Application of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Benign and Malignant Subpleural Pulmonary Lesions.

OBJECTIVE: To explore the clinical value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of benign and malignant subpleural pulmonary lesions (SPLs). METHODS: Among 959 patients with SPLs who were scheduled to undergo ultrasound-guided puncture in our department between January 2019 and June 2019, 506 patients were included and their B-mode ultrasound and CEUS features, including the lesion's location, size, margin, echo, perfusion pattern of ultrasound contrast agent, degree of enhancement, homogeneity, vascular signs, and necrosis, were retrospectively investigated. All malignant cases were diagnosed by pathology, while benign cases were diagnosed by two respiratory physicians after comprehensive analysis of pathology, etiology, imaging, and clinical symptoms. Statistical differences in these features between the benign and malignant groups were then analyzed. RESULTS: There were 506 cases in this study, including 219 benign cases and 287 malignant cases. Among them, 351 were males and 155 were females, with an average age of 59 ± 16 years. There were statistically significant differences between benign and malignant groups in the perfusion pattern, the degree of enhancement, and vascular signs. The features of the malignant group included local-to-whole perfusion pattern, hypo-enhancement, and curly hair sign, while those of the benign group included a centrifugal perfusion pattern, iso-enhancement and hyper-enhancement, and dendritic sign. There was no statistically significant difference between the two groups in homogeneity and necrosis. CONCLUSIONS: CEUS enhancement mode is different between benign and malignant SPLs, which can provide supplementary information for the differential diagnosis of SPLs in the existing imaging diagnosis.

US Contrast Agent Arrival Time Difference Ratio for Benign versus Malignant Subpleural Pulmonary Lesions.

Background US has proven valuable in the diagnosis of subpleural pulmonary lesions (SPLs); however, existing US indicators have limitations. Purpose To propose and validate a revised contrast-enhanced (CE) US indicator for differential diagnosis of benign and malignant SPLs and to compare its performance with existing CE US diagnostic criteria. Materials and Methods This prospective study (Chinese clinical trial registry, ChiCTR1800019828) enrolled patients with SPLs between May 2019 and August 2020. They were divided into a developmental cohort (DC) and a validation cohort (VC). In the DC, the optimal indicator was selected from five CE US indicators. In the VC, the selected indicator was compared with existing CE US diagnostic criteria using the area under the receiver operating characteristic curve (AUC). Pathologic analysis, microbial evidence, and clinical follow-up were used as reference standards for all SPLs. Results A total of 902 participants (DC, 424 participants; VC, 478 participants) with SPLs (mean age, 56 years ± 17; 593 men) were evaluated. The arrival time (AT) difference ratio proved to be the optimal indicator to distinguish benign from malignant SPLs. In the overall (regardless of lesion size), large (vertical diameter >3 cm), and small (vertical diameter ≤3 cm) lesion groups, the cutoff values of the AT difference ratio were 43%, 42%, and 50% and the AUCs obtained from the VC were 0.91 (95% CI: 0.88, 0.93), 0.97 (95% CI: 0.94, 0.98), and 0.77 (95% CI: 0.71, 0.83) respectively, which were higher than those of lesion-lung AT difference greater than 2.5 seconds (0.81 [P < .001], 0.85 [P < .001], and 0.7 [P = .005], respectively), lesion AT greater than 7.5 seconds (0.65 [P < .001], 0.64 [P < .001], and 0.63 [P < .001], respectively), and lesion AT greater than 10 seconds (0.67 [P < .001], 0.68 [P < .001], and 0.64 [P < .001] respectively). Conclusion The US contrast agent arrival time difference ratio enables better differentiation of benign and malignant subpleural lesions when compared with existing diagnostic criteria. Online supplemental material is available for this article. Published under a CC BY 4.0 license.

Clinical performance of Xpert MTB/RIF on contrast-enhanced ultrasound-guided core biopsy specimens for rapid diagnosis of superficial tuberculous lymphadenitis in high TB burden settings.

OBJECTIVE: The diagnosis of superficial tuberculous lymphadenitis (TBLN) remains difficult due to low detection rate of etiology. To increase the diagnostic value for TBLN, contrast-enhanced ultrasound (CEUS) guided core biopsy was introduced to obtain the specimen followed by Xpert MTB/RIF (Xpert) and other methods testing and to explore the optimum diagnostic pattern for TBLN in China. METHODS: A prospective study was performed on patients with suspected superficial TBLN. All patients underwent CEUS-guided core biopsy from which specimens were tested by histopathology, Xpert, acid-fast bacilli (AFB), and MGIT960 culture (MGIT960), respectively. The diagnostic values were calculated and compared. RESULTS: A total of 328 patients were included the study, 272 were diagnosed as TBLN (254 definite TB, 18 probable TB) and 56 cases with Non-TBLN, and 100% (272/272) of TBLN patients obtained diagnosis sampled by CEUS-guided core biopsy. The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of comprehensive diagnosis on the specimens by CEUS-guided core biopsy for TBLN were 100% ( 272/272, 95% CI 98.26-100.00), 94.64% (53/56, 95% CI 84.20-98.61), 98.91% (272/275, 95% CI 96.58-99.72), and 100% (53/53, 95% CI 91.58-100%), respectively. Xpert obtained 93.31% (237/254) of etiology detection rate on the specimens sampling by CEUS-guided biopsy. The etiology detection rate was associated with histopathological caseous necrosis. CONCLUSIONS: Current examinations on specimens by CEUS-guided core biopsy can achieve a high diagnostic efficacy for TBLN. Pathological differentiation of CEUS-guided biopsy tissue, then followed by Xpert, may be the best pattern for the diagnosis of TBLN in high TB burden areas.

Application of neck ultrasound in the diagnosis of sarcoidosis.

OBJECTIVE: To explore the significance of neck ultrasound (NUS) combined with contrast-enhanced ultrasound (CEUS) in the diagnosis of sarcoidosis. METHODS: 88 patients with evidence of intrathoracic lymphadenopathy and suspected sarcoidosis with enlarged cervical lymph nodes underwent NUS, CEUS, fine-needle aspiration and core needle biopsy when technically feasible were retrospectively analyzed in this study. Seven characteristics such as enhanced mode (EM), resolution time, color Doppler flow imaging (CDFI), fading time, peaking state-uniformity, strengthen the area and symmetry were considered to perform the logistic regression model. RESULTS: Of 88 patients included in this study, sarcoidosis was accounted in 20 cases, tuberculosis in 23 cases, malignancy in 22 cases and inflammatory lymph node in 23 cases. There were statistically significant differences in symmetry, lymphatic hilum, homogeneity, CDFI pattern and elasticity score between the sarcoidosis and non-sarcoidosis groups via NUS. Similarly, we also acknowledged a statistically significant differences in EM, homogeneity, presence or absence of necrosis between the sarcoidosis and non-sarcoidosis groups via CEUS to further group the non-sarcoidosis into tuberculosis, malignancy or inflammatory disorder. The percentage correction of prediction was 90% (18/20). CONCLUSION: NUS combined with CEUS has characteristic features in sarcoidosis with cervical lymph node involvement, which is helpful for its diagnosis and differential diagnosis. The binary classification model of NUS combined with CEUS features can help differentiate sarcoidosis from non-sarcoidosis groups.

Boundary Restored Network for Subpleural Pulmonary Lesion Segmentation on Ultrasound Images at Local and Global Scales.

To evaluate the application of machine learning for the detection of subpleural pulmonary lesions (SPLs) in ultrasound (US) scans, we propose a novel boundary-restored network (BRN) for automated SPL segmentation to avoid issues associated with manual SPL segmentation (subjectivity, manual segmentation errors, and high time consumption). In total, 1612 ultrasound slices from 255 patients in which SPLs were visually present were exported. The segmentation performance of the neural network based on the Dice similarity coefficient (DSC), Matthews correlation coefficient (MCC), Jaccard similarity metric (Jaccard), Average Symmetric Surface Distance (ASSD), and Maximum symmetric surface distance (MSSD) was assessed. Our dual-stage boundary-restored network (BRN) outperformed existing segmentation methods (U-Net and a fully convolutional network (FCN)) for the segmentation accuracy parameters including DSC (83.45 ± 16.60%), MCC (0.8330 ± 0.1626), Jaccard (0.7391 ± 0.1770), ASSD (5.68 ± 2.70 mm), and MSSD (15.61 ± 6.07 mm). It also outperformed the original BRN in terms of the DSC by almost 5%. Our results suggest that deep learning algorithms aid fully automated SPL segmentation in patients with SPLs. Further improvement of this technology might improve the specificity of lung cancer screening efforts and could lead to new applications of lung US imaging.

Spautin-A41 Attenuates Cerulein-Induced Acute Pancreatitis through Inhibition of Dysregulated Autophagy.

Autophagy plays key roles in the development of acute pancreatitis (AP) and the regulation of impaired autophagy has therapeutic potential. The objective of the present study was to investigate whether pharmacological inhibition of autophagy could ameliorate AP in mice and examine the underlying mechanisms. In current study, by imaging-based high-throughput screening, a novel spautin-1 derivative spautin-A41 was identified as a potent autophagy inhibitor. Mice treated with spautin-A41 were resistant to the cerulein-induced elevation of serum pancreatic enzyme activities and pancreatic apoptosis. Mechanistically, spautin-A41 effectively reduced the expression levels of Class III phosphatidylinositol 3 (PI3) kinase complexes and subsequently ameliorated pancreatitis by inhibiting the formation of autophagosome. Therefore, pharmacological inhibition of autophagy by spautin-A41 may serve as new target for treating or lessening the severity of AP.

Observation and mechanism study of bladder wound healing after transurethral holmium laser resection of bladder tumor.

This research aims to observe and compare the wound healing process of urethral bladder after transurethral holmium laser resection of bladder tumor (HoLRBT) and transurethral resection of bladder tumor (TURBT) and explore the possible mechanism of wound healing and bladder re-epithelialization after HoLRBT. An animal model of canine achieving HoLRBT and TURBT was established. Cystoscopy was performed at different time points (3 days and 1, 2, 3, and 4 weeks) after operation to observe the wound healing and re-epithelialization of bladder epithelium. Bladder mucosa specimens were obtained and histopathological changes of the bladder epithelium were observed under light microscope after HE staining. Immunochemistry was used to determine the cell expression ofCK5, CK14, EGF, EGFR; microRNA expressions of CK5, CK14, EGF, and EGFR were measured by qRT-PCR. The changes of urinary EGF concentration were detected by ELISA. The bladder epithelial wound was repaired and re-epithelialized at 1 week after HoLRBT. At the 4th week, the bladder wound was basically completed and re-epithelialized; repair of bladder epithelial wounds recapitulates the wounds with the proliferation and migration of residual epithelial cells under the wound and the bladder epithelium that proliferates alongside the wound surface to complete re-epithelialization. The process begins at 1 week after surgery and basically completes at 4 weeks after surgery. CK5 and CK14 positive cells were detected in the basal cells of the bladder epithelium after HoLRBT, and the expression of CK5 and CK14 mRNA in the basal cells of the bladder epithelium under hyperplasia was significantly higher than that of the normal bladder epithelial basal cells. Bladder epithelial wound repair of TURBT group was performed by the proliferative differentiation of the peri-bladder epithelium adjacent to the wound edge and crawled to the wound surface to complete the re-epithelialization process. The wound repair and re-epithelialization were significantly slower than HoLRBT group. The CK5 and CK14 positive cells can also be detected in the basal cells of marginal hyperplasia of basal margin, and the expression of CK5 and CK14 mRNA in the basal cells of the peri-bladder hyperplasia is obviously higher than that of the normal bladder epithelial basal cells. The expression of EGF in bladder regenerating epithelium gradually increased with time after HoLRBT. Bladder basal cells and bladder regenerating epithelium express high levels of EGFR after HoLRBT. The concentration of EGF in urine after HoLRBT and TURBT increased significantly after surgery, and peaked at 3 days after operation. The urinary EGF concentration in HoLRBT group was higher than that in TURBT group at 3 and 4 weeks after operation. The re-epithelialization process can be seen 1 week after the cystectomy with holmium laser cystectomy, and the epithelialization rate is faster than the traditional transection surgery. This is because the residual bladder epithelial stem cells and wound marginal epithelial cells are involved in the process of wound repair and re-epithelialization following HoLRBT. But only the marginal epithelial tissue participates in the re-epithelialization process after TURBT, so the repair rate of TURBT is slower. The repair of bladder epithelium after HoLRBT is related to the stimulation of tissue factor EGF. The regenerated bladder epithelium also participates in the wound repair process by means of autocrine of EGF.

Accurate diagnosis of severe coronary stenosis based on resting magnetocardiography: a prospective, single-center, cross-sectional analysis.

OBJECTIVE: To evaluate the role of resting magnetocardiography in identifying severe coronary artery stenosis in patients with suspected coronary artery disease. METHODS: A total of 513 patients with angina symptoms were included and divided into two groups based on the extent of coronary artery disease determined by angiography: the non-severe coronary stenosis group (< 70% stenosis) and the severe coronary stenosis group (≥ 70% stenosis). The diagnostic model was constructed using magnetic field map (MFM) parameters, either individually or in combination with clinical indicators. The performance of the models was evaluated using receiver operating characteristic curves, accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Calibration plots and decision curve analysis were performed to investigate the clinical utility and performance of the models, respectively. RESULTS: In the severe coronary stenosis group, QR_MCTDd, S_MDp, and TT_MAC50 were significantly higher than those in the non-severe coronary stenosis group (10.46 ± 10.66 vs. 5.11 ± 6.07, P < 0.001; 7.2 ± 8.64 vs. 4.68 ± 6.95, P = 0.003; 0.32 ± 57.29 vs. 0.26 ± 57.29, P < 0.001). While, QR_MVamp, R_MA, and T_MA in the severe coronary stenosis group were lower (0.23 ± 0.16 vs. 0.28 ± 0.16, P < 0.001; 55.06 ± 48.68 vs. 59.24 ± 53.01, P < 0.001; 51.67 ± 39.32 vs. 60.45 ± 51.33, P < 0.001). Seven MFM parameters were integrated into the model, resulting in an area under the curve of 0.810 (95% CI: 0.765-0.855). The sensitivity, specificity, PPV, NPV, and accuracy were 71.7%, 80.4%, 93.3%, 42.8%, and 73.5%; respectively. The combined model exhibited an area under the curve of 0.845 (95% CI: 0.798-0.892). The sensitivity, specificity, PPV, NPV, and accuracy were 84.3%, 73.8%, 92.6%, 54.6%, and 82.1%; respectively. Calibration curves demonstrated excellent agreement between the nomogram prediction and actual observation. The decision curve analysis showed that the combined model provided greater net benefit compared to the magnetocardiography model. CONCLUSIONS: The novel quantitative MFM parameters, whether used individually or in combination with clinical indicators, have been shown to effectively predict the risk of severe coronary stenosis in patients presenting with angina-like symptoms. Magnetocardiography, an emerging non-invasive diagnostic tool, warrants further exploration for its potential in diagnosing coronary heart disease.

Sonocatalytic Optimization of Titanium-Based Therapeutic Nanomedicine.

Recent considerable technological advances in ultrasound-based treatment modality provides a magnificent prospect for scientific communities to conquer the related diseases, which is featured with remarkable tissue penetration, non-invasive and non-thermal characteristics. As one of the critical elements that influences treatment outcomes, titanium (Ti)-based sonosensitizers with distinct physicochemical properties and exceptional sonodynamic efficiency have been applied extensively in the field of nanomedical applications. To date, a myriad of methodologies has been designed to manipulate the sonodynamic performance of titanium-involved nanomedicine and further enhance the productivity of reactive oxygen species for disease treatments. In this comprehensive review, the sonocatalytic optimization of diversified Ti-based nanoplatforms, including defect engineering, plasmon resonance modulation, heterojunction, modulating tumor microenvironment, as well as the development of synergistic therapeutic modalities is mainly focused. The state-of-the-art Ti-based nanoplatforms ranging from preparation process to the extensive medical applications are summarized and highlighted, with the goal of elaborating on future research prospects and providing a perspective on the bench-to-beside translation of these sonocatalytic optimization tactics. Furthermore, to spur further technological advancements in nanomedicine, the difficulties currently faced and the direction of sonocatalytic optimization of Ti-based therapeutic nanomedicine are proposed and outlooked.

A Model for Predicting Malignant Sub-pleural Solid Masses Using Grayscale Ultrasound and Ultrasound Elastography.

This article aimed to establish a prediction model of grayscale sonography and ultrasound elastography for malignant sub-pleural solid masses and evaluate its diagnostic value. The study included 153 patients, including 89 patients with malignant tumors and 64 patients with benign diseases. Statistical differences between the malignant and benign groups were found in the factors of age, air bronchogram, borderline, shape and elasticity score (p < 0.05). Age, elasticity score and borderline were effective factors for predicting malignant sub-pleural solid masses, offering an area under the receiver operating characteristic curve (AUROC) value of 0.72 (95% confidence interval [CI] 0.64-0.80), 0.73 (95% CI 0.65-0.79) and 0.70 (95% CI 0.62-0.77), respectively. The AUROC value of the prediction model for malignant sub-pleural solid masses was 0.88 (95% CI 0.81-0.92), which indicates that the prediction model was able to improve the diagnostic accuracy and that it may prove a useful auxiliary diagnostic tool for malignant sub-pleural solid masses, especially in primary health care institutions in developing countries.

Off-clamp Retroperitoneoscopic Tumour Evacuation for Sporadic Renal Angiomyolipomas with High RENAL Nephrometry Scores: A Novel Surgical Technique and Its Outcomes.

BACKGROUND: Partial nephrectomy or angioembolisation is commonly used for sporadic renal angiomyolipomas (RAMLs) with high RENAL scores, but there is a risk of reduced renal function, postoperative complications, and recurrence. OBJECTIVE: To describe a new technique for off-clamp laparoscopic evacuation of sporadic RAMLs with high RENAL scores that promotes maximal renal function maintenance and low postoperative complication and lesion recurrence rates. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort of patients undergoing off-clamp laparoscopic evacuation for sporadic RAMLs with RENAL scores ≥9 from January 2013 to June 2018 was included. SURGICAL PROCEDURE: We highlighted the curettage, suction, packing, and binding (CSPB) technique, a new off-clamp retroperitoneoscopic evacuation technique for sporadic RAMLs. MEASUREMENTS: Demographics, preoperative, intraoperative, and postoperative outcomes were assessed. RESULTS AND LIMITATIONS: A total of 141 cases were included. The median (interquartile range [IQR]) tumour size was 7 (6.2-8.2)cm. The median (IQR) RENAL score was 10 (9-11). The median (IQR) operative time was 80 (65-125) min, with a median (IQR) estimated blood loss of 130 (90-362.5)ml. Conversion to neither open surgery nor standard laparoscopy occurred. The warm ischaemia time was zero for all cases. Postoperatively, 13 minor complications (Clavien grade 1) were recorded. No blood transfusions were reported. The glomerular filtration rate did not change significantly from preoperative period to 12-mo follow-up. Recurrence did not occur at the median follow-up period of 48 (36-60) mo. The retrospective design and lack of a control group are limitations of this study. CONCLUSIONS: Off-clamp retroperitoneoscopic tumour evacuation using the CSPB technique is feasible, safe, and effective for treating complex sporadic RAMLs. PATIENT SUMMARY: We report a curettage, suction, packing, and binding technique for off-clamp retroperitoneoscopic evacuation of sporadic renal angiomyolipomas that leads to complete lesion clearance, excellent renal function preservation, and minimal perioperative complications.

Contrast-Enhanced Ultrasound of the Pleural Cavity: A Method to Locate Pleural Catheters and Identify Fibrous Septa.

We aimed to explore the value of contrast-enhanced ultrasound (CEUS) of the pleural cavity in locating catheters and identifying fibrous septa and to compare CEUS with multiple existing methods. We included 304 participants whose pleural effusion could not continue to be drained and compared the catheter-localization capabilities of empirical diagnosis, B-mode ultrasound with normal saline and CEUS, with computed tomography as the reference standard. CEUS performed the best (accuracy, 100%; sensitivity, 100%; specificity, 100%), followed by B-mode ultrasound with normal saline (accuracy, 77.78%; sensitivity, 62.5%; specificity, 100%), and finally empirical diagnosis (accuracy, 54.17%; sensitivity, 66.67%; specificity, 33.33%). The capabilities of CEUS and computed tomography to identify fibrous septa were evaluated, with B-mode ultrasound as the reference, and CEUS (accuracy, 100%; sensitivity, 100%; specificity, 100%) was superior to computed tomography (accuracy, 82.41%; sensitivity, 26.09%; specificity, 97.65%). Overall, CEUS can accurately locate catheters and identify fibrous septa, with performance superior to existing methods.

Development and Prospective Validation of an Ultrasound Prediction Model for the Differential Diagnosis of Benign and Malignant Subpleural Pulmonary Lesions: A Large Ambispective Cohort Study.

OBJECTIVE: To develop and prospective validate an ultrasound (US) prediction model to differentiate between benign and malignant subpleural pulmonary lesions (SPLs). METHODS: This study was conducted retrospectively from July 2017 to December 2018 (development cohort [DC], n = 592) and prospectively from January to April 2019 (validation cohort [VC], n = 220). A total of 18 parameters of B-mode US and contrast-enhanced US (CEUS) were acquired. Based on the DC, a model was developed using binary logistic regression. Then its discrimination and calibration were verified internally in the DC and externally in the VC, and its diagnostic performance was compared with those of the existing US diagnostic criteria in the two cohorts. The reference criteria were from the comprehensive diagnosis of clinical-radiological-pathological made by two senior respiratory physicians. RESULTS: The model was eventually constructed with 6 parameters: the angle between lesion border and thoracic wall, basic intensity, lung-lesion arrival time difference, ratio of arrival time difference, vascular sign, and non-enhancing region type. In both internal and external validation, the model provided excellent discrimination of benign and malignant SPLs (C-statistic: 0.974 and 0.980 respectively), which is higher than that of "lesion-lung AT difference ≥ 2.5 s" (C-statistic: 0.842 and 0.777 respectively, P <0.001) and "AT ≥ 10 s" (C-statistic: 0.688 and 0.641 respectively, P <0.001) and the calibration curves of the model showed good agreement between actual and predictive malignancy probabilities. As for the diagnosis performance, the sensitivity and specificity of the model [sensitivity: 94.82% (DC) and 92.86% (VC); specificity: 92.42% (DC) and 92.59% (VC)] were higher than those of "lesion-lung AT difference ≥ 2.5 s" [sensitivity: 88.11% (DC) and 80.36% (VC); specificity: 80.30% (DC) and 75.00% (VC)] and "AT ≥ 10 s" [sensitivity: 64.94% (DC) and 61.61% (VC); specificity: 72.73% (DC) and 66.67% (VC)]. CONCLUSION: The prediction model integrating multiple parameters of B-mode US and CEUS can accurately predict the malignancy probability, so as to effectively differentiate between benign and malignant SPLs, and has better diagnostic performance than the existing US diagnostic criteria. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR1800019828.

Combined use of cardiopulmonary ultrasound in the diagnosis of pulmonary edema in patients with heart failure: a retrospective analysis.

BACKGROUND: Heart failure (HF) is generally complicated with pulmonary edema (PE), the early diagnosis and treatment is essential. We aimed to evaluate the effects of combined use of cardiopulmonary ultrasound in the diagnosis of PE in HF patients, to provide reference for the management of HF. METHODS: HF patients treated in our hospital from January 1, 2019 to June 30, 2020 were included. All patients underwent echocardiography and lung ultrasonography, and analyzed the characteristics of patients and related detected results. Logistic regression analyses were conducted to identify the potential risk factors. And the receiver operating characteristic (ROC) curve was conducted to compare the predictive value of factors. RESULTS: A total of 183 HF patients were included, the incidence of PE in HF patients was 62.84%. Logistic regression analyses indicated that NT-proBNP (OR 2.24, 95% CI: 1.28-5.04), LAVI (OR 2.03, 95% CI: 1.02-4.45), E/e' (OR 1.57, 95% CI: 0.13-2.28), SPAP (OR 1.35, 95% CI: 0.02-2.84) were the independent risk factors for PE in patients with HF (all P<0.05). The AUC of NT-proBNP, LAVI, E/e' and SPAP were 0.705, 0.668, 0.674 and 0.691 respectively. NT-proBNP ≥8,842.37 ng/L, LAVI ≥42.14 mL/m2, E/e' ≥19.20, SPAP ≥38.16 mmHg were the independent risk factors for PE in patients with HF (all P<0.05). CONCLUSIONS: Combined use of cardiopulmonary ultrasound is beneficial to the early diagnosis of PE in patients with HF, and early interventions are needed for those patients with risk factors.

Effects of BIS-MEP on Reversing Amyloid Plaque Deposition and Spatial Learning and Memory Impairments in a Mouse Model of ß-Amyloid Peptide- and Ibotenic Acid-Induced Alzheimer's Disease.

Alzheimer's disease (AD) is the main type of dementia and is characterized by progressive memory loss and a notable decrease in cholinergic neuron activity. As classic drugs currently used in the clinic, acetylcholinesterase inhibitors (AChEIs) restore acetylcholine levels and relieve the symptoms of AD, but are insufficient at delaying the onset of AD. Based on the multi-target-directed ligand (MTDL) strategy, bis-(-)-nor-meptazinol (BIS-MEP) was developed as a multi-target AChEI that mainly targets AChE catalysis and the ß-amyloid (Aß) aggregation process. In this study, we bilaterally injected Aß oligomers and ibotenic acid (IBO) into the hippocampus of ICR mice and then subcutaneously injected mice with BIS-MEP to investigate its therapeutic effects and underlying mechanisms. According to the results from the Morris water maze test, BIS-MEP significantly improved the spatial learning and memory impairments in AD model mice. Compared with the vehicle control, the BIS-MEP treatment obviously inhibited the AChE activity in the mouse brain, consistent with the findings from the behavioral tests. The BIS-MEP treatment also significantly reduced the Aß plaque area in both the hippocampus and cortex, suggesting that BIS-MEP represents a direct intervention for AD pathology. Additionally, the immunohistochemistry and ELISA results revealed that microglia (ionized calcium-binding adapter molecule 1, IBA1) and astrocyte (Glial fibrillary acidic protein, GFAP) activation and the secretion of relevant inflammatory factors (TNFα and IL-6) induced by Aß were decreased by the BIS-MEP treatment. Furthermore, BIS-MEP showed more advantages than donepezil (an approved AChEI) as an Aß intervention. Based on our findings, BIS-MEP improved spatial learning and memory deficits in AD mice by regulating acetylcholinesterase activity, Aß deposition and the inflammatory response in the brain.

LincRNA-p21 suppresses development of human prostate cancer through inhibition of PKM2.

OBJECTIVES: Previously, we found that long intergenic non-coding RNA-p21 (lincRNA-p21) inhibited the development of human prostate cancer. However, the underlying molecular mechanisms are poorly understood. Here, we attempted to investigate the downstream targets of lincRNA-p21 in prostate cancer. MATERIALS AND METHODS: Expression of lincRNA-p21 and PKM2 was determined by qRT-PCR and Western blot. Lentivirus expressing shPKM2 or shCtrl was used to explore the role of PKM2 on the enhanced cell proliferation and glycolysis of lincRNA-p21-silenced prostate cancer cells. A xenograft mouse model was performed to investigate the effect of PKM2 suppression, glycolytic or mammalian target of rapamycin (mTOR) inhibitor on the tumorigenic capacity of lincRNA-p21-silenced prostate cancer cells. RESULTS: We revealed that lincRNA-p21 silencing in DU145 and LNCaP cells induced up-regulation of PKM2 and activation of glycolysis, which could be reversed by PKM2 knockdown or rapamycin treatment. We also found that the proliferation and tumorigenesis of lincRNA-p21-silenced prostate cancer cells were significantly inhibited after knocking down PKM2. 3-bromopyruvate (3-Brpa) or rapamycin treatment largely decreased the tumour burden. Importantly, PKM2 expression was inversely correlated with the lincRNA-p21 level and the survival of prostate cancer patients. CONCLUSIONS: We demonstrated that lincRNA-p21 blunted the prostate cancer cell proliferation and tumorigenic capacity through down-regulation of PKM2. Therefore, targeting PKM2 or glycolysis might be a therapeutic strategy in prostate cancer patients with lowly expressed lincRNA-p21.