Low-loss compact chalcogenide microresonators for efficient stimulated Brillouin lasers.

Chalcogenide glasses (ChGs) possess a high elasto-optic coefficient, making them ideal for applications in microwave photonics and narrow-linewidth lasers based on stimulated Brillouin scattering (SBS). However, current As2S3-based integrated devices suffer from poor stability and low laser-induced damage threshold, and planar ChG devices feature limited quality factors. In this Letter, we propose and demonstrate a high-quality integrated GeSbS ChG Brillouin photonic device. By introducing Euler bending structures, we suppress high-order optical modes and reduce propagation losses in a finger-shaped GeSbS microresonator, resulting in a compact footprint of 3.8 mm2 and a high intrinsic quality factor of 5.19 × 106. The combination of GeSbS material's high Brillouin gain and the resonator's high-quality factor enables the generation of stimulated Brillouin lasers with a low threshold of 0.96 mW and a fundamental linewidth of 58 Hz. Moreover, cascaded stimulated Brillouin lasers can be realized up to the seventh order, yielding microwave beat frequencies up to 40 GHz.

Construction of effective reproduction number of infectious disease individuals based on spatiotemporal discriminant search model: take hand-foot-mouth disease as an example.

OBJECTIVE: In order to facilitate the tracing of infectious diseases in a small area and to effectively carry out disease control and epidemiological investigations, this research proposes a novel spatiotemporal model to estimate effective reproduction number(Re)for infectious diseases, based on the fundamental concept of contact tracing. METHODS: This study utilizes the incidence of hand, foot, and mouth disease (HFMD) among children in Bishan District, Chongqing, China from 2015 to 2019. The study incorporates the epidemiological characteristics of HFMD and aims to construct a Spatiotemporal Correlation Discrimination of HFMD. Utilizing ARC ENGINE and C# programming for the creation of a spatio-temporal database dedicated to HFMD to facilitate data collection and analysis. The scientific validity of the proposed method was verified by comparing the effective reproduction number obtained by the traditional SEIR model. RESULTS: We have ascertained the optimal search radius for the spatiotemporal search model to be 1.5 km. Upon analyzing the resulting Re values, which range from 1.14 to 4.75, we observe a skewed distribution pattern from 2015 to 2019. The median and quartile Re value recorded is 2.42 (1.98, 2.72). Except for 2018, the similarity coefficient r of the years 2015, 2016, 2017, and 2019 were all close to 1, and p <0.05 in the comparison of the two models, indicating that the Re values obtained by using the search model and the traditional SEIR model are correlated and closely related. The results exhibited similarity between the Re curves of both models and the epidemiological characteristics of HFMD. Finally, we illustrated the regional distribution of Re values obtained by the search model at various time intervals on Geographic Information System (GIS) maps which highlighted variations in the incidence of diseases across different communities, neighborhoods, and even smaller areas. CONCLUSION: The model comprehensively considers both temporal variation and spatial heterogeneity in disease transmission and accounts for each individual's distinct time of onset and spatial location. This proposed method differs significantly from existing mathematical models used for estimating Re in that it is founded on reasonable scientific assumptions and computer algorithms programming that take into account real-world spatiotemporal factors. It is particularly well-suited for estimating the Re of infectious diseases in relatively stable mobile populations within small geographical areas.

Effects of spatial configuration and fundamental frequency on speech intelligibility in multiple-talker conditions in the ipsilateral horizontal plane and median planea).

Spatial separation and fundamental frequency (F0) separation are effective cues for improving the intelligibility of target speech in multi-talker scenarios. Previous studies predominantly focused on spatial configurations within the frontal hemifield, overlooking the ipsilateral side and the entire median plane, where localization confusion often occurs. This study investigated the impact of spatial and F0 separation on intelligibility under the above-mentioned underexplored spatial configurations. The speech reception thresholds were measured through three experiments for scenarios involving two to four talkers, either in the ipsilateral horizontal plane or in the entire median plane, utilizing monotonized speech with varying F0s as stimuli. The results revealed that spatial separation in symmetrical positions (front-back symmetry in the ipsilateral horizontal plane or front-back, up-down symmetry in the median plane) contributes positively to intelligibility. Both target direction and relative target-masker separation influence the masking release attributed to spatial separation. As the number of talkers exceeds two, the masking release from spatial separation diminishes. Nevertheless, F0 separation remains as a remarkably effective cue and could even facilitate spatial separation in improving intelligibility. Further analysis indicated that current intelligibility models encounter difficulties in accurately predicting intelligibility in scenarios explored in this study.

Dual-ring parity-time symmetric brillouin fiber laser with an unbalanced polarization Mach-Zehnder interferometer.

A dual-ring parity-time (PT) symmetric Brillouin fiber laser (BFL) with an unbalanced polarization Mach-Zehnder interferometer (UP-MZI) is proposed and experimentally investigated. An UP-MZI consisting of optical coupler, polarization beam combiner (PBC) and two asymmetric length arms with 10 km and 100 m single-mode fiber, is used to achieve Vernier effect and PT symmetry. Due to the orthogonally polarized lights created in the PBC, the dual-ring PT symmetry BFL with an UP-MZI implements two unbalanced length feedback rings that are connected to one another, one long length ring with a Brillouin gain and the other short length ring with a loss of the same magnitude, to break a PT symmetric and maintain the Vernier effect. By contrast with existing PT symmetry BFL studies, this design does not require same lengths of the gain and loss loops, but can manipulate freely PT symmetry status in accordance with a rational scaling factor between them. Experimental results reveal that the 3-dB linewidth of dual-ring PT symmetry BFL with an UP-MZI is about 4.85 Hz with the threshold input power of 9.5 mW, in accordance with the 97 Hz measured linewidth at the -20 dB power point. Within 60 mins of the stability experiment, the power and frequency stability fluctuation are ±0.02 dB and ±0.137 kHz, respectively. Thanks to the two asymmetric ring lengths, the sidemode suppression ratio (SMSR) is optimized by 54 dB compared to that with the only long ring structure, 26 dB when using only the Vernier effect or 12 dB for existing PT symmetry BFL. This BFL design with single longitudinal mode and high SMSR output can be applied to high coherent communication and Brillouin-based microwave photonics systems with low phase noise.

Narrow linewidth parity-time symmetric Brillouin fiber laser based on a dual-polarization cavity with a single micro-ring resonator.

A narrow linewidth parity-time (PT) symmetric Brillouin fiber laser (BFL) based on dual-polarization cavity (DPC) with single micro-ring resonator (MRR) is proposed and experimentally investigated. A 10 km single-mode fiber provides SBS gain, while a DPC consisting of optical coupler, polarization beam combiner and a MRR, is used to achieve PT symmetry. Due to the reciprocity of light propagation in the MRR, the PT symmetry BFL based on DPC implements two identical feedback loops that are connected to one another, one with a Brillouin gain coefficient and the other with a loss coefficient of the same magnitude, to break a PT symmetric. Compared with existing BFL studies, this design does not call for frequency matching of compound cavities structures or without ultra-narrow bandwidth bandpass filters. In the experiment, the 3-dB linewidth of PT symmetry BFL based on DPC with single MRR is 11.95 Hz with the threshold input power of 2.5 mW, according to the measured linewidth of 239 Hz at the -20 dB power point. And a 40 dB maximum mode suppression ratio are measured. Furthermore, the PT symmetry BFL's wavelength is tuned between 1549.60 and 1550.73 nm. This design with single longitudinal mode output can be applied to high coherent communication systems.

Rehabilitation programs for patients with COronaVIrus Disease 2019: consensus statements of Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation.

The COronaVIrus Disease 2019 (COVID-19), which developed into a pandemic in 2020, has become a major healthcare challenge for governments and healthcare workers worldwide. Despite several medical treatment protocols having been established, a comprehensive rehabilitation program that can promote functional recovery is still frequently ignored. An online consensus meeting of an expert panel comprising members of the Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation was held to provide recommendations for rehabilitation protocols in each of the five COVID-19 stages, namely (1) outpatients with mild disease and no risk factors, (2) outpatients with mild disease and epidemiological risk factors, (3) hospitalized patients with moderate to severe disease, (4) ventilator-supported patients with clear cognitive function, and (5) ventilator-supported patients with impaired cognitive function. Apart from medications and life support care, a proper rehabilitation protocol that facilitates recovery from COVID-19 needs to be established and emphasized in clinical practice.

Impact of multi-disciplinary treatment strategy on systolic heart failure outcome.

BACKGROUND: Patients with reduced ejection fraction have high rates of mortality and readmission after hospitalization for heart failure. In Taiwan, heart failure disease management programs (HFDMPs) have proven effective for reducing readmissions for decompensated heart failure or other cardiovascular causes by up to 30%. However, the benefits of HFDMP in different populations of heart failure patients is unknown. METHOD: This observational cohort study compared mortality and readmission in heart failure patients who participated in an HFDMP (HFDMP group) and heart failure patients who received standard care (non-HFDMP group) over a 1-year follow-up period after discharge (December 2014 retrospectively registered). The components of the intervention program included a patient education program delivered by the lead nurse of the HFDMP; a cardiac rehabilitation program provided by a physical therapist; consultation with a dietician, and consultation and assessment by a psychologist. The patients were followed up for at least 1 year after discharge or until death. Patient characteristics and clinical demographic data were compared between the two groups. Cox proportional hazards regression analysis was performed to calculate hazard ratios (HRs) for death or recurrent events of hospitalization in the HFDMP group in comparison with the non-HFDMP group while controlling for covariates. RESULTS: The two groups did not significantly differ in demographic characteristics. The risk of readmission was lower in the HFDMP group, but the difference was not statistically significant (HR = 0.36, p = 0.09). In patients with ischemic cardiomyopathy, the risk of readmission was significantly lower in the HFDMP group compared to the non-HFDMP group (HR = 0.13, p = 0.026). The total mortality rate did not have significant difference between this two groups. CONCLUSION: The HFDMP may be beneficial for reducing recurrent events of heart failure hospitalization, especially in patients with ischemic cardiomyopathy. TRIAL REGISTRATION: Longitudinal case-control study ISRCTN98483065 , 24/09/2019, retrospectively registered.

Comparative Effectiveness of Different Nonsurgical Treatments for Patellar Tendinopathy: A Systematic Review and Network Meta-analysis.

PURPOSE: To investigate the functional improvement and pain reduction of different nonsurgical treatments for patellar tendinopathy (PT), a systematic review with network meta-analysis was performed. METHODS: Studies were comprehensively searched for without language restrictions in the CENTRAL, MEDLINE, EMBASE, Web of Science, Physiotherapy Evidence Database, and SPORTDiscus databases from inception to May 2018. Randomized controlled trials about nonsurgical treatments for PT were included. The outcome measurements were the Victorian Institute of Sports Assessment (VISA) scale and pain scores (such as the visual analog scale or Numerical Rating Scale). Study quality was evaluated using the Physiotherapy Evidence Database score. Direct comparisons were performed using pairwise meta-analysis, whereas network meta-analysis was performed using a frequentist method in a multivariate random-effects model. RESULTS: Eleven studies with 430 affected patellar tendons were included in the systematic review. The summary mean difference of improvement in the VISA scale versus the control group for corticosteroid injection was -23.00 (95% confidence interval [CI] -36.73 to -9.27), for leukocyte-rich platelet-rich plasma (LR-PRP) was 13.22 (95% CI 2.37-24.07), for focused extracorporeal shockwave therapy (ESWT) was -1.28 (95% CI -6.25 to 3.68), for radial ESWT was -6.68 (95% CI -20.20 to 6.84), for ultrasound was -0.70 (95% CI -11.23 to 9.83), for autologous blood injection was -0.60 (95% CI -9.30 to 8.10), for dry needling was 17.51 (95% CI -2.57 to 37.60), for topical glyceryl trinitrate was -0.90 (95% CI -13.07 to 11.27), and for skin-derived tendon-like cells was 10.40 (95% CI -1.59 to 22.39). LR-PRP (Surface Under the Cumulative Ranking curve [SUCRA] = 87.5%) or dry needling (SUCRA = 90.5%) was most likely to be ranked the best in terms of improvement on the VISA scale. Compared with the control group, the summary mean difference of the change in pain score for corticosteroid injection was 0.80 (95% CI -3.48 to 5.08), for LR-PRP was -1.87 (95% CI -3.28 to -0.46), for focused ESWT was 0.13 (95% CI -0.68 to 0.93), for radial ESWT was 0.03 (95% CI -1.92 to 1.98), for ultrasound was -0.20 (95% CI -1.49 to 1.09), for autologous blood injection was 0.60 (95% CI -0.73 to 1.93), for dry needling was -0.37 (95% CI -2.71 to 1.97), and for topical glyceryl trinitrate was -0.50 (95% CI -2.55 to 1.55). The treatment most likely to be ranked the best in terms of change in pain score was LR-PRP (SUCRA = 94.9%). CONCLUSIONS: The network meta-analysis demonstrated that LR-PRP has the greatest functional improvement and pain reduction for PT compared with other treatment options. However, the treatment effect estimates can be biased by the possible intransitivity and should not be overestimated. LEVEL OF EVIDENCE: Level I, meta-analysis of Level I studies.

Ultrasonography has high positive predictive value for medial epicondyle lesions among adolescent baseball players.

PURPOSE: Only few studies have investigated medial epicondyle (MEC) lesions, particularly in the 12-18 age group. To the best of our knowledge, no study has compared ultrasonography (US), radiography and magnetic resonance imaging (MRI) in detecting MEC lesions. The aims of this study were to examine the value of US for detecting MEC lesions and to investigate correlations among diagnostic tools. METHODS: A prospective, comparative study was performed. Young baseball players from southern Taiwan were recruited, and basic characteristics, as well as passive range of motion (pROM) of the upper extremities, were recorded. Screening US was performed to identify MEC lesions, and players with MEC lesions received follow-up plain radiography and MRI. RESULTS: A total of 299 young baseball players were screened using US, and 28 of 299 players with possible MEC lesions were identified with a positive predictive value (PPV) of 88% according to MRI findings. The MEC lesions were primarily comprised of unfused ossicles and bony fragmentation. Other diagnoses, including UCL strain and medial epicondylitis, were also found by MRI in players with abnormal US screening results. The pROM of shoulder external rotation (ER) of the throwing hand was significantly reduced in players with MEC lesions (p = 0.006). CONCLUSIONS: Bony cortical discontinuity or fragmentation over the MEC warrants further research, and US provides good PPV for types of MEC lesions. Decreased shoulder ER may relate to MEC lesions and should be taken into consideration. The use of US may facilitate early detection and intervention. LEVEL OF EVIDENCE: IV, Cross-sectional study.

Effectiveness of ultrasonography screening and risk factor analysis of capitellar osteochondritis dissecans in adolescent baseball players.

BACKGROUND: Capitellar osteochondritis dissecans (COCD) is a common elbow injury in young baseball athletes. It may be asymptomatic at the early stage and may progress if left untreated. This study investigated the effectiveness of ultrasonography (US) screening for COCD in adolescent baseball players and identified risk factors of COCD. METHODS: A cross-sectional analysis study was conducted among baseball athletes aged 12 to 18 years. US screening of the throwing elbow was performed in all participants, and additional magnetic resonance imaging (MRI) was arranged for those with abnormal screening results. The prevalence of COCD was calculated according to MRI results. The US findings were compared with MRI findings. Data for characteristics, joint range of motion, and quality of pain were collected and analyzed using a logistic regression model to identify the risk factors of COCD. RESULTS: A total of 299 adolescent baseball players were screened, and 17 were found to have COCD according to US findings. MRI was performed in 15 of these 17 players, and the MRI findings further confirmed COCD in 10 players (66.7%). The presence of elbow pain while at rest, body height, and age at introduction to baseball were predictors of COCD. CONCLUSIONS: Although the effectiveness of diagnosing stage 1 COCD is satisfactory, US is a helpful tool for detecting stage 2 and higher-stage COCD. Elbow resting pain, lower body height, and introduction to baseball at a younger age are risk factors for COCD.

Evaluating posterior cruciate ligament injury by using two-dimensional ultrasonography and sonoelastography.

PURPOSE: This study aimed to elucidate the diagnostic criteria for posterior cruciate ligament (PCL) injury using ultrasonography. METHODS: Thirty-three patients with clinically suspected PCL injuries and 30 normal control subjects were recruited. Both groups were assessed using sonographic examination with reliability testing. Patients also underwent posterior stress radiography and magnetic resonance imaging (MRI). PCL thickness on two-dimensional ultrasonography (2D US), pixel intensity on sonoelastography, displacement on posterior stress view, and severity grading using MRI were analysed. Receiver operating characteristic (ROC) curves were plotted using MRI as the gold standard. Correlation coefficients among variables were calculated. RESULTS: Good to excellent reliabilities were noted for 2D US and red pixel intensity on sonoelastography. In injured knees, PCL thicknesses were significantly greater, and red pixel intensities were significantly lower, compared to non-injured knees of patients and healthy controls. This indicates increased swelling and softness in injured PCLs. The area under the PCL thickness ROC curve was 0.917 (p < 0.001), and the best diagnostic criterion was a thickness ≥6.5 mm (90.6 % sensitivity and 86.7 % specificity). Thickness correlated with red pixel intensity, International Knee Documentation Committee examination grade, and MRI severity grading. In addition, effusions were detected on 2D US in all knees with "tears" of other structures on MRI. CONCLUSIONS: 2D US is a useful tool to diagnose PCL injury, and PCL thickness ≥6.5 mm is the recommended diagnostic criterion. LEVEL OF EVIDENCE: II.

Effect of codeine on CYP450 isoform activity of rats.

CONTEXT: Codeine, also known as 3-methylmorphine, is an opiate used to treat pain, as a cough medicine and for diarrhoea. No study on the effects of codeine on the metabolic capacity of CYP enzyme is reported. OBJECTIVE: In order to investigate the effects of codeine on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B1, CYP2D1, CYP1A2, CYP3A2 and CYP2C11. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into codeine group (low, medium, high) and control group. The codeine group rats were given 4, 8, 16 mg/kg (low, medium, high) codeine by continuous intragastric administration for 14 days. Five probe drugs bupropion, metroprolol, phenacetin, midazolam and tolbutamide were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. RESULTS AND CONCLUSION: The pharmacokinetic parameters of bupropion and metroprolol experienced obvious change with AUC(0-t), Cmax increased and CL decreased for bupropion in medium dosage group and midazolam low dosage group. This result indicates that the 14 day-intragastric administration of codeine may inhibit the metabolism of bupropion (CYP2B1) and midazolam (CYP3A2) in rat. Additional, there are no statistical differences for albumin (ALB), alkaline phosphatase (ALP), creatinine (Cr) after 14 intragastric administration of codeine, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA) increased compared to control group. The biomedical test results show continuous 14 day-intragastric administration of codeine would cause liver damage.

Effects of inhaled fine particulate matter on the lung injury as well as gut microbiota in broilers.

Fine particulate matter (PM2.5) has been widely regarded as an important environmental risk factor that has widely influenced health of both animals and humans. Lung injury is the main cause of PM2.5 affecting respiratory tract health. Gut microbiota participates in the development of lung injury in many pathological processes. However, there is still unknown the specific effects of PM2.5 on the gut-lung axis in broilers. Thus, we conducted a broiler model based on 3-wk-old male Arbor Acres broiler to explore the underlying mechanism. Our results showed that PM2.5 exposure triggered TLR4 signaling pathway and induced the increase of IL-6, IFN-γ, TNF-α expression as well as the decrease of IL-10 expression in the lung. Inhaled PM2.5 exposure significantly altered the gut microbiota diversity and community. Specifically, PM2.5 exposure decreased α diversity and altered ß diversity of gut microbiota, and reduced the abundance of DTU089, Oscillospirales, Staphylococcus, and increased the Escherichia-Shigella abundance, leading to the increase of gut-derived lipopolysaccharides (LPS). Moreover, PM2.5 significantly disrupted the intestinal epithelial barrier by reducing the expression of muc2 and claudin-1 to increase intestinal permeability, which possibly facilitated the LPS translocation into the blood. Spearman analysis revealed that gut microbiota dysbiosis was positively related to TLR4, TNF-α, and IFN-γ expression in the lung. In summary, our results showed that PM2.5 exposure induced lung injury by causing inflammation and triggering TLR4 signaling pathway, and also induced gut microbiota dysbiosis resulting in the overproduction of gut-derived LPS. And gut microbiota dysbiosis may be associated with lung injury. The above results provide basis data to comprehend the potential role of gut microbiota dysbiosis in the lung injury as well as providing a new regulatory target for alleviating lung injury associated with environmental pollutants.

Benefit of cardiac rehabilitation in acute heart failure patients with cognitive impairment.

Aims: This study aimed to evaluate the prevalence of cognitive impairment among patients with acute heart failure (AHF), its prognosis, and the effects of cardiac rehabilitation (CR) on these patients' outcomes. Methods: Overall, 247 consecutive AHF patients (median age, 60 years; males, 78.5 %) were evaluated from March 2015 to May 2021. Patients received an AHF disease management program coordinated by an HF specialist nurse and underwent a Luria-Nebraska Neuropsychological battery-screening test (LNNB-S) assessment during admission. Cognitive impairment was defined as an LNNB-S score ≥10. Patients who underwent at least one session of phase II CR and continued with the home-based exercise program were considered to have received CR. The primary endpoint was composite all-cause mortality or readmission after a 3.30-year follow-up (interquartile range, 1.69-5.09 years). Results: Cognitive impairment occurred in 53.0 % and was associated with significantly higher composite endpoint, all-cause mortality, and readmission rates (p=<0.001, 0.001, and 0.015, respectively). In the total cohort, 40.9 % of patients experienced the composite endpoint. Multivariate analysis showed that the peak VO2 was a significant predictor of the composite endpoint. After adjustment, CR significantly decreased the event rate of the composite endpoint and the all-cause mortality in patients with cognitive impairment (log-rank p = 0.024 and 0.009, respectively). However, CR did not have a significant benefit on the composite endpoint and the all-cause mortality in patients without cognitive impairment (log-rank p = 0.682 and 0.701, respectively). Conclusion: Cognitive impairment is common in AHF patients and can lead to poor outcomes. CR is a standard treatment to improve prognosis.

Fine Particulate Matter Perturbs the Pulmonary Microbiota in Broiler Chickens.

(1) Fine particulate matter (PM2.5) seriously affects the respiratory tract health of both animals and humans. Growing evidence indicates that the pulmonary microbiota is involved in the development of respiratory tract health; however, there is still much that is unknown about the specific changes of pulmonary microbiota caused by PM2.5 in broilers. (2) In this experiment, a total of 48 broilers were randomly divided into a control group and PM-exposure group. The experiment lasted for 21 days. Microbiota, inflammation biomarkers, and histological markers in the lungs were determined. (3) On the last day of the experiment, PM significantly disrupted the structure of lung tissue and induced chronic pulmonary inflammation by increasing IL-6, TNFα, and IFNγ expression and decreasing IL-10 expression. PM exposure significantly altered the α and ß diversity of pulmonary microbiota. At the phylum level, PM exposure significantly decreased the Firmicutes abundance and increased the abundance of Actinobacteria and Proteobacteria. At the genus level, PM exposure significantly increased the abundance of Rhodococcus, Achromobacter, Pseudomonas, and Ochrobactrum. We also observed positive associations of the above altered genera with lung TNFα and IFNγ expression. (4) The results suggest that PM perturbs the pulmonary microbiota and induces chronic inflammation, and the pulmonary microbiota possibly contributes to the development of lung inflammation.

The construction and analysis of a prognostic assessment model based on P53-related multi-genes in breast carcinoma.

BACKGROUND: Breast cancer ranks second in female tumor mortality, with an estimation of 2 million new cases diagnosed each year worldwide. METHODS: In our current study, we screened 13 genes highly distributed on the P53 phenotype which were significantly expressed and had a strong correlation with survival in the Cancer Genome Atlas breast cancer dataset. Least absolute shrinkage and selection operator Cox regression was conducted to construct the risk assessment model. Based on bioinformatics and statistical methods, we confirmed the credibility and validity of the model by training set and testing set. RESULTS: The result of comparing the other two previous hypoxia models was also satisfying. We also verified the model on one of the Gene Expression Omnibus datasets-GSE20685. Using clinical data from patients in the Cancer Genome Atlas, we acknowledged the risk score as an independent influence on breast cancer survival prognosis, and strong relevance was suggested between risk signature and age, lymphatic metastasis, tumor size and clinical stage by performing univariate and multivariate analysis. Immunology analysis demonstrated that the macrophages subset was positively associated with a risk score and other immune cell types had a negative effect with the risk score increases. The risk score was also emerging as a valuable prognostic factor for the prediction of chemotherapy drug curative effect because Gemcitabine, vinorelbine, paclitaxel and cisplatin known as a generic drug for breast cancer had more pleasing sensitivity in high-scored patients than low-scored patients. CONCLUSION: The P53-related risk assessment model is promising to be a potential predictor for the prognosis of patients with breast cancer and a powerful guide for the selection of therapeutic strategies.

Optimizing exercise testing-based risk stratification to predict poor prognosis after acute heart failure.

AIMS: The timely selection of severe heart failure (HF) patients for cardiac transplantation and advanced HF therapy is challenging. Peak oxygen consumption (VO2 ) values obtained by the cardiopulmonary exercise testing are used to determine the transplant recipient list. This study reassessed the prognostic predictability of peak VO2 and compared it with the Heart Failure Survival Score (HFSS) in the modern optimized guideline-directed medical therapy (GDMT) era. METHODS AND RESULTS: We retrospectively selected 377 acute HF patients discharged from the hospital. The primary outcome was a composite of all-cause mortality, or urgent cardiac transplantation. We divided these patients into the more GDMT (two or more types of GDMT) and less GDMT groups (fewer than two types of GDMT) and compared the performance of their peak VO2 and HFSS in predicting primary outcomes. The median follow-up period was 3.3 years. The primary outcome occurred in 57 participants. Peak VO2 outperformed HFSS when predicting 1 year (0.81 vs. 0.61; P = 0.017) and 2 year (0.78 vs. 0.58; P < 0.001) major outcomes. The cutoff peak VO2 for predicting a 20% risk of a major outcome within 2 years was 10.2 (11.8-7.0) for the total cohort. Multivariate Cox regression analyses showed that peak VO2 , sodium, previous implantable cardioverter defibrillator (ICD) implantation, and estimated glomerular filtration rate were significant predictors of major outcomes. CONCLUSIONS: Optimizing the cutoff value of peak VO2 is required in the current GDMT era for advanced HF therapy. Other clinical factors such as ICD use, hyponatraemia, and chronic kidney disease could also be used to predict poor prognosis. The improvement of resource allocation and patient outcomes could be achieved by careful selection of appropriate patients for advanced HF therapies, such as cardiac transplantation.

Inhibition of histone acetylation by curcumin reduces alcohol-induced expression of heart development-related transcription factors in cardiac progenitor cells.

Alcohol exposure during pregnancy may cause congenital heart disease (CHD). In our previous studies, we found that alcohol selectively increased acetylation of histone H3 at lysine 9 (H3K9) and enhanced the expression of heart development-related genes in cardiac progenitor cells. The objective of this study is to investigate the protective effects of histone acetyltransferases (HATs) inhibitor, curcumin, on histone hyperacetylation and the over-expression of heart development genes induced by alcohol. Western blot analysis was employed to detect the acetylation levels of histone H3K9 and real-time PCR was applied to measure the expressions of heart development-related transcription factors, GATA4, Mef2c and Tbx5 (GMT). Our results showed that alcohol increased the acetylation of H3K9 by 2.76-fold (P<0.05) and significantly enhanced the expression of GATA4 and Mef2c (P<0.05). When cells were treated with alcohol plus 25 µM curcumin, the hyperacetylation of H3K9 and over-expression of GATA4 and Mef2c by alcohol was reversed. These data indicate that curcumin can correct the over-expression of cardiac genes by reversing the alcohol induced hyperacetylation of histone H3 at lysine 9 in cardiac progenitor cells, suggesting that curcumin is protective against alcohol-induced cardiac gene over-expression that may result in heart malformations.

[Paeonol inhibits the phosphorylation of NF-κB p65 and the expression of inflammatory cytokines in mouse BV2 microglia induced by lipopolysaccharide].

Objective This study is aimed to investigate the effect of paeonol on inflammation of BV2 microglia induced by lipopolysaccharide (LPS), and the underlying mechanism. Methods Mouse BV2 microglia was cultured in vitro. BV2 microglia was pretreated with paeonol of different concentration for 24 hours, then stimulated by LPS for 12 hours. Cell viability was detected by CCK-8 assay. Morphological changes of microglia were monitored by microscopy. The mRNA expression of TNF-α, IL-1ß, IL-12 and IL-6 by BV2 microglia was measured by real time quantitative-PCR. The protein expression of NF-κB p65 and phosphorylated NF-κB p65 (p-NF-κB p65) was determined by Western blot analysis. Results Paeonol treatment improved cell viability, and inhibited over-activation of BV2 microglia challenged by LPS. Paeonol treatment concentration-dependently suppressed LPS induced mRNA expression of inflammatory cytokines including TNF-α, IL-1ß, IL-6, and IL-12 by BV2 microglia. Phosphorylation of NF-κB p65, but not protein level of NF-κB p65, was suppressed by paeonol treatment in a concentration-dependent manner. Conclusion Paeonol inhibits LPS induced phosphorylation of NF-κB p65 and transcription of downstream proinflammatory cytokines in BV2 microglia.

Mobility Status Plays an Important Role in the Risk of Cardiovascular Rehospitalizations in Patients with Heart Failure Undergoing Cardiac Rehabilitation: A Retrospective Cohort Study.

The aim of this study was to investigate the association between mobility status and cardiovascular rehospitalizations in patients with heart failure undergoing cardiac rehabilitation. This retrospective cohort study included patients with heart failure undergoing cardiac rehabilitation. Mobility status was evaluated using functional ambulation categories (FAC), and each cardiovascular hospitalization was recorded by the case manager. A Poisson regression model was used to analyze the association between mobility status and cardiovascular rehospitalizations. This study included 154 patients with heart failure undergoing cardiac rehabilitation. For cardiovascular rehospitalizations within 6 months, the Poisson regression model reported that the impaired mobility group had a higher risk than the fair mobility group (incidence rate ratio (IRR) = 2.38, 95% CI 1.27-4.46, p = 0.007). For cardiovascular rehospitalizations within 12 months, the Poisson regression model also reported that the impaired mobility group had a higher risk than the fair mobility group (IRR = 1.91, 95% CI 1.16-3.13, p = 0.010). Other covariates, such as LVEF, peak oxygen consumption, and PAOD, could have impacted the risk of cardiovascular rehospitalizations. Among patients with heart failure undergoing cardiac rehabilitation, the impaired mobility group had a twofold risk of cardiovascular rehospitalizations, compared with the fair mobility group within both 6 and 12 months.