/s] and 1.35 ± 0.33 [×10-3 mm2/s]) compared to the benign group (0.47 ± 0.08, 5.49 ± 4.05, 2.85 ± 0.60 [×10-3 mm2/s] and 1.67 ± 0.33 [×10-3 mm2/s]). The MD and ADC were significantly lower, and the MTV and TLG were significantly higher in the high-grade malignant SPLs group (2.11 ± 0.51 [×10-3 mm2/s], 1.35 ± 0.33 [×10-3 mm2/s], 35.87 ± 42.24 and 119.58 ± 163.65) than in the non-high-grade malignant SPLs group (2.46 ± 0.46 [×10-3 mm2/s], 1.67 ± 0.33[×10-3 mm2/s], 20.17 ± 32.34 and 114.20 ± 178.68). In the identification of benign and malignant SPLs, the SUVmax and MK were independent predictors, the AUCs of the combination of SUVmax and MK, SUVmax, MK, MD, and ADC were 0.875, 0.787, 0.848, 0.769, and 0.822, respectively. In the identification of high-grade and non-high-grade malignant SPLs, the AUCs of MD, ADC, MTV, and TLG were 0.729, 0.680, 0.693, and 0.711, respectively. Conclusion: DWI, DKI, and PET in PET/MRI are all effective methods to distinguish benign from malignant SPLs, and are also helpful in evaluating the pathological grading of malignant SPLs.

Microfluidic preparation, shrinkage, and surface modification of monodispersed alginate microbeads for 3D cell culture.

Functionalized alginate microbeads (MB) have been widely used for three-dimensional (3D) culture of cells and creating biomimetic tissue models. However, conventional methods for preparing these MB suffer from poor polydispersity, due to coalescence of droplets during the gelation process and post-aggregation. It remains an immense challenge to prepare alginate MB with narrow size distribution and uniform shape, especially when their diameters are similar to the size of cells. In this work, we developed a simple method to produce monodispersed, cell-size alginate MB through microfluidic emulsification, followed by a controlled shrinkage process and gelation in mineral oil with low concentration of calcium ion (Ca2+). During the gelation process caused by the diffusion of Ca2+ from the oil to water phase, a large amount of satellite droplets with sub-micrometer sizes was formed at the water/oil interface. As a result, each original droplet was transformed to one shrunken-MB with much smaller size and numerous submicron-size satellites. To explore the feasibility of the shrunken-MB for culturing with cells, we have successfully modified a variety of polymer nanofilms on MB surfaces using a layer-by-layer assembly approach. Finally, the nanofilm-modified MB was applied to a 3D culture of GFP-expressing fibroblast cells and demonstrated good biocompatibility.

Effective reduction of non-specific binding of blood cells in a microfluidic chip for isolation of rare cancer cells.

The high purity of target cells enriched from blood samples plays an important role in the clinical detection of diseases. However, non-specific binding of blood cells in the isolated cell samples can complicate downstream molecular and genetic analysis. In this work, we report a simple solution to non-specific binding of blood cells by modifying the surface of microchips with a multilayer nanofilm, with the outmost layer containing both PEG brushes for reducing blood cell adhesion and antibodies for enriching target cells. This layer-by-layer (LbL) polysaccharide nanofilm was modified with neutravindin and then conjugated with a mixture of biotinylated PEG molecules and biotinylated antibodies. Using EpCAM-expressing and HER2-expressing cancer cells in blood as model platforms, we were able to dramatically reduce the non-specific binding of blood cells to approximately 1 cell per mm2 without sacrificing the high capture efficiency of the microchip. To support the rational extension of this approach to other applications for cell isolation and blood cell resistance, we conducted extensive characterization on the nanofilm formation and degradation, antifouling with PEG brushes and introducing functional antibodies. This simple, yet effective, approach can be applied to a variety of microchip applications that require high purity of sample cells containing minimal contamination from blood cells.

Maternal embryonic leucine zipper kinase inhibits epithelial-mesenchymal transition by regulating transforming growth factor-ß signaling.

Maternal embryonic leucine zipper kinase (MELK) performs an important role in self-renewal and proliferation of progenitor cells or tumor stem cells, and is expressed in aggressive cancers, contributing to tumorigenesis. However, the function of MELK in metastasis is unknown. In the present study, the lung cancer A549 cell line was utilized in order to study the role of MELK in epithelial-mesenchymal transitions (EMTs), the initial step of tumor metastasis. It was identified that transforming growth factor-ß (TGF-ß) could downregulate the expression of MELK, and that MELK could inhibit EMT by regulating TGF-ß signaling. MELK can interact with Smad proteins, which represses TGF-ß/Smad-mediated signaling activity. The findings of the present study identified the effect of MELK in TGF-ß signaling and the EMT process.

Epidemiology of bronchial asthma and asthma control assessment in Henan Province, China.

BACKGROUND: Prevalence of bronchial asthma, asthma treatment assessment, and estimation of the control level among asthma patients in Henan Province, China are reported in this paper. METHODS: We selected 10 among the 109 cities and districts in Henan province using a multistage stratified cluster random sampling method. A total of 500 households from each city and district were chosen. Approximately 20,000 residents from a total of 5,000 households were randomly selected to answer a questionnaire recommended by the China Asthma Alliance. Asthma patients were asked to answer a detailed questionnaire using the symptom-based guidelines to assess the levels of disease control. RESULTS: The overall prevalence of asthma was 0.73% ± 0.12%. Urban and rural residents had asthma prevalence rates of 1.1% ± 0.23% (88/7,924) and 0.48% ± 0.12% (57/11,792), respectively. Among the asthma patients, only 33.8% (52) received regular medication, 25% (13) used oral glucocorticoids, and 71.1% (37) used oral theophylline. The classified control levels of patients were as follows: 33.1% controlled, 49.7% partially controlled, and 17.2% uncontrolled. A total of 38.5% and 27.5% of regularly and irregularly treated asthma patients reached controlled level, respectively. The two groups significantly differed in asthma control level. CONCLUSION: Asthma prevalence is low in Henan Province, China. Urban residents have higher prevalence of asthma than rural residents do. Patients with asthma receive insufficient medication, resulting in suboptimal asthma control. Improvement in diagnosis and treatment of asthma patients is urgently needed.