Targeted Ultrasound Nanobubbles Therapy for Prostate Cancer via Immuno-Sonodynamic Effect.

Background: Prostate cancer (PCa) poses a significant global health threaten. Immunotherapy has emerged as a novel strategy to augment the inhibition of tumor proliferation. However, the sole use of anti-PD-L1 Ab for PCa has not yielded improvements, mirroring outcomes observed in other tumor types. Methods: This study employed the thin film hydration method to develop lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab (Ce6@aPD-L1 NBs). Our experimental approach included cellular assays and mouse immunization, providing a comprehensive evaluation of Ce6@aPD-L1 NBs' impact. Results: The Ce6@aPD-L1 NBs effectively induced reactive oxygen species generation, leading to tumor cells death. In mice, they demonstrated a remarkable enhancement of immune responses compared to control groups. These immune responses encompassed immunogenic cell death induced by sonodynamic therapy and PD-1/PD-L1 blockade, activating dendritic cells maturation and effectively stimulating CD8+T cells. Conclusion: Ce6@aPD-L1 NBs facilitate tumor-targeted delivery, activating anti-tumor effects through direct sonodynamic therapy action and immune system reactivation in the tumor microenvironment. Ce6@aPD-L1 NBs exhibit substantial potential for achieving synergistic anti-cancer effects in PCa.

Low-intensity pulsed ultrasound treatment mitigates ventricular arrhythmias via inhibiting microglia-mediated neuroinflammation in heart failure rat model.

BACKGROUND: Sympathetic overactivation plays an important role in heart failure (HF)-induced ventricular arrhythmias (VAs). Microglia-mediated neuroinflammation could contribute to sympathetic overactivation. A previous study demonstrated that low-intensity pulsed ultrasound (LIPUS) could inhibit neuroinflammation. However, whether LIPUS could attenuate HF-induced VAs via inhibiting microglia-mediated neuroinflammation remains largely unknown. METHODS: Forth Sprague-Dawley male rats were averagely randomized into four groups: CTL (control) group, CTL + LIPUS group, HF group and HF + LIPUS. Surgical ligation of the coronary artery was used for induction of HF. In vivo electrophysiological study was performed to check VAs susceptibility. Left stellate ganglion (LSG) neural activity and heart rate variability (HRV) were used to test sympathetic nerve activity. RESULTS: Compared to the HF group, LIPUS treatment significantly ameliorated HF-induced cardiac hypertrophy, fibrosis, and dysfunction. In addition, LIPUS treatment markedly inhibited HF-induced VAs susceptibility and reversed gap junction remodeling. LIPUS treatment obviously inhibited microglial activation and neuroinflammation in PVN, sympathetic hyperactivity in the LSG and proinflammatory cytokines releases in the ventricle. P2X7/NLRP3 signaling pathway may be involved in the anti-arrhythmic effect of LIPUS treatment following HF. CONCLUSIONS: Our data demonstrated that LIPUS treatment protected against HF-induced VAs via alleviating microglia-mediated neuroinflammation, sympathetic overactivation and proinflammatory cytokines releases through inhibiting P2X7/NLRP3 signaling. This study provides novel insight into the therapeutic potential of LIPUS.

Macrophage-targeted ultrasound nanobubbles for highly efficient sonodynamic therapy of atherosclerotic plaques by modulating M1-to-M2 polarization.

BACKGROUND AND AIMS: Sonodynamic therapy (SDT) is a new approach for the treatment of atherosclerosis (AS), yet the poor targeting ability of sonosensitizers limits its therapeutic efficacy. Herein, we reported a plaque-targeted nanoplatform modified with macrophage type A scavenger receptor (SR-A)-targeted peptide (designated as SR-A-Ce6NB) to augment the efficacy of low-intensity pulsed ultrasound (LIPUS)-mediated SDT of atherosclerotic plaque. METHODS: SR-A-Ce6NB was fabricated by thin hydration method and biotin-avidin system, and its physicochemical properties, biocompatibility and plaque-targeting ability were investigated. RAW 264.7 cells were used for in vitro experimental studies. Male 6-week-old apolipoprotein E-deficient mice were fed a high-fat diet for 16 weeks to induce aortic atherosclerotic plaques. Plaque-bearing mice were randomly allocated into five groups (n = 6): control group, Ce6 + LIPUS group, Ce6NB + LIPUS group, SR-A-Ce6NB + LIPUS group and atorvastatin group. After treatment in each group, the aortic artery was harvested for Oil red O, H&E, Masson's trichrome staining, immunohistochemical and immunofluorescent staining. RESULTS: SR-A-Ce6NB with high stability and excellent biocompatibility was successfully fabricated. SR-A-Ce6NB could actively target activated macrophages and selectively accumulate in the plaque. SR-A-Ce6NB could be triggered by LIPUS and had a more potent sonodynamic effect than free Ce6 to potentiate SDT. SR-A-Ce6NB-mediated SDT enhanced the anti-atherogenic effect via modulating M1-to-M2 macrophage polarization and had an earlier onset of action on plaque than the statin-mediated effect. No apparent side effect was observed after intravenous SR-A-Ce6NB injection and LIPUS exposure. CONCLUSIONS: Macrophage-targeted nanoplatform SR-A-Ce6NB-mediated SDT provides a safe, effective and preferable anti-atherogenic therapy by mediating M1-to-M2 macrophage polarization.

[Evolution of Research Related to Macrophage Polarization in Atherosclerosis:A Visualization Analysis].

Objective To explore the research status,hotspots,and development tendency of macrophage polarization (MP) in atherosclerosis (AS) by systematically reviewing and visually analyzing the articles published recently in this field,so as to provide new ideas for the basic research and translational research on MP in the prevention and treatment of AS.Methods SCI-Expanded was used as the data source for the retrieval of the articles involving MP in AS from 2012 to 2022.CiteSpace 6.1.R3 was employed to visualize the node information of the publishing country/region,institutions,authors,keywords,and citations.Results A total of 381 papers were included.The number of publications in the world showed an increasing trend year by year.China and the United States were leading this field in the number and centrality of publications,and Shandong University in China contributed the largest number of publications.The analysis of the key words and citations showed that the hotspots and frontiers in this field mainly included the pathogenesis of AS,MP markers,macrophage plasticity regulation,and potential therapeutic targets for AS.Conclusions The research on MP in AS was booming during 2012-2022.The differential gene expression and the molecular mechanism of targeted therapy of MP in AS are the research trends in this field,which will provide new measures for the prevention and treatment of AS.

Low-intensity pulsed ultrasound of different intensities differently affects myocardial ischemia/reperfusion injury by modulating cardiac oxidative stress and inflammatory reaction.

Introduction: The prevalence of ischemic heart disease has reached pandemic levels worldwide. Early revascularization is currently the most effective therapy for ischemic heart diseases but paradoxically induces myocardial ischemia/reperfusion (MI/R) injury. Cardiac inflammatory reaction and oxidative stress are primarily involved in the pathology of MI/R injury. Low-intensity pulsed ultrasound (LIPUS) has been demonstrated to reduce cell injury by protecting against inflammatory reaction and oxidative stress in many diseases, including cardiovascular diseases, but rarely on MI/R injury. Methods: This study was designed to clarify whether LIPUS alleviates MI/R injury by alleviating inflammatory reaction and oxidative stress. Simultaneously, we have also tried to confirm which intensity of the LIPUS might be more suitable to ameliorate the MI/R injury, as well as to clarify the signaling mechanisms. MI/R and simulated ischemia/reperfusion (SI/R) were respectively induced in Sprague Dawley rats and human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). LIPUS treatment, biochemical measurements, cell death assay, estimation of cardiac oxidative stress and inflammatory reaction, and protein detections by western blotting were performed according to the protocol. Results: In our study, both in vivo and in vitro, LIPUS of 0.1 W/cm2 (LIPUS0.1) and 0.5 W/cm2 (LIPUS0.5) make no significant difference in the cardiomyocytes under normoxic condition. Under the hypoxic condition, MI/R injury, inflammatory reaction, and oxidative stress were partially ameliorated by LIPUS0.5 but were significantly aggravated by LIPUS of 2.5 W/cm2 (LIPUS2.5) both in vivo and in vitro. The activation of the apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) pathway in cardiomyocytes with MI/R injury was partly rectified LIPUS0.5 both in vivo and in vitro. Conclusion: Our study firstly demonstrated that LIPUS of different intensities differently affects MI/R injury by regulating cardiac inflammatory reaction and oxidative stress. Modulations on the ASK1/JNK pathway are the signaling mechanism by which LIPUS0.5 exerts cardioprotective effects. LIPUS0.5 is promising for clinical translation in protecting against MI/R injury. This will be great welfare for patients suffering from MI/R injury.

Ultrasound-controlled nano oxygen carriers enhancing cell viability in 3D GelMA hydrogel for the treatment of myocardial infarction.

Heart failure is a critical and ultimate phase of cardiovascular ailment that leads to a considerable incidence of disability and mortality. Among various factors contributing to heart failure, myocardial infarction is one of the most frequent and significant causes, which is still difficult to manage effectively. An innovative therapeutic strategy, namely a 3D bio-printed cardiac patch, has recently emerged as a promising approach to substitute damaged cardiomyocytes in a localized infarct region. Nevertheless, the efficacy of this treatment primarily relies on the long-term viability of the transplanted cells. In this study, we aimed to construct acoustically sensitive nano oxygen carriers to improve cell survival inside the bio-3D printed patch. In this study, we initially created nanodroplets capable of phase transition triggered by ultrasound and integrated them into GelMA (Gelatin Methacryloyl) hydrogels, which were then employed for 3D bioprinting. After adding nanodroplets and ultrasonic irradiation, numerous pores appeared inside the hydrogel with improved permeability. We further encapsulated hemoglobin into nanodroplets (ND-Hb) to construct oxygen carriers. Results of in vitro experiments showed the highest cell survival within the patch of ND-Hb irradiated by the low-intensity pulsed ultrasound (LIPUS) group. The genomic analysis discovered that the increased survival of seeded cells within the patch might be related to the protection of mitochondrial function owing to the improved hypoxic state. Eventually, in vivo studies revealed that the LIPUS+ND-Hb group had improved cardiac function and increased revascularization after myocardial infarction. To summarize, our study successfully improved the permeability of the hydrogel in a non-invasive and efficient manner, facilitating the exchange of substances in the cardiac patch. Moreover, ultrasound-controlled oxygen release augmented the viability of the transplanted cells and expedited the repair of infarcted tissues.

Molecular imaging research in atherosclerosis: A 23-year scientometric and visual analysis.

Background: Cardiovascular and cerebrovascular diseases are major global health problems, and the main cause is atherosclerosis. Recently, molecular imaging has been widely employed in the diagnosis and therapeutic applications of a variety of diseases, including atherosclerosis. Substantive facts have announced that molecular imaging has broad prospects in the early diagnosis and targeted treatment of atherosclerosis. Objective: We conducted a scientometric analysis of the scientific publications over the past 23 years on molecular imaging research in atherosclerosis, so as to identify the key progress, hotspots, and emerging trends. Methods: Original research and reviews regarding molecular imaging in atherosclerosis were retrieved from the Web of Science Core Collection database. Microsoft Excel 2021 was used to analyze the main findings. CiteSpace, VOSviewer, and a scientometric online platform were used to perform visualization analysis of the co-citation of journals and references, co-occurrence of keywords, and collaboration between countries/regions, institutions, and authors. Results: A total of 1755 publications were finally included, which were published by 795 authors in 443 institutions from 59 countries/regions. The United States was the top country in terms of the number and centrality of publications in this domain, with 810 papers and a centrality of 0.38, and Harvard University published the largest number of articles (182). Fayad, ZA was the most productive author, with 73 papers, while LIBBY P had the most co-citations (493). CIRCULATION was the top co-cited journal with a frequency of 1,411, followed by ARTERIOSCL THROM VAS (1,128). The co-citation references analysis identified eight clusters with a well-structured network (Q = 0.6439) and highly convincing clustering (S = 0.8865). All the studies calculated by keyword co-occurrence were divided into five clusters: "nanoparticle," "magnetic resonance imaging," "inflammation," "positron emission tomography," and "ultrasonography". Hot topics mainly focused on cardiovascular disease, contrast media, macrophage, vulnerable plaque, and microbubbles. Sodium fluoride ⁃PET, targeted drug delivery, OCT, photoacoustic imaging, ROS, and oxidative stress were identified as the potential trends. Conclusion: Molecular imaging research in atherosclerosis has attracted extensive attention in academia, while the challenges of clinical transformation faced in this field have been described in this review. The findings of the present research can inform funding agencies and researchers toward future directions.

Levels of systemic inflammation response index are correlated with tumor-associated bacteria in colorectal cancer.

The relationship between systemic inflammation and tumor-associated bacteria is largely unknown in colorectal cancer (CRC). The primary aim of this study was to investigate the prognostic effects of the systemic inflammation response index (SIRI) on the survival outcomes of CRC patients who experienced surgical therapy, and the second aim was to reveal the potential association between SIRI levels and tumor-associated bacteria in CRC. We recruited a cohort of 298 CRC patients who experienced surgical resection in Wuhan Union Hospital. These patients were assigned to the low and high groups based on the cut-off value of SIRI. We utilized 1:1 propensity score matching (PSM) to reduce the potential confounding factors between the low SIRI group (N = 83) and the high SIRI group (N = 83). The total DNA of 166 paraffin-embedded tumor tissues and 24 frozen tumor tissues was extracted and amplified, and 16 S rRNA sequencing was employed to uncover the composition of microbiota between low and high SIRI groups. Survival analysis uncovered that the high SIRI cohort exhibited significantly shorter overall and disease-free survival time than low SIRI companions after PSM. The ROC analyses showed that the prediction abilities of SIRI were much higher than other serum inflammatory biomarkers for survival outcomes. The microbial richness and diversity in the low SIRI group were remarkably higher than those in the high SIRI group. At the phylum level, we found that Proteobacteria, Synergistetes, WPS-2, Thermil, Fusobacteria were enriched in the high SIRI group. Cupriavidus, Thermus, Ochrobactrum, Cupriavidus, Acidovorax were enriched in the high SIRI group at the genus level. 16 S rRNA based on frozen samples also obtained similar results. SIRI is a promising and novel prognostic biomarker among CRC sufferers who underwent surgical removal. There existed significant differences in the diversity and compositions of tumor-associated bacteria between the low and high SIRI groups.

Predictive Value of the Transthoracic Echocardiography Index for Acute Kidney Injury after Cardiac Valve Surgery.

Background: We aimed to demonstrate whether the preoperative transthoracic echocardiography index (TTEI) could improve the predictive value of clinical parameters for cardiac valve surgery-associated acute kidney injury (CVS−AKI). Methods: A total of 213 patients who underwent surgical CVS at Renmin Hospital of Wuhan University were consecutively recruited in this retrospective study. TTE assessments were performed within 7 days before surgery and logistic regression was used to determine TTEI. A nomogram was constructed by integrating TTEI and clinical features, and the net reclassification index (NRI) and integrated discrimination improvement (IDI) were applied to evaluate the improvement in TTEI for CVS−AKI. Results: Among them, 66 patients (30.9%) developed CVS−AKI. The TTEI was calculated as follows: −6.579 + 0.068 × pulmonary artery systolic pressure (mmHg) −0.742 × LVEF (>55%, yes or no) + 0.346 × left ventricle posterior wall thickness (mm). The nomogram based on the TEEI and other clinical factors possessed excellent performance (C-index = 0.880), had great calibration and discrimination, and was clinically useful. Furthermore, NRI (0.07, 95% confidence interval, 95%CI, 0.01−0.12, p = 0.02) and IDI (0.08, 95%CI, 0.01−0.20, p = 0.02) indicated that TTEI could significantly improve the predictive value of clinical features for CVS−AKI. Conclusions: As a simple access and cost-effective parameter, the preoperative TTEI may be a reliable and useful factor for CVS−AKI.

APOA1 mRNA and protein in kidney renal clear cell carcinoma correlate with the disease outcome.

Renal cancer is one of the most common malignant tumors with high mortality, and kidney renal clear cell carcinoma (KIRC) is the most common type of renal cancer. We attempted to evaluate the clinical and prognostic significance of Apolipoprotein A1 (APOA1) mRNA and protein in KIRC patients. Clinical data along with RNA-sequencing data were downloaded from UCSC Xena. The Human Protein Atlas database was searched to reveal APOA1 protein expression profiles in KIRC and normal renal tissues. The TIMER database was applied to determine the correlations of APOA1 with immune cells and PD-1 and PD-L1 in KIRC. Ninety-one cases of KIRC patients and 93 healthy controls from our hospital were enrolled for clinical validation. Levels of APOA1 mRNA in KIRC tissues (N = 535) are not only lower than the levels in normal renal tissues (N = 117), but also in paired normal renal tissues (N = 72). High expression of APOA1 mRNA at the time of surgery was correlated with worse overall survival (OS) (HR 1.66; p = 0.037) and disease-free survival (DFS) (HR 1.65; p = 0.047), and APOA1 DNA methylation was linked to worse OS (HR 2.1; p = 0.001) rather than DFS (HR 1.12; p = 0.624) in KIRC patients. Concentrations of preoperative serum APOA1 protein were markedly decreased in KIRC patients compared to healthy controls (p < 0.01), and low levels of APOA1 protein predicted less favorable OS than those with high levels (HR = 2.84, p = 0.0407). APOA1 negatively correlated with various immune cell infiltrates and PD-L1 expression (r = - 0.283, p = 2.74e-11) according to the TIMER database. Low levels of APOA1 mRNA at the time of surgery predict favorable survival in KIRC patients. Our results provide insights to identify a novel prognostic index with great clinical utility.

Nomograms based on lactate dehydrogenase to albumin ratio for predicting survival in colorectal cancer.

Purpose: We aimed to determine if lactate dehydrogenase to albumin ratio (LAR) might play a prognostic role for patients with operable colorectal cancer (CRC). Patients and Methods: 1334 operable CRC patients in Wuhan Union Hospital Between July 2013 and September 2017 were enrolled in this study and were randomly appointed them into training (n=954) and validation (n=380) sets. The relationship between LAR and overall survival (OS) and disease-free survival (DFS) were determined by restricted cubic splines (RCS) with Cox regression models. LAR was then divided into three categories based on the RCS and compared to the well-known TNM stage system. Finally, survival nomograms were developed by compounding the LAR and other clinical factors. Results: Baseline LAR values and the all-cause mortality were U shaped, which slowly decreased until around 4.50 and then started to increase rapidly when the LAR ranged from 4.50-6.68 and then became flat thereafter (P for non-linearity <0.001). LAR was superior to TNM stage for OS as well as DFS and LAR plus TNM stage could add more net benefit than clinical model alone. Moreover, the survival nomograms based on LAR achieved great predictive ability for OS and DFS in operable CRC patients. Conclusions: LAR could be served as a reliable prognostic factor for OS as well as DFS, with more accurate prognostic prediction than current TNM stage for patients with operable CRC.

Low-intensity pulsed ultrasound promotes cell viability and inhibits apoptosis of H9C2 cardiomyocytes in 3D bioprinting scaffolds via PI3K-Akt and ERK1/2 pathways.

The aim of this study was to investigate whether low-intensity pulsed ultrasound (LIPUS) promotes myocardial cell viability in three-dimensional (3D) cell-laden gelatin methacryloyl (GelMA) scaffolds. Cardiomyoblasts (H9C2s) were mixed in 6% (w/v) GelMA bio-inks and printed using an extrusion-based 3D bioprinter. These scaffolds were exposed to LIPUS with different parameters or sham-irradiated to optimize the LIPUS treatment. The viability of H9C2s was measured using Cell Counting Kit-8 (CCK8), cell cycle, and live and dead cell double-staining assays. Western blot analysis was performed to determine the protein expression levels. We successfully fabricated 3D bio-printed cell-laden GelMA scaffolds. CCK8 and live and dead cell double-staining assays indicated that the optimal conditions for LIPUS were a frequency of 0.5 MHz and an exposure time of 10 min. Cell cycle analysis showed that LIPUS promoted the entry of cells into the S and G2/M phases from the G0/G1 phase. Western blot analysis revealed that LIPUS promoted the phosphorylation and activation of ERK1/2 and PI3K-Akt. The ERK1/2 inhibitor (U0126) and PI3K inhibitor (LY294002) significantly reduced LIPUS-induced phosphorylation of ERK1/2 and PI3K-Akt, respectively, which in turn reduced the LIPUS-induced viability of H9C2s in 3D bio-printed cell-laden GelMA scaffolds. A frequency of 0.5 MHz and exposure time of 10 min for LIPUS exposure can be adapted to achieve optimized culture effects on myocardial cells in 3D bio-printed cell-laden GelMA scaffolds via the ERK1/2 and PI3K-Akt signaling pathways.

Prognostic value of myocardial contrast echocardiography in acute anterior wall ST-segment elevation myocardial infarction with successful epicardial recanalization.

Although myocardial contrast echocardiography (MCE) can evaluate microvascular perfusion abnormalities, its prognostic value is uncertain in acute anterior wall ST-Segment elevation myocardial infarction (STEMI) with successful epicardial recanalization. Therefore, the study aims to investigate the prognostic role of qualitative and quantitative MCE in acute anterior wall STEMI with successful epicardial recanalization. 153 STEMI patients were assessed by MCE within 7 days after successful epicardial recanalization. Qualitative perfusion parameters (microvascular perfusion score index, MPSI) and quantitative perfusion parameters (A, ß, and Aß) were acquired using a 17-segment model. And corrected A and Aß were calculated. Patients were all followed for major adverse cardiovascular events (MACEs). During median follow-up of 27 (4) months, 39 (25.49%) patients experienced MACEs, while 114 (74.51%) were free from MACEs. Patients with MACEs had higher MPSI (1.65 ± 0.13 vs. No-MACEs 1.35 ± 0.20, P < 0.001), lower ß (1.09 ± 0.19 s-1 vs. No-MACEs 1.34 ± 0.30 s-1, P < 0.001), corrected A (0.17 ± 0.03 dB vs. No-MACEs 0.19 ± 0.04 dB, P = 0.039) and lower corrected Aß (0.19 ± 0.06 dB/s vs. No-MACEs 0.25 ± 0.08 dB/s, P < 0.001). MPSI of 1.44 provided an area under the curve (AUC) of 0.872, while ß of 1.18 s-1 and corrected Aß of 0.22 dB/s provided AUCs of 0.759 and 0.724, respectively. The combination of MPSI, ß and corrected Aß provided an increased AUC of 0.964 (all P < 0.05). Time-dependent ROC analysis showed that the AUCs of the MPSI, ß, corrected Aß and the combination at 1, 1.5 and 2 years indicated a strong predictive power for MACEs (AUC = 0.900/0.894/0.881 for MPSI, 0.648/0.704/0.732 for ß, 0.674/0.686/0.722 for corrected Aß, and 0.947/0.962/0.967 for the combination, respectively). Patients with MPSI < 1.44, ß > 1.18 s-1, or corrected Aß > 0.22 dB/s had lower event rate (all Log Rank P ≤ 0.001). MPSI, ß, corrected Aß, GLS and WBC were independent predictors of MACEs with adjusted hazard ratio of 34.41 (8.18-144.87), P < 0.001 for MPSI; 39.29 (27.46-65.44), P < 0.001 for ß; 8.93 (1.46-54.55), P = 0.018 for corrected Aß; 10.88 (2.83-41.86), P = 0.001 for GLS; and 1.43 (1.16-1.75), P = 0.001 for WBC. Qualitative and quantitative MCE can accurately predict MACEs in acute anterior wall STEMI with successful epicardial recanalization, and their combined predictive value is higher.

Utilization of Echocardiography After Acute Kidney Injury Was Associated with Improved Outcomes in Patients in Intensive Care Unit.

BACKGROUND: We aimed to investigate the association between usage of transthoracic echocardiography (TTE) within 24 hours after acute kidney injury (AKI) and the prognosis of patients in intensive care unit (ICU). METHODS: The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to identify AKI patients with and without TTE administration. The primary outcome was 28-day mortality. Multivariable regression was used to clarify the association between TTE and clinical outcomes and propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to validate our findings. RESULTS: Among 23,945 eligible AKI patients, 3361 patients who received TTE and 3361 who did not conduct TTE had similar propensity scores which were included in this study. After matching, the TTE group had a significantly lower 28-day mortality (OR 0.80, 95% CI 0.72-0.88, P<0.001). Patients in the TTE group received more fluid on day 1 and day 2 and had a more urine volume on day 1 and day 3, and the reduction in serum creatinine was greater than that in the no TTE group. The mediating effect of creatinine reduction was remarkable for the whole cohort (P=0.02 for the average causal mediation effect). CONCLUSION: TTE utilization was associated with decreased risk-adjusted 28-day mortality for AKI patients in ICU and was proportionally mediated through creatinine reduction.

Prognostic nutritional index predicts acute kidney injury and mortality of patients in the coronary care unit.

The current study aimed to investigate whether prognostic nutritional index (PNI) is an independent predictor of acute kidney injury (AKI) and mortality of patients in the coronary care unit (CCU). In the present two-stage observational study of patients in the CCU, 6,444 patients from the Medical Information Mart for Intensive Care (MIMIC) III database were first enrolled (test cohort), after which 412 patients from Zhongnan Hospital of Wuhan University were recruited in the validation cohort. AKI was defined based on the Kidney Disease Improving Global Outcomes AKI criteria. The primary endpoint was the incidence of AKI stratified by severity, while the second endpoint included in-hospital mortality and 2-year mortality. In the test cohort, 4,457 (69.2%) patients developed AKI during hospitalization. Following multivariable adjustment, the highest quartile of the PNI value was associated with a 1.8-fold increased risk of AKI compared with the lowest quartile. For the prediction of AKI, the area under the receiver operating characteristic curve outperformed the acute physiology score III score and clinical model in patients with or without preexisting chronic kidney disease, and this was further validated in the hospital cohort used in the present study. A total of 2,219 patients suffered mortality during the 2-year follow-up, and PNI was indicated to independently predict the risk of in-hospital mortality and 2-year mortality in the test cohort and in the validation cohort. Decision curve analysis indicated that the PNI values were clinically useful; Therefore, the current study demonstrated that the PNI value is an independent predictor of AKI and mortality in patients within the CCU.

Three-dimensional printing for cardiovascular diseases: from anatomical modeling to dynamic functionality.

Three-dimensional (3D) printing is widely used in medicine. Most research remains focused on forming rigid anatomical models, but moving from static models to dynamic functionality could greatly aid preoperative surgical planning. This work reviews literature on dynamic 3D heart models made of flexible materials for use with a mock circulatory system. Such models allow simulation of surgical procedures under mock physiological conditions, and are; therefore, potentially very useful to clinical practice. For example, anatomical models of mitral regurgitation could provide a better display of lesion area, while dynamic 3D models could further simulate in vitro hemodynamics. Dynamic 3D models could also be used in setting standards for certain parameters for function evaluation, such as flow reserve fraction in coronary heart disease. As a bridge between medical image and clinical aid, 3D printing is now gradually changing the traditional pattern of diagnosis and treatment.

Irradiation of carotid baroreceptor with low-intensity pulsed ultrasound exerts different metabolic protection in perirenal, epididymal white adipose tissue and interscapular brown adipose tissue of obese rats.

This study was designed to clarify whether the irradiation of carotid baroreceptor (CB) with low-intensity pulsed ultrasound (LIPUS) protects against obesity by rebalancing the autonomic nervous system (ANS). Obesity was induced using a high-fat diet (HFD) for 8 weeks in Sprague-Dawley rats. Irradiation with LIPUS was daily (20 minutes a day) applied to the right CB. In our study, LIPUS significantly ameliorated metabolic disorders in obese rats. LIPUS partly restored norepinephrine (NE) and acetylcholine (ACH) levels in the perirenal white adipose tissue (PWAT), epididymal white adipose tissue (EWAT), interscapular brown adipose tissue (IBAT), and plasma of obese rats. LIPUS partially rectified the dysregulated AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor (PPAR) α/É£ pathway in the PWAT, EWAT, and IBAT of obese rats. PPARγ and PPARγ target genes respond more sensitively to HFD and LIPUS in PWAT and EWAT than in IBAT. NE, ACH, uncoupling protein-1, phosphorylated AMPK, PPARα, and PPARα target genes respond more sensitively to HFD and LIPUS in IBAT than in PWAT and EWAT. Conclusion: LIPUS irradiation of CB exerts different metabolic protection in PWAT, EWAT, and IBAT by rebalancing the ANS and rectifying the AMPK/PPARα/É£ pathway in obese rats.

Psychological impact of healthcare workers in China during COVID-19 pneumonia epidemic: A multi-center cross-sectional survey investigation.

BACKGROUND: Since the outbreak of 2019 new coronavirus (COVID-19) pneumonia, healthcare workers (HCW) have suffered psychological stress. The present study is to examine the prevalence of stress, anxiety and depression of HCW in China during the COVID-19 epidemic, and to determine the risk factors predicting psychological morbidities that can be used as psychological intervention targets. METHODS: A cross-sectional survey was conducted to investigate the psychological levels of HCW in multiple centers in China. The prevalence of stress, anxiety and depression were determined by using Perceived Stress Scale (PSS-14) and Hospital Anxiety / Depression scale (HAD). Psychology related factors were evaluated and correlation between job title and contact history was analyzed. RESULTS: We received 958 of effective responses, 73.6% of which were from Wuhan and 67.2% were female participants. 55.1% of respondents had psychological stress that is higher than that of HCW during SARS. 54.2% and 58% of participants had symptoms of anxiety and depression. Stress levels of HCW were different in job titles and years of work experience. Anxiety and depression levels were different between different gender, job titles, degrees of protective measures and levels of contact history. Gender, intermediate title, protective measures and contact history were the independent risk factors for anxiety. Protective measures and contact history were the independent risk factors for depression. CONCLUSIONS: The COVID-19 epidemic has induced stress levels for HCW, and high percentages of HCW have anxiety and depression. The situation of HCW is worrying and intervention service is urgent.

An expression atlas of miRNAs in Arabidopsis thaliana.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate a variety of biological processes. MiRNA expression often exhibits spatial and temporal specificity. However, genome-wide miRNA expression patterns in different organs during development of Arabidopsis thaliana have not yet been systemically investigated. In this study, we sequenced small RNA libraries generated from 27 different organ/tissue types, which cover the entire life cycle of Arabidopsis. Analysis of the sequencing data revealed that most miRNAs are ubiquitously expressed, whereas a small set of miRNAs display highly specific expression patterns. In addition, different miRNA members within the same family have distinct spatial and temporal expression patterns. Moreover, we found that some miRNAs are produced from different arms of their hairpin precursors at different developmental stages. This work provides new insights into the regulation of miRNA biogenesis and a rich resource for future investigation of miRNA functions in Arabidopsis.

Red Blood Cell Distribution Width is an Independent Predictor of AKI and Mortality in Patients in the Coronary Care Unit.

BACKGROUND/AIMS: We investigated the hypothesis that RDW is an independent predictor of acute kidney injury (AKI) and mortality in patients in the coronary care unit (CCU). METHODS: In this prospective, observational study, we screened 412 adults admitted to the CCU at Zhongnan Hospital of Wuhan University from January 1, 2014 to June 1, 2015. AKI was defined based on the KDIGO-AKI criteria. The survivors were followed up for up to 2 years after hospital discharge. The primary endpoint of the study was the incidence of AKI, while the secondary endpoints of the study were in-hospital mortality and 2-year mortality. RESULTS: RDW was significantly correlated with the acute physiology and chronic health evaluation II (APACHEII) score, hemoglobin, mean corpuscular volume, inflammatory marker levels, nutrition and renal function at the time of CCU admission. The incidence of AKI was much higher in the high RDW group (RDW ≥14.0%) than in the low RDW group, a finding that was confirmed by multivariable logistic regression, which showed that RDW was independently associated with the incidence of AKI (odds ratio (OR), 1.059, 95% coincidence interval (95% CI), 1.024-1.095, P=0.001). A total of 61 patients died during their hospital stay, and baseline RDW was also an independent predictor of in-hospital mortality (hazard ratio (HR), 1.129, 95% CI 1.005-1.268, P=0.041). Patients with a high RDW exhibited significantly higher 2-year mortality than patients with a low RDW during a median follow-up period of 19.8 months (P<0.001), and RDW independently predicted the risk of 2-year mortality (HR, 1.189, 95% CI 1.045 to 1.354, P=0.009) in the multivariate Cox proportional hazard analysis after adjustments for other clinical and laboratory variables. CONCLUSION: RDW is an independent predictor of AKI and mortality in patients in the CCU.