Comparison of small biopsy and cytology specimens: Subtyping of pulmonary adenocarcinoma.

Objectives: The aims of this study was to investigate the use of cytologic samples for subclassification of lung adenocarcinoma and the cytologic-histologic correlation in lung adenocarcinoma subtypes using small samples. Methods and Methods: Cytological characteristics of lung adenocarcinoma subtypes were summarized by a literature review. Cytology samples from 115 patients with lung adenocarcinoma confirmed by small biopsies were classified by subtype. The diagnostic concordance of subtypes between biopsy and cytology samples was assessed. Results: Among the 115 cases, 62 (53.9%) had acinar predominant pattern, 16 (13.9%) were papillary predominant pattern, 29 (25.2%) had solid predominant pattern, 3 (2.6%) had lepidic predominant pattern, and 5 (4.3%) had micropapillary predominant pattern. All corresponding cytologic samples were classified into five subtypes based on cytomorphology features, with concordance rates of 74.2% (46 patients) in c-acinar subtype, 56.3% (nine patients) in c-papillary subtype, 24.1% (seven patients) in c-solid subtype, 66.7% (two patients) in c-lepidic subtype, and 40% (two patients) in c-micropapillary subtype. Collectively, the cytology and small biopsy concordance rate was approximately 57.4%. Conclusion: Subtyping of lung adenocarcinoma using cytologic specimens is challenging and the consistency rate varies with the subtype. Acinar predominant tumors have an excellent cytologic-histologic correlation compared to tumors with predominant solid or micropapillary pattern. Evaluating cytomorphologic features of different lung adenocarcinoma subtypes can reduce the false-negative rate of lung adenocarcinoma, particularly for the mild, atypical micropapillary subtype, and improve diagnostic accuracy.

Nomogram analysis of the influencing factors of rapid renal decline in patients with biopsy-proven diabetic nephropathy in type 2 diabetes.

BACKGROUND: HbA1c variability may be related to risk of poor prognoses in chronic kidney disease patients with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether HbA1c variability is associated with rapid renal function decline and the related risk factors in type 2 diabetic nephropathy (DN). MATERIALS AND METHODS: An observational analysis was performed on 387 DN patients who were diagnosed by kidney biopsy from January 2006 through January 2016 at the Department of Nephrology, Jinling Hospital Affiliated to Nanjing University. The rapid decliners were defined as an estimated glomerular filtration rate (eGFR) decline slope ≥ 5 mL/min/1.73m2/year. HbA1c variability and 24 baseline clinicopathologic parameters was evaluated using the least absolute shrinkage and selection operator regression (LASSO) and multivariate logistic regression. The nomogram method was applied to score the factors, and a scoring model was constructed. RESULTS: HbA1c variability positively correlated with the rate of renal function decline (r = 0.277; p < 0.001). Higher baseline eGFR, lower serum calcium concentration, glomerular lesions, arteriosclerosis, and interstitial fibrosis and tubular atrophy (IFTA) were selected into the nomogram. The calibration curve for the probability of survival showed good agreement between the prediction by nomogram and actual observation. The C-index for predicting survival was 0.811 (95% confidence interval (CI) 0.680 - 0.785). CONCLUSION: The proposed nomogram and score provide a useful risk estimate of fast renal function decline in patients with type 2 diabetic nephropathy.

Awareness of Dysphagia-Related Complications and Risks and the Importance of Early Intervention in Patients with Parkinson's Disease: A Qualitative Study.

Objective: To investigate the awareness of dysphagia-related complications and risks and the importance of early intervention in patients with Parkinson's disease (PD). Methods: Using the phenomenological approach of the qualitative study, 18 patients with PD in a Grade A tertiary hospital in Nantong were selected, and semistructured personal in-depth interviews were conducted. The interview content was analyzed using Colaizzi's seven-step method, and the topics and subtopics were further refined. Results: Awareness of dysphagia-related complications and risks and the importance of early intervention in patients with PD can be summarized into three topics: lack of knowledge about PD and dysphagia, changes in emotional cognition, and low need for early intervention for dysphagia. Conclusions: Patients with PD have a low awareness of dysphagia, do not follow any preventative measures, and have difficulty in recognizing the disease symptoms; hence, there is a vital need for early intervention. Medical staff need to create awareness among patients and their families, provide health education through multiple channels, popularize the knowledge of PD complications such as dysphagia, improve patient compliance with respect to medication, regular consultation, and medical treatment, guide the transformation of negative emotions in patients to positive emotions, and help patients with PD to actively prevent dysphagia and other complications and improve their quality of life.

Long-term cumulative high-sensitivity cardiac troponin T and mortality among patients with acute heart failure.

AIMS: This study aimed to evaluate the cumulative high-sensitivity cardiac troponin T (hs-cTNT) from admission to 12 months after discharge and its association with mortality after 12 months among patients with acute heart failure (HF). METHODS: We used data from the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study), which enrolled patients hospitalized primarily for HF from 52 hospitals between 2016 and 2018. We included patients who survived within 12 months and had hs-cTNT data at admission (within 48 h of admission) and 1 and 12 months after discharge. To evaluate the long-term cumulative hs-cTNT, we calculated cumulative hs-cTNT levels and cumulative times of high hs-cTNT level. Patients were divided into groups according to the quartiles of cumulative hs-cTNT levels (Quartiles 1-4) and cumulative times of high hs-cTNT levels (0-3 times). Multivariable Cox models were constructed to examine the association of cumulative hs-cTNT with mortality during the follow-up period. RESULTS: We included 1137 patients with a median age of 64 [interquartile range (IQR), 54-73] years; 406 (35.7%) were female. The median cumulative hs-cTNT level was 150 (IQR, 91-241) ng/L*month. Based on the cumulative times of high hs-cTNT levels, 404 (35.5%) patients were with zero time, 203 (17.9%) with one time, 174 (15.3%) with two times, and 356 (31.3%) with three times. During a median follow-up of 4.76 (IQR, 4.25-5.07) years, 303 (26.6%) all-cause deaths occurred. The increasing cumulative hs-cTNT level and cumulative times of high hs-cTNT level were independently associated with excess all-cause mortality. Compared with Quartile 1 group, Quartile 4 had the highest hazard ratio (HR) of all-cause mortality [4.14; 95% confidence interval (CI): 2.51-6.85], followed by Quartile 3 (HR: 3.35; 95% CI: 2.05-5.48) and Quartile 2 (HR: 2.47; 95% CI: 1.49-4.08) groups. Similarly, taking the patients with zero time of high hs-cTNT level as the reference, the HRs were 1.60 (95% CI: 1.05-2.45), 2.61 (95% CI: 1.76-3.87), and 2.86 (95% CI: 1.98-4.14) in patients who had one, two, and three times of high hs-cTNT level, respectively. CONCLUSIONS: Elevated cumulative hs-cTNT from admission to 12 months after discharge was independently associated with mortality after 12 months among patients with acute HF. Repeated measurements of hs-cTNT after discharge may help monitor the cardiac damage and identify patients with high risk of death.

Photo-scanning Electrochemical Microscopy Observation of Overall Water Splitting at a Single Aluminum-Doped Strontium Titanium Oxide Microcrystal.

Particulate photocatalysts for the overall water splitting (OWS) reaction offer promise as devices for hydrogen fuel generation. Even though such photocatalysts have been studied for nearly 5 decades, much of the understanding of their function is derived from observations of catalyst ensembles and macroscopic photoelectrodes. This is because the sub-micrometer size of most OWS photocatalysts makes spatially resolved measurements of their local reactivity very difficult. Here, we employ photo-scanning electrochemical microscopy (photo-SECM) to quantitatively measure hydrogen and oxygen evolution at individual OWS photocatalyst particles for the first time. Micrometer-sized Al-doped SrTiO3/Rh2-yCryO3 photocatalyst particles were immobilized on a glass substrate and interrogated with a chemically modified SECM nanotip. The tip simultaneously served as a light guide to illuminate the photocatalyst and as an electrochemical nanoprobe to observe oxygen and hydrogen fluxes from the OWS. Local O2 and H2 fluxes obtained from chopped light experiments and photo-SECM approach curves using a COMSOL Multiphysics finite-element model confirmed stoichiometric H2/O2 evolution of 9.3/4.6 µmol cm-2 h-1 with no observable lag during chopped illumination cycles. Additionally, photoelectrochemical experiments on a single microcrystal attached to a nanoelectrode tip revealed a strong light intensity dependence of the OWS reaction. These results provide the first confirmation of OWS at single micrometer-sized photocatalyst particles. The developed experimental approach is an important step toward assessing the activity of photocatalyst particles at the nanometer scale.

Environmental stress stimulates microbial activities as indicated by cyclopropane fatty acid enhancement.

Soil microbial responses to environmental stress remain a critical question in microbial ecology. The content of cyclopropane fatty acid (CFA) in cytomembrane has been widely used to evaluate environmental stress on microorganisms. Here, we used CFA to investigate the ecological suitability of microbial communities and found a stimulating impact of CFA on microbial activities during wetland reclamation in Sanjiang Plain, Northeastern China. The seasonality of environmental stress resulted in the fluctuation of CFA content in the soil, which suppressed microbial activities due to nutrient loss upon wetland reclamation. After land conversion, the aggravation of temperature stress to microbes increased the CFA content by 5 % (autumn) to 163 % (winter), which led to the suppression of microbial activities by 7 %-47 %. By contrast, the warmer soil temperature and permeability decreased the CFA content by 3 % to 41 % and consequently aggravated the microbial reduction by 15 %-72 % in spring and summer. Complex microbial communities of 1300 CFA-produced species were identified using a sequencing approach, suggesting that soil nutrients dominated the differentiation in these microbial community structures. Further analysis with structural equation modeling highlighted the important function of CFA content to environmental stress and the stimulating influence of CFA induced by environmental stress on microbial activities. Our study shows the biological mechanisms of seasonal CFA content for microbial adaption to environmental stress under wetland reclamation. It advances our knowledge of microbial physiology affecting soil element cycling caused by anthropogenic activities.

miR-223-3p mediates the diabetic kidney disease progression by targeting IL6ST/STAT3 pathway.

Diabetic kidney disease (DKD), the most pervasive complication in diabetic patients, has become a major health threat to the aging population. Our previous miRNA profiling identified hsa-miR-223-3p as a dysregulated miRNA in the DKD samples, which may serve as a biomarker for DKD diagnosis. However, the specific mechanism of miR-223-3p in the pathogenesis of DKD remains to be elucidated. In this study, we first verified that miR-223-3p level was significantly decreased in the in vitro cell model and in vivo db/db DKD model, accompanied with endothelial cell damage. Importantly, inhibiting the expression of miR-223-3p exacerbated high-glucose induced damages in Human Umbilical Vein Endothelial Cells (HUVECs) and Human Renal Glomerular Endothelial Cells (HRGECs), while miR-223-3p overexpression showed the opposite effect. We further demonstrated that miR-223-3p associated with IL6T mRNA and attenuated the progression of DKD by suppressing the downstream STAT3 activation, indicative of the implication of miR-223-3p/IL6T/STAT3 axis in the pathogenesis of DKD.

Mechanism of arterial injury exacerbated by hyperhomocysteinemia in spontaneously hypertensive rats.

Hypertension associated with hyperhomocysteinemia (HHcy) accounts for 75% of hypertension in China. HHcy plays a synergistic role with hypertension in vascular injury and significantly increases the incidence of cardiovascular and cerebrovascular diseases. The present study aimed to explore the molecular mechanism of HHcy-induced arterial injury in hypertension. Spontaneously hypertensive rats (SHR) were injected intraperitoneally with DL-homocysteine (Hcy) to construct the model of hypertension associated with HHcy (HHcy + SHR). Biological network was employed to identify the material basis of arterial injury in hypertension associated with HHcy. The prediction molecules in oxidative stress and inflammation pathways were experimentally verified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) analysis. The HHcy + SHR group significantly increased oxidative stress pathway molecules: nicotinamide adenine dinucleotide phosphate oxidase (Nox); inflammatory pathway molecules: vascular adhesion protein-1 (VAP-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a); as well as inflammatory pathway regulatory factors: nuclear factor-κ-gene binding (NF-κB) p65 and protein kinase B (Akt1). Among them, IL-6 was also significantly increased in the HHcy group. Both oxidative stress and inflammation contributed to the arterial injury of hypertension associated with HHcy, and inflammation mechanism might play a leading role in HHcy aggravating arterial injury, at least partially through the Akt1/NF-κB p65/IL-6 signaling pathway.

Effect of Strain Rate on Nano-Scale Mechanical Behavior of A-Plane (112¯0) ZnO Single Crystal by Nanoindentation.

In this study, nanoindentation tests at three different strain rates within 100 nm indentation depth were conducted on an a-plane (112¯0) ZnO single crystal to investigate the effect of strain rate on its nano-scale mechanical behavior. The load-indentation-depth curves, pop-in events, hardness and Young's moduli of an a-plane (112¯0) ZnO single crystal at different strain rates were investigated at the nano-scale level. The results indicated that, with the indentation depth increasing, the load increased gradually at each maximum indentation depth, hma, during the loading process. A distinct pop-in event occurred on each loading curve except that corresponding to the hmax of 10 nm. The applied load at the same indentation depth increased with the increasing strain rate during the nanoindentation of the a-plane (112¯0) ZnO single crystal. The higher strain rate deferred the pop-in event to a higher load and deeper indentation depth, and made the pop-in extension width larger. The hardness showed reverse indentation size effect (ISE) before the pop-in, and exhibited normal ISE after the pop-in. Both the hardness and the Young's modulus of the a-plane (112¯0) ZnO single crystal increased with the increasing strain rate, exhibiting the positive strain-rate sensitivity.

[Exploration on acupuncture treatment ideas for knee osteoarthritis from the perspective of Dongyuan needling technology].

The treatment ideas with acupuncture for knee osteoarthritis (KOA) are explored on the base of Dongyuan needling technology. Regarding the rules of acupoint selection, Zusanli (ST 36) is predominant, the back-shu points are used for the disorders related to the invasion of exogenous factors, and the front-mu points are for the cases caused by internal injury. Besides, the xing-spring points and shu-stream points are preferred. In treatment of KOA, besides the local points, the front-mu points, i.e. Zhongwan (CV 12), Tianshu (ST 25) and Guanyuan (CV 4), are selected specially to tonifying the spleen and stomach. The earth points and acupoints on the earth meridians (i.e. Yinlingquan [SP 9], Xuehai [SP 10], Liangqiu [ST 34], Dubi [ST 35], Zusanli [ST 36] and Yanglingquan [GB 34]) are optional to coordinate yin and yang, essence and qi , and regulate the qi movement of spleen and stomach. The shu-stream points of liver, spleen and kidney meridians (Taichong [LR 3], Taibai [SP 3] and Taixi [KI 3]) are chosen to promote meridian circulation and regulate zangfu functions.

Antibody-free approach for ubiquitination profiling by selectively clicking the ubiquitination sites.

Ubiquitination is a reversible post-translational modification that plays a pivotal role in numerous biological processes. Antibody-based approaches, as the most used methods for identifying ubiquitination sites, exist sequence recognition bias, high cost, and ubiquitin-like protein modification interference, limiting their widespread application. Here, we proposed an Antibody-Free approach for Ubiquitination Profiling, termed AFUP, by selectively clicking the ubiquitinated lysine to enrich and profile endogenous ubiquitinated peptides using mass spectrometry. Briefly, protein amines were blocked with formaldehyde, and then the ubiquitin molecules were hydrolyzed from the ubiquitinated proteins by non-specific deubiquitinases USP2 and USP21 to release the free ε-amine of lysine. Peptides containing free ε-amines were selectively enriched with streptavidin beads upon NHS-SS-biotin labeling. Finally, the enriched peptides were eluted by DTT and analyzed by LC-MS/MS, resulting in ubiquitination profiling. Preliminary experiment showed that 349 ± 7 ubiquitination sites were identified in 0.8 mg HeLa lysates with excellent reproducibility (CV = 2%) and high quantitative stability (Pearson, r ≥ 0.91) using our method. With the combination of AFUP and simple basic C18 pre-fractionation, approximately 4000 ubiquitination sites were identified in a single run of 293T cells. In addition, we showed that 209 ubiquitination sites were significantly regulated in UBE2O knockdown cells after normalized to protein abundance. In conclusion, our results demonstrated that AFUP is a robust alternative strategy for ubiquitomics research.

Design and performance evaluation of a miniature I-shaped linear ultrasonic motor with two vibrators.

In this study, a novel miniature I-shaped linear ultrasonic motor is proposed. The motor is constructed by two rectangular piezoelectric vibrators which are mounted in parallel with the slider to make the structure look like the letter "I". The symmetric and antisymmetric modes of the motor based on the first-order flexural vibrations of the two vibrators are chosen as the working modes. The finite element method is adopted to optimize the structure and study the vibration behavior of the motor. A prototype of the proposed linear ultrasonic motor is fabricated and its mechanical characteristics are tested. The dimension of the stator is 39.8 × 17.6 × 6 mm3 and the weight of the prototype is only 18.2 g. The typical outputs of the prototype are maximum speed of 364 mm/s, maximum thrust of 500 g and thrust-weight ratio of 24.47. The experimental results confirm that the developed linear ultrasonic motor has the advantages of structural design and miniaturization.

Lung ultrasound score as a predictor of ventilator use in preterm infants with dyspnea within 24 h after dhospitalization.

BACKGROUND: Selecting the correct ventilation strategy is crucial for the survival of preterm infants with dyspnea in NICU. Lung ultrasound score (LUSsc) is a potential predictor for respiratory support patterns in preterm infants. METHODS: We prospectively included 857 preterm infants. LUS was performed in the first 2 h after admission, and LUSsc was determined by two specialist sonographers. Participants were divided into two categories according to gestational age (<32+0 weeks and 32+0-36+6 weeks) and randomly divided into a training set and a validation set. There were two main outcomes: invasive and non-invasive respiratory support. In the training set, clinical factors were analyzed to find the best cut-off value of LUSsc, and consistency was verified in the verification set. The choice of invasive respiratory support was based on neonatal mechanical ventilation strategies. RESULTS: Preterm infants with invasive respiratory support had a higher LUSsc, greater use of Pulmonary Surfactant（PS）, and lower Oxygenation Index（OI）、birth weight than those with non-invasive support. In the <32+0 weeks group, the area under the curve (AUC) for the receiver operating characteristic curve plotted with 2-h LUSsc was 0.749 (95% CI: 0.689-0.809), the cut-off point of LUSsc was 8, and the sensitivity and specificity were 74.0% and 68.3%, respectively. In the 32+0-36+6 weeks group, the AUC was 0.863 (95% CI: 0.811-0.911), with a cut-off point of 7. Sensitivity and specificity were 75.3% and 0.836%, respectively. In the validation set, using the actual clinical respiratory support selection results for verification, the validation results showed for the <32+0 weeks group (Kappa value 0.660, P < 0.05, McNemar test P > 0.05) for preterm 32+0-36+6 weeks (Kappa value 0.779, P < 0.05, McNemar test P > 0.05). CONCLUSION: The LUSsc showed good reliability in predicting respiratory support mode for preterm infants with dyspnea. Registered at ClinicalTrials.gov (identifier: chiCTR1900023869).

Isolation and preliminary functional analysis of FvICE1, involved in cold and drought tolerance in Fragaria vesca through overexpression and CRISPR/Cas9 technologies.

Cold and drought stresses are serious problems of strawberry cultivation in temperate and subtropical regions. In the molecular regulation system of cold and drought stresses, ICE transcription factors (TFs) are crucial. In this research, the FvICE1 was isolated from Fragaria vesca 'Hawaii 4', a bioinformatics analysis was conducted, overexpression vector and CRISPR/cas9 vector were constructed. The results showed that FvICE1 was a member of the bHLH TF family, with a length of 1608 bp, encoding 535 amino acids, and its molecular formula was C2504H3987N745O811S22. By observing the fusion protein 35S-FvICE1-GFP, it was found that FvICE1 was a nuclear protein. The qRT-PCR results demonstrated that FvICE1 was significantly upregulated in different tissues of Fragaria vesca after cold, drought, salt and heat treatments. The wild type (WT) strawberry was selected as the control group, FvICE1-overexpression strawberries showed high tolerance to cold and drought treatments at the phenotypic and physiological levels. On the contrary, fvice1 mutant strawberries obtained by CRISPR/cas9 editing technology had lower tolerance to cold and drought treatments. Moreover, the expression of FvCBF1, FvCBF2, FvCBF3, FvCOR413, FvRD22 and FvKIN1 was positively regulated in the FvICE1-overexpression strawberries and inhibited in fvice1 mutant strawberries. Overall, the current results suggested that FvICE1 functioned as a positively regulator of cold and drought resistances.

Structural characteristics of dissolved black carbon and its interactions with organic and inorganic contaminants: A critical review.

Biochar (BC) is a sustainable and renewable carbonaceous material, and its soluble component, dissolved black carbon (DBC), is the key to understanding BC's geological and environmental processes. Although the relationship between the changes in DBC structure and its properties, functions, and associated environmental risks has been explored, a gap remains in our understanding of DBC's fate and behavior in the natural environment. Thus, in this review, we have highlighted the molecular and chemical compositions and the structural evolution of DBC during pyrolysis, the influence of DBC's physicochemical properties on its fate and transport, DBC's interaction with soil and its contaminants, and DBC stability in soil and water environments along with potential risks. Based on our in-depth assessment of DBC and its biogeochemical roles, we believe that future studies should focus on the following: (1) using advanced techniques to understand the chemical and molecular structure of DBC deeply and concisely and, thus, determine its fundamental role in the natural environment; (2) investigating the multi-functional properties of DBC and its interaction mechanisms; and (3) evaluating the environmental behaviors of and risks associated with DBC after BC application. In future, it is necessary to gain a deeper insight into the fate and transport of DBC with contaminants and study its associated risks under BC application in the environment.

ComMap: a software to perform large-scale structure-based mapping for cross-linking mass spectrometry.

MOTIVATION: Chemical cross-linking combined with mass spectrometry (CXMS) is now a well-established method for profiling existing protein-protein interactions (PPIs) with partially known structures. It is expected to map the results of CXMS with existing structure databases to study the protein dynamic profile in the structure analysis. However, currently available structure-based analysis software suffers from the difficulty of achieving large-scale analysis. Besides, it is infeasible for structure analysis and data mining on a large scale, since of lacking global measurement of dynamic structure mapping results. RESULTS: ComMap (protein complex structure mapping) is a software designed to perform large-scale structure-based mapping by integrating CXMS data with existing structures. It allows complete the distance calculation of PPIs with existing structures in batch within minutes and provides scores for different PPI-structure pairs of testable hypothetical structural dynamism via a global view. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Deciphering in vivo metabolic profile and pharmacological mechanisms of Jitongning Tablet for the treatment of Ankylosing spondylitis.

Jitongning tablet (JTNT) is a Traditional Chinese Medicine (TCM) prescription used for the treatment of Ankylosing spondylitis (AS). Currently, it is in phase II clinical trial (NCT03932019) for patients with active axial Spondyloarthritis (axSpA), showing great promise for the treatment of AS. However, the potential material basis and the underlying mechanisms for JTNT to treat AS remain elusive. Here, we performed UPLC-Q-TOF-MS to determine the in vivo metabolic profile of JTNT in rats and conducted in vivo studies including acetic acid-induced writhing, hot plate models, and collagen-induced arthritis (CIA) in rats to evaluate and validate the analgesic and anti-inflammatory effects of JTNT, two main symptoms for AS. Additionally, network pharmacology combined with molecular docking was performed to investigate the potential underlying mechanisms. As a result, a total of 116 xenobiotics were identified from the plasma, urine, and brain tissues of rats after oral administration of JTN extracts. Pharmacological evaluation revealed that fractions JTN-3 and JTN-4 exerted significant analgesic activities by reducing the number of writhes in an acetic acid-induced writhing mice model. JTN extract also exerted excellent therapeutic effects in the CIA model by ameliorating paw edema and decreasing systemic manifestation of inflammation and the level of circulating immune complex (CIC) and interferon γ (IFN-γ). Fractions of JTN extract, especially JTN-2 and JTN-4, on the other hand, ameliorated the secondary lesions caused by chicken type II collagen (CII) to a certain extent. Further, network pharmacology combined with molecular docking suggested crucial roles of inflammation and immune-related genes such as MAPK1, MAPK14, NOS3, and RELA in the treatment of AS by JTNT. In conclusion, our studies suggest that the isoquinoline and diterpenoid alkaloids from Corydalis Rhizoma and Aconiti Radix Cocta, along with coumarins from Angelicae Pubescentis Radix, may be the main bioactive components, and the AS treatment mechanism may mainly involve immune regulation of JTNT. These results help clarify the potential material basis and underlying mechanisms of JTNT for the treatment of AS, facilitating the broad application of this TCM in clinical practice.

Distinct Associations Between Postdischarge Cognitive Change Patterns and 1-year Outcomes in Patients Hospitalized for Heart Failure.

BACKGROUND: The patterns of patients' cognitive function after hospital discharge for heart failure (HF), their prognostic implication and the predictors for new-onset cognitive impairment remain unknown. METHODS AND RESULTS: We included 2307 patients (64 ± 14 years, 36.4% female sex) hospitalized for HF from a cohort who completed cognitive testing before discharge and after 1 month. Among 1658 patients with normal cognition before discharge, 229 (13.8%) and 1429 (86.2%) had new-onset cognitive impairment and normal cognition at 1 month, respectively. Of the 649 with cognitive impairment, 315 (48.5%) and 334 (51.5%) had transient and persistent cognitive impairment, respectively. Multivariable analyses showed that, compared with normal cognition, patients with new-onset cognitive impairment had an increased risk of cardiovascular death or HF rehospitalization (hazard ratio 1.35, 95% confidence interval 1.07-1.70); patients with persistent cognitive impairment showed an increased risk, but it was not statistically significant (hazard ratio 1.17, 95% confidence interval 0.95-1.44); patients with transient cognitive impairment had a similar risk (hazard ratio 0.91, 95% confidence interval 0.73-1.13). Older age, females, lower education level, prior atherosclerotic cardiovascular diseases, lower health status, and lower Mini-Cog score before discharge predicted new-onset cognitive impairment. CONCLUSIONS: Acute HF substantially affects short-term cognition. Patients who have developed new-onset cognitive impairment have an increased risk of adverse outcomes. Monitoring cognition is necessary, particularly in high-risk patients.

Long-Term Trajectories of High-Sensitivity C-Reactive Protein Level Among Patients with Acute Heart Failure.

Background: Inflammation contributes to the progression of heart failure (HF). However, long-term inflammatory trajectories and their associations with outcomes in patients with acute HF remain unclear. Methods: Data was obtained from the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, and high-sensitivity C-reactive protein (hsCRP) was used to reflect the inflammatory level. Only patients who survived over 12-month and had hsCRP data at admission, 1-, and 12-month after discharge were included. The latent class trajectory modeling was used to characterize hsCRP trajectories. Multivariable Cox regression models were used to explore the association between hsCRP trajectories and following mortality. Results: Totally, 1281 patients with a median 4.77 (interquartile range [IQR]: 4.24-5.07) years follow-up were included. The median age was 64 years (IQR: 54-73 years); 453 (35.4%) were female. Four distinct inflammatory trajectories were characterized: persistently low (n = 419, 32.7%), very high-marked decrease (n = 99, 7.7%), persistently high (n = 649, 50.7%), and persistently very high (n = 114, 8.9%). Compared with the persistently low trajectory, the all-cause mortality was increased in a graded pattern in the persistently high (hazard ratio [HR]: 1.59, 95% confidence interval [CI]: 1.23-2.07) and persistently very high (HR: 2.56, 95% CI: 1.83-3.70) trajectories; nevertheless, the mortality was not significantly increased in very high-marked decrease trajectory (HR: 0.94, 95% CI: 0.57-1.54). Conclusion: Four distinct inflammatory trajectories were identified among patients with acute HF who survived over 12-month. Patients with persistently high and very high trajectories had significantly higher mortality than those with the persistently low trajectory.