Heart failure with preserved ejection fraction in post myocardial infarction patients: a myocardial magnetic resonance (MR) tissue tracking study.

Background: This study aimed to explore the value of cardiac magnetic resonance tissue tracking (CMR-TT) technology in evaluating heart failure with preserved ejection fraction (HFpEF) in patients with chronic myocardial infarction (CMI). Methods: Between June 2016 and March 2022, we included a consecutive series of 92 patients with CMI and 40 healthy controls in this retrospective study. The CMI patients enrolled were divided into different subgroups [HFpEF-CMI group (n=54) and non- heart failure (HF)-CMI group (n=38)] according to the Heart Failure Association (HFA)-PEFF (step 1: P, pre-test assessment; step 2: E, echocardiography and natriuretic peptide score; step 3: F1, functional testing; step 4: F2, final aetiology) diagnostic algorithm. CMR scan was performed at the First Hospital of China Medical University. Quantitative measurements of myocardial damage, such as myocardial strain parameters of both ventricles derived by CMR-TT and infarct size and transmurality by late gadolinium enhancement (LGE), were assessed. One-way analysis of variance, independent samples t-test, and rank sum test were used to compare myocardial impairment among groups. Pearson or Spearman correlation coefficient was used to measure correlations between left ventricular (LV) strains and clinical and functional parameters. Logistic regression analysis and receiver operating characteristic (ROC) curve were performed to identify the best parameter for diagnosing HFpEF-CMI. Results: HFpEF-CMI patients demonstrated significantly impaired LV strains and strain rates in all of the three directions (radial, circumferential and longitudinal) compared to non-HF-CMI patients and healthy controls (P<0.001 for all), whereas only global longitudinal strain (GLS) was significantly impaired in HFpEF-CMI patients vs. controls for right ventricular strain parameters (P<0.001). LV strains showed moderate correlation with N-terminal pro-brain natriuretic peptide (radial, circumferential and longitudinal strain, R=-0.401, R=0.408, R=0.407, respectively, P<0.001 for all). LV strains in the three directions (radial, circumferential and longitudinal) [area under ROC curve (AUC) =0.707, 95% confidence interval (CI): 0.603-0.797; AUC =0.708, 95% CI: 0.604-0.798; AUC =0.731, 95% CI: 0.628-0.818; respectively, P<0.01 for all] were discriminators for HFpEF-CMI and non-HF-CMI. LV strains and myocardial infarction volume were independent factors in multi-logistic regression analysis after adjusting for body mass index, age, and sex (P<0.05 for all). Conclusions: CMR-TT provides clinicians with useful additional imaging parameters to facilitate the assessment of CMI patients with HFpEF. LV strain parameters can detect early cardiac insufficiency in patients with HFpEF-CMI and have potential value for discriminating between HFpEF and non-HF patients post-CMI.

D-chiro-inositol increases antioxidant capacity and longevity of Caenorhabditis elegans via activating Nrf-2/SKN-1 and FOXO/DAF-16.

D-chiro-inositol (DCI) is an isomer of inositol, abundant in many foods, such as beans and buckwheat, with insulin-sensitizing, anti-inflammatory, and antioxidant effects. DCI has been used to relieve insulin resistance in diabetes and polycystic ovary syndrome in combination with inositol or D-pinitol. Here, we investigated the effect of DCI on aging and stress resistance in C. elegans. We found that DCI could prolong the lifespan of C. elegans by up to 29.6 %. DCI significantly delayed the onset of neurodegenerative diseases in models of C. elegans. DCI decreased the accumulation of Aß1-42, alpha-synuclein, and poly-glutamine, the pathological causes of Alzheimer's, Parkinson's, and Huntington's diseases, respectively. DCI significantly increased the stress resistances against pathogens, oxidants and heat shock. Moreover, D-chiro-inositol reduced the content of ROS and malondialdehyde by increasing the total antioxidant capacity and the activity of superoxide dismutase and catalase. Above effects of DCI requires the transcription factors FOXO/DAF-16 and Nrf-2/SKN-1. DCI also increased the expression of downstream genes regulated by FOXO/DAF-16 and Nrf-2/SKN-1. In conclusion, DCI enhanced the antioxidant capacity and healthy lifespan of C. elegans by activating DAF-16, SKN-1, and HSF-1. Our results showed that DCI could be a promising antiaging agent that is worth further research on the mechanism and health supplemental application of DCI.

Field variation of groundwater recharge and its uncertainty via multiple tracers' method in deep loess vadose zone.

Accurate estimation of groundwater recharge is a precondition for assessing its spatial variation at different scales, especially field scale. In the field, the limitations and uncertainties of different methods are first evaluated based on site-specific conditions. In this study, we evaluated field variation in groundwater recharge via multiple tracers in the deep vadose zone on the Chinese Loess Plateau. Five deep soil profiles (approximately 20 m deep) were collected in the field. Soil water content and particle compositions were measured to analyse soil variation, and soil water isotope (3H, 18O, and 2H) and anion (NO3- and Cl-) profiles were used to estimate recharge rates. Distinct peaks in soil water isotope and nitrate profiles indicated a vertical one-dimensional water flow in the vadose zone. Although the soil water content and particle composition were moderately variable, no significant differences were observed in recharge rates among the five sites (p > 0.05) owing to the identical climate and land use. The recharge rates did not show a significant difference (p > 0.05) between different tracers' methods. However, recharge estimates by the chloride mass balance method indicated higher variations (23.5 %) than those by the peak depth method (11.2 % to 18.7 %) among five sites. Moreover, if considering the contribution of immobile water in vadose zone, groundwater recharge would be overestimated (25.4 % to 37.8 %) using the peak depth method. This study provides a favourable reference for accurate groundwater recharge and its variation evaluated using different tracers' methods in deep vadose zone.

Soil arthropods promote litter enzyme activity by regulating microbial carbon limitation and ecoenzymatic stoichiometry in a subalpine forest.

Soil arthropods are crucial decomposers of litter at both global and local scales, yet their functional roles in mediating microbial activity during litter decomposition remain poorly understood. Here, we conducted a two-year field experiment using litterbags to assess the effects of soil arthropods on the extracellular enzyme activities (EEAs) in two litter substrates (Abies faxoniana and Betula albosinensis) in a subalpine forest. A biocide (naphthalene) was used to permit (nonnaphthalene) or exclude (naphthalene application) the presence of soil arthropods in litterbags during decomposition. Our results showed that biocide application was effective in reducing the abundance of soil arthropods in litterbags, with the density and species richness of soil arthropods decreasing by 64.18-75.45 % and 39.19-63.30 %, respectively. Litter with soil arthropods had a greater activity of C-degrading (ß-glucosidase, cellobiohydrolase, polyphenol oxidase, peroxidase), N-degrading (N-acetyl-ß-D-glucosaminidase, leucine arylamidase) and P-degrading (phosphatase) enzymes than litter from which soil arthropods were excluded. The contributions of soil arthropods to C-, N- and P-degrading EEAs in the fir litter were 38.09 %, 15.62 % and 61.69 %, and those for the birch litter were 27.97 %, 29.18 % and 30.40 %, respectively. Furthermore, the stoichiometric analyses of enzyme activity indicated that there was potential C and P colimitation in both the soil arthropod inclusion and exclusion litterbags, and the presence of soil arthropods decreased C limitation in the two litter species. Our structural equation models suggested that soil arthropods indirectly promoted C-, N- and P-degrading EEAs by regulating the litter C content and litter stoichiometry (e.g., N/P, LN/N and C/P) during litter decomposition. These results demonstrate that soil arthropods play an important functional role in modulating EEAs during litter decomposition.

Structural and magnetic properties of Y3(GaAlFe)5O12 liquid-phase epitaxy films with low ferromagnetic resonance losses.

Ultra-thin rare earth iron garnet (RIG) films with a narrow ferromagnetic resonance (FMR) line width and a low damping factor have attracted a great deal of attention for microwave and spintronic applications. In this work, 200 nm Y3(GaAlFe)5O12 garnet (GaAl-YIG) films were prepared on gadolinium gallium garnet (GGG) substrates by liquid-phase epitaxy (LPE) with low saturation magnetization. The microstructural properties, chemical composition, and magnetostatic and dynamic magnetization characteristics of the films are discussed in detail. According to the structural analysis, these films exhibit a low surface roughness of less than 0.5 nm. The GaAl-YIG films show an obvious temperature dependence of lattice parameter and strain state, and the film's parameter is perfectly matched with that of the GGG substrate at 810°C. There is a clear variation in the Pb level, which brings about a gradual enhancement of the coercivity and a diminution of the squareness ratio of magnetic hysteresis loops as the growth temperature is reduced. Slight changes in surface roughness, strain condition and content of Pb induce the FMR line width and damping factor to vary on a small scale. The line width is less than 10.17 Oe at 12 GHz and the damping factor is of the order of 10-4. All these properties demonstrate that these ultra-thin GaAl-YIG films are of benefit for the development of devices operated at lower frequencies and in lower fields.

Hypoxia-responsive circular RNA circAAGAB reduces breast cancer malignancy by activating p38 MAPK and sponging miR-378 h.

BACKGROUND: Breast cancer is a prevalent disease in women, with high prevalence worldwide. The hypoxic microenvironment of solid tumors develops during the progress of carcinogenesis and leads to greater malignancy and treatment resistance. Recently, accumulating evidence indicates that non-coding RNAs, such as circular RNAs (circRNAs), play a pivotal role in altering cellular functions. However, the underlying mechanisms of circRNAs in breast cancer are still unclear. Therefore, the purpose of this study was to investigate the role of a tumor-suppressive circRNA, circAAGAB, in breast cancer by assuming down-regulation of circAAGAB under hypoxia and the properties of a tumor suppressor. METHODS: Firstly, circAAGAB was identified from expression profiling by next generation sequencing. Next, the stability of circAAGAB increased by interacting with the RNA binding protein FUS. Moreover, cellular and nuclear fractionation showed that most circAAGAB resided in the cytoplasm and that it up-regulated KIAA1522, NKX3-1, and JADE3 by sponging miR-378 h. Lastly, the functions of circAAGAB were explored by identifying its down-stream genes using Affymetrix microarrays and validated by in vitro assays. RESULTS: The results showed that circAAGAB reduced cell colony formation, cell migration, and signaling through p38 MAPK pathway, as well as increased radiosensitivity. CONCLUSION: These findings suggest that the oxygen-responsive circAAGAB acts as a tumor suppressor in breast cancer, and may contribute to the development of a more specific therapeutic regimen for breast cancer.

Sinoflavonoids NJ and NK, anti-inflammatory prenylated flavonoids from the fruits of Podophyllum hexandrum Royle.

Two new prenylated flavonoids named sinoflavonoids NJ and NK (1-2), along with ten known compounds were isolated from the fruits of Podophyllum hexandrum Royle. The chemical structures were determined through NMR spectroscopic data and MS analysis. Sinoflavonoid NJ (1) with an unusual 5,11-dioxabenzo[b]fluoren-10-one skeleton was firstly reported from Berberidaceae. The isolated flavonoids were tested with LPS-induced RAW 264.7 mouse macrophages model for their anti-inflammatory activity. Sinoflavonoid NJ (1) showed the most potent inhibition on nitric oxide production with IC50 value as 0.06 µM.

Simultaneous determination of twenty-nine active compounds in fuzhengjiedu granules by HPLC-QQQ-MS/MS.

As an empirical medicine of traditional Chinese medicine, Fuzhengjiedu Granules have shown an effect against COVID-19 in clinical and inflammatory animal models. It is formulated with eight herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Glycyrrhizae Radix Et Rhizoma, Lonicerae Japonicae Flos, Gleditsiae Spina, Fici Radix, Pogostemonis Herba, and Citri Reticulatae Pericarpium. This study established a high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS) method by simultaneously determining 29 active compounds in the granules with significant content differences. Separation by gradient elution using acetonitrile and water (0.1% formic acid) as mobile phases was performed on a Waters Acquilty UPLC T3 column (2.1 mm × 100 mm, 1.7 µm). A triple quadrupole mass spectrometer, operating in positive and negative ionization modes, was used for multiple reaction monitoring to detect the 29 compounds. All calibration curves showed good linear regression (r2 > 0.998). RSDs of precision, reproducibility, and stability of active compounds were all lower than 5.0%. The recovery rates were 95.4-104.9%, with RSDs< 5.0%. This method was successfully used to analyze the samples, and the results showed that 26 representative active components from 8 herbs were detected in the granules. While aconitine, mesaconitine, and hypaconitine were not detected, indicating that the existing samples were safe. The granules had the maximum and minimum content of hesperidin (27.3 ± 0.375 mg/g) and benzoylaconine (38.2 ± 0.759 ng/g). To conclude, a fast, accurate, sensitive, and reliable HPLC-QQQ-MS/MS method was established, which can simultaneously detect 29 active compounds that have a considerable difference in the content of Fuzhengjiedu Granules. This study can be used to control the quality and safety of Fuzhengjiedu Granules and provide a basis and guarantee for further experimental research and clinical application.

Protective effect of compatible herbs in Jin-Gu-Lian formula against Alangium chinense-induced neurotoxicity via oxidative stress, neurotransmitter metabolisms, and pharmacokinetics.

Background: A. chinense frequently used in Miao medicine to treat rheumatic diseases. However, as a famous toxic herb, Alangium chinense and its representative components exhibit ineluctable neurotoxicity, thus creating significant challenges for clinical application. The combined application with compatible herbs in Jin-Gu-Lian formula attenuates such neurotoxicity according to the compatible principle of traditional Chinese medicines. Purpose: We aimed to investigate the detoxification of the compatible herbs in Jin-Gu-Lian formula on A. chinense-induced neurotoxicity and investigate its mechanism. Methods: Neurobehavioral and pathohistological analysis were used to determine the neurotoxicity in rats administered with A. chinense extract (AC), extract of compatible herbs in Jin-Gu-Lian formula (CH) and combination of AC with CH for 14 days. The mechanism underlying the reduction of toxicity by combination with CH was assessed by enzyme-linked immunosorbent assays, spectrophotometric assays, liquid chromatography tandem-mass spectrometry and real-time reverse transcription-quantitative polymerase chain reaction. Results: Compatible herbs attenuated the AC-induced neurotoxicity as evidenced by increased locomotor activity, enhanced grip strength, the decreased frequency of AC-induced morphological damage in neurons, as well as a reduction of neuron-specific enolase (NSE) and neurofilament light chain (NEFL) levels. The combination of AC and CH ameliorated AC-induced oxidative damage by modulating the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). AC treatment significantly reduced the levels of monoamine and acetylcholine neurotransmitters in the brains of rats, including acetylcholine (Ach), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), and serotonin (5-HT). Combined AC and CH treatment regulated the abnormal concentrations and metabolisms of neurotransmitters. Pharmacokinetic studies showed that the co-administration of AC and CH significantly decreased plasma exposure levels of two main components of AC, as evidenced by the reduction of maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC) compared to AC. In addition, the AC-induced downregulation in mRNA expression of cytochrome P450 enzymes was significantly reduced in response to combined AC and CH treatment. Conclusion: Compatible herbs in Jin-Gu-Lian formula alleviated the neurotoxicity induced by A. chinense by ameliorating oxidative damage, preventing abnormality of neurotransmitters and modulating pharmacokinetics.

Prediction of early treatment response to the combination therapy of TACE plus lenvatinib and anti-PD-1 antibody immunotherapy for unresectable hepatocellular carcinoma: Multicenter retrospective study.

Background and aim: The purpose of this study was to investigate and validate the efficacy of a nomogram model in predicting early objective response rate (ORR) in u-HCC patients receiving a combination of TACE, Lenvatinib, and anti-PD-1 antibody treatment after 3 months (triple therapy). Method: This study included 169 u-HCC cases from five different hospitals. As training cohorts (n = 102), cases from two major centers were used, and external validation cohorts (n = 67) were drawn from the other three centers. The clinical data and contrast-enhanced MRI characteristics of patients were included in this retrospective study. For evaluating MRI treatment responses, the modified revaluation criteria in solid tumors (mRECIST) were used. Univariate and multivariate logistic regression analyses were used to select relevant variables and develop a nomogram model. Our as-constructed nomogram was highly consistent and clinically useful, as confirmed by the calibration curve and decision curve analysis (DCA); an independent external cohort also calibrated the nomogram. Results: The ORR was 60.7% and the risk of early ORR was independently predicted by AFP, portal vein tumor thrombus (PVTT), tumor number, and size in both the training (C-index = 0.853) and test (C-index = 0.731) cohorts. The calibration curve revealed that the nomogram-predicted values were consistent with the actual response rates in both cohorts. Furthermore, DCA indicated that our developed nomogram performed well in clinical settings. Conclusion: The nomogram model accurately predicts early ORR achieved by triple therapy in u-HCC patients, which aids in individual decision-making and modifying additional therapies for u-HCC cases.

Serial Cardiac MRI for Quantification of the Dynamics of Anthracycline-Induced Subclinical Myocardial Injury.

BACKGROUND: Anthracyclines are known to be associated with chemotherapy-induced cardiotoxicity. Limited data focus on dynamic myocardial injury during the course of chemotherapy in patients with breast cancer. PURPOSE: To investigate the variation of tissue characterization and myocardial deformation derived by cardiac MRI during anthracycline chemotherapy. STUDY TYPE: Prospective. POPULATION: Fifty-eight female breast cancer patients (mean age: 52.82 ± 2.61 years) were enrolled. FIELD STRENGTH/SEQUENCE: A 3.0-T, cardiac MRI including cine balanced steady-state free precession, a modified Looker-Locker inversion recovery (MOLLI), and a fast spin echo (FSE) T2-weighted sequences were performed. ASSESSMENT: Cardiac MRI was performed baseline and after two, four, and six cycles of chemotherapy. Assessment of global longitudinal strain (GLS), global circumstance strain (GCS), global radial strain (GRS), and strain rate (GLS-s, GCS-s, GRS-s) and T1, T2 and T2* were accomplished by CVI42. The anthracycline dose and risk factors were also collected before each cardiac MRI. STATISTICAL TESTS: Analysis of variance (ANOVA) for repeated measures was used to compare the changes in LVEF cardiac function, strain and T1/T2/T2* parameters over time. Pearson correlation analyses were performed to estimate the potential associations between differences in myocardial characteristics (∆) and the chemotherapy cycle. A P value <0.05 was considered statistically significant. RESULTS: LVEF was not significantly different from pretreatment MRI regarding each cycle of chemotherapy (P = 0.54). Compared with baseline, patients had significantly lower GLS (-15.85% ± 0.83%, -14.50% ± 0.88%, -12.34% ± 1.01% vs. -18.82% ± 0.92%) and GLS-s (-0.71% ± 0.07%, -0.65% ± 0.05%, -0.64% ± 0.04% vs. -0.95 ± 0.06%) and increased T2 values (57.21 ± 4.27 msec, 58.60 ± 3.93 msec, 58.10 ± 3.17 msec vs. 43.88 ± 3.28 msec) at two, four and six cycles of chemotherapy treatment. ∆GLS and ∆GLS-s were significantly associated with the chemotherapy cycle (correlation coefficients for GLS = 0.75, GLS-s = 0.75). DATA CONCLUSION: Cardiac MRI can precisely detect the dynamic changes of anthracycline-induced subclinical myocardial injury that is represented as a gradually decrease in GLS and GLS-s. These parameters may provide new insight for monitoring risk and therapy in patients with breast cancer. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 1.

Ferroptosis in pancreatic diseases: potential opportunities and challenges that require attention.

The pancreas is an abdominal organ with both endocrine and exocrine functions, and patients with pancreatic diseases suffer tremendously. The regulated cell death of various cells in the pancreas is thought to play a key role in disease development. As one of the newly discovered regulated cell death modalities, ferroptosis has the potential for therapeutic applications in the study of multiple diseases. Ferroptosis has been observed in several pancreatic diseases, but its role in pancreatic diseases has not been systematically elucidated or reviewed. Understanding the occurrence of ferroptosis in various pancreatic diseases after damage to the different cell types is crucial in determining disease progression, evaluating targeted therapies, and predicting disease prognosis. Herein, we summarize the research progress associated with ferroptosis in four common pancreatic diseases, namely acute pancreatitis, chronic pancreatitis, pancreatic ductal adenocarcinoma, and diabetes mellitus. Furthermore, the elucidation of ferroptosis in rare pancreatic diseases may provide sociological benefits in the future.

Predictors of cognitive deterioration in subjective cognitive decline: evidence from longitudinal studies and implications for SCD-plus criteria.

BACKGROUND: Subjective cognitive decline (SCD) is an early manifestation of cognitive deterioration (CD) in some individuals. Therefore, it is worthwhile to conduct a systematic review and meta-analysis to summarise predictors of CD among individuals with SCD. METHOD: PubMed, Embase, and Cochrane Library were searched until May 2022. Longitudinal studies that assessed factors associated with CD in SCD population were included. Multivariable-adjusted effect estimates were pooled using random-effects models. The credibility of evidence was assessed. The study protocol was registered with PROSPERO. RESULTS: A total of 69 longitudinal studies were identified for systematic review, of which 37 were included for the meta-analysis. The mean conversion rate of SCD to any CD was 19.8%, including all-cause dementia (7.3%) and Alzheimer's disease (4.9%). Sixteen factors (66.67%) were found as predictors, including 5 SCD features (older age at onset, stable SCD, both self- and informant-reported SCD, worry and SCD in the memory clinic), 4 biomarkers (cerebral amyloid ß-protein deposition, lower scores of Hulstaert formula, higher total tau in the cerebrospinal fluid and hippocampus atrophy), 4 modifiable factors (lower education, depression, anxiety and current smoking), 2 unmodifiable factors (apolipoprotein E4 and older age) and worse performance on Trail Making Test B. The robustness of overall evidence was impaired by risk of bias and heterogeneity. CONCLUSION: This study constructed a risk factor profile for SCD to CD conversion, supporting and supplementing the existing list of features for identifying SCD populations at high risk of objective cognitive decline or dementia. These findings could promote early identification and management of high-risk populations to delay dementia onset. PROSPERO REGISTRATION NUMBER: CRD42021281757.

Variations and patterns of C and N stoichiometry in the first five root branch orders across 218 woody plant species.

Despite the vital role in carbon (C) sequestration and nutrient retention, variations and patterns in root C and nitrogen (N) stoichiometry of the first five root orders across woody plant species remains unclear. We compiled a dataset to explore variations and patterns of root C and N stoichiometry in the first five orders of 218 woody plant species. Across the five orders, root N concentrations were greater in deciduous, broadleaf, and arbuscular mycorrhizal species than in evergreen, coniferous species, and ectomycorrhizal associations species, respectively. Contrasting trends were found for root C:N ratios. Most root branch orders showed clear latitudinal and altitudinal trends in root C and N stoichiometry. There were opposite patterns in N concentrations between latitude and altitude. Such variations were mainly driven by plant species, and climatic factors together. Our results indicate divergent C and N use strategies among plant types and convergence and divergence in the patterns of C and N stoichiometry between latitude and altitude across the first five root orders. These findings provide important data on the root economics spectrum and biogeochemical models to improve understanding and prediction of climate change effects on C and nutrient dynamics in terrestrial ecosystems.

Nomograms for Predicting Disease-Free Survival Based on Core Needle Biopsy and Surgical Specimens in Female Breast Cancer Patients with Non-Pathological Complete Response to Neoadjuvant Chemotherapy.

PURPOSE: While a pathologic complete response (pCR) is regarded as a surrogate endpoint for pos-itive outcomes in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC), fore-casting the prognosis of non-pCR patients is still an open issue. This study aimed to create and evaluate nomogram models for estimating the likelihood of disease-free survival (DFS) for non-pCR patients. METHODS: A retrospective analysis of 607 non-pCR BC patients was conducted (2012-2018). After converting continuous variables to categorical variables, variables entering the model were progressively identified by univariate and multivariate Cox regression analyses, and then pre-NAC and post-NAC nomogram models were developed. Regarding their discrimination, ac-curacy, and clinical value, the performance of the models was evaluated by internal and external validation. Two risk assessments were performed for each patient based on two models; patients were separated into different risk groups based on the calculated cut-off values for each model, including low-risk (assessed by the pre-NAC model) to low-risk (assessed by the post-NAC model), high-risk to low-risk, low-risk to high-risk, and high-risk to high-risk groups. The DFS of different groups was assessed using the Kaplan-Meier method. RESULTS: Both pre-NAC and post-NAC nomogram models were built with clinical nodal (cN) status and estrogen receptor (ER), Ki67, and p53 status (all p < 0.05), showing good discrimination and calibration in both internal and external validation. We also assessed the performance of the two models in four subtypes, with the tri-ple-negative subtype showing the best prediction. Patients in the high-risk to high-risk subgroup have significantly poorer survival rates (p < 0.0001). CONCLUSION: Two robust and effective nomo-grams were developed to personalize the prediction of DFS in non-pCR BC patients treated with NAC.

Baicalein alleviates fibrosis and inflammation in systemic sclerosis by regulating B-cell abnormalities.

BACKGROUND: Systemic sclerosis (SSc; also known as "scleroderma") is an autoimmune disorder characterized by extensive fibrosis, vascular changes, and immunologic dysregulation. Baicalein (phenolic flavonoid derived from Scutellaria baicalensis Georgi) has been used to treat the pathological processes of various fibrotic and inflammatory diseases. In this study, we investigated the effect of baicalein on the major pathologic characteristics of SSc: fibrosis, B-cell abnormalities, and inflammation. METHODS: The effect of baicalein on collagen accumulation and expression of fibrogenic markers in human dermal fibroblasts were analyzed. SSc mice were produced by injecting bleomycin and treated with baicalein (25, 50, or 100 mg/kg). The antifibrotic features of baicalein and its mechanisms were investigated by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay, western blotting and flow cytometry. RESULTS: Baicalein (5-120 µM) significantly inhibited the accumulation of the extracellular matrix and fibroblast activation in transforming growth factor (TGF)-ß1- and platelet derived growth factor (PDGF)-induced human dermal fibroblasts, as evidenced by abrogated deposition of total collagen, decreased secretion of soluble collagen, reduced collagen contraction capability and downregulation of various fibrogenesis molecules. In a bleomycin-induced model of dermal fibrosis in mice, baicalein (25-100 mg/kg) restored dermal architecture, ameliorated inflammatory infiltrates, and attenuated dermal thickness and collagen accumulation in a dose-dependent manner. According to flow cytometry, baicalein reduced the proportion of B cells (B220+ lymphocytes) and increased the proportion of memory B cells (B220+CD27+ lymphocytes) in the spleens of bleomycin-induced mice. Baicalein treatment potently attenuated serum levels of cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta) and autoantibodies (anti-scleroderma 70 (Scl-70), anti-polymyositis-scleroderma (PM-Scl), anti-centromeres, anti-double stranded DNA (dsDNA). In addition, baicalein treatment can significantly inhibit the activation of TGF-ß1 signaling in dermal fibroblasts and bleomycin-induce mice of SSc, evidenced by reducing the expression of TGF-ß1 and IL-11, as well as inhibiting both small mother against decapentaplegic homolog 3 (SMAD3) and extracellular signal-related kinase (ERK) activation. CONCLUSIONS: These findings suggest that baicalein has therapeutic potential against SSc, exerting modulating B-cell abnormalities, anti-inflammatory effects, and antifibrosis.

Epidemiological, clinical, and household transmission characteristics of children and adolescents infected with SARS-CoV-2 Omicron variant in Shanghai, China: a retrospective, multicenter observational study.

OBJECTIVES: To describe the epidemiological, clinical, and household transmission characteristics of pediatric COVID-19 cases in Shanghai, China. METHODS: Pediatric patients with COVID-19 hospitalized in Shanghai from March-May 2022 were enrolled in this retrospective, multicenter cohort study. The symptoms and the risk factors associated with disease severity were analyzed. RESULTS: In total, 2620 cases (age range, 24 days-17 years) were enrolled in this study. Of these, 1011 (38.6%) were asymptomatic, whereas 1415 (54.0%), 190 (7.3%), and 4 (0.2%) patients developed mild, moderate, and severe illnesses, respectively. Household infection rate was negatively correlated with household vaccination coverage. Children aged 0-3 years, those who are unvaccinated, those with underlying diseases, and overweight/obese children had a higher risk of developing moderate to severe disease than children aged 12-17 years, those who were vaccinated, those without any underlying disease, and those with normal weight, respectively (all P <0.05). A prolonged duration of viral shedding was associated with disease severity, presence of underlying diseases, vaccination status, and younger age (all P <0.05). CONCLUSION: Children aged younger than 3 years who were not eligible for vaccination had a high risk of developing moderate to severe COVID-19 with a prolonged duration of viral shedding. Vaccination could protect children from COVID-19 at the household level.

Applying Convolutional Neural Network to Predict Soil Erosion: A Case Study of Coastal Areas.

The development of ecological restoration projects is unsatisfactory, and soil erosion is still a problem in ecologically restored areas. Traditional soil erosion studies are mostly based on satellite remote sensing data and traditional soil erosion models, which cannot accurately characterize the soil erosion conditions in ecological restoration areas (mainly plantation forests). This paper uses high-resolution unmanned aerial vehicle (UAV) images as the base data, which could improve the accuracy of the study. Considering that traditional soil erosion models cannot accurately express the complex relationships between erosion factors, this paper applies convolutional neural network (CNN) models to identify the soil erosion intensity in ecological restoration areas, which can solve the problem of nonlinear mapping of soil erosion. In this study area, compared with the traditional method, the accuracy of soil erosion identification by applying the CNN model improved by 25.57%, which is better than baseline methods. In addition, based on research results, this paper analyses the relationship between land use type, vegetation cover, and slope and soil erosion. This study makes five recommendations for the prevention and control of soil erosion in the ecological restoration area, which provides a scientific basis and decision reference for subsequent ecological restoration decisions.